Trial Outcomes & Findings for Trametinib and Navitoclax in Treating Patients With Advanced or Metastatic Solid Tumors (NCT NCT02079740)

NCT ID: NCT02079740

Last Updated: 2026-04-29

Results Overview

Dose escalation uses a 3+3 enrollment design per dose level. The occurrence of 1 dose limiting toxicity (DLT) will prompt expansion of a given dose level to 6 participants. The occurrence of 2 DLTs in a given dose level will indicate that the maximal tolerated dose (MTD) has been exceeded, and expansion of the prior dose level to 6 participants will occur, if not already performed. The recommended phase 2 dose (RP2D) will be the highest dose level at which no more than 1 out of 6 participants experiences a DLT. Dose escalation will proceed until the MTD/RP2D have been determined.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE1/PHASE2

Target enrollment

96 participants

Primary outcome timeframe

Within the first 42 days of treatment

Results posted on

2026-04-29

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort 1A = Trametinib 1 mg + Navitoclax 150 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 2A = Trametinib 1.5 mg + Navitoclax 150 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3A = Trametinib 1.5 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 1B = Trametinib 1 mg + Navitoclax 150 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3B = Trametinib 1.5 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3C = Trametinib 1.5 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 4C = Trametinib 2 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 5C = Trametinib 2 mg + Navitoclax 250 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 6C = Trametinib 2 mg + Navitoclax 300 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Expansion Cohort 1 = Pancreatic Cancer Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 2 = GYN Cancer Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 3 = Lung Cancer Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 4 = All Other NRAS Mutation-positive Solid Tumor Types Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.
Phase 1b: Dose Escalation STARTED	3	3	3	3	8	3	3	8	4	0	0	0	0
Phase 1b: Dose Escalation COMPLETED	3	3	3	3	6	3	3	6	4	0	0	0	0
Phase 1b: Dose Escalation NOT COMPLETED	0	0	0	0	2	0	0	2	0	0	0	0	0
Phase 2: Expansion Cohorts STARTED	0	0	0	0	0	0	0	0	0	14	25	7	12
Phase 2: Expansion Cohorts COMPLETED	0	0	0	0	0	0	0	0	0	12	25	6	10
Phase 2: Expansion Cohorts NOT COMPLETED	0	0	0	0	0	0	0	0	0	2	0	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 3B = Trametinib 1.5 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 5C = Trametinib 2 mg + Navitoclax 250 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Expansion Cohort 1 = Pancreatic Cancer Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 3 = Lung Cancer Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 4 = All Other NRAS Mutation-positive Solid Tumor Types Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.
Phase 1b: Dose Escalation Adverse Event	1	0	0	0	0
Phase 1b: Dose Escalation Physician Decision	1	0	0	0	0
Phase 1b: Dose Escalation Clinical Progression	0	1	0	0	0
Phase 1b: Dose Escalation Concurrent anticoagulation prohibited on study	0	1	0	0	0
Phase 2: Expansion Cohorts Withdrawal by Subject	0	0	2	1	2

Baseline Characteristics

Trametinib and Navitoclax in Treating Patients With Advanced or Metastatic Solid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1A = Trametinib 1 mg + Navitoclax 150 mg n=3 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 2A = Trametinib 1.5 mg + Navitoclax 150 mg n=3 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3A = Trametinib 1.5 mg + Navitoclax 200 mg n=3 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 1B = Trametinib 1 mg + Navitoclax 150 mg n=3 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3B = Trametinib 1.5 mg + Navitoclax 200 mg n=8 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3C = Trametinib 1.5 mg + Navitoclax 200 mg n=3 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 4C = Trametinib 2 mg + Navitoclax 200 mg n=3 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 5C = Trametinib 2 mg + Navitoclax 250 mg n=8 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 6C = Trametinib 2 mg + Navitoclax 300 mg n=4 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Expansion Cohort 1 = Pancreatic Cancer n=14 Participants Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 2 = GYN Cancer n=25 Participants Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 3 = Lung Cancer n=7 Participants Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 4 = All Other NRAS Mutation-positive Solid Tumor Types n=12 Participants Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Total n=96 Participants Total of all reporting groups
Race (NIH/OMB) White	3 Participants n=9 Participants	3 Participants n=24 Participants	2 Participants n=23 Participants	3 Participants n=73 Participants	6 Participants n=451 Participants	2 Participants n=60 Participants	2 Participants n=162 Participants	6 Participants n=6 Participants	3 Participants n=15 Participants	13 Participants n=3 Participants	23 Participants n=57 Participants	6 Participants n=15 Participants	11 Participants n=15 Participants	83 Participants n=36 Participants
Race (NIH/OMB) More than one race	0 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants	0 Participants n=73 Participants	0 Participants n=451 Participants	0 Participants n=60 Participants	0 Participants n=162 Participants	0 Participants n=6 Participants	0 Participants n=15 Participants	0 Participants n=3 Participants	0 Participants n=57 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants	0 Participants n=73 Participants	1 Participants n=451 Participants	1 Participants n=60 Participants	0 Participants n=162 Participants	1 Participants n=6 Participants	1 Participants n=15 Participants	1 Participants n=3 Participants	0 Participants n=57 Participants	1 Participants n=15 Participants	0 Participants n=15 Participants	6 Participants n=36 Participants
Cancer Type Pancreatic Cancer	0 Participants n=9 Participants	1 Participants n=24 Participants	0 Participants n=23 Participants	0 Participants n=73 Participants	3 Participants n=451 Participants	1 Participants n=60 Participants	0 Participants n=162 Participants	1 Participants n=6 Participants	1 Participants n=15 Participants	14 Participants n=3 Participants	0 Participants n=57 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	21 Participants n=36 Participants
Cancer Type Lung Cancer	1 Participants n=9 Participants	2 Participants n=24 Participants	3 Participants n=23 Participants	1 Participants n=73 Participants	1 Participants n=451 Participants	0 Participants n=60 Participants	0 Participants n=162 Participants	1 Participants n=6 Participants	0 Participants n=15 Participants	0 Participants n=3 Participants	0 Participants n=57 Participants	7 Participants n=15 Participants	0 Participants n=15 Participants	16 Participants n=36 Participants
Cancer Type GYN Cancer	0 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants	1 Participants n=73 Participants	1 Participants n=451 Participants	0 Participants n=60 Participants	0 Participants n=162 Participants	4 Participants n=6 Participants	1 Participants n=15 Participants	0 Participants n=3 Participants	25 Participants n=57 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	32 Participants n=36 Participants
Cancer Type Colorectal Cancer	2 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants	1 Participants n=73 Participants	2 Participants n=451 Participants	1 Participants n=60 Participants	1 Participants n=162 Participants	2 Participants n=6 Participants	1 Participants n=15 Participants	0 Participants n=3 Participants	0 Participants n=57 Participants	0 Participants n=15 Participants	4 Participants n=15 Participants	14 Participants n=36 Participants
Cancer Type Esophageal Cancer	0 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants	0 Participants n=73 Participants	1 Participants n=451 Participants	0 Participants n=60 Participants	0 Participants n=162 Participants	0 Participants n=6 Participants	0 Participants n=15 Participants	0 Participants n=3 Participants	0 Participants n=57 Participants	0 Participants n=15 Participants	1 Participants n=15 Participants	2 Participants n=36 Participants
Cancer Type Melanoma	0 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants	0 Participants n=73 Participants	0 Participants n=451 Participants	1 Participants n=60 Participants	1 Participants n=162 Participants	0 Participants n=6 Participants	0 Participants n=15 Participants	0 Participants n=3 Participants	0 Participants n=57 Participants	0 Participants n=15 Participants	4 Participants n=15 Participants	6 Participants n=36 Participants
Cancer Type Cholangiocarcinoma	0 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants	0 Participants n=73 Participants	0 Participants n=451 Participants	0 Participants n=60 Participants	1 Participants n=162 Participants	0 Participants n=6 Participants	0 Participants n=15 Participants	0 Participants n=3 Participants	0 Participants n=57 Participants	0 Participants n=15 Participants	1 Participants n=15 Participants	2 Participants n=36 Participants
Cancer Type Gastric Cancer	0 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants	0 Participants n=73 Participants	0 Participants n=451 Participants	0 Participants n=60 Participants	0 Participants n=162 Participants	0 Participants n=6 Participants	1 Participants n=15 Participants	0 Participants n=3 Participants	0 Participants n=57 Participants	0 Participants n=15 Participants	1 Participants n=15 Participants	2 Participants n=36 Participants
Cancer Type Thyroid Cancer	0 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants	0 Participants n=73 Participants	0 Participants n=451 Participants	0 Participants n=60 Participants	0 Participants n=162 Participants	0 Participants n=6 Participants	0 Participants n=15 Participants	0 Participants n=3 Participants	0 Participants n=57 Participants	0 Participants n=15 Participants	1 Participants n=15 Participants	1 Participants n=36 Participants
Age, Categorical <=18 years	0 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants	0 Participants n=73 Participants	0 Participants n=451 Participants	0 Participants n=60 Participants	0 Participants n=162 Participants	0 Participants n=6 Participants	0 Participants n=15 Participants	0 Participants n=3 Participants	0 Participants n=57 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=36 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=9 Participants	3 Participants n=24 Participants	1 Participants n=23 Participants	2 Participants n=73 Participants	6 Participants n=451 Participants	2 Participants n=60 Participants	2 Participants n=162 Participants	7 Participants n=6 Participants	3 Participants n=15 Participants	9 Participants n=3 Participants	16 Participants n=57 Participants	5 Participants n=15 Participants	8 Participants n=15 Participants	66 Participants n=36 Participants
Age, Categorical >=65 years	1 Participants n=9 Participants	0 Participants n=24 Participants	2 Participants n=23 Participants	1 Participants n=73 Participants	2 Participants n=451 Participants	1 Participants n=60 Participants	1 Participants n=162 Participants	1 Participants n=6 Participants	1 Participants n=15 Participants	5 Participants n=3 Participants	9 Participants n=57 Participants	2 Participants n=15 Participants	4 Participants n=15 Participants	30 Participants n=36 Participants
Sex: Female, Male Female	1 Participants n=9 Participants	1 Participants n=24 Participants	1 Participants n=23 Participants	3 Participants n=73 Participants	5 Participants n=451 Participants	2 Participants n=60 Participants	1 Participants n=162 Participants	8 Participants n=6 Participants	2 Participants n=15 Participants	8 Participants n=3 Participants	25 Participants n=57 Participants	4 Participants n=15 Participants	8 Participants n=15 Participants	69 Participants n=36 Participants
Sex: Female, Male Male	2 Participants n=9 Participants	2 Participants n=24 Participants	2 Participants n=23 Participants	0 Participants n=73 Participants	3 Participants n=451 Participants	1 Participants n=60 Participants	2 Participants n=162 Participants	0 Participants n=6 Participants	2 Participants n=15 Participants	6 Participants n=3 Participants	0 Participants n=57 Participants	3 Participants n=15 Participants	4 Participants n=15 Participants	27 Participants n=36 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants	0 Participants n=73 Participants	0 Participants n=451 Participants	0 Participants n=60 Participants	0 Participants n=162 Participants	0 Participants n=6 Participants	0 Participants n=15 Participants	0 Participants n=3 Participants	0 Participants n=57 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Asian	0 Participants n=9 Participants	0 Participants n=24 Participants	1 Participants n=23 Participants	0 Participants n=73 Participants	0 Participants n=451 Participants	0 Participants n=60 Participants	1 Participants n=162 Participants	1 Participants n=6 Participants	0 Participants n=15 Participants	0 Participants n=3 Participants	1 Participants n=57 Participants	0 Participants n=15 Participants	1 Participants n=15 Participants	5 Participants n=36 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants	0 Participants n=73 Participants	0 Participants n=451 Participants	0 Participants n=60 Participants	0 Participants n=162 Participants	0 Participants n=6 Participants	0 Participants n=15 Participants	0 Participants n=3 Participants	0 Participants n=57 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Black or African American	0 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants	0 Participants n=73 Participants	1 Participants n=451 Participants	0 Participants n=60 Participants	0 Participants n=162 Participants	0 Participants n=6 Participants	0 Participants n=15 Participants	0 Participants n=3 Participants	1 Participants n=57 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	2 Participants n=36 Participants

PRIMARY outcome

Timeframe: Within the first 42 days of treatment

Outcome measures

Outcome measures
Measure	Treatment (Trametinib, Navitoclax) n=38 Participants Patients receive trametinib PO QD and navitoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. If unacceptable toxicity is observed, patients may receive trametinib PO QD on days 1-14. Biopsy: Undergo biopsy Biospecimen Collection: Undergo collection of blood samples Computed Tomography: Undergo conventional CT or PET/CT Magnetic Resonance Imaging: Undergo MRI Navitoclax: Given PO Positron Emission Tomography: Undergo PET/CT Trametinib: Given PO	Expansion Cohort 2 = GYN Cancer Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Cohort 3A = Trametinib 1.5 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 1B = Trametinib 1 mg + Navitoclax 150 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3B = Trametinib 1.5 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3C = Trametinib 1.5 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 4C = Trametinib 2 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 5C = Trametinib 2 mg + Navitoclax 250 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 6C = Trametinib 2 mg + Navitoclax 300 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Expansion Cohort 4 = All Other NRAS Mutation-positive Solid Tumor Types Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: Pancreatic Cancer GYN Cancer Lung Cancer all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 1 = Pancreatic Cancer Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: Pancreatic Cancer GYN Cancer Lung Cancer all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.
(Phase 1b) Maximal Tolerated Dose of Trametinib and Navitoclax Trametinib on Days 1-14	2 milligrams per day	—	—	—	—	—	—	—	—	—	—
(Phase 1b) Maximal Tolerated Dose of Trametinib and Navitoclax Navitoclax on Days 1-28	250 milligrams per day	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Within the first 42 days of treatment

Population: In Cohort 3B, 2 of 8 participants were deemed not evaluable for DLT. In Cohort 5C, 2 of 8 participants were deemed not evaluable for DLT.

Dose-limiting toxicity (DLT) are adverse events (AEs) that are serious enough to prevent an increase in dose level of that treatment. Grading based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. CTCAE version 5.0 will be utilized beginning April 1, 2018.

Outcome measures

Outcome measures
Measure	Treatment (Trametinib, Navitoclax) n=3 Participants Patients receive trametinib PO QD and navitoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. If unacceptable toxicity is observed, patients may receive trametinib PO QD on days 1-14. Biopsy: Undergo biopsy Biospecimen Collection: Undergo collection of blood samples Computed Tomography: Undergo conventional CT or PET/CT Magnetic Resonance Imaging: Undergo MRI Navitoclax: Given PO Positron Emission Tomography: Undergo PET/CT Trametinib: Given PO	Expansion Cohort 2 = GYN Cancer n=3 Participants Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Cohort 3A = Trametinib 1.5 mg + Navitoclax 200 mg n=3 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 1B = Trametinib 1 mg + Navitoclax 150 mg n=3 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3B = Trametinib 1.5 mg + Navitoclax 200 mg n=6 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3C = Trametinib 1.5 mg + Navitoclax 200 mg n=3 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 4C = Trametinib 2 mg + Navitoclax 200 mg n=3 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 5C = Trametinib 2 mg + Navitoclax 250 mg n=6 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 6C = Trametinib 2 mg + Navitoclax 300 mg n=4 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Expansion Cohort 4 = All Other NRAS Mutation-positive Solid Tumor Types Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: Pancreatic Cancer GYN Cancer Lung Cancer all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 1 = Pancreatic Cancer Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: Pancreatic Cancer GYN Cancer Lung Cancer all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.
(Phase 1b) Dose-Limiting Toxicities of Trametinib and Navitoclox Grade 3 Enterocolitis	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—	—
(Phase 1b) Dose-Limiting Toxicities of Trametinib and Navitoclox Grade 3 AST/ALT increased	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—
(Phase 1b) Dose-Limiting Toxicities of Trametinib and Navitoclox Grade 4 hypokalemia	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—
(Phase 1b) Dose-Limiting Toxicities of Trametinib and Navitoclox Grade 3 Bilirubin increase	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—	—

PRIMARY outcome

Timeframe: Up to 6 months

Population: There were a total of 10 participants in phase 2 that were not evaluable for response because they did not have a restaging scan-- 1 from expansion cohort 1, 6 from expansion cohort 2, 1 from expansion cohort 3, and 2 from expansion cohort 4.

Response rate is defined as the number of participants who achieve complete response (CR) or partial response (PR), according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1: * CR = Disappearance of target lesion(s). Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm * PR = At least a 30% decrease in the sum of the longest diameter(s) of target lesion(s) Participants are considered evaluable for response if they had measurable disease present at baseline, received at least one cycle of therapy, and had their disease re-evaluated at least once after initiating therapy.

Outcome measures

Outcome measures
Measure	Treatment (Trametinib, Navitoclax) n=11 Participants Patients receive trametinib PO QD and navitoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. If unacceptable toxicity is observed, patients may receive trametinib PO QD on days 1-14. Biopsy: Undergo biopsy Biospecimen Collection: Undergo collection of blood samples Computed Tomography: Undergo conventional CT or PET/CT Magnetic Resonance Imaging: Undergo MRI Navitoclax: Given PO Positron Emission Tomography: Undergo PET/CT Trametinib: Given PO	Expansion Cohort 2 = GYN Cancer n=19 Participants Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Cohort 3A = Trametinib 1.5 mg + Navitoclax 200 mg n=5 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 1B = Trametinib 1 mg + Navitoclax 150 mg n=8 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3B = Trametinib 1.5 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3C = Trametinib 1.5 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 4C = Trametinib 2 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 5C = Trametinib 2 mg + Navitoclax 250 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 6C = Trametinib 2 mg + Navitoclax 300 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Expansion Cohort 4 = All Other NRAS Mutation-positive Solid Tumor Types Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: Pancreatic Cancer GYN Cancer Lung Cancer all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 1 = Pancreatic Cancer Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: Pancreatic Cancer GYN Cancer Lung Cancer all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.
(Phase 2) Response Rate Complete Response	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—
(Phase 2) Response Rate Partial Response	0 Participants	6 Participants	0 Participants	1 Participants	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Up to 31 months

Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progressive disease (PD) or death, whichever occurs first. PD is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 as at least a 20% increase in the (sum of the) longest diameter(s) of target lesion(s), and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

Outcome measures

Outcome measures
Measure	Treatment (Trametinib, Navitoclax) n=12 Participants Patients receive trametinib PO QD and navitoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. If unacceptable toxicity is observed, patients may receive trametinib PO QD on days 1-14. Biopsy: Undergo biopsy Biospecimen Collection: Undergo collection of blood samples Computed Tomography: Undergo conventional CT or PET/CT Magnetic Resonance Imaging: Undergo MRI Navitoclax: Given PO Positron Emission Tomography: Undergo PET/CT Trametinib: Given PO	Expansion Cohort 2 = GYN Cancer n=25 Participants Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Cohort 3A = Trametinib 1.5 mg + Navitoclax 200 mg n=6 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 1B = Trametinib 1 mg + Navitoclax 150 mg n=10 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3B = Trametinib 1.5 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3C = Trametinib 1.5 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 4C = Trametinib 2 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 5C = Trametinib 2 mg + Navitoclax 250 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 6C = Trametinib 2 mg + Navitoclax 300 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Expansion Cohort 4 = All Other NRAS Mutation-positive Solid Tumor Types Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: Pancreatic Cancer GYN Cancer Lung Cancer all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 1 = Pancreatic Cancer Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: Pancreatic Cancer GYN Cancer Lung Cancer all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.
(Phase 2) Progression-free Survival	1.37 months Interval 0.6 to 2.87	5.87 months Interval 0.37 to 31.6	6.57 months Interval 1.33 to 26.77	5.17 months Interval 0.03 to 30.97	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: up to 29 months on treatment

Treatment emergent adverse events (TEAEs) are undesirable events not present prior to study treatment, or an already present event that worsens either in intensity or frequency while on treatment. TEAEs are assessed as grade 3 or higher according to Common Terminology Criteria for Adverse Events (CTCAE) criteria version 4.0. CTCAE criteria version 5.0 will be utilized beginning April 1, 2018. TEAEs are also assessed as possibly, probably, or definitely related to study treatment.

Outcome measures

Outcome measures
Measure	Treatment (Trametinib, Navitoclax) n=12 Participants Patients receive trametinib PO QD and navitoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. If unacceptable toxicity is observed, patients may receive trametinib PO QD on days 1-14. Biopsy: Undergo biopsy Biospecimen Collection: Undergo collection of blood samples Computed Tomography: Undergo conventional CT or PET/CT Magnetic Resonance Imaging: Undergo MRI Navitoclax: Given PO Positron Emission Tomography: Undergo PET/CT Trametinib: Given PO	Expansion Cohort 2 = GYN Cancer n=25 Participants Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Cohort 3A = Trametinib 1.5 mg + Navitoclax 200 mg n=6 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 1B = Trametinib 1 mg + Navitoclax 150 mg n=10 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3B = Trametinib 1.5 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3C = Trametinib 1.5 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 4C = Trametinib 2 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 5C = Trametinib 2 mg + Navitoclax 250 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 6C = Trametinib 2 mg + Navitoclax 300 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Expansion Cohort 4 = All Other NRAS Mutation-positive Solid Tumor Types Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: Pancreatic Cancer GYN Cancer Lung Cancer all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 1 = Pancreatic Cancer Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: Pancreatic Cancer GYN Cancer Lung Cancer all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.
(Phase 2) Treatment Emergent Adverse Events Grade 3 hyponatremia	0 Participants	1 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—
(Phase 2) Treatment Emergent Adverse Events Grade 3 neutrophil count decrease	0 Participants	4 Participants	1 Participants	0 Participants	—	—	—	—	—	—	—
(Phase 2) Treatment Emergent Adverse Events Grade 4 neutrophil count decrease	0 Participants	1 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—
(Phase 2) Treatment Emergent Adverse Events Grade 3 platelet count decrease	1 Participants	2 Participants	0 Participants	4 Participants	—	—	—	—	—	—	—
(Phase 2) Treatment Emergent Adverse Events Grade 3 white blood cell decrease	0 Participants	3 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—
(Phase 2) Treatment Emergent Adverse Events Grade 3 abdominal pain	1 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—
(Phase 2) Treatment Emergent Adverse Events Grade 3 ALT increase	0 Participants	3 Participants	1 Participants	0 Participants	—	—	—	—	—	—	—
(Phase 2) Treatment Emergent Adverse Events Grade 3 anemia	1 Participants	1 Participants	0 Participants	1 Participants	—	—	—	—	—	—	—
(Phase 2) Treatment Emergent Adverse Events Grade 3 AST increase	0 Participants	2 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—
(Phase 2) Treatment Emergent Adverse Events Grade 3 blood bilirubin increased	0 Participants	1 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—
(Phase 2) Treatment Emergent Adverse Events Grade 3 dehydration	0 Participants	1 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—
(Phase 2) Treatment Emergent Adverse Events Grade 3 diarrhea	0 Participants	1 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—
(Phase 2) Treatment Emergent Adverse Events Grade 3 hypertension	0 Participants	0 Participants	0 Participants	1 Participants	—	—	—	—	—	—	—
(Phase 2) Treatment Emergent Adverse Events Grade 3 hypokalemia	0 Participants	0 Participants	1 Participants	0 Participants	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 day 7 and day 21

Population: No data was collected for this outcome for phase 1 cohorts 1B, 3B, 3C, 4C, 5C or 6C.

Pharmacokinetic blood draw samples collected for the following parameter and reported as mean values per day: maximum observed plasma drug concentration (Cmax). Schedule A: * C1 D7 = pre-nav (0h) then 2h, 4h, 6h, 8h * C1 D8 = pre-tram (-1h = 23h post-nav) * C1 D21 = pre-tram (-1h); pre-nav (0h); then 2h, 4h, 6h, 8h post-nav * C1 D22 = pre-tram (-1h = 23h post-nav) * D1 of Cycle 2,4,8,12 (single trough) = pre-tram (-1h) Schedule B: * C1 D7, D14 = pre-tram (-1h); pre-nav (0h); then 2h, 4h, 6h, 8h post-nav * C1 D8, D15 = pre-tram (-1h = 23h post-nav) * D1 of Cycle 2,4,8,12 (single trough) = pre-tram (-1h) Schedule C: * C1 D7, D14 = pre-navitoclax (0h) then 2h, 4h, 6h, 8h * C1 D8, D15 = pre-trametinib (-1h = 23h post-navitoclax) * D1 of Cycle 2,4,8,12 (single trough) = pre-nav (0h)

Outcome measures

Outcome measures
Measure	Treatment (Trametinib, Navitoclax) n=3 Participants Patients receive trametinib PO QD and navitoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. If unacceptable toxicity is observed, patients may receive trametinib PO QD on days 1-14. Biopsy: Undergo biopsy Biospecimen Collection: Undergo collection of blood samples Computed Tomography: Undergo conventional CT or PET/CT Magnetic Resonance Imaging: Undergo MRI Navitoclax: Given PO Positron Emission Tomography: Undergo PET/CT Trametinib: Given PO	Expansion Cohort 2 = GYN Cancer n=3 Participants Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Cohort 3A = Trametinib 1.5 mg + Navitoclax 200 mg n=2 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 1B = Trametinib 1 mg + Navitoclax 150 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3B = Trametinib 1.5 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3C = Trametinib 1.5 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 4C = Trametinib 2 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 5C = Trametinib 2 mg + Navitoclax 250 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 6C = Trametinib 2 mg + Navitoclax 300 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Expansion Cohort 4 = All Other NRAS Mutation-positive Solid Tumor Types Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: Pancreatic Cancer GYN Cancer Lung Cancer all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 1 = Pancreatic Cancer Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: Pancreatic Cancer GYN Cancer Lung Cancer all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.
(Phase 1b) Pharmacokinetic Parameter Cmax for Trametinib and Navitoclax When Administered in Combination Day 7 Navitoclax Cmax	3120.0 ng/mL Interval 1710.0 to 4190.0	2374.0 ng/mL Interval 562.0 to 4480.0	3040.0 ng/mL Interval 2890.0 to 3190.0	—	—	—	—	—	—	—	—
(Phase 1b) Pharmacokinetic Parameter Cmax for Trametinib and Navitoclax When Administered in Combination Day 21 Navitoclax Cmax	2325.0 ng/mL Interval 374.0 to 4740.0	1349.0 ng/mL Interval 347.0 to 1860.0	1405.0 ng/mL Interval 1380.0 to 1430.0	—	—	—	—	—	—	—	—
(Phase 1b) Pharmacokinetic Parameter Cmax for Trametinib and Navitoclax When Administered in Combination Day 21 Trametinib Cmax	12.2 ng/mL Interval 8.37 to 20.5	19.6 ng/mL Interval 14.2 to 29.8	23.2 ng/mL Interval 21.5 to 25.0	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 day 7 and day 21

Population: No data was collected for this outcome for phase 1 cohorts 1B, 3B, 3C, 4C, 5C or 6C.

Pharmacokinetic blood draw samples collected for the following parameter and reported as mean values per day: area under the concentration time curve from zero (pre-dose) to 24 hours (AUC 0-24). Schedule A: * C1 D7 = pre-nav (0h) then 2h, 4h, 6h, 8h * C1 D8 = pre-tram (-1h = 23h post-nav) * C1 D21 = pre-tram (-1h); pre-nav (0h); then 2h, 4h, 6h, 8h post-nav * C1 D22 = pre-tram (-1h = 23h post-nav) * D1 of Cycle 2,4,8,12 (single trough) = pre-tram (-1h) Schedule B: * C1 D7, D14 = pre-tram (-1h); pre-nav (0h); then 2h, 4h, 6h, 8h post-nav * C1 D8, D15 = pre-tram (-1h = 23h post-nav) * D1 of Cycle 2,4,8,12 (single trough) = pre-tram (-1h) Schedule C: * C1 D7, D14 = pre-navitoclax (0h) then 2h, 4h, 6h, 8h * C1 D8, D15 = pre-trametinib (-1h = 23h post-navitoclax) * D1 of Cycle 2,4,8,12 (single trough) = pre-nav (0h)

Outcome measures

Outcome measures
Measure	Treatment (Trametinib, Navitoclax) n=3 Participants Patients receive trametinib PO QD and navitoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. If unacceptable toxicity is observed, patients may receive trametinib PO QD on days 1-14. Biopsy: Undergo biopsy Biospecimen Collection: Undergo collection of blood samples Computed Tomography: Undergo conventional CT or PET/CT Magnetic Resonance Imaging: Undergo MRI Navitoclax: Given PO Positron Emission Tomography: Undergo PET/CT Trametinib: Given PO	Expansion Cohort 2 = GYN Cancer n=3 Participants Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Cohort 3A = Trametinib 1.5 mg + Navitoclax 200 mg n=2 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 1B = Trametinib 1 mg + Navitoclax 150 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3B = Trametinib 1.5 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3C = Trametinib 1.5 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 4C = Trametinib 2 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 5C = Trametinib 2 mg + Navitoclax 250 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 6C = Trametinib 2 mg + Navitoclax 300 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Expansion Cohort 4 = All Other NRAS Mutation-positive Solid Tumor Types Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: Pancreatic Cancer GYN Cancer Lung Cancer all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 1 = Pancreatic Cancer Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: Pancreatic Cancer GYN Cancer Lung Cancer all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.
(Phase 1b) Pharmacokinetic Parameter AUC for Trametinib and Navitoclax When Administered in Combination Day 7 Navitoclax AUC	52219.0 h*ng/mL Interval 26752.0 to 66795.0	35451.0 h*ng/mL Interval 9148.5 to 67610.0	48714.0 h*ng/mL Interval 48038.5 to 49390.0	—	—	—	—	—	—	—	—
(Phase 1b) Pharmacokinetic Parameter AUC for Trametinib and Navitoclax When Administered in Combination Day 21 Navitoclax AUC	30575.0 h*ng/mL Interval 7385.0 to 44056.0	24224.0 h*ng/mL Interval 6177.0 to 38322.0	25804.0 h*ng/mL Interval 24609.0 to 26999.0	—	—	—	—	—	—	—	—
(Phase 1b) Pharmacokinetic Parameter AUC for Trametinib and Navitoclax When Administered in Combination Day 21 Trametinib AUC	206.0 h*ng/mL Interval 160.0 to 308.0	311.0 h*ng/mL Interval 221.0 to 483.0	305.0 h*ng/mL Interval 283.0 to 329.0	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 day 7 and day 21

Pharmacokinetic blood draw samples collected for the following parameter and reported as mean values per day: trough plasma drug concentration (C0). Schedule A: * C1 D7 = pre-nav (0h) then 2h, 4h, 6h, 8h * C1 D8 = pre-tram (-1h = 23h post-nav) * C1 D21 = pre-tram (-1h); pre-nav (0h); then 2h, 4h, 6h, 8h post-nav * C1 D22 = pre-tram (-1h = 23h post-nav) * D1 of Cycle 2,4,8,12 (single trough) = pre-tram (-1h) Schedule B: * C1 D7, D14 = pre-tram (-1h); pre-nav (0h); then 2h, 4h, 6h, 8h post-nav * C1 D8, D15 = pre-tram (-1h = 23h post-nav) * D1 of Cycle 2,4,8,12 (single trough) = pre-tram (-1h) Schedule C: * C1 D7, D14 = pre-navitoclax (0h) then 2h, 4h, 6h, 8h * C1 D8, D15 = pre-trametinib (-1h = 23h post-navitoclax) * D1 of Cycle 2,4,8,12 (single trough) = pre-nav (0h)

Outcome measures

Outcome measures
Measure	Treatment (Trametinib, Navitoclax) n=3 Participants Patients receive trametinib PO QD and navitoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. If unacceptable toxicity is observed, patients may receive trametinib PO QD on days 1-14. Biopsy: Undergo biopsy Biospecimen Collection: Undergo collection of blood samples Computed Tomography: Undergo conventional CT or PET/CT Magnetic Resonance Imaging: Undergo MRI Navitoclax: Given PO Positron Emission Tomography: Undergo PET/CT Trametinib: Given PO	Expansion Cohort 2 = GYN Cancer n=3 Participants Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Cohort 3A = Trametinib 1.5 mg + Navitoclax 200 mg n=2 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 1B = Trametinib 1 mg + Navitoclax 150 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3B = Trametinib 1.5 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3C = Trametinib 1.5 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 4C = Trametinib 2 mg + Navitoclax 200 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 5C = Trametinib 2 mg + Navitoclax 250 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 6C = Trametinib 2 mg + Navitoclax 300 mg During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Expansion Cohort 4 = All Other NRAS Mutation-positive Solid Tumor Types Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: Pancreatic Cancer GYN Cancer Lung Cancer all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 1 = Pancreatic Cancer Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: Pancreatic Cancer GYN Cancer Lung Cancer all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.
(Phase 1b) Pharmacokinetic Parameter C0 for Trametinib and Navitoclax When Administered in Combination Day 7 Navitoclax C0	1156.7 ng/mL Interval 510.0 to 1520.0	1012.0 ng/mL Interval 314.0 to 1710.0	910.5 ng/mL Interval 551.0 to 1270.0	—	—	—	—	—	—	—	—
(Phase 1b) Pharmacokinetic Parameter C0 for Trametinib and Navitoclax When Administered in Combination Day 21 Navitoclax C0	1110 ng/mL Interval 221.0 to 1860.0	584 ng/mL Interval 207.0 to 1080.0	949 ng/mL Interval 857.0 to 1040.0	—	—	—	—	—	—	—	—
(Phase 1b) Pharmacokinetic Parameter C0 for Trametinib and Navitoclax When Administered in Combination Day 21 Trametinib C0	6.4 ng/mL Interval 4.8 to 9.43	9.7 ng/mL Interval 7.5 to 14.9	9.9 ng/mL Interval 8.8 to 11.1	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 4 months

Population: There were a total of 6 participants in phase 1 that were not evaluable for response because they did not have a restaging scan-- 1 from cohort 1A (clinical progression), 3 from cohort 3B, and 2 from cohort 5C.

Outcome measures

Outcome measures
Measure	Treatment (Trametinib, Navitoclax) n=2 Participants Patients receive trametinib PO QD and navitoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. If unacceptable toxicity is observed, patients may receive trametinib PO QD on days 1-14. Biopsy: Undergo biopsy Biospecimen Collection: Undergo collection of blood samples Computed Tomography: Undergo conventional CT or PET/CT Magnetic Resonance Imaging: Undergo MRI Navitoclax: Given PO Positron Emission Tomography: Undergo PET/CT Trametinib: Given PO	Expansion Cohort 2 = GYN Cancer n=3 Participants Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Cohort 3A = Trametinib 1.5 mg + Navitoclax 200 mg n=3 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 1B = Trametinib 1 mg + Navitoclax 150 mg n=3 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3B = Trametinib 1.5 mg + Navitoclax 200 mg n=5 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3C = Trametinib 1.5 mg + Navitoclax 200 mg n=3 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 4C = Trametinib 2 mg + Navitoclax 200 mg n=3 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 5C = Trametinib 2 mg + Navitoclax 250 mg n=6 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 6C = Trametinib 2 mg + Navitoclax 300 mg n=4 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Expansion Cohort 4 = All Other NRAS Mutation-positive Solid Tumor Types Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: Pancreatic Cancer GYN Cancer Lung Cancer all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 1 = Pancreatic Cancer Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: Pancreatic Cancer GYN Cancer Lung Cancer all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.
(Phase 1b) Response Rate Complete Response	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	—
(Phase 1b) Response Rate Partial Response	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Day 1 of cycles 2, 4, 8, and 12

Population: No data was collected for this outcome in the phase 2 expansion cohorts.

Pharmacokinetic (PK) blood draw samples collected for the following parameters: * Maximum observed plasma drug concentration (Cmax) * Area under the concentration time curve from zero (pre-dose) to 24 hours (AUC 0-24) * Pre-dose (trough) drug concentration at the end of the dosing interval (C0) * Half-life (t1/2) Recommended phase 2 dose (RP2D) schedule: \- Day 1 of cycles 2, 4, 8, 12 = pre-trametinib (-1h)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 50 days

Paired pre-treatment and on treatment tumor biopsies will be obtained to assess the pharmacodynamic response to therapy (e.g., change in levels of proteins/mRNAs implicated in MAPK signaling). Results will be reported as a mean percent (%) change in MAPK transcripts day 15 vs day 0. Pre-treatment tumor tissue for analysis will be obtained either from archival tissue remaining from a participant's prior surgery, diagnostic biopsy, or other procedure performed during routine clinical care. Alternatively, study-related pre-treatment biopsies will be obtained between days -21 and -1 of treatment if necessary. On-treatment biopsies will be obtained after \~2 weeks of Cycle 1 combination dosing: * Phase 1b Schedule A = Day 22 +/- 7 days * Phase 1b Schedule B or C = Day 15 +/- 7 days * Phase 2 RP2D = Day 15 +/- 7 days

Outcome measures

Outcome measures
Measure	Treatment (Trametinib, Navitoclax) n=1 Participants Patients receive trametinib PO QD and navitoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. If unacceptable toxicity is observed, patients may receive trametinib PO QD on days 1-14. Biopsy: Undergo biopsy Biospecimen Collection: Undergo collection of blood samples Computed Tomography: Undergo conventional CT or PET/CT Magnetic Resonance Imaging: Undergo MRI Navitoclax: Given PO Positron Emission Tomography: Undergo PET/CT Trametinib: Given PO	Expansion Cohort 2 = GYN Cancer n=1 Participants Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Cohort 3A = Trametinib 1.5 mg + Navitoclax 200 mg n=2 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 1B = Trametinib 1 mg + Navitoclax 150 mg n=1 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3B = Trametinib 1.5 mg + Navitoclax 200 mg n=4 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3C = Trametinib 1.5 mg + Navitoclax 200 mg n=2 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 4C = Trametinib 2 mg + Navitoclax 200 mg n=2 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 5C = Trametinib 2 mg + Navitoclax 250 mg n=1 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 6C = Trametinib 2 mg + Navitoclax 300 mg n=6 Participants During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Expansion Cohort 4 = All Other NRAS Mutation-positive Solid Tumor Types n=1 Participants Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: Pancreatic Cancer GYN Cancer Lung Cancer all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 1 = Pancreatic Cancer n=2 Participants Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: Pancreatic Cancer GYN Cancer Lung Cancer all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.
(Phase 1b and 2) Percent Change in Levels of Proteins/Messenger Ribonucleic Acids Implicated in Mitogen-activated Protein Kinase Signaling	15.2 percentage of change MAPK transcripts Standard Error 0	-98.3 percentage of change MAPK transcripts Standard Error 0	-39.5 percentage of change MAPK transcripts Standard Error 25	-98.3 percentage of change MAPK transcripts Standard Error 0	6.0 percentage of change MAPK transcripts Standard Error 67	8.7 percentage of change MAPK transcripts Standard Error 19	-49.0 percentage of change MAPK transcripts Standard Error 50	-42.5 percentage of change MAPK transcripts Standard Error 0	6.8 percentage of change MAPK transcripts Standard Error 99	132.0 percentage of change MAPK transcripts Standard Error 0	175.3 percentage of change MAPK transcripts Standard Error 229

Deaths: 4 deaths

Expansion Cohort 4 = All Other NRAS Mutation-positive Solid Tumor Types

Serious events: 0 serious events

Other events: 7 other events

Deaths: 6 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1A = Trametinib 1 mg + Navitoclax 150 mg n=3 participants at risk During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 2A = Trametinib 1.5 mg + Navitoclax 150 mg n=3 participants at risk During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3A = Trametinib 1.5 mg + Navitoclax 200 mg n=3 participants at risk During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 1B = Trametinib 1 mg + Navitoclax 150 mg n=3 participants at risk During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3B = Trametinib 1.5 mg + Navitoclax 200 mg n=8 participants at risk During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3C = Trametinib 1.5 mg + Navitoclax 200 mg n=3 participants at risk During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 4C = Trametinib 2 mg + Navitoclax 200 mg n=3 participants at risk During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 5C = Trametinib 2 mg + Navitoclax 250 mg n=8 participants at risk During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 6C = Trametinib 2 mg + Navitoclax 300 mg n=4 participants at risk During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Expansion Cohort 1 = Pancreatic Cancer n=12 participants at risk Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 2 = GYN Cancer n=25 participants at risk Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 3 = Lung Cancer n=6 participants at risk Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 4 = All Other NRAS Mutation-positive Solid Tumor Types n=10 participants at risk Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Metabolism and nutrition disorders Hypokalemia	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Metabolism and nutrition disorders Hyponatremia	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Gastrointestinal disorders Nausea	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
General disorders Non-cardiac chest pain	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Investigations Platelet count decreased	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Infections and infestations Sepsis	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	25.0% 1/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Gastrointestinal disorders Vomiting	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	8.3% 1/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Investigations Creatinine increased	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Gastrointestinal disorders Enterocolitis	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	25.0% 1/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
General disorders Fatigue	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months

Other adverse events

Other adverse events
Measure	Cohort 1A = Trametinib 1 mg + Navitoclax 150 mg n=3 participants at risk During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 2A = Trametinib 1.5 mg + Navitoclax 150 mg n=3 participants at risk During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3A = Trametinib 1.5 mg + Navitoclax 200 mg n=3 participants at risk During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 1B = Trametinib 1 mg + Navitoclax 150 mg n=3 participants at risk During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3B = Trametinib 1.5 mg + Navitoclax 200 mg n=8 participants at risk During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 3C = Trametinib 1.5 mg + Navitoclax 200 mg n=3 participants at risk During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 4C = Trametinib 2 mg + Navitoclax 200 mg n=3 participants at risk During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 5C = Trametinib 2 mg + Navitoclax 250 mg n=8 participants at risk During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Cohort 6C = Trametinib 2 mg + Navitoclax 300 mg n=4 participants at risk During Phase 1b dose escalation, participants received trametinib orally (PO) once daily (QD) and navitoclax PO QD on days 1-28 of each cycle until disease progression or unacceptable toxicity. A 7-day lead-in dosing of Navitoclax 150 mg will be evaluated in Cycle 1 for dose levels 3-7 before proceeding to their target doses: * Schedule A = 7-day lead-in dosing of navitoclax as a single agent, prior to the initiation of trametinib dosing. * Schedule B = 7-day lead-in dosing of navitoclax simultaneous with the initiation of trametinib dosing. Dose levels 1-3 will be enrolled according to Schedule A (i.e., cohorts 1A, 2A, 3A). If significant safety concerns are noted, study will proceed according to Schedule A (i.e., cohorts 4A, 5A, 6A, 7A). If no significant safety concerns are noted, and it is deemed safe to proceed, dosing will return to dose level 1 according to schedule B (i.e., cohort 1B), then proceed directly cohort 3B. If \>1 DLT within cohort 1B or 3B, then Schedule B will be abandoned, and study will proceed with cohorts 4A, 5A, 6A, 7A. If cohort 3B is completed with \</= 1 DLT, and Schedule B demonstrates a comparable or improved safety profile relative to Schedule A, then study will proceed with cohorts 4B, 5B, 6B, 7B. If, however, unacceptable toxicity is observed at a given dose level independent of Schedule A or B, then an alternative dosing Schedule C will be explored with Trametinib dosing on days 1-14 only, beginning at last dose level completed.	Expansion Cohort 1 = Pancreatic Cancer n=12 participants at risk Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 2 = GYN Cancer n=25 participants at risk Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 3 = Lung Cancer n=6 participants at risk Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.	Expansion Cohort 4 = All Other NRAS Mutation-positive Solid Tumor Types n=10 participants at risk Phase 2 expansion cohorts use recommended phase 2 dosing (RP2D) determined in Phase 1b. Participants with KRAS or NRAS mutation-positive solid tumors will be enrolled into up to 4 different disease-specific expansion cohorts: 1. Pancreatic Cancer 2. GYN Cancer 3. Lung Cancer 4. all other NRAS mutation-positive solid tumor types exclusive of pancreatic, GYN, and lung cancers Initially 12 participants will be enrolled to each expansion cohort in Stage 1. If no responses are observed in a given cohort among the first 12 patients, then that cohort will be stopped for futility. However, if one or more responses are observed in a given cohort, the cohort will proceed to Stage 2, and an additional 13 patients will be enrolled for a total of 25 patients in that cohort.
Investigations Blood bilirubin increased	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	50.0% 2/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	16.0% 4/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	10.0% 1/10 • Up to 34 months
Eye disorders Blurred vision	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	8.0% 2/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Injury, poisoning and procedural complications Bruising	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Skin and subcutaneous tissue disorders Bullous dermatitis	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
General disorders Chills	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Gastrointestinal disorders Constipation	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	25.0% 1/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	8.0% 2/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	10.0% 1/10 • Up to 34 months
Investigations Creatinine increased	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	10.0% 1/10 • Up to 34 months
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	8.0% 2/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Gastrointestinal disorders Diarrhea	66.7% 2/3 • Up to 34 months	100.0% 3/3 • Up to 34 months	100.0% 3/3 • Up to 34 months	66.7% 2/3 • Up to 34 months	75.0% 6/8 • Up to 34 months	33.3% 1/3 • Up to 34 months	100.0% 3/3 • Up to 34 months	75.0% 6/8 • Up to 34 months	75.0% 3/4 • Up to 34 months	41.7% 5/12 • Up to 34 months	68.0% 17/25 • Up to 34 months	50.0% 3/6 • Up to 34 months	50.0% 5/10 • Up to 34 months
Nervous system disorders Dizziness	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	66.7% 2/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	25.0% 1/4 • Up to 34 months	8.3% 1/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Eye disorders Dry eye	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	16.7% 1/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Gastrointestinal disorders Dry mouth	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	25.0% 1/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Skin and subcutaneous tissue disorders Dry skin	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	16.0% 4/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	10.0% 1/10 • Up to 34 months
Nervous system disorders Dysgeusia	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	25.0% 2/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	8.3% 1/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Gastrointestinal disorders Dyspepsia	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	8.3% 1/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
General disorders Edema face	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	16.7% 1/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
General disorders Edema limbs	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	33.3% 1/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	25.0% 2/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	8.3% 1/12 • Up to 34 months	16.0% 4/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Investigations Ejection fraction decreased	33.3% 1/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Respiratory, thoracic and mediastinal disorders Epistaxis	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	25.0% 2/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Eye disorders Eye disorders other	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Injury, poisoning and procedural complications Fall	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	25.0% 1/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
General disorders Fatigue	33.3% 1/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	25.0% 2/8 • Up to 34 months	33.3% 1/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	37.5% 3/8 • Up to 34 months	25.0% 1/4 • Up to 34 months	16.7% 2/12 • Up to 34 months	56.0% 14/25 • Up to 34 months	16.7% 1/6 • Up to 34 months	20.0% 2/10 • Up to 34 months
General disorders Fever	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Gastrointestinal disorders Flatulence	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	16.7% 2/12 • Up to 34 months	32.0% 8/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Eye disorders Floaters	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	8.3% 1/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Vascular disorders Flushing	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Gastrointestinal disorders Bloating	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	8.3% 1/12 • Up to 34 months	16.0% 4/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	10.0% 1/10 • Up to 34 months
Gastrointestinal disorders Mucositis oral	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	66.7% 2/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	8.3% 1/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	10.0% 1/10 • Up to 34 months
Gastrointestinal disorders gastrointestinal disorders other specify	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Skin and subcutaneous tissue disorders Nail discoloration	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Nervous system disorders Headache	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	25.0% 2/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Hepatobiliary disorders hepatobiliary disorders other specify	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	10.0% 1/10 • Up to 34 months
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Vascular disorders Hypertension	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	25.0% 2/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	20.0% 2/10 • Up to 34 months
Metabolism and nutrition disorders Hypoalbuminemia	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	25.0% 1/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	8.0% 2/25 • Up to 34 months	16.7% 1/6 • Up to 34 months	10.0% 1/10 • Up to 34 months
Metabolism and nutrition disorders Hypocalcemia	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	25.0% 2/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	16.7% 1/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Metabolism and nutrition disorders Hypokalemia	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	8.3% 1/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	16.7% 1/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Metabolism and nutrition disorders Hypomagnesemia	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	8.3% 1/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	10.0% 1/10 • Up to 34 months
Metabolism and nutrition disorders Hyponatremia	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	8.0% 2/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	10.0% 1/10 • Up to 34 months
Vascular disorders Hypotension	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	25.0% 1/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Skin and subcutaneous tissue disorders Nail loss	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Infections and infestations Infections and infestations Other, specify	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Gastrointestinal disorders Nausea	33.3% 1/3 • Up to 34 months	66.7% 2/3 • Up to 34 months	100.0% 3/3 • Up to 34 months	66.7% 2/3 • Up to 34 months	87.5% 7/8 • Up to 34 months	66.7% 2/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	50.0% 4/8 • Up to 34 months	25.0% 1/4 • Up to 34 months	8.3% 1/12 • Up to 34 months	52.0% 13/25 • Up to 34 months	33.3% 2/6 • Up to 34 months	10.0% 1/10 • Up to 34 months
Investigations Neutrophil count decreased	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	37.5% 3/8 • Up to 34 months	50.0% 2/4 • Up to 34 months	33.3% 4/12 • Up to 34 months	52.0% 13/25 • Up to 34 months	33.3% 2/6 • Up to 34 months	10.0% 1/10 • Up to 34 months
Gastrointestinal disorders Oral pain	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Skin and subcutaneous tissue disorders Papulopustular rash	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Investigations INR increased	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	16.7% 1/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
General disorders Localized edema	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	16.7% 1/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	16.7% 1/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Reproductive system and breast disorders Genital edema	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Vascular disorders Lymphedema	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Investigations Lymphocyte count decreased	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
General disorders Malaise	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	10.0% 1/10 • Up to 34 months
Skin and subcutaneous tissue disorders Pruritus	33.3% 1/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	25.0% 2/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	8.3% 1/12 • Up to 34 months	16.0% 4/25 • Up to 34 months	16.7% 1/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Skin and subcutaneous tissue disorders Rash acneiform	66.7% 2/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	66.7% 2/3 • Up to 34 months	66.7% 2/3 • Up to 34 months	37.5% 3/8 • Up to 34 months	33.3% 1/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	62.5% 5/8 • Up to 34 months	75.0% 3/4 • Up to 34 months	25.0% 3/12 • Up to 34 months	64.0% 16/25 • Up to 34 months	16.7% 1/6 • Up to 34 months	50.0% 5/10 • Up to 34 months
Skin and subcutaneous tissue disorders Rash maculo-papular	33.3% 1/3 • Up to 34 months	66.7% 2/3 • Up to 34 months	66.7% 2/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	50.0% 4/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	25.0% 3/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	10.0% 1/10 • Up to 34 months
Renal and urinary disorders Dysuria	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Cardiac disorders Sinus tachycardia	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	50.0% 2/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Gastrointestinal disorders Stomach pain	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Vascular disorders Thromboembolic event	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	25.0% 1/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Infections and infestations Paronychia	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	8.0% 2/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Eye disorders Periorbital edema	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Investigations Platelet count decreased	66.7% 2/3 • Up to 34 months	66.7% 2/3 • Up to 34 months	100.0% 3/3 • Up to 34 months	100.0% 3/3 • Up to 34 months	62.5% 5/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	66.7% 2/3 • Up to 34 months	75.0% 6/8 • Up to 34 months	25.0% 1/4 • Up to 34 months	83.3% 10/12 • Up to 34 months	72.0% 18/25 • Up to 34 months	50.0% 3/6 • Up to 34 months	50.0% 5/10 • Up to 34 months
Skin and subcutaneous tissue disorders PPE syndrome	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Infections and infestations Urinary tract infection	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Reproductive system and breast disorders Vaginal hemorrhage	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Gastrointestinal disorders Vomiting	66.7% 2/3 • Up to 34 months	66.7% 2/3 • Up to 34 months	100.0% 3/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	62.5% 5/8 • Up to 34 months	33.3% 1/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	50.0% 4/8 • Up to 34 months	25.0% 1/4 • Up to 34 months	8.3% 1/12 • Up to 34 months	40.0% 10/25 • Up to 34 months	16.7% 1/6 • Up to 34 months	50.0% 5/10 • Up to 34 months
Investigations Weight loss	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	4.0% 1/25 • Up to 34 months	16.7% 1/6 • Up to 34 months	10.0% 1/10 • Up to 34 months
Investigations White blood cell decreased	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	37.5% 3/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	16.7% 2/12 • Up to 34 months	36.0% 9/25 • Up to 34 months	16.7% 1/6 • Up to 34 months	10.0% 1/10 • Up to 34 months
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders Other, specify	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	16.7% 1/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Metabolism and nutrition disorders Anorexia	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	100.0% 3/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	25.0% 2/8 • Up to 34 months	25.0% 1/4 • Up to 34 months	8.3% 1/12 • Up to 34 months	12.0% 3/25 • Up to 34 months	50.0% 3/6 • Up to 34 months	0.00% 0/10 • Up to 34 months
Investigations Aspartate aminotransferase increased	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	66.7% 2/3 • Up to 34 months	66.7% 2/3 • Up to 34 months	25.0% 2/8 • Up to 34 months	33.3% 1/3 • Up to 34 months	66.7% 2/3 • Up to 34 months	87.5% 7/8 • Up to 34 months	100.0% 4/4 • Up to 34 months	58.3% 7/12 • Up to 34 months	72.0% 18/25 • Up to 34 months	66.7% 4/6 • Up to 34 months	40.0% 4/10 • Up to 34 months
Investigations Alanine aminotransferase increased	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	66.7% 2/3 • Up to 34 months	25.0% 2/8 • Up to 34 months	33.3% 1/3 • Up to 34 months	33.3% 1/3 • Up to 34 months	37.5% 3/8 • Up to 34 months	50.0% 2/4 • Up to 34 months	41.7% 5/12 • Up to 34 months	84.0% 21/25 • Up to 34 months	50.0% 3/6 • Up to 34 months	60.0% 6/10 • Up to 34 months
Blood and lymphatic system disorders Anemia	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	66.7% 2/3 • Up to 34 months	37.5% 3/8 • Up to 34 months	50.0% 2/4 • Up to 34 months	25.0% 3/12 • Up to 34 months	48.0% 12/25 • Up to 34 months	33.3% 2/6 • Up to 34 months	20.0% 2/10 • Up to 34 months
Gastrointestinal disorders Abdominal Pain	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	0.00% 0/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	10.0% 1/10 • Up to 34 months
Investigations Alkaline phosphatase increased	33.3% 1/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	66.7% 2/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	12.5% 1/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	16.7% 2/12 • Up to 34 months	24.0% 6/25 • Up to 34 months	16.7% 1/6 • Up to 34 months	20.0% 2/10 • Up to 34 months
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/3 • Up to 34 months	0.00% 0/8 • Up to 34 months	0.00% 0/4 • Up to 34 months	0.00% 0/12 • Up to 34 months	8.0% 2/25 • Up to 34 months	0.00% 0/6 • Up to 34 months	0.00% 0/10 • Up to 34 months

Additional Information

Ryan Corcoran, MD PhD

Massachusetts General Hospital

Phone: 617-724-4000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60