Trial Outcomes & Findings for GDC-0084 in Combination With Trastuzumab for Patients With HER2-Positive Breast Cancer Brain Metastases (NCT NCT03765983)

Last Updated: 2026-05-27

Results Overview

Defined as the proportion of patients with partial or complete response in the CNS, per RANO-BM criteria (Complete response \[CR\]: disappearance of all CNS target lesions sustained for at least 4 weeks, no new lesions, no corticosteroids, stable or improved clinically; Partial response \[PR\]: At least 30% decrease in the sum of longest diameter of CNS target lesions, taking as reference the baseline sum, sustained for at least 4 weeks, no new lesions, stable to decreased corticosteroid dose, stable or improved clinically; Progressive disease \[PD\]: At least a 20% increase in the sum of longest diameter of CNS target lesions, taking as reference the smallest sum on study; Stable disease \[SD\]: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of long diameter of CNS target lesions while on study; Objective response = CR+PR)

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

17 participants

Primary outcome timeframe

Assessed every 2 cycles for the first 4 cycles, and then every 3 cycles thereafter, until CNS progression or initiation of new anticancer therapy, up to ~34 weeks.

Results posted on

2026-05-27

Participant Flow

Patients were enrolled at Dana-Farber Cancer Institute between 2/25/2019 and 3/21/2024

The study planned to first enroll a safety run-in cohort of 6 patients at DL1 to evaluate for DLTs in the first cycle of therapy, to identify the RP2D. If DLT was observed in \>1/6 patients, a second safety run-in cohort of 6 patients would be enrolled at DL-1, and would follow the same evaluation. If DLT was observed in \>1/6 patients treated at DL-1, the study would close. If the RP2D was identified, the study would continue to the target phase II accrual. No patients were enrolled to Cohort B.

Participant milestones

Participant milestones
Measure	Cohort A Safety Run-In Dose Level 1: GDC-0084 (45 mg) Plus Trastuzumab GDC-0084 45 mg administered orally once daily Trastuzumab administered at a dose of 8 mg/kg intravenously (IV) loading dose; followed by 6 mg/kg IV every 3 weeks thereafter	Cohort A Safety Run-In Dose Level -1 and Phase 2 Expansion: GDC-0084 (30 mg) Plus Trastuzumab GDC-0084 30 mg administered orally once daily Trastuzumab administered at a dose of 8 mg/kg intravenously (IV) loading dose; followed by 6 mg/kg IV every 3 weeks thereafter
Safety run-in DL1 (45 mg) STARTED	5	0
Safety run-in DL1 (45 mg) COMPLETED	5	0
Safety run-in DL1 (45 mg) NOT COMPLETED	0	0
Safety run-in DL-1 (30 mg) and Phase 2 STARTED	0	12
Safety run-in DL-1 (30 mg) and Phase 2 Safety Run-in Phase	0	6
Safety run-in DL-1 (30 mg) and Phase 2 Expansion Phase	0	6
Safety run-in DL-1 (30 mg) and Phase 2 COMPLETED	0	12
Safety run-in DL-1 (30 mg) and Phase 2 NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

GDC-0084 in Combination With Trastuzumab for Patients With HER2-Positive Breast Cancer Brain Metastases

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A Safety Run-In Dose Level 1: GDC-0084 (45 mg) Plus Trastuzumab n=5 Participants GDC-0084 45 mg administered orally once daily Trastuzumab administered at a dose of 8 mg/kg intravenously (IV) loading dose; followed by 6 mg/kg IV every 3 weeks thereafter	Cohort A Safety Run-In Dose Level -1 and Phase 2 Expansion: GDC-0084 (30 mg) Plus Trastuzumab n=12 Participants GDC-0084 30 mg administered orally once daily Trastuzumab administered at a dose of 8 mg/kg intravenously (IV) loading dose; followed by 6 mg/kg IV every 3 weeks thereafter	Cohort B Phase 2 Expansion: GDC-0084 (RP2D) Plus Trastuzumab GDC-0084 at the RP2D identified in Cohort A safety run-in, administered orally once daily Trastuzumab administered at a dose of 8 mg/kg intravenously (IV) loading dose; followed by 6 mg/kg IV every 3 weeks thereafter Surgical brain metastasis resection	Total n=17 Participants Total of all reporting groups
Age, Continuous	42.2 years n=51 Participants	44.9 years n=14 Participants	—	44.3 years n=24 Participants
Age, Customized Age category · <50 years	4 Participants n=51 Participants	7 Participants n=14 Participants	0 Participants n=65 Participants	11 Participants n=24 Participants
Age, Customized Age category · >=50 years	1 Participants n=51 Participants	5 Participants n=14 Participants	0 Participants n=65 Participants	6 Participants n=24 Participants
Sex: Female, Male Female	5 Participants n=51 Participants	12 Participants n=14 Participants	0 Participants n=65 Participants	17 Participants n=24 Participants
Sex: Female, Male Male	0 Participants n=51 Participants	0 Participants n=14 Participants	0 Participants n=65 Participants	0 Participants n=24 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=51 Participants	0 Participants n=14 Participants	0 Participants n=65 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Asian	0 Participants n=51 Participants	1 Participants n=14 Participants	0 Participants n=65 Participants	1 Participants n=24 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=51 Participants	0 Participants n=14 Participants	0 Participants n=65 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Black or African American	1 Participants n=51 Participants	2 Participants n=14 Participants	0 Participants n=65 Participants	3 Participants n=24 Participants
Race (NIH/OMB) White	4 Participants n=51 Participants	8 Participants n=14 Participants	0 Participants n=65 Participants	12 Participants n=24 Participants
Race (NIH/OMB) More than one race	0 Participants n=51 Participants	0 Participants n=14 Participants	0 Participants n=65 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=51 Participants	1 Participants n=14 Participants	0 Participants n=65 Participants	1 Participants n=24 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=51 Participants	0 Participants n=14 Participants	0 Participants n=65 Participants	0 Participants n=24 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=51 Participants	12 Participants n=14 Participants	0 Participants n=65 Participants	17 Participants n=24 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=51 Participants	0 Participants n=14 Participants	0 Participants n=65 Participants	0 Participants n=24 Participants
Eastern Cooperative Oncology Group Performance Status 0: Fully active; no restrictions on pre-disease performance	2 Participants n=51 Participants	8 Participants n=14 Participants	0 Participants n=65 Participants	10 Participants n=24 Participants
Eastern Cooperative Oncology Group Performance Status 1: Restricted in physically strenuous activity but ambulatory; able to do light work	3 Participants n=51 Participants	3 Participants n=14 Participants	0 Participants n=65 Participants	6 Participants n=24 Participants
Eastern Cooperative Oncology Group Performance Status 2: Ambulatory and capable of all self-care; unable to work; up and about >50% of waking hours	0 Participants n=51 Participants	1 Participants n=14 Participants	0 Participants n=65 Participants	1 Participants n=24 Participants
Stage at primary diagnosis I	2 Participants n=51 Participants	1 Participants n=14 Participants	0 Participants n=65 Participants	3 Participants n=24 Participants
Stage at primary diagnosis II	1 Participants n=51 Participants	3 Participants n=14 Participants	0 Participants n=65 Participants	4 Participants n=24 Participants
Stage at primary diagnosis III	0 Participants n=51 Participants	3 Participants n=14 Participants	0 Participants n=65 Participants	3 Participants n=24 Participants
Stage at primary diagnosis IV - de novo metastatic	2 Participants n=51 Participants	5 Participants n=14 Participants	0 Participants n=65 Participants	7 Participants n=24 Participants

PRIMARY outcome

Timeframe: Assessed every 2 cycles for the first 4 cycles, and then every 3 cycles thereafter, until CNS progression or initiation of new anticancer therapy, up to ~34 weeks.

Population: The protocol-defined efficacy analysis population was patients treated at the RP2D (DL-1). As such, efficacy outcomes were not evaluated for the patients treated at DL1.

Outcome measures

Outcome measures
Measure	Cohort A: GDC-0084 Plus Trastuzumab for HER2+ MBC With CNS Metastases n=12 Participants GDC-0084 at the RP2D (30mg) mg administered orally once daily Trastuzumab administered at a dose of 8 mg/kg intravenously (IV) loading dose; followed by 6 mg/kg IV every 3 weeks thereafter
Objective Response Rate in the CNS	0 Participants

PRIMARY outcome

Timeframe: 2 Years

Population: There was no enrollment to Cohort B

to correlate on-treatment p4EBP1 levels in the resected brain tumor tissue collected from patients to intracranial response to GDC-0084/trastuzumab and survival in the PDX model generated from the same patient

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Assessed every 2 cycles for the first 4 cycles, and then every 3 cycles thereafter, until CNS progression or initiation of new anticancer therapy, up to ~34 weeks

Population: The protocol-defined efficacy analysis population was patients treated at the RP2D (DL-1). As such, efficacy outcomes were not evaluated for the patients treated at DL1.

Defined as the proportion of participants with CNS response or stable disease in the CNS \>=18 or 24 weeks, per RANO-BM criteria (Complete response \[CR\]: disappearance of all CNS target lesions sustained for at least 4 weeks, no new lesions, no corticosteroids, stable or improved clinically; Partial response \[PR\]: At least 30% decrease in the sum of longest diameter of CNS target lesions, taking as reference the baseline sum, sustained for at least 4 weeks, no new lesions, stable to decreased corticosteroid dose, stable or improved clinically; Progressive disease \[PD\]: At least a 20% increase in the sum of longest diameter of CNS target lesions, taking as reference the smallest sum on study; Stable disease \[SD\]: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of long diameter of CNS target lesions while on study; Clinical benefit 18 weeks = CR+PR+SD\>=18 weeks; Clinical benefit 24 weeks = CR+PR+SD\>=24 weeks)

Outcome measures

Outcome measures
Measure	Cohort A: GDC-0084 Plus Trastuzumab for HER2+ MBC With CNS Metastases n=12 Participants GDC-0084 at the RP2D (30mg) mg administered orally once daily Trastuzumab administered at a dose of 8 mg/kg intravenously (IV) loading dose; followed by 6 mg/kg IV every 3 weeks thereafter
Clinical Benefit Rate in the CNS Clinical Benefit Rate: 18 weeks · 18 weeks	1 Participants
Clinical Benefit Rate in the CNS Clinical Benefit Rate: 24 weeks · 18 weeks	0 Participants

SECONDARY outcome

Timeframe: Assessed every 2 cycles for the first 4 cycles, and then every 3 cycles thereafter, until CNS progression or initiation of new anticancer therapy, up to ~34 weeks

Population: The protocol-defined efficacy analysis population was patients treated at the RP2D (DL-1). As such, efficacy outcomes were not evaluated for the patients treated at DL1.

Defined as the proportion of participants with non-CNS response or stable disease in non-CNS lesions \>=18 or 24 weeks, per RECIST 1.1 criteria (Complete response \[CR\]: Disappearance of all target lesions; Partial response \[PR\]: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum; Progressive disease \[PD\]: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study; Stable disease \[SD\]: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters on study; Clinical benefit 18 weeks = CR+PR+SD\>=18 weeks; Clinical benefit 24 weeks = CR+PR+SD\>=24 weeks)

Outcome measures

Outcome measures
Measure	Cohort A: GDC-0084 Plus Trastuzumab for HER2+ MBC With CNS Metastases n=12 Participants GDC-0084 at the RP2D (30mg) mg administered orally once daily Trastuzumab administered at a dose of 8 mg/kg intravenously (IV) loading dose; followed by 6 mg/kg IV every 3 weeks thereafter
Clinical Benefit Rate in Extra-CNS Clinical Benefit Rate: 18 weeks	0 Participants
Clinical Benefit Rate in Extra-CNS Clinical Benefit Rate: 24 weeks	0 Participants

SECONDARY outcome

Timeframe: Assessed every 2 cycles for the first 4 cycles, and then every 3 cycles thereafter, until CNS progression or initiation of new anticancer therapy, up to ~34 weeks.

Population: The protocol-defined efficacy analysis population was patients treated at the RP2D (DL-1). As such, efficacy outcomes were not evaluated for the patients treated at DL1.

Defined as the proportion of patients with partial or complete response in non-CNS lesions, per RECIST 1.1 criteria (Complete response \[CR\]: Disappearance of all target lesions; Partial response \[PR\]: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum; Progressive disease \[PD\]: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study; Stable disease \[SD\]: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters on study; Objective response = CR+PR)

Outcome measures

Outcome measures
Measure	Cohort A: GDC-0084 Plus Trastuzumab for HER2+ MBC With CNS Metastases n=12 Participants GDC-0084 at the RP2D (30mg) mg administered orally once daily Trastuzumab administered at a dose of 8 mg/kg intravenously (IV) loading dose; followed by 6 mg/kg IV every 3 weeks thereafter
Objective Response Rate in Extra-CNS	0 Participants

SECONDARY outcome

Timeframe: Assessed every 2 cycles for the first 4 cycles, and then every 3 cycles thereafter, until CNS progression or initiation of new anticancer therapy, up to ~34 weeks.

Population: The protocol-defined efficacy analysis population was patients treated at the RP2D (DL-1). As such, efficacy outcomes were not evaluated for the patients treated at DL1. There were 0 efficacy-evaluable patients with CNS response, thus duration of response was not estimable.

Defined as the time measurement criteria are met for CR or PR in the CNS (whichever is first recorded) until the first date that progressive disease is objectively documented

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Assessed every 2 cycles for the first 4 cycles, and then every 3 cycles thereafter, until CNS progression or initiation of new anticancer therapy, up to ~34 weeks.

Population: The protocol-defined efficacy analysis population was patients treated at the RP2D (DL-1). As such, efficacy outcomes were not evaluated for the patients treated at DL1.

Defined as the time from registration to the first occurrence of progression in the CNS (per RANO-BM criteria), the body (per RECIST 1.1 criteria), or death, whichever comes first. Patients free from progression in the CNS or body are censored at the date of last disease evaluation

Outcome measures

Outcome measures
Measure	Cohort A: GDC-0084 Plus Trastuzumab for HER2+ MBC With CNS Metastases n=12 Participants GDC-0084 at the RP2D (30mg) mg administered orally once daily Trastuzumab administered at a dose of 8 mg/kg intravenously (IV) loading dose; followed by 6 mg/kg IV every 3 weeks thereafter
Bi-compartmental Progression-free Survival	7.4 Weeks Interval 5.7 to Insufficient sample size/number of events

SECONDARY outcome

Timeframe: Assessed every 6 months until death of off-study, up to ~62 months

Population: The protocol-defined efficacy analysis population was patients treated at the RP2D (DL-1). As such, efficacy outcomes were not evaluated for the patients treated at DL1.

Defined as the time from registration to death from any cause. Patients still living are censored at the date last known alive

Outcome measures

Outcome measures
Measure	Cohort A: GDC-0084 Plus Trastuzumab for HER2+ MBC With CNS Metastases n=12 Participants GDC-0084 at the RP2D (30mg) mg administered orally once daily Trastuzumab administered at a dose of 8 mg/kg intravenously (IV) loading dose; followed by 6 mg/kg IV every 3 weeks thereafter
Overall Survival	16.5 months Interval 7.8 to Insufficient sample size/number of events

Adverse Events

Cohort A Safety Run-In Dose Level 1: GDC-0084 (45 mg) Plus Trastuzumab

Serious events: 1 serious events

Other events: 4 other events

Deaths: 3 deaths

Cohort A Safety Run-In Dose Level -1 and Phase 2 Expansion: GDC-0084 (30 mg) Plus Trastuzumab

Serious events: 2 serious events

Other events: 12 other events

Deaths: 6 deaths

Serious adverse events

Other adverse events

Additional Information

Jose P. Leone, MD

Dana-Farber Cancer Institute

Phone: 617-632-3800

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort A Safety Run-In Dose Level 1: GDC-0084 (45 mg) Plus Trastuzumab n=5 participants at risk GDC-0084 45 mg administered orally once daily Trastuzumab administered at a dose of 8 mg/kg intravenously (IV) loading dose; followed by 6 mg/kg IV every 3 weeks thereafter	Cohort A Safety Run-In Dose Level -1 and Phase 2 Expansion: GDC-0084 (30 mg) Plus Trastuzumab n=12 participants at risk GDC-0084 30 mg administered orally once daily Trastuzumab administered at a dose of 8 mg/kg intravenously (IV) loading dose; followed by 6 mg/kg IV every 3 weeks thereafter
Gastrointestinal disorders Diarrhea	0.00% 0/5 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE	8.3% 1/12 • Number of events 1 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE
Gastrointestinal disorders Nausea	20.0% 1/5 • Number of events 1 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE	0.00% 0/12 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE
Gastrointestinal disorders Vomiting	20.0% 1/5 • Number of events 1 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE	0.00% 0/12 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE
Immune system disorders Cytokine release syndrome	0.00% 0/5 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE	8.3% 1/12 • Number of events 1 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE
Metabolism and nutrition disorders Anorexia	20.0% 1/5 • Number of events 1 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE	0.00% 0/12 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE
Metabolism and nutrition disorders Dehydration	20.0% 1/5 • Number of events 1 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE	8.3% 1/12 • Number of events 1 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE
Metabolism and nutrition disorders Hyperglycemia	20.0% 1/5 • Number of events 1 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE	0.00% 0/12 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE
Metabolism and nutrition disorders Hypokalemia	20.0% 1/5 • Number of events 1 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE	0.00% 0/12 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE
Metabolism and nutrition disorders Hypomagnesemia	20.0% 1/5 • Number of events 1 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE	0.00% 0/12 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE
Metabolism and nutrition disorders Hyponatremia	20.0% 1/5 • Number of events 1 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE	8.3% 1/12 • Number of events 1 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/5 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE	8.3% 1/12 • Number of events 1 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/5 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE	8.3% 1/12 • Number of events 1 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/5 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE	8.3% 1/12 • Number of events 1 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE
Reproductive system and breast disorders Pelvic pain	0.00% 0/5 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE	8.3% 1/12 • Number of events 1 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/5 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE	8.3% 1/12 • Number of events 1 • Adverse Events were collected at screening/enrollment, day 1 of each treatment cycle, and at end of treatment, up to ~34 weeks. All-Cause Mortality was assessed every 6 months until death or off-study, up to ~62 months SAEs defined as: adverse events classified as SAE by the investigator (and meeting the Results Data Element Definition of SAE), as well as grade 4 treatment-related adverse events (whether or not classified as an SAE by the investigator) OAEs defined as: all other adverse events not meeting the definition of SAE