Trial Outcomes & Findings for Dasatinib in Relapsed or Refractory Non-Hodgkin's Lymphoma (NCT NCT00550615)

NCT ID: NCT00550615

Last Updated: 2023-09-26

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

38 participants

Primary outcome timeframe

after 1-28 day cycle of therapy

Results posted on

2023-09-26

Participant Flow

Participant milestones

Participant milestones
Measure	Phase I Dose Cohort # 1 (100 mg Per Day) Dasatinib will be orally administered once daily for 28 day cycles.	Phase I Dose Cohort # 2 (150 mg Per Day) Dasatinib will be orally administered once daily for 28 day cycles.	Phase I Dose Cohort # 3 (200 mg Per Day) Dasatinib will be orally administered once daily for 28 day cycles.	Phase II Participants Dasatinib: No DLT was encountered and hence the MTD was determined to be 200 mg PO daily. This was subsequently reduced to 150 mg PO daily when a higher incidence of grade 3 pleural effusions was noted.
Overall Study STARTED	3	3	10	22
Overall Study COMPLETED	3	3	6	12
Overall Study NOT COMPLETED	0	0	4	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I Dose Cohort # 1 (100 mg Per Day) Dasatinib will be orally administered once daily for 28 day cycles.	Phase I Dose Cohort # 2 (150 mg Per Day) Dasatinib will be orally administered once daily for 28 day cycles.	Phase I Dose Cohort # 3 (200 mg Per Day) Dasatinib will be orally administered once daily for 28 day cycles.	Phase II Participants Dasatinib: No DLT was encountered and hence the MTD was determined to be 200 mg PO daily. This was subsequently reduced to 150 mg PO daily when a higher incidence of grade 3 pleural effusions was noted.
Overall Study Withdrawal by Subject	0	0	2	3
Overall Study Not evaluable	0	0	2	7

Baseline Characteristics

Dasatinib in Relapsed or Refractory Non-Hodgkin's Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I Participants n=16 Participants Dasatinib will be orally administered once daily for 28 day cycles. There will be three dose cohorts for the Dasatinib in the Phase I portion of this trial. A minimum of three patients will be enrolled into each of the following dose cohorts: Dose cohort # 1 will be 100 mg per day Dose cohort # 2 will be 150 mg per day Dose cohort # 3 will be 200 mg per day	Phase II Participants n=22 Participants Dasatinib: The MTD will be determined in the Phase I portion of this trial. An additional 29 patients using the Two-Stage Simon design will be enrolled into Phase II using the MTD determined in Phase I.	Total n=38 Participants Total of all reporting groups
Age, Continuous	59 years n=39 Participants	61 years n=41 Participants	59 years n=35 Participants
Sex: Female, Male Female	7 Participants n=39 Participants	8 Participants n=41 Participants	15 Participants n=35 Participants
Sex: Female, Male Male	9 Participants n=39 Participants	14 Participants n=41 Participants	23 Participants n=35 Participants
Race/Ethnicity, Customized Ethnic Origin · Caucasian	16 Participants n=39 Participants	19 Participants n=41 Participants	35 Participants n=35 Participants
Race/Ethnicity, Customized Ethnic Origin · Black, Not Hispanic	0 Participants n=39 Participants	1 Participants n=41 Participants	1 Participants n=35 Participants
Race/Ethnicity, Customized Ethnic Origin · Hispanic	0 Participants n=39 Participants	1 Participants n=41 Participants	1 Participants n=35 Participants
Race/Ethnicity, Customized Ethnic Origin · Other	0 Participants n=39 Participants	1 Participants n=41 Participants	1 Participants n=35 Participants
Region of Enrollment United States	16 Participants n=39 Participants	22 Participants n=41 Participants	38 Participants n=35 Participants

PRIMARY outcome

Timeframe: after 1-28 day cycle of therapy

Population: Two subjects enrolled in Phase 1 of the study were never treated and not included in the analysis.

Outcome measures

Outcome measures
Measure	All Phase I Participants n=14 Participants All participants who enrolled and treated with a minimum of 1 cycle of Dasatinib.
Maximum Tolerated Dose	200 milligrams PO daily

SECONDARY outcome

Timeframe: after 2-28 day cycles of therapy

Population: Of the 38 participants consented only 24 for were evaluable. See the participant flow section.

The Objective response rate (CR+PR) and the Clinical Benefit Rate (CR+PR+SD) were calculated according to revised response criteria for malignant lymphoma (Cheson) CR - Complete response is defined as: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy. PR - Partial response is defined as: ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. SD - Stable Disease is define as: Failing to attain the criteria needed for a PR, but not fulfilling those for progressive disease.

Outcome measures

Outcome measures
Measure	All Phase I Participants n=24 Participants All participants who enrolled and treated with a minimum of 1 cycle of Dasatinib.
Number of Participants With Clinical Response Rates Objective response rate	7 Participants
Number of Participants With Clinical Response Rates Clinical Benefit Rate	17 Participants

Adverse Events

Phase I Participants

Serious events: 7 serious events

Other events: 14 other events

Deaths: 1 deaths

Phase II Participants

Serious events: 9 serious events

Other events: 18 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

Julie M Vose

University of Nebraska Medical Center

Phone: 402-559-348

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Phase I Participants n=14 participants at risk All participants that were dose were monitored for adverse events.	Phase II Participants n=19 participants at risk All participants that were dose were monitored for adverse events.
Respiratory, thoracic and mediastinal disorders Pleural effusion	14.3% 2/14 • Number of events 3 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	10.5% 2/19 • Number of events 3 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Respiratory, thoracic and mediastinal disorders dyspnea	7.1% 1/14 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	0.00% 0/19 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Investigations platelet count decreased	0.00% 0/14 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	5.3% 1/19 • Number of events 2 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Musculoskeletal and connective tissue disorders Avascular necrosis	7.1% 1/14 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	0.00% 0/19 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
General disorders Fever	14.3% 2/14 • Number of events 2 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	15.8% 3/19 • Number of events 4 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Respiratory, thoracic and mediastinal disorders pneumonia	14.3% 2/14 • Number of events 2 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	0.00% 0/19 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Infections and infestations Other, Infection not specify	21.4% 3/14 • Number of events 3 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Renal and urinary disorders Other, acute renal insufficiency	0.00% 0/14 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Endocrine disorders Adrenal insufficiency	7.1% 1/14 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	0.00% 0/19 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Blood and lymphatic system disorders Anemia	0.00% 0/14 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Metabolism and nutrition disorders Anorexia	7.1% 1/14 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	0.00% 0/19 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Surgical and medical procedures Other, appendectomy	7.1% 1/14 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	0.00% 0/19 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Infections and infestations Appendicitis	7.1% 1/14 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	0.00% 0/19 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Eye disorders cataracts	7.1% 1/14 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	0.00% 0/19 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Musculoskeletal and connective tissue disorders Other, cellulitis	14.3% 2/14 • Number of events 2 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Metabolism and nutrition disorders dehydration	0.00% 0/14 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Metabolism and nutrition disorders Other, failure to thrive	0.00% 0/14 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Respiratory, thoracic and mediastinal disorders pulmonary edema	0.00% 0/14 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
General disorders flu like symptoms	7.1% 1/14 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	0.00% 0/19 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Metabolism and nutrition disorders hyponatremia	7.1% 1/14 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	0.00% 0/19 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Respiratory, thoracic and mediastinal disorders hypoxia	7.1% 1/14 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	0.00% 0/19 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Infections and infestations Enterocolitis infectious	7.1% 1/14 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	0.00% 0/19 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.

Other adverse events
Measure	Phase I Participants n=14 participants at risk All participants that were dose were monitored for adverse events.	Phase II Participants n=19 participants at risk All participants that were dose were monitored for adverse events.
Respiratory, thoracic and mediastinal disorders Pleural effusion	78.6% 11/14 • Number of events 15 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	31.6% 6/19 • Number of events 7 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Investigations platelet count decreased	42.9% 6/14 • Number of events 6 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	57.9% 11/19 • Number of events 17 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Blood and lymphatic system disorders anemia	7.1% 1/14 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	0.00% 0/19 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
General disorders Fatigue	42.9% 6/14 • Number of events 7 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	42.1% 8/19 • Number of events 8 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Gastrointestinal disorders diarrhea	21.4% 3/14 • Number of events 4 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	47.4% 9/19 • Number of events 9 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Gastrointestinal disorders Nausea	35.7% 5/14 • Number of events 6 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	36.8% 7/19 • Number of events 7 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Investigations White blood cell decreased	28.6% 4/14 • Number of events 4 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	26.3% 5/19 • Number of events 12 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Investigations Neutrophil count decreased	14.3% 2/14 • Number of events 4 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	31.6% 6/19 • Number of events 12 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Gastrointestinal disorders vomiting	35.7% 5/14 • Number of events 5 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	15.8% 3/19 • Number of events 3 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
General disorders fever	14.3% 2/14 • Number of events 2 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	26.3% 5/19 • Number of events 5 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Gastrointestinal disorders Anorexia	21.4% 3/14 • Number of events 3 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	15.8% 3/19 • Number of events 3 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Nervous system disorders headache	28.6% 4/14 • Number of events 4 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	10.5% 2/19 • Number of events 2 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Infections and infestations Other - rash	28.6% 4/14 • Number of events 7 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	10.5% 2/19 • Number of events 2 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Infections and infestations Infection	14.3% 2/14 • Number of events 11 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	0.00% 0/19 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Psychiatric disorders insomnia	14.3% 2/14 • Number of events 3 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	0.00% 0/19 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Musculoskeletal and connective tissue disorders myalgia	7.1% 1/14 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Cardiac disorders pericardial effusion	14.3% 2/14 • Number of events 2 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	10.5% 2/19 • Number of events 3 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
General disorders weakness	0.00% 0/14 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	21.1% 4/19 • Number of events 4 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Gastrointestinal disorders abdominal pain	7.1% 1/14 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	15.8% 3/19 • Number of events 3 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
General disorders Pain	7.1% 1/14 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
General disorders chills	7.1% 1/14 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	10.5% 2/19 • Number of events 2 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Respiratory, thoracic and mediastinal disorders dyspnea	14.3% 2/14 • Number of events 3 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
General disorders Other - edema	14.3% 2/14 • Number of events 2 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	15.8% 3/19 • Number of events 4 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Metabolism and nutrition disorders hypokalemia	21.4% 3/14 • Number of events 3 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	0.00% 0/19 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Nervous system disorders Other - neuropathy	7.1% 1/14 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	10.5% 2/19 • Number of events 2 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
General disorders Other - cold feeling sensation	0.00% 0/14 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	10.5% 2/19 • Number of events 2 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
General disorders edema limbs	0.00% 0/14 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Infections and infestations skin infection	14.3% 2/14 • Number of events 5 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	0.00% 0/19 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Respiratory, thoracic and mediastinal disorders cough	7.1% 1/14 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	0.00% 0/19 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Nervous system disorders dysgeusia	0.00% 0/14 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	10.5% 2/19 • Number of events 2 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Investigations creatinine increased	14.3% 2/14 • Number of events 8 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	0.00% 0/19 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Infections and infestations Lung infection	14.3% 2/14 • Number of events 3 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	0.00% 0/19 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Investigations Electrocardiogram QT corrected interval prolonged	7.1% 1/14 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Skin and subcutaneous tissue disorders pruritus	7.1% 1/14 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Infections and infestations sinusitis	7.1% 1/14 • Number of events 2 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Gastrointestinal disorders gastrointestinal pain	14.3% 2/14 • Number of events 2 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	0.00% 0/19 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Cardiac disorders palpitation	0.00% 0/14 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Immune system disorders allergic reaction	0.00% 0/14 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Immune system disorders Other - alveolar inflitrates	7.1% 1/14 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	0.00% 0/19 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.
Musculoskeletal and connective tissue disorders back pain	7.1% 1/14 • Number of events 1 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.	0.00% 0/19 • Adverse Events were collected from the time of enrollment until 30 days after the participant completed study treatment. All doses for Phase I participants are combined as occasionally, subjects experienced adverse events leading to dose reductions so may not complete treatment at starting dose. Additionally, final adverse event reporting is most important at the maximum tolerated dose determined and use in Phase II of study.