Trial Outcomes & Findings for Pembrolizumab and Doxorubicin Hydrochloride in Treating Patients With Sarcoma That is Metastatic or Cannot Be Removed by Surgery (NCT NCT02888665)

Last Updated: 2021-05-26

Results Overview

Defined as a dose limiting toxicity (DLT) in less than 2 of 6 subjects. Only Phase 1 subjects will be evaluated for MTD.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

37 participants

Primary outcome timeframe

Up to 42 days (6 weeks)

Results posted on

2021-05-26

Participant Flow

Participant milestones

Participant milestones
Measure	Phase 1, Part 1 Subjects received 45 mg/m2 doxorubicin plus 200 mg flat dose of pembrolizumab.	Phase 1, Part 2 Subjects received 75 mg/m2 doxorubicin + 200 mg flat dose of pembrolizumab.	Phase 2 Subjects received 75 mg/m2 doxorubicin + 200 mg flat dose pembrolizumab.
Overall Study STARTED	3	3	31
Overall Study COMPLETED	3	3	31
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pembrolizumab and Doxorubicin Hydrochloride in Treating Patients With Sarcoma That is Metastatic or Cannot Be Removed by Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1, Part 1 n=3 Participants Subjects received 45 mg/m2 doxorubicin plus 200 mg flat dose of pembrolizumab.	Phase 1, Part 2 n=3 Participants Subjects received 75 mg/m2 doxorubicin + 200 mg flat dose of pembrolizumab.	Phase 2 n=31 Participants Subjects received 75 mg/m2 doxorubicin + 200 mg flat dose pembrolizumab.	Total n=37 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=93 Participants	2 Participants n=4 Participants	23 Participants n=27 Participants	27 Participants n=483 Participants
Age, Categorical >=65 years	1 Participants n=93 Participants	1 Participants n=4 Participants	8 Participants n=27 Participants	10 Participants n=483 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	1 Participants n=4 Participants	14 Participants n=27 Participants	15 Participants n=483 Participants
Sex: Female, Male Male	3 Participants n=93 Participants	2 Participants n=4 Participants	17 Participants n=27 Participants	22 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	1 Participants n=4 Participants	4 Participants n=27 Participants	5 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=93 Participants	2 Participants n=4 Participants	26 Participants n=27 Participants	31 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants	2 Participants n=483 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants	2 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants
Race (NIH/OMB) White	3 Participants n=93 Participants	2 Participants n=4 Participants	22 Participants n=27 Participants	27 Participants n=483 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	1 Participants n=4 Participants	4 Participants n=27 Participants	5 Participants n=483 Participants

PRIMARY outcome

Timeframe: Up to 42 days (6 weeks)

Population: Only Phase 1 subjects were evaluated for a Maximum Tolerated Dose (MTD) based off of Dose-Limiting Toxicities experienced per subject as defined in the protocol.

Defined as a dose limiting toxicity (DLT) in less than 2 of 6 subjects. Only Phase 1 subjects will be evaluated for MTD.

Outcome measures

Outcome measures
Measure	Phase 1 Cohort 1 n=3 Participants Subjects received 45 mg/m2 of doxorubicin plus 200 mg flat dose of pembrolizumab.	Phase 1 Cohort 2 n=3 Participants Subjects received 75 mg/m2 of doxorubicin plus 200 mg flat dose of pembrolizumab.
Maximum Tolerated Dose (MTD) of Doxorubicin Hydrochloride Plus Pembrolizumab According to the National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) Version 4.0 (Phase I)	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 2 years

Population: Only Phase 2 subjects were evaluated for this outcome as Phase 1 subjects were only included in the protocol for safety evaluation.

Evaluated per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT. Complete Response (CR) is a complete elimination of the tumor; Partial Response (PR) is 30% reduction. If a subject experienced a PR, this was required to be confirmed with a second scan at the next appropriate cycle.

Outcome measures

Outcome measures
Measure	Phase 1 Cohort 1 n=31 Participants Subjects received 45 mg/m2 of doxorubicin plus 200 mg flat dose of pembrolizumab.	Phase 1 Cohort 2 Subjects received 75 mg/m2 of doxorubicin plus 200 mg flat dose of pembrolizumab.
Objective Response Rate (ORR) (Phase II)	13 percent of participants	—

SECONDARY outcome

Timeframe: Up to 2 years

Population: Only 5 appropriate subjects had partial responses for evaluation.

Duration of response is the mean time to progression for all subjects who responded.

Outcome measures

Outcome measures
Measure	Phase 1 Cohort 1 n=5 Participants Subjects received 45 mg/m2 of doxorubicin plus 200 mg flat dose of pembrolizumab.	Phase 1 Cohort 2 Subjects received 75 mg/m2 of doxorubicin plus 200 mg flat dose of pembrolizumab.
Duration of Response	247 Days Standard Deviation 180	—

SECONDARY outcome

Timeframe: Up to 2 years

Population: This combined the phase I and phase II populations as we had intended for this analysis.

The Kaplan-Meier method will be used to estimate median PFS.

Outcome measures

Outcome measures
Measure	Phase 1 Cohort 1 n=37 Participants Subjects received 45 mg/m2 of doxorubicin plus 200 mg flat dose of pembrolizumab.	Phase 1 Cohort 2 Subjects received 75 mg/m2 of doxorubicin plus 200 mg flat dose of pembrolizumab.
Median Progression-free Survival (PFS)	8.1 months Interval 7.6 to 10.8	—

SECONDARY outcome

Timeframe: Up to 2 years

Population: This combined the phase I and phase II populations as we had intended for this analysis.

The Kaplan-Meier method will be used to estimate median OS.

Outcome measures

Outcome measures
Measure	Phase 1 Cohort 1 n=37 Participants Subjects received 45 mg/m2 of doxorubicin plus 200 mg flat dose of pembrolizumab.	Phase 1 Cohort 2 Subjects received 75 mg/m2 of doxorubicin plus 200 mg flat dose of pembrolizumab.
Overall Survival (OS)	27.6 months Interval 18.7 to At the time of the final analysis, the upper limit had not yet been reached.	—

SECONDARY outcome

Timeframe: Up to 2 years

Population: Only 5 appropriate subjects had partial responses for evaluation.

Average time to response

Outcome measures

Outcome measures
Measure	Phase 1 Cohort 1 n=5 Participants Subjects received 45 mg/m2 of doxorubicin plus 200 mg flat dose of pembrolizumab.	Phase 1 Cohort 2 Subjects received 75 mg/m2 of doxorubicin plus 200 mg flat dose of pembrolizumab.
Time to Response	152.2 Days Standard Deviation 65	—

Adverse Events

Phase 1 Cohort 1

Serious events: 1 serious events

Other events: 3 other events

Deaths: 2 deaths

Phase 1 Cohort 2

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Phase 2

Serious events: 13 serious events

Other events: 31 other events

Deaths: 15 deaths

Serious adverse events

Other adverse events

Additional Information

Seth Pollack, MD, Director of Sarcoma Program

Northwestern University

Phone: 312-503-5320

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Phase 1 Cohort 1 n=3 participants at risk Subjects received 45 mg/m2 doxorubicin plus 200 mg flat dose of pembrolizumab.	Phase 1 Cohort 2 n=3 participants at risk Subjects received 75 mg/m2 doxorubicin plus 200 mg flat dose of pembrolizumab.	Phase 2 n=31 participants at risk Subjects received 75 mg/m2 doxorubicin plus 200 mg flat dose pembrolizumab.
Gastrointestinal disorders Abdominal Pain	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	9.7% 3/31 • Number of events 3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Blood and lymphatic system disorders Febrile Neutropenia	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	6.5% 2/31 • Number of events 2 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Investigations Elevated troponin	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	3.2% 1/31 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Investigations Pancytopenia	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	3.2% 1/31 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
General disorders Atypical Chest Pain	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/31 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
General disorders Postprandial Chest Pain	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/31 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
General disorders Failure to thrive	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	3.2% 1/31 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
General disorders Non-cardiac chest pain	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	3.2% 1/31 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
General disorders Fever	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	3.2% 1/31 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Gastrointestinal disorders Diarrhea	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	3.2% 1/31 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Gastrointestinal disorders Constipation	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	3.2% 1/31 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Gastrointestinal disorders Partial Bowel Obstruction	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	33.3% 1/3 • Number of events 2 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/31 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Gastrointestinal disorders Mid-esophageal erythema	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/31 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Gastrointestinal disorders Denuded mucosa	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/31 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Gastrointestinal disorders Malignant bowel obstruction	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	3.2% 1/31 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Gastrointestinal disorders Small bowel obstruction	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	3.2% 1/31 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Gastrointestinal disorders Odynophagia	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	3.2% 1/31 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Gastrointestinal disorders Ascites	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	3.2% 1/31 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Gastrointestinal disorders Mucositis oral	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	6.5% 2/31 • Number of events 2 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Nervous system disorders Lightheadedness	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	3.2% 1/31 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Nervous system disorders Convulsions	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	3.2% 1/31 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Nervous system disorders Vasovalgal reaction	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/31 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	3.2% 1/31 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Respiratory, thoracic and mediastinal disorders Hemoptysis	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	3.2% 1/31 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Respiratory, thoracic and mediastinal disorders Right lower lobe infiltrate	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/31 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Respiratory, thoracic and mediastinal disorders Pleural effusion	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/31 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	3.2% 1/31 • Number of events 4 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	3.2% 1/31 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Musculoskeletal and connective tissue disorders Pelvic soft tissue necrosis	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/31 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Cardiac disorders Ejection fraction decreased	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/31 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Cardiac disorders Pulmonary infarct	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/31 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Cardiac disorders Heart failure	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/31 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Blood and lymphatic system disorders Leukocytosis	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/31 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Blood and lymphatic system disorders Tumor thrombus	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/31 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Infections and infestations Oropharyngeal thrush	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	3.2% 1/31 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Infections and infestations Thrush	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	3.2% 1/31 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Infections and infestations Urinary tract infection	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/31 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Infections and infestations Pelvic infection	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/31 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Infections and infestations Kidney Infection	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	3.2% 1/31 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Infections and infestations Lung infection	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	3.2% 1/31 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)

Other adverse events
Measure	Phase 1 Cohort 1 n=3 participants at risk Subjects received 45 mg/m2 doxorubicin plus 200 mg flat dose of pembrolizumab.	Phase 1 Cohort 2 n=3 participants at risk Subjects received 75 mg/m2 doxorubicin plus 200 mg flat dose of pembrolizumab.	Phase 2 n=31 participants at risk Subjects received 75 mg/m2 doxorubicin plus 200 mg flat dose pembrolizumab.
Gastrointestinal disorders Nausea	100.0% 3/3 • Number of events 3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	100.0% 3/3 • Number of events 3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	87.1% 27/31 • Number of events 37 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
General disorders Fatigue	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	100.0% 3/3 • Number of events 3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	67.7% 21/31 • Number of events 26 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Metabolism and nutrition disorders Anorexia	66.7% 2/3 • Number of events 3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	66.7% 2/3 • Number of events 3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	45.2% 14/31 • Number of events 19 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Gastrointestinal disorders Constipation	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	100.0% 3/3 • Number of events 3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	38.7% 12/31 • Number of events 16 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
General disorders Fever	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	66.7% 2/3 • Number of events 2 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	41.9% 13/31 • Number of events 15 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Skin and subcutaneous tissue disorders Alopecia	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	66.7% 2/3 • Number of events 2 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	35.5% 11/31 • Number of events 11 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Gastrointestinal disorders Dry Mouth	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	45.2% 14/31 • Number of events 14 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Respiratory, thoracic and mediastinal disorders Cough	66.7% 2/3 • Number of events 2 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	35.5% 11/31 • Number of events 12 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Gastrointestinal disorders Vomiting	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	100.0% 3/3 • Number of events 3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	29.0% 9/31 • Number of events 12 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Gastrointestinal disorders Mucositis oral	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	66.7% 2/3 • Number of events 3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	38.7% 12/31 • Number of events 16 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Nervous system disorders Dysgeusia	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	66.7% 2/3 • Number of events 3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	29.0% 9/31 • Number of events 9 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Nervous system disorders Headache	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	38.7% 12/31 • Number of events 16 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Skin and subcutaneous tissue disorders Pruritis	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	25.8% 8/31 • Number of events 9 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Investigations Neutrophil Count Decreased	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	66.7% 2/3 • Number of events 3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	22.6% 7/31 • Number of events 13 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	29.0% 9/31 • Number of events 11 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Psychiatric disorders Insomnia	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	66.7% 2/3 • Number of events 2 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	22.6% 7/31 • Number of events 8 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	66.7% 2/3 • Number of events 2 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	22.6% 7/31 • Number of events 9 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Eye disorders Dry Eye	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	100.0% 3/3 • Number of events 3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	16.1% 5/31 • Number of events 5 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Investigations Weight Loss	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	22.6% 7/31 • Number of events 18 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
General disorders Pain	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	33.3% 1/3 • Number of events 3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	22.6% 7/31 • Number of events 7 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
General disorders Edema Limbs	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	19.4% 6/31 • Number of events 6 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Gastrointestinal disorders Diarrhea	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	66.7% 2/3 • Number of events 2 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	22.6% 7/31 • Number of events 13 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Psychiatric disorders Anxiety	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	22.6% 7/31 • Number of events 7 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Musculoskeletal and connective tissue disorders Bone Pain	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	25.8% 8/31 • Number of events 9 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Musculoskeletal and connective tissue disorders Back Pain	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	22.6% 7/31 • Number of events 7 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Musculoskeletal and connective tissue disorders Pain in Extremity	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	25.8% 8/31 • Number of events 11 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Infections and infestations Upper Respiratory Infection	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	25.8% 8/31 • Number of events 11 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Metabolism and nutrition disorders Hypokalemia	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	25.8% 8/31 • Number of events 8 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Nervous system disorders Dizziness	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	16.1% 5/31 • Number of events 7 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Blood and lymphatic system disorders Anemia	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	19.4% 6/31 • Number of events 8 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Skin and subcutaneous tissue disorders Rash Maculo-papular	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	66.7% 2/3 • Number of events 2 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	9.7% 3/31 • Number of events 4 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor Pain	33.3% 1/3 • Number of events 2 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	16.1% 5/31 • Number of events 7 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Endocrine disorders Hypothyroidism	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	25.8% 8/31 • Number of events 11 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Skin and subcutaneous tissue disorders Rash	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	16.1% 5/31 • Number of events 7 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Skin and subcutaneous tissue disorders Dry Skin	66.7% 2/3 • Number of events 2 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	9.7% 3/31 • Number of events 3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
General disorders Chills	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	12.9% 4/31 • Number of events 4 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Respiratory, thoracic and mediastinal disorders Pleural Effusion	33.3% 1/3 • Number of events 1 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	33.3% 1/3 • Number of events 2 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	12.9% 4/31 • Number of events 4 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Psychiatric disorders Depression	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	16.1% 5/31 • Number of events 5 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	16.1% 5/31 • Number of events 5 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)
Metabolism and nutrition disorders Hypoalbuminemia	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	0.00% 0/3 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)	16.1% 5/31 • Number of events 6 • Adverse event data was collected beginning from date of consent to 30 days post discontinuation of study treatment. (Up to 2 years of therapy with 1 cycle equaling 21 days)