Trial Outcomes & Findings for A Phase II Multi-Strata Study of PM01183 as a Single Agent or in Combination With Conventional Chemotherapy in Metastatic and/or Unresectable Sarcomas (NCT NCT02448537)

Last Updated: 2021-03-03

Results Overview

The number of participants that achieved either Stable Disease (SD) or a Partial Response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) at 24 weeks. * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. * Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

42 participants

Primary outcome timeframe

24 Weeks

Results posted on

2021-03-03

Participant Flow

Participant milestones

Participant milestones
Measure	PM01183 and Doxorubicin Anthracycline-naïve patients will receive combination of PM01183 and Doxorubicin per cycle. * PM01183 predetermined dose daily via IV per cycle * Doxorubicin predetermined dose daily via IV per cycle PM01183 Doxorubicin	PM01183 and Gemcitabine Prior anthracycline exposure and without prior gemcitabine exposure * PM01183 predetermined dose given twice via IV per cycle * Gemcitabine predetermined dose given twice via IV per cycle PM01183 Gemcitabine	Single Agent PM01183 Patients who have received at least both prior anthracycline and prior gemcitabine -PM01183 predetermined dose once via IV per cycle PM01183
Overall Study STARTED	20	10	12
Overall Study COMPLETED	19	9	11
Overall Study NOT COMPLETED	1	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	PM01183 and Doxorubicin Anthracycline-naïve patients will receive combination of PM01183 and Doxorubicin per cycle. * PM01183 predetermined dose daily via IV per cycle * Doxorubicin predetermined dose daily via IV per cycle PM01183 Doxorubicin	PM01183 and Gemcitabine Prior anthracycline exposure and without prior gemcitabine exposure * PM01183 predetermined dose given twice via IV per cycle * Gemcitabine predetermined dose given twice via IV per cycle PM01183 Gemcitabine	Single Agent PM01183 Patients who have received at least both prior anthracycline and prior gemcitabine -PM01183 predetermined dose once via IV per cycle PM01183
Overall Study Withdrawal by Subject	1	1	1

Baseline Characteristics

A Phase II Multi-Strata Study of PM01183 as a Single Agent or in Combination With Conventional Chemotherapy in Metastatic and/or Unresectable Sarcomas

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PM01183 and Doxorubicin n=20 Participants Anthracycline-naïve patients will receive combination of PM01183 and Doxorubicin per cycle. * PM01183 predetermined dose daily via IV per cycle * Doxorubicin predetermined dose daily via IV per cycle PM01183 Doxorubicin	PM01183 and Gemcitabine n=10 Participants Prior anthracycline exposure and without prior gemcitabine exposure * PM01183 predetermined dose given twice via IV per cycle * Gemcitabine predetermined dose given twice via IV per cycle PM01183 Gemcitabine	Single Agent PM01183 n=12 Participants Patients who have received at least both prior anthracycline and prior gemcitabine -PM01183 predetermined dose once via IV per cycle PM01183	Total n=42 Participants Total of all reporting groups
Age, Continuous	52.6 years n=5 Participants	44.2 years n=7 Participants	55.3 years n=5 Participants	51.9 years n=4 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants	26 Participants n=4 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	16 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants	37 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized White	15 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants	33 Participants n=4 Participants
Race/Ethnicity, Customized Black or African-American	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized More Than One Race	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment United States	20 participants n=5 Participants	10 participants n=7 Participants	12 participants n=5 Participants	42 participants n=4 Participants

PRIMARY outcome

Timeframe: 24 Weeks

Population: Two participants (one from the PM01183 and Doxorubicin arm and one from the PM01183 alone arm) were not able to be evaluated for response.

Outcome measures

Outcome measures
Measure	PM01183 and Doxorubicin n=20 Participants Anthracycline-naïve patients will receive combination of PM01183 and Doxorubicin per cycle. * PM01183 predetermined dose daily via IV per cycle * Doxorubicin predetermined dose daily via IV per cycle PM01183 Doxorubicin	PM01183 and Gemcitabine n=10 Participants Prior anthracycline exposure and without prior gemcitabine exposure * PM01183 predetermined dose given twice via IV per cycle * Gemcitabine predetermined dose given twice via IV per cycle PM01183 Gemcitabine	Single Agent PM01183 n=12 Participants Patients who have received at least both prior anthracycline and prior gemcitabine -PM01183 predetermined dose once via IV per cycle PM01183
Disease Control Rate	13 Participants	2 Participants	3 Participants

SECONDARY outcome

Timeframe: Every 6 weeks for the first 8 cycles (cycle is 21 days) and then every 9 weeks thereafter until disease progression

The overall response rate is the number of participants that achieved either Stable Disease (SD), a Partial Response (PR), or a Complete Response (CR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The overall response rate is the best response recorded from the start of treatment until disease progression/recurrence. * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. * Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Outcome measures

Outcome measures
Measure	PM01183 and Doxorubicin n=20 Participants Anthracycline-naïve patients will receive combination of PM01183 and Doxorubicin per cycle. * PM01183 predetermined dose daily via IV per cycle * Doxorubicin predetermined dose daily via IV per cycle PM01183 Doxorubicin	PM01183 and Gemcitabine n=10 Participants Prior anthracycline exposure and without prior gemcitabine exposure * PM01183 predetermined dose given twice via IV per cycle * Gemcitabine predetermined dose given twice via IV per cycle PM01183 Gemcitabine	Single Agent PM01183 n=12 Participants Patients who have received at least both prior anthracycline and prior gemcitabine -PM01183 predetermined dose once via IV per cycle PM01183
Overall Response Rate Complete Response	0 Participants	0 Participants	0 Participants
Overall Response Rate Partial Response	7 Participants	1 Participants	0 Participants
Overall Response Rate Stable Disease	6 Participants	1 Participants	3 Participants
Overall Response Rate Unknown	1 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: From the start of treatment until 30 days after the end of treatment

Summary of the serious adverse events (SAE) experienced by participants that were deemed to be at least possibly related to PM01183 when administered alone or with Doxorubicin or Gemcitabine. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE v4).

Outcome measures

Outcome measures
Measure	PM01183 and Doxorubicin n=20 Participants Anthracycline-naïve patients will receive combination of PM01183 and Doxorubicin per cycle. * PM01183 predetermined dose daily via IV per cycle * Doxorubicin predetermined dose daily via IV per cycle PM01183 Doxorubicin	PM01183 and Gemcitabine n=10 Participants Prior anthracycline exposure and without prior gemcitabine exposure * PM01183 predetermined dose given twice via IV per cycle * Gemcitabine predetermined dose given twice via IV per cycle PM01183 Gemcitabine	Single Agent PM01183 n=12 Participants Patients who have received at least both prior anthracycline and prior gemcitabine -PM01183 predetermined dose once via IV per cycle PM01183
Treatment Related Serious Adverse Events Any Treatment Related SAE	4 participants	5 participants	2 participants
Treatment Related Serious Adverse Events Diarrhea	1 participants	0 participants	1 participants
Treatment Related Serious Adverse Events Febrile neutropenia	1 participants	1 participants	0 participants
Treatment Related Serious Adverse Events Lymphocyte count decreased	2 participants	1 participants	0 participants
Treatment Related Serious Adverse Events Nausea	1 participants	0 participants	1 participants
Treatment Related Serious Adverse Events Neutrophil count decreased	4 participants	4 participants	1 participants
Treatment Related Serious Adverse Events Platelet count decreased	1 participants	1 participants	0 participants
Treatment Related Serious Adverse Events Port Infection	0 participants	1 participants	0 participants
Treatment Related Serious Adverse Events Vomiting	1 participants	0 participants	1 participants
Treatment Related Serious Adverse Events White blood cell decreased	3 participants	1 participants	0 participants

Adverse Events

Stratum A

Serious events: 6 serious events

Other events: 20 other events

Deaths: 0 deaths

Stratum B

Serious events: 6 serious events

Other events: 10 other events

Deaths: 0 deaths

Stratum C

Serious events: 4 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Gregory Cote, M.D., Ph.D

Massachusetts General Hospital

Phone: 617-724-4000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Stratum A n=20 participants at risk Anthracycline-naïve patients will receive combination of PM01183 and Doxorubicin per cycle. * PM01183 predetermined dose daily via IV per cycle * Doxorubicin predetermined dose daily via IV per cycle PM01183 Doxorubicin	Stratum B n=10 participants at risk Prior anthracycline exposure and without prior gemcitabine exposure * PM01183 predetermined dose given twice via IV per cycle * Gemcitabine predetermined dose given twice via IV per cycle PM01183 Gemcitabine	Stratum C n=12 participants at risk Patients who have received at least both prior anthracycline and prior gemcitabine -PM01183 predetermined dose once via IV per cycle PM01183
Blood and lymphatic system disorders Anemia	0.00% 0/20 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	10.0% 1/10 • Number of events 2 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Gastrointestinal disorders Constipation	0.00% 0/20 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	8.3% 1/12 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Gastrointestinal disorders Diarrhea	5.0% 1/20 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	8.3% 1/12 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Blood and lymphatic system disorders Febrile neutropenia	5.0% 1/20 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	10.0% 1/10 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Gastrointestinal disorders Ileus	5.0% 1/20 • Number of events 3 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Infections and infestations Infections and infestations - Other, Port Infection	0.00% 0/20 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	10.0% 1/10 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Infections and infestations Infections and infestations - Other, Spontaneous Bacterial Peritonitis	5.0% 1/20 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Nervous system disorders Intracranial hemorrhage	0.00% 0/20 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	10.0% 1/10 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Investigations Lymphocyte count decreased	10.0% 2/20 • Number of events 3 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	10.0% 1/10 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Gastrointestinal disorders Nausea	5.0% 1/20 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	8.3% 1/12 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Investigations Neutrophil count decreased	20.0% 4/20 • Number of events 6 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	40.0% 4/10 • Number of events 5 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	8.3% 1/12 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Investigations Platelet count decreased	5.0% 1/20 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	10.0% 1/10 • Number of events 6 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/20 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	8.3% 1/12 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Gastrointestinal disorders Small intestinal obstruction	5.0% 1/20 • Number of events 3 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	8.3% 1/12 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Surgical and medical procedures Surgical and medical procedures - Other, Grade 3 Decompression and Spinal Stabilization	5.0% 1/20 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Renal and urinary disorders Urinary incontinence	5.0% 1/20 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Cardiac disorders Ventricular arrhythmia	5.0% 1/20 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Gastrointestinal disorders Vomiting	5.0% 1/20 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	8.3% 1/12 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Investigations White blood cell decreased	15.0% 3/20 • Number of events 5 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	10.0% 1/10 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.

Other adverse events
Measure	Stratum A n=20 participants at risk Anthracycline-naïve patients will receive combination of PM01183 and Doxorubicin per cycle. * PM01183 predetermined dose daily via IV per cycle * Doxorubicin predetermined dose daily via IV per cycle PM01183 Doxorubicin	Stratum B n=10 participants at risk Prior anthracycline exposure and without prior gemcitabine exposure * PM01183 predetermined dose given twice via IV per cycle * Gemcitabine predetermined dose given twice via IV per cycle PM01183 Gemcitabine	Stratum C n=12 participants at risk Patients who have received at least both prior anthracycline and prior gemcitabine -PM01183 predetermined dose once via IV per cycle PM01183
Gastrointestinal disorders Abdominal pain	15.0% 3/20 • Number of events 4 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	10.0% 1/10 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Investigations Alanine aminotransferase increased	0.00% 0/20 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	10.0% 1/10 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	8.3% 1/12 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Investigations Alkaline phosphatase increased	0.00% 0/20 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	8.3% 1/12 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Skin and subcutaneous tissue disorders Alopecia	40.0% 8/20 • Number of events 8 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	20.0% 2/10 • Number of events 2 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Blood and lymphatic system disorders Anemia	10.0% 2/20 • Number of events 2 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	30.0% 3/10 • Number of events 9 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	8.3% 1/12 • Number of events 3 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Metabolism and nutrition disorders Anorexia	45.0% 9/20 • Number of events 12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	30.0% 3/10 • Number of events 3 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	16.7% 2/12 • Number of events 2 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Psychiatric disorders Anxiety	30.0% 6/20 • Number of events 6 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	30.0% 3/10 • Number of events 3 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Musculoskeletal and connective tissue disorders Arthralgia	10.0% 2/20 • Number of events 2 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Investigations Aspartate aminotransferase increased	0.00% 0/20 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	8.3% 1/12 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Musculoskeletal and connective tissue disorders Back pain	25.0% 5/20 • Number of events 6 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Eye disorders Blurred vision	10.0% 2/20 • Number of events 3 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Musculoskeletal and connective tissue disorders Bone pain	10.0% 2/20 • Number of events 2 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Injury, poisoning and procedural complications Bruising	0.00% 0/20 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	20.0% 2/10 • Number of events 2 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Investigations Carbon monoxide diffusing capacity decreased	0.00% 0/20 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	8.3% 1/12 • Number of events 2 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Cardiac disorders Cardiac disorders - Other, Heart Murmur	5.0% 1/20 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Cardiac disorders Cardiac disorders - Other, Systolic Ejection Murmur	0.00% 0/20 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	10.0% 1/10 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Cardiac disorders Cardiac disorders - Other, tachycardia	5.0% 1/20 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	10.0% 1/10 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Cardiac disorders Cardiac disorders - Other, Unspecified	5.0% 1/20 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Eye disorders Cataract	5.0% 1/20 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Cardiac disorders Chest pain - cardiac	0.00% 0/20 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	10.0% 1/10 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Eye disorders Conjunctivitis	5.0% 1/20 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Gastrointestinal disorders Constipation	50.0% 10/20 • Number of events 19 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	50.0% 5/10 • Number of events 6 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	16.7% 2/12 • Number of events 2 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Respiratory, thoracic and mediastinal disorders Cough	20.0% 4/20 • Number of events 5 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	30.0% 3/10 • Number of events 3 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	25.0% 3/12 • Number of events 3 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Metabolism and nutrition disorders Dehydration	15.0% 3/20 • Number of events 3 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	10.0% 1/10 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Psychiatric disorders Depression	10.0% 2/20 • Number of events 2 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	10.0% 1/10 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Gastrointestinal disorders Diarrhea	30.0% 6/20 • Number of events 8 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	30.0% 3/10 • Number of events 3 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	8.3% 1/12 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Nervous system disorders Dizziness	15.0% 3/20 • Number of events 3 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Eye disorders Dry eye	5.0% 1/20 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Gastrointestinal disorders Duodenal hemorrhage	5.0% 1/20 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Nervous system disorders Dysgeusia	15.0% 3/20 • Number of events 3 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	8.3% 1/12 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Reproductive system and breast disorders Dyspareunia	5.0% 1/20 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Gastrointestinal disorders Dyspepsia	5.0% 1/20 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Respiratory, thoracic and mediastinal disorders Dyspnea	15.0% 3/20 • Number of events 3 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	40.0% 4/10 • Number of events 4 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	8.3% 1/12 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Ear and labyrinth disorders Ear and labyrinth disorders - Other, Ear Rash	5.0% 1/20 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Ear and labyrinth disorders Ear pain	5.0% 1/20 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
General disorders Edema limbs	15.0% 3/20 • Number of events 3 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	8.3% 1/12 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Endocrine disorders Endocrine disorders - Other, Polydispia/Polyuria	0.00% 0/20 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	8.3% 1/12 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Skin and subcutaneous tissue disorders Erythema multiforme	0.00% 0/20 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	10.0% 1/10 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Gastrointestinal disorders Esophageal necrosis	5.0% 1/20 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.
Eye disorders Eye disorders - Other, Left Eyelid Stye	5.0% 1/20 • Number of events 1 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/10 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.	0.00% 0/12 • From the start of treatment until 30 days after the end of treatment.Treatment continued until the participant had disease progression, intercurrent illness that prevented further administration of treatment, an unacceptable adverse event, the participant withdrew from the study, or until the treating investigator decided it would be in the participants best interest.