Trial Outcomes & Findings for Testing the Safety and Efficacy of the Combination of the Antibody Pembrolizumab and Entinostat in Patients With Myelodysplastic Syndrome Who Are Not Responding to Hypomethylating Agents (NCT NCT02936752)

Last Updated: 2025-03-25

Results Overview

Toxicities will be tabulated and graded according to the Common Terminology Criteria for Adverse Events version 5. Dose-limiting toxicities will be assessed after the first 2 cycles of combined therapy. Presented are the counts of participants that experienced DLT in the period up to 42 days.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

28 participants

Primary outcome timeframe

Up to 42 days

Results posted on

2025-03-25

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Entinostat, Pembrolizumab) Dose Level 1 Patients receive lower dose entinostat PO on days 1 and 8 or higher dose entinostat PO on days 1, 8, and 15, and pembrolizumab IV over 30 minutes on day 1 of cycle 2 and cycles thereafter. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve an objective response or maintain a SD status after the first 4 cycles may continue to receive entinostat and pembrolizumab for up to 1 year. Entinostat: Given PO Pembrolizumab: Given IV	Treatment (Entinostat, Pembrolizumab) Dose Level 2 Patients receive lower dose entinostat PO on days 1 and 8 or higher dose entinostat PO on days 1, 8, and 15, and pembrolizumab IV over 30 minutes on day 1 of cycle 2 and cycles thereafter. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve an objective response or maintain a SD status after the first 4 cycles may continue to receive entinostat and pembrolizumab for up to 1 year. Entinostat: Given PO Pembrolizumab: Given IV
Overall Study STARTED	22	6
Overall Study COMPLETED	16	3
Overall Study NOT COMPLETED	6	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Entinostat, Pembrolizumab) Dose Level 1 Patients receive lower dose entinostat PO on days 1 and 8 or higher dose entinostat PO on days 1, 8, and 15, and pembrolizumab IV over 30 minutes on day 1 of cycle 2 and cycles thereafter. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve an objective response or maintain a SD status after the first 4 cycles may continue to receive entinostat and pembrolizumab for up to 1 year. Entinostat: Given PO Pembrolizumab: Given IV	Treatment (Entinostat, Pembrolizumab) Dose Level 2 Patients receive lower dose entinostat PO on days 1 and 8 or higher dose entinostat PO on days 1, 8, and 15, and pembrolizumab IV over 30 minutes on day 1 of cycle 2 and cycles thereafter. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve an objective response or maintain a SD status after the first 4 cycles may continue to receive entinostat and pembrolizumab for up to 1 year. Entinostat: Given PO Pembrolizumab: Given IV
Overall Study Death	2	1
Overall Study Physician Decision	4	0
Overall Study Withdrawal by Subject	0	2

Baseline Characteristics

Testing the Safety and Efficacy of the Combination of the Antibody Pembrolizumab and Entinostat in Patients With Myelodysplastic Syndrome Who Are Not Responding to Hypomethylating Agents

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Entinostat, Pembrolizumab) Dose Level 1 n=22 Participants Patients receive lower dose entinostat PO on days 1 and 8 or higher dose entinostat PO on days 1, 8, and 15, and pembrolizumab IV over 30 minutes on day 1 of cycle 2 and cycles thereafter. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve an objective response or maintain a SD status after the first 4 cycles may continue to receive entinostat and pembrolizumab for up to 1 year. Entinostat: Given PO Pembrolizumab: Given IV	Treatment (Entinostat, Pembrolizumab) Dose Level 2 n=6 Participants Patients receive lower dose entinostat PO on days 1 and 8 or higher dose entinostat PO on days 1, 8, and 15, and pembrolizumab IV over 30 minutes on day 1 of cycle 2 and cycles thereafter. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve an objective response or maintain a SD status after the first 4 cycles may continue to receive entinostat and pembrolizumab for up to 1 year. Entinostat: Given PO	Total n=28 Participants Total of all reporting groups
Age, Continuous	74 years n=5 Participants	71 years n=7 Participants	73.5 years n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	3 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=5 Participants	6 Participants n=7 Participants	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants	5 Participants n=7 Participants	25 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	22 participants n=5 Participants	6 participants n=7 Participants	28 participants n=5 Participants
ECOG performance status 0	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
ECOG performance status 1	16 Participants n=5 Participants	3 Participants n=7 Participants	19 Participants n=5 Participants
ECOG performance status 2	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Disease acute myeloid leukemia (AML)	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Disease myelodysplastic syndromes/neoplasms (MDS)	19 Participants n=5 Participants	6 Participants n=7 Participants	25 Participants n=5 Participants
Number prior lines of therapy	1 prior therapy lines n=5 Participants	1.5 prior therapy lines n=7 Participants	1 prior therapy lines n=5 Participants
Prior Therapy Types Prior HMA	22 Participants n=5 Participants	6 Participants n=7 Participants	28 Participants n=5 Participants
Prior Therapy Types Azacitidine	16 Participants n=5 Participants	6 Participants n=7 Participants	22 Participants n=5 Participants
Prior Therapy Types Decitabine	8 Participants n=5 Participants	1 Participants n=7 Participants	9 Participants n=5 Participants
Prior Therapy Types HMA combination	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Prior Therapy Types ASTX727	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Prior Therapy Types Prior allo-HCT (%)	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Prior Therapy Types ≥3 lines of therapy	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 42 days

Population: 13 participants were eligible for dose escalation.

Outcome measures

Outcome measures
Measure	Treatment (Entinostat, Pembrolizumab) Dose Level 1 n=7 Participants Patients receive lower dose entinostat PO on days 1 and 8 or higher dose entinostat PO on days 1, 8, and 15, and pembrolizumab IV over 30 minutes on day 1 of cycle 2 and cycles thereafter. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve an objective response or maintain a SD status after the first 4 cycles may continue to receive entinostat and pembrolizumab for up to 1 year. Entinostat: Given PO Pembrolizumab: Given IV	Treatment (Entinostat, Pembrolizumab) Dose Level 2 n=6 Participants Patients receive lower dose entinostat PO on days 1 and 8 or higher dose entinostat PO on days 1, 8, and 15, and pembrolizumab IV over 30 minutes on day 1 of cycle 2 and cycles thereafter. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve an objective response or maintain a SD status after the first 4 cycles may continue to receive entinostat and pembrolizumab for up to 1 year. Entinostat: Given PO Pembrolizumab: Given IV
Maximum Tolerated Dose of Entinostat Given in Combination With Pembrolizumab	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 6 months after the last dose of entinostat in combination with pembrolizumab ((treatment period: Up to 3, 21-day cycles)

Population: All those enrolled.

Will be defined by the modified International Working Group 2006. Rates of CR, PR and HI will be summarized separately by cohort and reported with an exact 95% confidence interval. Upon results entry- best response to combination therapy (number of patients \[%\]; response assessment after 3 cycles) is presented as counts of the best response.

Outcome measures

Outcome measures
Measure	Treatment (Entinostat, Pembrolizumab) Dose Level 1 n=22 Participants Patients receive lower dose entinostat PO on days 1 and 8 or higher dose entinostat PO on days 1, 8, and 15, and pembrolizumab IV over 30 minutes on day 1 of cycle 2 and cycles thereafter. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve an objective response or maintain a SD status after the first 4 cycles may continue to receive entinostat and pembrolizumab for up to 1 year. Entinostat: Given PO Pembrolizumab: Given IV	Treatment (Entinostat, Pembrolizumab) Dose Level 2 n=6 Participants Patients receive lower dose entinostat PO on days 1 and 8 or higher dose entinostat PO on days 1, 8, and 15, and pembrolizumab IV over 30 minutes on day 1 of cycle 2 and cycles thereafter. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve an objective response or maintain a SD status after the first 4 cycles may continue to receive entinostat and pembrolizumab for up to 1 year. Entinostat: Given PO Pembrolizumab: Given IV
Overall Response Rate (Complete Response [CR], Partial Response [PR], Hematologic Improvement [HI]) Complete Response (CR)	0 Participants	0 Participants
Overall Response Rate (Complete Response [CR], Partial Response [PR], Hematologic Improvement [HI]) Partial Response (PR)	0 Participants	0 Participants
Overall Response Rate (Complete Response [CR], Partial Response [PR], Hematologic Improvement [HI]) Stable Disease (SD)	8 Participants	3 Participants
Overall Response Rate (Complete Response [CR], Partial Response [PR], Hematologic Improvement [HI]) Progressive Disease (PD)	5 Participants	0 Participants
Overall Response Rate (Complete Response [CR], Partial Response [PR], Hematologic Improvement [HI]) marrow Complete response (mCR)	2 Participants	0 Participants
Overall Response Rate (Complete Response [CR], Partial Response [PR], Hematologic Improvement [HI]) Not evaluable	6 Participants	3 Participants
Overall Response Rate (Complete Response [CR], Partial Response [PR], Hematologic Improvement [HI]) Hematologic Improvement (HI) Neutrophils	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Assessed for up to 10 months after the last dose of entinostat in combination with pembrolizumab (treatment period: Up to 3, 21-day cycles)

Population: All participants

Median progression-free survival (PFS) is being reported as the median time with the full range. The outcome was updated at the time of results entry to include the correct presentation of the data and the updated time frame for longest PFS follow up time.

Outcome measures

Outcome measures
Measure	Treatment (Entinostat, Pembrolizumab) Dose Level 1 n=22 Participants Patients receive lower dose entinostat PO on days 1 and 8 or higher dose entinostat PO on days 1, 8, and 15, and pembrolizumab IV over 30 minutes on day 1 of cycle 2 and cycles thereafter. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve an objective response or maintain a SD status after the first 4 cycles may continue to receive entinostat and pembrolizumab for up to 1 year. Entinostat: Given PO Pembrolizumab: Given IV	Treatment (Entinostat, Pembrolizumab) Dose Level 2 n=6 Participants Patients receive lower dose entinostat PO on days 1 and 8 or higher dose entinostat PO on days 1, 8, and 15, and pembrolizumab IV over 30 minutes on day 1 of cycle 2 and cycles thereafter. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve an objective response or maintain a SD status after the first 4 cycles may continue to receive entinostat and pembrolizumab for up to 1 year. Entinostat: Given PO Pembrolizumab: Given IV
Median Progression-free Survival	3.45 months Interval 0.5 to 9.4	3.68 months Interval 0.9 to 8.8

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 6 months after the last dose of entinostat in combination with pembrolizumab

Median response duration for responders will be determined.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 6 months after the last dose of entinostat in combination with pembrolizumab

Median time of progression to acute myeloid leukemia will be determined.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From start of study to death, assessed for up to 6 months after the last dose of entinostat in combination with pembrolizumab

Will be reported with a 95% confidence interval.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From start of study to death, assessed for up to 1 year

Will be reported with a 95% confidence interval.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From start of study to death, assessed for up to 2 years

Will be reported with a 95% confidence interval.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 1 year

Will correlate with any observed clinical responses. Will be estimated using mixed effects models to take into account the within-patient correlation. Likelihood ratio tests will be performed to confirm if random intercepts and slopes are necessary in the model. The fixed effect for change in MDSCs over time will be evaluated for significance. The variability in the rate of change in MDSCs across patients will also be examined. The association between the clinical outcome and a meaningful reduction in MDSCs, which will be defined after a review of the data, will be assessed with the chi-square test. The quantity of MDSCs at baseline and during treatment as continuous variables can also be compared between responding and non-responding patients using a t-test or Mann-Whitney U-Test, if more appropriate.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (Entinostat, Pembrolizumab) Dose Level 1

Serious events: 12 serious events

Other events: 22 other events

Deaths: 4 deaths

Treatment (Entinostat, Pembrolizumab) Dose Level 2

Serious events: 5 serious events

Other events: 6 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Amer Zeidan, MBBS

Yale School of Medicine

Phone: (203) 200-4363

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Treatment (Entinostat, Pembrolizumab) Dose Level 1 n=22 participants at risk Patients receive lower dose entinostat PO on days 1 and 8 or higher dose entinostat PO on days 1, 8, and 15, and pembrolizumab IV over 30 minutes on day 1 of cycle 2 and cycles thereafter. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve an objective response or maintain a SD status after the first 4 cycles may continue to receive entinostat and pembrolizumab for up to 1 year. Entinostat: Given PO Pembrolizumab: Given IV	Treatment (Entinostat, Pembrolizumab) Dose Level 2 n=6 participants at risk Patients receive lower dose entinostat PO on days 1 and 8 or higher dose entinostat PO on days 1, 8, and 15, and pembrolizumab IV over 30 minutes on day 1 of cycle 2 and cycles thereafter. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve an objective response or maintain a SD status after the first 4 cycles may continue to receive entinostat and pembrolizumab for up to 1 year. Entinostat: Given PO Pembrolizumab: Given IV
Blood and lymphatic system disorders Febrile neutropenia	4.5% 1/22 • Number of events 1 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.	16.7% 1/6 • Number of events 1 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.
Cardiac disorders Heart failure	0.00% 0/22 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.	16.7% 1/6 • Number of events 1 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.
Gastrointestinal disorders Constipation	4.5% 1/22 • Number of events 1 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.	0.00% 0/6 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.
Gastrointestinal disorders Mucositis oral	0.00% 0/22 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.	16.7% 1/6 • Number of events 1 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.
General disorders Disease Progression	4.5% 1/22 • Number of events 1 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.	0.00% 0/6 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.
General disorders Mixed shock	4.5% 1/22 • Number of events 1 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.	0.00% 0/6 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.
General disorders Multi-organ failure	0.00% 0/22 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.	16.7% 1/6 • Number of events 1 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.
Immune system disorders Immunotherapy -induced pneumonitis	4.5% 1/22 • Number of events 1 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.	0.00% 0/6 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.
Infections and infestations Blood infection	4.5% 1/22 • Number of events 1 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.	0.00% 0/6 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.
Infections and infestations Bone infection	4.5% 1/22 • Number of events 1 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.	0.00% 0/6 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.
Infections and infestations COVID-19	4.5% 1/22 • Number of events 1 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.	0.00% 0/6 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.
Infections and infestations Lung infection	18.2% 4/22 • Number of events 4 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.	16.7% 1/6 • Number of events 1 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.
Injury, poisoning and procedural complications Fall	13.6% 3/22 • Number of events 3 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.	0.00% 0/6 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.
Investigations Disease Progression	4.5% 1/22 • Number of events 1 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.	0.00% 0/6 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.
Metabolism and nutrition disorders Dehydration	0.00% 0/22 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.	16.7% 1/6 • Number of events 1 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	4.5% 1/22 • Number of events 1 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.	0.00% 0/6 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.
Nervous system disorders Syncope	9.1% 2/22 • Number of events 2 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.	0.00% 0/6 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.
Respiratory, thoracic and mediastinal disorders Adult respiratory distress syndrome	4.5% 1/22 • Number of events 1 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.	0.00% 0/6 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	4.5% 1/22 • Number of events 1 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.	0.00% 0/6 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.
Respiratory, thoracic and mediastinal disorders Pneumonitis	4.5% 1/22 • Number of events 1 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.	16.7% 1/6 • Number of events 1 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.
Respiratory, thoracic and mediastinal disorders Respiratory failure	9.1% 2/22 • Number of events 2 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.	33.3% 2/6 • Number of events 2 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.
Vascular disorders Hypotension	4.5% 1/22 • Number of events 1 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.	0.00% 0/6 • Up to 4 months following treatment (treatment period: Up to 3, 21-day cycles), All-Cause Mortality was assessed up to 10 months after the last dose.