Trial Outcomes & Findings for Pembrolizumab (MK-3475) Plus Gemcitabine/Cisplatin Versus Placebo Plus Gemcitabine/Cisplatin for First-Line Advanced and/or Unresectable Biliary Tract Carcinoma (BTC) (MK-3475-966/KEYNOTE-966)-China Extension Study (NCT NCT04924062)

NCT ID: NCT04924062

Last Updated: 2025-04-17

Results Overview

Overall survival was defined as the time from randomization to death due to any cause. Per protocol the final reported outcome for OS did not include any sensitivity or supportive analysis.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 158 participants
• Primary outcome timeframe: Up to approximately 29 months
• Results posted on: 2025-04-17

Participant Flow

As of the data cut-off (DCO) (15-DEC-2022) for the final analysis (FA), a total of 158 participants were randomized to the Intent-to-Treat (ITT) population (75 in the pembrolizumab plus chemotherapy group and 83 in the placebo plus chemotherapy group)

Participant milestones

Measure	Arm A (Pembrolizumab+Gemcitabine+Cisplatin) Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles. Participants in Arm A who stopped study intervention after achieving stable-disease (SD) or better may have been eligible to receive additional pembrolizumab for up to 17 cycles if they experienced radiographic disease progression while off study intervention, according to the protocol-defined criteria. Gemcitabine may have been continued until progressive disease (PD) or unacceptable toxicity during second course at investigator's discretion.	Arm B (Placebo+Gemcitabine+Cisplatin) Placebo to Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.
Overall Study STARTED	75	83
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	75	83

Reasons for withdrawal

Measure	Arm A (Pembrolizumab+Gemcitabine+Cisplatin) Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles. Participants in Arm A who stopped study intervention after achieving stable-disease (SD) or better may have been eligible to receive additional pembrolizumab for up to 17 cycles if they experienced radiographic disease progression while off study intervention, according to the protocol-defined criteria. Gemcitabine may have been continued until progressive disease (PD) or unacceptable toxicity during second course at investigator's discretion.	Arm B (Placebo+Gemcitabine+Cisplatin) Placebo to Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.
Overall Study Death	49	63
Overall Study Participant On-going	26	20

Baseline Characteristics

Pembrolizumab (MK-3475) Plus Gemcitabine/Cisplatin Versus Placebo Plus Gemcitabine/Cisplatin for First-Line Advanced and/or Unresectable Biliary Tract Carcinoma (BTC) (MK-3475-966/KEYNOTE-966)-China Extension Study

Baseline characteristics by cohort

Measure	Arm A (Pembrolizumab+Gemcitabine+Cisplatin) n=75 Participants Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles. Participants in Arm A who stopped study intervention after achieving stable-disease (SD) or better may have been eligible to receive additional pembrolizumab for up to 17 cycles if they experienced radiographic disease progression while off study intervention, according to the protocol-defined criteria. Gemcitabine may have been continued until progressive disease (PD) or unacceptable toxicity during second course at investigator's discretion.	Arm B (Placebo+Gemcitabine+Cisplatin) n=83 Participants Placebo to Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.	Total n=158 Participants Total of all reporting groups
Age, Continuous	59.5 Years STANDARD_DEVIATION 8.3 • n=5 Participants	58.6 Years STANDARD_DEVIATION 9.5 • n=7 Participants	59.0 Years STANDARD_DEVIATION 8.9 • n=5 Participants
Sex: Female, Male Female	39 Participants n=5 Participants	36 Participants n=7 Participants	75 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	47 Participants n=7 Participants	83 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	75 Participants n=5 Participants	83 Participants n=7 Participants	158 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	75 Participants n=5 Participants	83 Participants n=7 Participants	158 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Geographic Region Asian	75 Participants n=5 Participants	83 Participants n=7 Participants	158 Participants n=5 Participants
Disease Status Locally Advance	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Disease Status Metastatic	63 Participants n=5 Participants	69 Participants n=7 Participants	132 Participants n=5 Participants
Site of Origin Gallbladder	19 Participants n=5 Participants	12 Participants n=7 Participants	31 Participants n=5 Participants
Site of Origin Intrahepatic	45 Participants n=5 Participants	60 Participants n=7 Participants	105 Participants n=5 Participants
Site of Origin Extrahepatic	11 Participants n=5 Participants	11 Participants n=7 Participants	22 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to approximately 29 months

Population: All randomized participants

Overall survival was defined as the time from randomization to death due to any cause. Per protocol the final reported outcome for OS did not include any sensitivity or supportive analysis.

Outcome measures

Measure	Arm A (Pembrolizumab+Gemcitabine+Cisplatin) n=75 Participants Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles. Participants in Arm A who stopped study intervention after achieving stable-disease (SD) or better may have been eligible to receive additional pembrolizumab for up to 17 cycles if they experienced radiographic disease progression while off study intervention, according to the protocol-defined criteria. Gemcitabine may have been continued until progressive disease (PD) or unacceptable toxicity during second course at investigator's discretion.	Arm B (Placebo+Gemcitabine+Cisplatin) n=83 Participants Placebo to Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.
Overall Survival (OS)	14.1 Months Interval 10.4 to 17.7	9.9 Months Interval 8.6 to 13.0

SECONDARY outcome

Timeframe: Up to approximately 29 months

Population: All randomized participants

Progression-free survival was defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurred first.

Outcome measures

Measure	Arm A (Pembrolizumab+Gemcitabine+Cisplatin) n=75 Participants Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles. Participants in Arm A who stopped study intervention after achieving stable-disease (SD) or better may have been eligible to receive additional pembrolizumab for up to 17 cycles if they experienced radiographic disease progression while off study intervention, according to the protocol-defined criteria. Gemcitabine may have been continued until progressive disease (PD) or unacceptable toxicity during second course at investigator's discretion.	Arm B (Placebo+Gemcitabine+Cisplatin) n=83 Participants Placebo to Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.
Progression-free Survival (PFS) Per RECIST 1.1 as Assessed by BICR	5.6 Months Interval 3.2 to 7.4	5.7 Months Interval 4.4 to 6.9

SECONDARY outcome

Timeframe: Up to approximately 29 months

Population: All randomized participants

ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: a ≥30% decrease in the sum of diameters [SOD] of target lesions) as assessed by BICR per RECIST 1.1, which was adjusted for this study to allow a maximum of 10 target lesions in total and 5 per organ.

Outcome measures

Measure	Arm A (Pembrolizumab+Gemcitabine+Cisplatin) n=75 Participants Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles. Participants in Arm A who stopped study intervention after achieving stable-disease (SD) or better may have been eligible to receive additional pembrolizumab for up to 17 cycles if they experienced radiographic disease progression while off study intervention, according to the protocol-defined criteria. Gemcitabine may have been continued until progressive disease (PD) or unacceptable toxicity during second course at investigator's discretion.	Arm B (Placebo+Gemcitabine+Cisplatin) n=83 Participants Placebo to Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)	36.0 Percentage Interval 25.2 to 47.9	28.9 Percentage Interval 19.5 to 39.9

SECONDARY outcome

Timeframe: Up to approximately 29 months

Population: All responders (participants that achieved complete or partial response)

For participants who demonstrated a confirmed CR or PR, DOR was the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurred first.

Outcome measures

Measure	Arm A (Pembrolizumab+Gemcitabine+Cisplatin) n=27 Participants Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles. Participants in Arm A who stopped study intervention after achieving stable-disease (SD) or better may have been eligible to receive additional pembrolizumab for up to 17 cycles if they experienced radiographic disease progression while off study intervention, according to the protocol-defined criteria. Gemcitabine may have been continued until progressive disease (PD) or unacceptable toxicity during second course at investigator's discretion.	Arm B (Placebo+Gemcitabine+Cisplatin) n=24 Participants Placebo to Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR	10.2 Months Interval 5.4 to Upper limit not reached	5.7 Months Interval 4.2 to 14.0

SECONDARY outcome

Timeframe: Up to approximately 29 months

Population: All Participants as Treated (APaT) population, which consisted of all randomized participants who received at least 1 dose of study intervention

An adverse event (AE) was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study.

Outcome measures

Measure	Arm A (Pembrolizumab+Gemcitabine+Cisplatin) n=74 Participants Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles. Participants in Arm A who stopped study intervention after achieving stable-disease (SD) or better may have been eligible to receive additional pembrolizumab for up to 17 cycles if they experienced radiographic disease progression while off study intervention, according to the protocol-defined criteria. Gemcitabine may have been continued until progressive disease (PD) or unacceptable toxicity during second course at investigator's discretion.	Arm B (Placebo+Gemcitabine+Cisplatin) n=82 Participants Placebo to Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.
Number of Participants Who Experience One or More Adverse Events (AE)	73 Participants	82 Participants

SECONDARY outcome

Timeframe: Up to approximately 29 months

Population: APaT population, which consisted of all randomized participants who received at least 1 dose of study intervention

An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study.

Outcome measures

Measure	Arm A (Pembrolizumab+Gemcitabine+Cisplatin) n=74 Participants Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles. Participants in Arm A who stopped study intervention after achieving stable-disease (SD) or better may have been eligible to receive additional pembrolizumab for up to 17 cycles if they experienced radiographic disease progression while off study intervention, according to the protocol-defined criteria. Gemcitabine may have been continued until progressive disease (PD) or unacceptable toxicity during second course at investigator's discretion.	Arm B (Placebo+Gemcitabine+Cisplatin) n=82 Participants Placebo to Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.
Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE)	18 Participants	14 Participants

Adverse Events

Pembrolizumab + Chemotherapy First Course

Serious events: 28 serious events

Other events: 73 other events

Deaths: 49 deaths

Placebo + Chemotherapy First Course

Serious events: 29 serious events

Other events: 82 other events

Deaths: 63 deaths

Serious adverse events

Measure	Pembrolizumab + Chemotherapy First Course n=74 participants at risk Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.	Placebo + Chemotherapy First Course n=82 participants at risk Placebo to Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.
Blood and lymphatic system disorders Anaemia	6.8% 5/74 • Number of events 5 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	3.7% 3/82 • Number of events 3 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/74 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	1.2% 1/82 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Blood and lymphatic system disorders Myelosuppression	2.7% 2/74 • Number of events 2 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	1.2% 1/82 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Cardiac disorders Myocardial infarction	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	1.2% 1/82 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Cardiac disorders Myocarditis	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	2.4% 2/82 • Number of events 2 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/74 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	1.2% 1/82 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Gastrointestinal disorders Ascites	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	0.00% 0/82 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Gastrointestinal disorders Ileus	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	0.00% 0/82 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Gastrointestinal disorders Intestinal ischaemia	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	0.00% 0/82 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/74 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	1.2% 1/82 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Gastrointestinal disorders Vomiting	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	0.00% 0/82 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
General disorders Death	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	2.4% 2/82 • Number of events 2 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
General disorders Multiple organ dysfunction syndrome	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	0.00% 0/82 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
General disorders Pyrexia	2.7% 2/74 • Number of events 2 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	1.2% 1/82 • Number of events 2 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Hepatobiliary disorders Bile duct stone	0.00% 0/74 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	1.2% 1/82 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Hepatobiliary disorders Biliary obstruction	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	2.4% 2/82 • Number of events 2 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Hepatobiliary disorders Hepatic cyst	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	0.00% 0/82 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Hepatobiliary disorders Hepatic function abnormal	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	0.00% 0/82 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Hepatobiliary disorders Jaundice cholestatic	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	6.1% 5/82 • Number of events 5 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Hepatobiliary disorders Liver injury	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	0.00% 0/82 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Infections and infestations Bacteraemia	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	0.00% 0/82 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Infections and infestations Biliary tract infection	5.4% 4/74 • Number of events 6 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	4.9% 4/82 • Number of events 4 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Infections and infestations Enterocolitis infectious	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	0.00% 0/82 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Infections and infestations Gastroenteritis	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	0.00% 0/82 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Infections and infestations Liver abscess	0.00% 0/74 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	1.2% 1/82 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Infections and infestations Peritonitis	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	0.00% 0/82 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Infections and infestations Pneumonia	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	1.2% 1/82 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Infections and infestations Sepsis	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	0.00% 0/82 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Infections and infestations Urinary tract infection	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	1.2% 1/82 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Investigations Alanine aminotransferase increased	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	2.4% 2/82 • Number of events 2 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Investigations Blood bilirubin increased	0.00% 0/74 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	1.2% 1/82 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Investigations Myocardial necrosis marker increased	0.00% 0/74 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	1.2% 1/82 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Investigations Neutrophil count decreased	6.8% 5/74 • Number of events 6 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	2.4% 2/82 • Number of events 2 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Investigations Neutrophil count increased	0.00% 0/74 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	1.2% 1/82 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Investigations Platelet count decreased	12.2% 9/74 • Number of events 9 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	8.5% 7/82 • Number of events 11 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Investigations White blood cell count decreased	4.1% 3/74 • Number of events 3 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	3.7% 3/82 • Number of events 3 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/74 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	1.2% 1/82 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Metabolism and nutrition disorders Electrolyte imbalance	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	0.00% 0/82 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/74 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	1.2% 1/82 • Number of events 2 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	2.7% 2/74 • Number of events 2 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	0.00% 0/82 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Nervous system disorders Cerebral infarction	0.00% 0/74 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	1.2% 1/82 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Nervous system disorders Haemorrhage intracranial	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	0.00% 0/82 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Nervous system disorders Myasthenia gravis	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	0.00% 0/82 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Renal and urinary disorders Acute kidney injury	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	0.00% 0/82 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/74 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	1.2% 1/82 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	1.2% 1/82 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/74 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	1.2% 1/82 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Respiratory, thoracic and mediastinal disorders Tachypnoea	0.00% 0/74 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	1.2% 1/82 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Vascular disorders Embolism	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	0.00% 0/82 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Vascular disorders Hypertension	0.00% 0/74 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	2.4% 2/82 • Number of events 2 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Vascular disorders Thrombosis	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	0.00% 0/82 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.

Other adverse events

Measure	Pembrolizumab + Chemotherapy First Course n=74 participants at risk Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.	Placebo + Chemotherapy First Course n=82 participants at risk Placebo to Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m\^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.
Blood and lymphatic system disorders Anaemia	79.7% 59/74 • Number of events 101 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	79.3% 65/82 • Number of events 100 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Endocrine disorders Hyperthyroidism	5.4% 4/74 • Number of events 4 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	2.4% 2/82 • Number of events 2 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Endocrine disorders Hypothyroidism	14.9% 11/74 • Number of events 13 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	3.7% 3/82 • Number of events 3 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Gastrointestinal disorders Abdominal distension	9.5% 7/74 • Number of events 10 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	9.8% 8/82 • Number of events 10 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Gastrointestinal disorders Abdominal pain	6.8% 5/74 • Number of events 10 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	7.3% 6/82 • Number of events 7 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Gastrointestinal disorders Abdominal pain upper	8.1% 6/74 • Number of events 9 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	13.4% 11/82 • Number of events 22 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Gastrointestinal disorders Ascites	0.00% 0/74 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	8.5% 7/82 • Number of events 7 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Gastrointestinal disorders Constipation	20.3% 15/74 • Number of events 26 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	24.4% 20/82 • Number of events 30 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Gastrointestinal disorders Diarrhoea	16.2% 12/74 • Number of events 16 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	6.1% 5/82 • Number of events 7 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Gastrointestinal disorders Nausea	51.4% 38/74 • Number of events 97 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	42.7% 35/82 • Number of events 88 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Gastrointestinal disorders Vomiting	41.9% 31/74 • Number of events 82 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	45.1% 37/82 • Number of events 88 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
General disorders Asthenia	18.9% 14/74 • Number of events 40 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	13.4% 11/82 • Number of events 25 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
General disorders Chest discomfort	6.8% 5/74 • Number of events 6 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	6.1% 5/82 • Number of events 6 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
General disorders Fatigue	6.8% 5/74 • Number of events 5 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	8.5% 7/82 • Number of events 7 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
General disorders Malaise	16.2% 12/74 • Number of events 21 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	13.4% 11/82 • Number of events 20 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
General disorders Oedema peripheral	6.8% 5/74 • Number of events 5 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	6.1% 5/82 • Number of events 7 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
General disorders Pyrexia	14.9% 11/74 • Number of events 16 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	12.2% 10/82 • Number of events 17 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Hepatobiliary disorders Hepatic function abnormal	6.8% 5/74 • Number of events 16 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	7.3% 6/82 • Number of events 11 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Hepatobiliary disorders Hepatic pain	5.4% 4/74 • Number of events 5 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	2.4% 2/82 • Number of events 2 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Infections and infestations Upper respiratory tract infection	6.8% 5/74 • Number of events 5 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	6.1% 5/82 • Number of events 6 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Investigations Alanine aminotransferase increased	21.6% 16/74 • Number of events 27 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	34.1% 28/82 • Number of events 45 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Investigations Aspartate aminotransferase increased	25.7% 19/74 • Number of events 36 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	36.6% 30/82 • Number of events 57 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Investigations Blood alkaline phosphatase increased	14.9% 11/74 • Number of events 11 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	9.8% 8/82 • Number of events 10 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Investigations Blood bilirubin increased	12.2% 9/74 • Number of events 10 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	18.3% 15/82 • Number of events 24 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Investigations Blood creatinine increased	4.1% 3/74 • Number of events 10 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	11.0% 9/82 • Number of events 20 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Investigations Blood lactate dehydrogenase increased	6.8% 5/74 • Number of events 9 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	7.3% 6/82 • Number of events 21 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Investigations Gamma-glutamyltransferase increased	10.8% 8/74 • Number of events 13 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	14.6% 12/82 • Number of events 18 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Investigations Lymphocyte count decreased	17.6% 13/74 • Number of events 35 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	15.9% 13/82 • Number of events 26 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Investigations Neutrophil count decreased	74.3% 55/74 • Number of events 328 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	70.7% 58/82 • Number of events 316 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Investigations Neutrophil count increased	5.4% 4/74 • Number of events 8 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	1.2% 1/82 • Number of events 2 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Investigations Platelet count decreased	63.5% 47/74 • Number of events 211 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	56.1% 46/82 • Number of events 152 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Investigations Total bile acids increased	5.4% 4/74 • Number of events 5 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	7.3% 6/82 • Number of events 10 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Investigations Weight decreased	13.5% 10/74 • Number of events 10 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	17.1% 14/82 • Number of events 19 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Investigations Weight increased	5.4% 4/74 • Number of events 4 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	7.3% 6/82 • Number of events 6 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Investigations White blood cell count decreased	78.4% 58/74 • Number of events 376 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	75.6% 62/82 • Number of events 323 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Metabolism and nutrition disorders Decreased appetite	27.0% 20/74 • Number of events 47 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	34.1% 28/82 • Number of events 56 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Metabolism and nutrition disorders Electrolyte imbalance	6.8% 5/74 • Number of events 5 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	6.1% 5/82 • Number of events 5 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Metabolism and nutrition disorders Hyperglycaemia	8.1% 6/74 • Number of events 9 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	9.8% 8/82 • Number of events 11 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Metabolism and nutrition disorders Hyperuricaemia	12.2% 9/74 • Number of events 41 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	13.4% 11/82 • Number of events 21 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Metabolism and nutrition disorders Hypoalbuminaemia	13.5% 10/74 • Number of events 13 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	19.5% 16/82 • Number of events 27 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Metabolism and nutrition disorders Hypocalcaemia	1.4% 1/74 • Number of events 3 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	7.3% 6/82 • Number of events 8 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Metabolism and nutrition disorders Hypochloraemia	2.7% 2/74 • Number of events 5 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	12.2% 10/82 • Number of events 16 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Metabolism and nutrition disorders Hypokalaemia	13.5% 10/74 • Number of events 15 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	15.9% 13/82 • Number of events 18 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Metabolism and nutrition disorders Hypomagnesaemia	8.1% 6/74 • Number of events 13 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	14.6% 12/82 • Number of events 28 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Metabolism and nutrition disorders Hyponatraemia	8.1% 6/74 • Number of events 17 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	18.3% 15/82 • Number of events 21 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Metabolism and nutrition disorders Hypoproteinaemia	4.1% 3/74 • Number of events 3 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	7.3% 6/82 • Number of events 13 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Musculoskeletal and connective tissue disorders Back pain	2.7% 2/74 • Number of events 2 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	6.1% 5/82 • Number of events 6 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Nervous system disorders Dizziness	4.1% 3/74 • Number of events 3 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	9.8% 8/82 • Number of events 9 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Nervous system disorders Headache	6.8% 5/74 • Number of events 7 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	3.7% 3/82 • Number of events 3 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Psychiatric disorders Insomnia	5.4% 4/74 • Number of events 4 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	6.1% 5/82 • Number of events 5 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Renal and urinary disorders Renal impairment	5.4% 4/74 • Number of events 9 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	2.4% 2/82 • Number of events 2 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Respiratory, thoracic and mediastinal disorders Cough	5.4% 4/74 • Number of events 6 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	3.7% 3/82 • Number of events 3 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Skin and subcutaneous tissue disorders Alopecia	16.2% 12/74 • Number of events 12 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	13.4% 11/82 • Number of events 11 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Skin and subcutaneous tissue disorders Pruritus	5.4% 4/74 • Number of events 5 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	3.7% 3/82 • Number of events 3 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Skin and subcutaneous tissue disorders Rash	20.3% 15/74 • Number of events 19 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	9.8% 8/82 • Number of events 15 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	5.4% 4/74 • Number of events 4 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	2.4% 2/82 • Number of events 2 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Vascular disorders Hypertension	1.4% 1/74 • Number of events 1 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	6.1% 5/82 • Number of events 10 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.
Vascular disorders Thrombosis	5.4% 4/74 • Number of events 4 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.	0.00% 0/82 • Up to approximately 29 months All-Cause Mortality included all allocated participants. Serious and Other AEs were reported according to treatment course for all participants who received ≥1 dose of study treatment. As of DCO (15-DEC-2022) for the FA, none of the participants received the optional 2nd course of treatment.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@msd.com

Results disclosure agreements

• Principal investigator is a sponsor employee The investigator agreed to submit all manuscripts or abstracts to the Sponsor before submission. This allowed the Sponsor to protect proprietary information and to provide comments.
• Publication restrictions are in place

Restriction type: OTHER