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) (KEYNOTE-966)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT04003636

Recruitment Status : Active, not recruiting

First Posted : July 1, 2019

Results First Posted : December 22, 2023

Last Update Posted : March 5, 2024

View this study on the modernized ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Merck Sharp & Dohme LLC

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Biliary Tract Carcinoma
Interventions	Biological: Pembrolizumab Drug: Gemcitabine Drug: Cisplatin Drug: Placebo
Enrollment	1069

Participant Flow

Recruitment Details	As of the data cut-off (DCO) (15-DEC-2022) for the final analysis (FA), a total of 1069 participants were randomized to the Intent-to-Treat (ITT) population (533 in the pembrolizumab plus chemotherapy group and 536 in the placebo plus chemotherapy group)
Pre-assignment Details


Arm/Group Title	Arm A (Pembrolizumab+Gemcitabine+Cisplatin)	Arm B (Placebo+Gemcitabine+Cisplatin)
Arm/Group Description	Pembrolizumab, 200 mg, every 3 week...	Placebo to Pembrolizumab, 200 mg, e...
Arm/Group Description	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.	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.
Period Title: Overall Study
Started	533	536
Completed	0	0
Not Completed	533	536
Reason Not Completed
Death	409	443
Lost to Follow-up	0	1
Withdrawal by Subject	5	2
Participant On-going	119	90

Baseline Characteristics

Arm/Group Title		Arm A (Pembrolizumab+Gemcitabine+Cisplatin)	Arm B (Placebo+Gemcitabine+Cisplatin)	Total
Arm/Group Description		Pembrolizumab, 200 mg, every 3 week...	Placebo to Pembrolizumab, 200 mg, e...	Total of all reporting groups
Arm/Group Description		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.	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 of all reporting groups
Overall Number of Baseline Participants		533	536	1069
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	533 participants	536 participants	1069 participants
		63.3 (10.3)	61.8 (11.0)	62.5 (10.7)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	533 participants	536 participants	1069 participants
	Female	253 47.5%	264 49.3%	517 48.4%
	Male	280 52.5%	272 50.7%	552 51.6%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	533 participants	536 participants	1069 participants
	Hispanic or Latino	59 11.1%	52 9.7%	111 10.4%
	Not Hispanic or Latino	433 81.2%	449 83.8%	882 82.5%
	Unknown or Not Reported	41 7.7%	35 6.5%	76 7.1%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	533 participants	536 participants	1069 participants
	American Indian or Alaska Native	2 0.4%	1 0.2%	3 0.3%
	Asian	245 46.0%	250 46.6%	495 46.3%
	Native Hawaiian or Other Pacific Islander	1 0.2%	0 0.0%	1 0.1%
	Black or African American	11 2.1%	3 0.6%	14 1.3%
	White	256 48.0%	268 50.0%	524 49.0%
	More than one race	5 0.9%	2 0.4%	7 0.7%
	Unknown or Not Reported	13 2.4%	12 2.2%	25 2.3%
Geographic Region Measure Type: Number Unit of measure: Number of Participants	Number Analyzed	533 participants	536 participants	1069 participants
Asian		242	244	486
Non-Asian		291	292	583
Disease Status Measure Type: Number Unit of measure: Participants	Number Analyzed	533 participants	536 participants	1069 participants
Locally Advanced		60	66	126
Metastatic		473	470	943
Site of Origin Measure Type: Number Unit of measure: Participants	Number Analyzed	533 participants	536 participants	1069 participants
Gallbladder		115	118	233
Intrahepatic		320	313	633
Extrahepatic		98	105	203

Outcome Measures

1.Primary Outcome


Title	Overall Survival (OS)
Description	Overall survival was defined as the time from randomization to death d...
Description	Overall survival was defined as the time from randomization to death due to any cause.
Time Frame	Up to approximately 38 months

Outcome Measure Data

Analysis Population Description

All randomized participants


Arm/Group Title	Arm A (Pembrolizumab+Gemcitabine+Cisplatin)	Arm B (Placebo+Gemcitabine+Cisplatin)
Arm/Group Description:	Pembrolizumab, 200 mg, every 3 week...	Placebo to Pembrolizumab, 200 mg, e...
Arm/Group Description:	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.	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 Number of Participants Analyzed	533	536
Median (95% Confidence Interval) Unit of Measure: Months
	12.7 (11.5 to 13.6)	10.9 (9.9 to 11.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Pembrolizumab+Gemcitabine+Cisplatin), Arm B (Placebo+Gemcitabine+Cisplatin)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0034
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	One-sided p-value based on log-rank test stratified by geographic region, disease status, site of origin with small strata collapsed

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95% 0.72 to 0.95
	Estimation Comments	HR=Arm A/Arm B

2.Secondary Outcome


Title	Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (BICR)
Description	PFS was defined as the time from randomization to the first documented...
Description	PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 by BICR, or death due to any cause, whichever occurred first.
Time Frame	Up to approximately 26 months

Outcome Measure Data

Analysis Population Description

All randomized participants


Arm/Group Title	Arm A (Pembrolizumab+Gemcitabine+Cisplatin)	Arm B (Placebo+Gemcitabine+Cisplatin)
Arm/Group Description:	Pembrolizumab, 200 mg, every 3 week...	Placebo to Pembrolizumab, 200 mg, e...
Arm/Group Description:	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.	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 Number of Participants Analyzed	533	536
Median (95% Confidence Interval) Unit of Measure: Months
	6.5 (5.7 to 6.9)	5.6 (5.1 to 6.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Pembrolizumab+Gemcitabine+Cisplatin), Arm B (Placebo+Gemcitabine+Cisplatin)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0225
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	One-sided p-value based on log-rank test stratified by geographic region, disease status, site of origin with small strata collapsed

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95% 0.75 to 1.00
	Estimation Comments	HR=Arm A/Arm B

3.Secondary Outcome


Title	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)
Description	ORR was defined as the percentage of participants who have a confirmed...
Description	ORR was defined as the percentage of participants who have 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.
Time Frame	Up to approximately 26 months

Outcome Measure Data

Analysis Population Description

All randomized participants


Arm/Group Title	Arm A (Pembrolizumab+Gemcitabine+Cisplatin)	Arm B (Placebo+Gemcitabine+Cisplatin)
Arm/Group Description:	Pembrolizumab, 200 mg, every 3 week...	Placebo to Pembrolizumab, 200 mg, e...
Arm/Group Description:	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.	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 Number of Participants Analyzed	533	536
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: Percentage of Participants
	28.7 (24.9 to 32.8)	28.5 (24.8 to 32.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Pembrolizumab+Gemcitabine+Cisplatin), Arm B (Placebo+Gemcitabine+Cisplatin)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.4735
	Comments	One-sided p-value for testing. H0: difference in % = 0 versus H1: difference in % > 0
	Method	Miettinen & Nurminen
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference in Percentages
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95% -5.2 to 5.6
	Estimation Comments	Difference=Arm A minus Arm B

4.Secondary Outcome


Title	Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
Description	For participants who demonstrate a confirmed CR or PR, DOR was the tim...
Description	For participants who demonstrate 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.
Time Frame	Up to approximately 38 months

Outcome Measure Data

Analysis Population Description

All randomized participants with CR or PR


Arm/Group Title	Arm A (Pembrolizumab+Gemcitabine+Cisplatin)	Arm B (Placebo+Gemcitabine+Cisplatin)
Arm/Group Description:	Pembrolizumab, 200 mg, every 3 week...	Placebo to Pembrolizumab, 200 mg, e...
Arm/Group Description:	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.	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 Number of Participants Analyzed	153	153
Median (95% Confidence Interval) Unit of Measure: Months
	9.7 (1.2 to 22.7)	6.9 (0.0 to 19.2)

5.Secondary Outcome


Title	Number of Participants Who Experience One or More Adverse Events (AE)
Description	An adverse event (AE) was defined as any unfavorable and unintended si...
Description	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.
Time Frame	Up to approximately 38 months

Outcome Measure Data

Analysis Population Description

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


Arm/Group Title	Arm A (Pembrolizumab+Gemcitabine+Cisplatin)	Arm B (Placebo+Gemcitabine+Cisplatin)
Arm/Group Description:	Pembrolizumab, 200 mg, every 3 week...	Placebo to Pembrolizumab, 200 mg, e...
Arm/Group Description:	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.	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 Number of Participants Analyzed	529	534
Measure Type: Count of Participants Unit of Measure: Participants
	524 99.1%	532 99.6%

6.Secondary Outcome


Title	Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE)
Description	An AE was defined as any unfavorable and unintended sign including an ...
Description	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 occurs during the course of the study.
Time Frame	Up to approximately 38 months

Outcome Measure Data

Analysis Population Description

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


Arm/Group Title	Arm A (Pembrolizumab+Gemcitabine+Cisplatin)	Arm B (Placebo+Gemcitabine+Cisplatin)
Arm/Group Description:	Pembrolizumab, 200 mg, every 3 week...	Placebo to Pembrolizumab, 200 mg, e...
Arm/Group Description:	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.	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 Number of Participants Analyzed	529	534
Measure Type: Count of Participants Unit of Measure: Participants
	138 26.1%	122 22.8%

Adverse Events

Time Frame	Up to approximately 38 months
Adverse Event Reporting Description	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.

Arm/Group Title	Pembrolizumab + Chemotherapy		Placebo + Chemotherapy		Pembrolizumab Second Course
Arm/Group Description	Pembrolizumab, 200 mg, every 3 week...		Placebo to Pembrolizumab, 200 mg, e...		Participants in Arm A who stopped s...
Arm/Group Description	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 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.		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.
All-Cause Mortality
	Pembrolizumab + Chemotherapy		Placebo + Chemotherapy		Pembrolizumab Second Course
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	413/533 (77.49%)		443/536 (82.65%)		1/2 (50.00%)
Serious Adverse Events Serious Adverse Events
	Pembrolizumab + Chemotherapy		Placebo + Chemotherapy		Pembrolizumab Second Course
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	276/529 (52.17%)		263/534 (49.25%)		0/2 (0.00%)
Blood and lymphatic system disorders
Anaemia ^† 1	13/529 (2.46%)	13	10/534 (1.87%)	10	0/2 (0.00%)	0
Coombs negative haemolytic anaemia ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Disseminated intravascular coagulation ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Febrile bone marrow aplasia ^† 1	1/529 (0.19%)	1	1/534 (0.19%)	1	0/2 (0.00%)	0
Febrile neutropenia ^† 1	7/529 (1.32%)	8	8/534 (1.50%)	8	0/2 (0.00%)	0
Immune thrombocytopenia ^† 1	2/529 (0.38%)	2	0/534 (0.00%)	0	0/2 (0.00%)	0
Leukocytosis ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Microangiopathic haemolytic anaemia ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Myelosuppression ^† 1	2/529 (0.38%)	2	1/534 (0.19%)	1	0/2 (0.00%)	0
Pancytopenia ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Thrombotic microangiopathy ^† 1	3/529 (0.57%)	3	1/534 (0.19%)	1	0/2 (0.00%)	0
Cardiac disorders
Acute coronary syndrome ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Acute myocardial infarction ^† 1	3/529 (0.57%)	3	1/534 (0.19%)	1	0/2 (0.00%)	0
Angina pectoris ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Atrial fibrillation ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Cardiac arrest ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Cardiac failure ^† 1	6/529 (1.13%)	6	3/534 (0.56%)	3	0/2 (0.00%)	0
Cardiac failure congestive ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Cardiomyopathy ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Myocardial infarction ^† 1	2/529 (0.38%)	2	3/534 (0.56%)	3	0/2 (0.00%)	0
Myocarditis ^† 1	1/529 (0.19%)	1	1/534 (0.19%)	1	0/2 (0.00%)	0
Pericardial effusion ^† 1	2/529 (0.38%)	2	0/534 (0.00%)	0	0/2 (0.00%)	0
Pericarditis ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Ear and labyrinth disorders
Deafness neurosensory ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Sudden hearing loss ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Vertigo ^† 1	0/529 (0.00%)	0	2/534 (0.37%)	2	0/2 (0.00%)	0
Endocrine disorders
Adrenal insufficiency ^† 1	1/529 (0.19%)	1	1/534 (0.19%)	1	0/2 (0.00%)	0
Hyperthyroidism ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Hypophysitis ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Hypopituitarism ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Hypothyroidism ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Inappropriate antidiuretic hormone secretion ^† 1	1/529 (0.19%)	1	1/534 (0.19%)	1	0/2 (0.00%)	0
Eye disorders
Retinal detachment ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Gastrointestinal disorders
Abdominal pain ^† 1	6/529 (1.13%)	7	7/534 (1.31%)	7	0/2 (0.00%)	0
Abdominal pain upper ^† 1	1/529 (0.19%)	1	1/534 (0.19%)	1	0/2 (0.00%)	0
Ascites ^† 1	6/529 (1.13%)	7	13/534 (2.43%)	14	0/2 (0.00%)	0
Autoimmune colitis ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Colitis ^† 1	3/529 (0.57%)	3	2/534 (0.37%)	2	0/2 (0.00%)	0
Colonic fistula ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Constipation ^† 1	2/529 (0.38%)	2	2/534 (0.37%)	2	0/2 (0.00%)	0
Diarrhoea ^† 1	3/529 (0.57%)	3	6/534 (1.12%)	6	0/2 (0.00%)	0
Diverticular perforation ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Duodenal obstruction ^† 1	2/529 (0.38%)	2	0/534 (0.00%)	0	0/2 (0.00%)	0
Duodenal ulcer ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Duodenal ulcer haemorrhage ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Dysphagia ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Enterocolitis ^† 1	2/529 (0.38%)	2	0/534 (0.00%)	0	0/2 (0.00%)	0
Fistula of small intestine ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Gastric stenosis ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Gastric ulcer ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Gastritis ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Gastrointestinal haemorrhage ^† 1	5/529 (0.95%)	5	0/534 (0.00%)	0	0/2 (0.00%)	0
Gastrointestinal toxicity ^† 1	1/529 (0.19%)	2	0/534 (0.00%)	0	0/2 (0.00%)	0
Haematemesis ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Haemoperitoneum ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Haemorrhoids ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Ileus ^† 1	4/529 (0.76%)	4	4/534 (0.75%)	6	0/2 (0.00%)	0
Ileus paralytic ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Immune-mediated enterocolitis ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Inguinal hernia ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Intestinal ischaemia ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Intestinal obstruction ^† 1	1/529 (0.19%)	1	3/534 (0.56%)	3	0/2 (0.00%)	0
Intestinal perforation ^† 1	2/529 (0.38%)	2	0/534 (0.00%)	0	0/2 (0.00%)	0
Intestinal varices haemorrhage ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Jejunal perforation ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Large intestine perforation ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Malignant gastrointestinal obstruction ^† 1	0/529 (0.00%)	0	2/534 (0.37%)	2	0/2 (0.00%)	0
Mechanical ileus ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Melaena ^† 1	0/529 (0.00%)	0	2/534 (0.37%)	4	0/2 (0.00%)	0
Nausea ^† 1	2/529 (0.38%)	2	2/534 (0.37%)	2	0/2 (0.00%)	0
Obstruction gastric ^† 1	3/529 (0.57%)	3	0/534 (0.00%)	0	0/2 (0.00%)	0
Oesophageal stenosis ^† 1	1/529 (0.19%)	1	1/534 (0.19%)	1	0/2 (0.00%)	0
Oesophageal varices haemorrhage ^† 1	2/529 (0.38%)	2	1/534 (0.19%)	1	0/2 (0.00%)	0
Oesophagitis ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Pancreatitis ^† 1	3/529 (0.57%)	3	1/534 (0.19%)	1	0/2 (0.00%)	0
Pancreatitis acute ^† 1	0/529 (0.00%)	0	2/534 (0.37%)	2	0/2 (0.00%)	0
Pancreatolithiasis ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Pneumatosis intestinalis ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Prepyloric stenosis ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Small intestinal haemorrhage ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Small intestinal obstruction ^† 1	4/529 (0.76%)	5	1/534 (0.19%)	1	0/2 (0.00%)	0
Stomatitis ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Subileus ^† 1	2/529 (0.38%)	2	0/534 (0.00%)	0	0/2 (0.00%)	0
Upper gastrointestinal haemorrhage ^† 1	3/529 (0.57%)	3	3/534 (0.56%)	3	0/2 (0.00%)	0
Vomiting ^† 1	7/529 (1.32%)	7	4/534 (0.75%)	4	0/2 (0.00%)	0
General disorders
Asthenia ^† 1	2/529 (0.38%)	3	3/534 (0.56%)	3	0/2 (0.00%)	0
Death ^† 1	3/529 (0.57%)	3	5/534 (0.94%)	5	0/2 (0.00%)	0
Fatigue ^† 1	2/529 (0.38%)	2	2/534 (0.37%)	2	0/2 (0.00%)	0
General physical health deterioration ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Hyperpyrexia ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Influenza like illness ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Malaise ^† 1	1/529 (0.19%)	1	1/534 (0.19%)	1	0/2 (0.00%)	0
Oedema peripheral ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Pain ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Peripheral swelling ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Puncture site haemorrhage ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Pyrexia ^† 1	30/529 (5.67%)	34	12/534 (2.25%)	15	0/2 (0.00%)	0
Systemic inflammatory response syndrome ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Hepatobiliary disorders
Bile duct stenosis ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Bile duct stone ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Biliary dilatation ^† 1	1/529 (0.19%)	1	1/534 (0.19%)	1	0/2 (0.00%)	0
Biliary obstruction ^† 1	12/529 (2.27%)	14	16/534 (3.00%)	18	0/2 (0.00%)	0
Biloma ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Cholangitis ^† 1	31/529 (5.86%)	39	24/534 (4.49%)	38	0/2 (0.00%)	0
Cholangitis acute ^† 1	7/529 (1.32%)	8	3/534 (0.56%)	3	0/2 (0.00%)	0
Cholecystitis ^† 1	3/529 (0.57%)	3	3/534 (0.56%)	3	0/2 (0.00%)	0
Cholecystitis acute ^† 1	1/529 (0.19%)	1	1/534 (0.19%)	1	0/2 (0.00%)	0
Cholestasis ^† 1	1/529 (0.19%)	1	1/534 (0.19%)	1	0/2 (0.00%)	0
Drug-induced liver injury ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Gallbladder rupture ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Hepatic cirrhosis ^† 1	1/529 (0.19%)	1	1/534 (0.19%)	1	0/2 (0.00%)	0
Hepatic displacement ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Hepatic function abnormal ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Hepatic haemorrhage ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Hepatic ischaemia ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Hepatorenal syndrome ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Hyperbilirubinaemia ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Immune-mediated hepatitis ^† 1	3/529 (0.57%)	3	4/534 (0.75%)	4	0/2 (0.00%)	0
Jaundice cholestatic ^† 1	3/529 (0.57%)	3	5/534 (0.94%)	6	0/2 (0.00%)	0
Liver injury ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Portal hypertension ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Portal vein thrombosis ^† 1	1/529 (0.19%)	1	1/534 (0.19%)	1	0/2 (0.00%)	0
Steatohepatitis ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Immune system disorders
Contrast media allergy ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Infusion related hypersensitivity reaction ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Infections and infestations
Abdominal abscess ^† 1	3/529 (0.57%)	3	0/534 (0.00%)	0	0/2 (0.00%)	0
Abdominal infection ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Abdominal wall abscess ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Arthritis bacterial ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Bacteraemia ^† 1	8/529 (1.51%)	8	1/534 (0.19%)	1	0/2 (0.00%)	0
Biliary sepsis ^† 1	1/529 (0.19%)	1	3/534 (0.56%)	3	0/2 (0.00%)	0
Biliary tract infection ^† 1	17/529 (3.21%)	21	18/534 (3.37%)	25	0/2 (0.00%)	0
Bronchiolitis ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Bronchopulmonary aspergillosis ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Burkholderia cepacia complex infection ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
COVID-19 ^† 1	7/529 (1.32%)	7	8/534 (1.50%)	8	0/2 (0.00%)	0
COVID-19 pneumonia ^† 1	6/529 (1.13%)	6	3/534 (0.56%)	3	0/2 (0.00%)	0
Cellulitis ^† 1	1/529 (0.19%)	1	3/534 (0.56%)	3	0/2 (0.00%)	0
Chlamydial infection ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Cholangitis infective ^† 1	0/529 (0.00%)	0	3/534 (0.56%)	4	0/2 (0.00%)	0
Device related infection ^† 1	3/529 (0.57%)	3	1/534 (0.19%)	1	0/2 (0.00%)	0
Diarrhoea infectious ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Diverticulitis ^† 1	2/529 (0.38%)	2	0/534 (0.00%)	0	0/2 (0.00%)	0
Encephalitis ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Enterobacter sepsis ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Enterocolitis infectious ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Escherichia bacteraemia ^† 1	1/529 (0.19%)	1	1/534 (0.19%)	2	0/2 (0.00%)	0
Febrile infection ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Fungal sepsis ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Gastroenteritis ^† 1	2/529 (0.38%)	2	0/534 (0.00%)	0	0/2 (0.00%)	0
Helicobacter infection ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Hepatic infection ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Herpes zoster ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Infection ^† 1	4/529 (0.76%)	4	0/534 (0.00%)	0	0/2 (0.00%)	0
Intervertebral discitis ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Klebsiella bacteraemia ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Klebsiella infection ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Liver abscess ^† 1	4/529 (0.76%)	4	11/534 (2.06%)	13	0/2 (0.00%)	0
Lower respiratory tract infection ^† 1	3/529 (0.57%)	3	0/534 (0.00%)	0	0/2 (0.00%)	0
Lung abscess ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Mucosal infection ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Neutropenic infection ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Neutropenic sepsis ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Peritonitis ^† 1	4/529 (0.76%)	4	3/534 (0.56%)	3	0/2 (0.00%)	0
Peritonitis bacterial ^† 1	1/529 (0.19%)	1	1/534 (0.19%)	1	0/2 (0.00%)	0
Pleural infection ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Pneumococcal bacteraemia ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Pneumococcal sepsis ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Pneumocystis jirovecii pneumonia ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Pneumonia ^† 1	8/529 (1.51%)	9	8/534 (1.50%)	9	0/2 (0.00%)	0
Pneumonia acinetobacter ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Pneumonia aspiration ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Pneumonia bacterial ^† 1	0/529 (0.00%)	0	3/534 (0.56%)	3	0/2 (0.00%)	0
Pneumonia viral ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Postoperative abscess ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Pseudomembranous colitis ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Pyelonephritis ^† 1	3/529 (0.57%)	3	0/534 (0.00%)	0	0/2 (0.00%)	0
Pyelonephritis acute ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Sepsis ^† 1	13/529 (2.46%)	15	16/534 (3.00%)	17	0/2 (0.00%)	0
Septic embolus ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Septic shock ^† 1	1/529 (0.19%)	1	4/534 (0.75%)	4	0/2 (0.00%)	0
Skin infection ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Spontaneous bacterial peritonitis ^† 1	1/529 (0.19%)	1	1/534 (0.19%)	1	0/2 (0.00%)	0
Systemic candida ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Tuberculosis ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Upper respiratory tract infection ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Urinary tract infection ^† 1	10/529 (1.89%)	10	6/534 (1.12%)	6	0/2 (0.00%)	0
Urosepsis ^† 1	1/529 (0.19%)	2	2/534 (0.37%)	2	0/2 (0.00%)	0
Injury, poisoning and procedural complications
Brain contusion ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Contusion ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Craniocerebral injury ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Fall ^† 1	2/529 (0.38%)	2	0/534 (0.00%)	0	0/2 (0.00%)	0
Foreign body in gastrointestinal tract ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Humerus fracture ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Post procedural bile leak ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Post procedural complication ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Post procedural fever ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Postoperative adhesion ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Procedural pain ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Road traffic accident ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Spinal compression fracture ^† 1	1/529 (0.19%)	1	1/534 (0.19%)	1	0/2 (0.00%)	0
Spinal fracture ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Stoma site ulcer ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Toxicity to various agents ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Ureteric injury ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Investigations
Alanine aminotransferase increased ^† 1	2/529 (0.38%)	2	4/534 (0.75%)	4	0/2 (0.00%)	0
Aspartate aminotransferase increased ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Blood alkaline phosphatase increased ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Blood bilirubin increased ^† 1	5/529 (0.95%)	5	4/534 (0.75%)	4	0/2 (0.00%)	0
Blood creatinine increased ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Gamma-glutamyltransferase increased ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Neutrophil count decreased ^† 1	11/529 (2.08%)	13	1/534 (0.19%)	1	0/2 (0.00%)	0
Neutrophil count increased ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Platelet count decreased ^† 1	19/529 (3.59%)	19	10/534 (1.87%)	12	0/2 (0.00%)	0
Transaminases increased ^† 1	2/529 (0.38%)	2	1/534 (0.19%)	1	0/2 (0.00%)	0
Troponin increased ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
White blood cell count decreased ^† 1	1/529 (0.19%)	1	2/534 (0.37%)	2	0/2 (0.00%)	0
Metabolism and nutrition disorders
Alkalosis ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Cachexia ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Decreased appetite ^† 1	4/529 (0.76%)	4	5/534 (0.94%)	5	0/2 (0.00%)	0
Dehydration ^† 1	2/529 (0.38%)	2	0/534 (0.00%)	0	0/2 (0.00%)	0
Diabetes mellitus ^† 1	2/529 (0.38%)	2	0/534 (0.00%)	0	0/2 (0.00%)	0
Electrolyte imbalance ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Food refusal ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Hyperglycaemia ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Hyperkalaemia ^† 1	3/529 (0.57%)	3	0/534 (0.00%)	0	0/2 (0.00%)	0
Hypernatraemia ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Hypoalbuminaemia ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Hypoglycaemia ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Hypokalaemia ^† 1	2/529 (0.38%)	2	1/534 (0.19%)	2	0/2 (0.00%)	0
Hyponatraemia ^† 1	1/529 (0.19%)	1	4/534 (0.75%)	4	0/2 (0.00%)	0
Hypophagia ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back pain ^† 1	1/529 (0.19%)	1	1/534 (0.19%)	1	0/2 (0.00%)	0
Bone pain ^† 1	1/529 (0.19%)	1	1/534 (0.19%)	1	0/2 (0.00%)	0
Chest wall haematoma ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Intervertebral disc protrusion ^† 1	2/529 (0.38%)	2	0/534 (0.00%)	0	0/2 (0.00%)	0
Muscular weakness ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Osteoporotic fracture ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Pathological fracture ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Benign neoplasm of testis ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Bladder cancer ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Cancer pain ^† 1	0/529 (0.00%)	0	3/534 (0.56%)	3	0/2 (0.00%)	0
Lymphangiosis carcinomatosa ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Malignant neoplasm progression ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Oesophageal carcinoma ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Squamous cell carcinoma ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Tumour associated fever ^† 1	1/529 (0.19%)	1	2/534 (0.37%)	2	0/2 (0.00%)	0
Nervous system disorders
Altered state of consciousness ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Aphasia ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Carpal tunnel syndrome ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Cerebellar infarction ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Cerebral haemorrhage ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Cerebral infarction ^† 1	2/529 (0.38%)	2	3/534 (0.56%)	3	0/2 (0.00%)	0
Cerebral venous sinus thrombosis ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Cerebrovascular accident ^† 1	5/529 (0.95%)	5	4/534 (0.75%)	4	0/2 (0.00%)	0
Epilepsy ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Haemorrhage intracranial ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Headache ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Hepatic encephalopathy ^† 1	2/529 (0.38%)	2	1/534 (0.19%)	1	0/2 (0.00%)	0
Ischaemic stroke ^† 1	0/529 (0.00%)	0	2/534 (0.37%)	3	0/2 (0.00%)	0
Lethargy ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Loss of consciousness ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Myasthenia gravis ^† 1	1/529 (0.19%)	1	1/534 (0.19%)	1	0/2 (0.00%)	0
Radicular pain ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Syncope ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Transient ischaemic attack ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Product Issues
Device dislocation ^† 1	2/529 (0.38%)	3	0/534 (0.00%)	0	0/2 (0.00%)	0
Device malfunction ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Device occlusion ^† 1	2/529 (0.38%)	2	1/534 (0.19%)	1	0/2 (0.00%)	0
Psychiatric disorders
Confusional state ^† 1	1/529 (0.19%)	1	2/534 (0.37%)	2	0/2 (0.00%)	0
Delirium ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Depressed mood ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Renal and urinary disorders
Acute kidney injury ^† 1	4/529 (0.76%)	5	10/534 (1.87%)	12	0/2 (0.00%)	0
Chronic kidney disease ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Haematuria ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Renal failure ^† 1	1/529 (0.19%)	1	2/534 (0.37%)	3	0/2 (0.00%)	0
Renal impairment ^† 1	1/529 (0.19%)	2	0/534 (0.00%)	0	0/2 (0.00%)	0
Renal vein thrombosis ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Ureterolithiasis ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Urinary retention ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Chronic obstructive pulmonary disease ^† 1	0/529 (0.00%)	0	2/534 (0.37%)	2	0/2 (0.00%)	0
Dyspnoea ^† 1	2/529 (0.38%)	2	4/534 (0.75%)	4	0/2 (0.00%)	0
Hypoxia ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Interstitial lung disease ^† 1	1/529 (0.19%)	2	0/534 (0.00%)	0	0/2 (0.00%)	0
Pleural effusion ^† 1	0/529 (0.00%)	0	4/534 (0.75%)	4	0/2 (0.00%)	0
Pleuritic pain ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Pneumonitis ^† 1	7/529 (1.32%)	7	3/534 (0.56%)	3	0/2 (0.00%)	0
Pneumothorax ^† 1	2/529 (0.38%)	2	1/534 (0.19%)	1	0/2 (0.00%)	0
Pulmonary embolism ^† 1	11/529 (2.08%)	11	8/534 (1.50%)	8	0/2 (0.00%)	0
Pulmonary oedema ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Respiratory failure ^† 1	0/529 (0.00%)	0	2/534 (0.37%)	2	0/2 (0.00%)	0
Sleep apnoea syndrome ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Tachypnoea ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Upper respiratory tract inflammation ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Skin and subcutaneous tissue disorders
Cutaneous vasculitis ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Dermatitis exfoliative ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Rash ^† 1	2/529 (0.38%)	2	0/534 (0.00%)	0	0/2 (0.00%)	0
Stevens-Johnson syndrome ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Surgical and medical procedures
Euthanasia ^† 1	2/529 (0.38%)	2	1/534 (0.19%)	1	0/2 (0.00%)	0
Vascular disorders
Aortic aneurysm ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Deep vein thrombosis ^† 1	2/529 (0.38%)	2	1/534 (0.19%)	1	0/2 (0.00%)	0
Embolism ^† 1	0/529 (0.00%)	0	2/534 (0.37%)	2	0/2 (0.00%)	0
Haematoma ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Hypertension ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Hypovolaemic shock ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Inferior vena caval occlusion ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Peripheral artery thrombosis ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Shock ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
Shock haemorrhagic ^† 1	1/529 (0.19%)	1	0/534 (0.00%)	0	0/2 (0.00%)	0
Thrombosis ^† 1	1/529 (0.19%)	1	1/534 (0.19%)	1	0/2 (0.00%)	0
Vena cava embolism ^† 1	0/529 (0.00%)	0	1/534 (0.19%)	1	0/2 (0.00%)	0
1 Term from vocabulary, MedDRA 25.1 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Pembrolizumab + Chemotherapy		Placebo + Chemotherapy		Pembrolizumab Second Course
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	512/529 (96.79%)		522/534 (97.75%)		2/2 (100.00%)
Blood and lymphatic system disorders
Anaemia ^† 1	315/529 (59.55%)	528	306/534 (57.30%)	486	0/2 (0.00%)	0
Endocrine disorders
Hypothyroidism ^† 1	45/529 (8.51%)	46	14/534 (2.62%)	14	0/2 (0.00%)	0
Gastrointestinal disorders
Abdominal distension ^† 1	37/529 (6.99%)	41	34/534 (6.37%)	43	0/2 (0.00%)	0
Abdominal pain ^† 1	88/529 (16.64%)	122	117/534 (21.91%)	152	0/2 (0.00%)	0
Abdominal pain upper ^† 1	40/529 (7.56%)	53	56/534 (10.49%)	72	0/2 (0.00%)	0
Ascites ^† 1	29/529 (5.48%)	31	33/534 (6.18%)	34	0/2 (0.00%)	0
Constipation ^† 1	185/529 (34.97%)	227	188/534 (35.21%)	233	2/2 (100.00%)	2
Diarrhoea ^† 1	102/529 (19.28%)	149	93/534 (17.42%)	149	0/2 (0.00%)	0
Dyspepsia ^† 1	33/529 (6.24%)	36	55/534 (10.30%)	64	1/2 (50.00%)	1
Nausea ^† 1	232/529 (43.86%)	418	245/534 (45.88%)	421	0/2 (0.00%)	0
Stomatitis ^† 1	26/529 (4.91%)	30	34/534 (6.37%)	37	1/2 (50.00%)	1
Vomiting ^† 1	120/529 (22.68%)	234	127/534 (23.78%)	268	0/2 (0.00%)	0
Oesophagitis ^† 1	1/529 (0.19%)	1	2/534 (0.37%)	2	1/2 (50.00%)	1
General disorders
Asthenia ^† 1	75/529 (14.18%)	134	93/534 (17.42%)	165	0/2 (0.00%)	0
Fatigue ^† 1	186/529 (35.16%)	281	170/534 (31.84%)	231	0/2 (0.00%)	0
Malaise ^† 1	36/529 (6.81%)	65	31/534 (5.81%)	59	0/2 (0.00%)	0
Mucosal inflammation ^† 1	28/529 (5.29%)	34	23/534 (4.31%)	31	0/2 (0.00%)	0
Oedema peripheral ^† 1	73/529 (13.80%)	87	85/534 (15.92%)	124	0/2 (0.00%)	0
Pyrexia ^† 1	118/529 (22.31%)	228	96/534 (17.98%)	172	0/2 (0.00%)	0
Infections and infestations
Urinary tract infection ^† 1	29/529 (5.48%)	37	23/534 (4.31%)	26	0/2 (0.00%)	0
Investigations
Alanine aminotransferase increased ^† 1	86/529 (16.26%)	142	110/534 (20.60%)	169	0/2 (0.00%)	0
Aspartate aminotransferase increased ^† 1	88/529 (16.64%)	160	98/534 (18.35%)	187	0/2 (0.00%)	0
Blood alkaline phosphatase increased ^† 1	42/529 (7.94%)	59	52/534 (9.74%)	72	0/2 (0.00%)	0
Blood bilirubin increased ^† 1	46/529 (8.70%)	69	61/534 (11.42%)	80	0/2 (0.00%)	0
Blood creatinine increased ^† 1	56/529 (10.59%)	101	58/534 (10.86%)	103	0/2 (0.00%)	0
Gamma-glutamyltransferase increased ^† 1	23/529 (4.35%)	30	29/534 (5.43%)	39	0/2 (0.00%)	0
Lymphocyte count decreased ^† 1	23/529 (4.35%)	49	29/534 (5.43%)	48	0/2 (0.00%)	0
Neutrophil count decreased ^† 1	328/529 (62.00%)	1386	327/534 (61.24%)	1269	0/2 (0.00%)	0
Platelet count decreased ^† 1	207/529 (39.13%)	571	211/534 (39.51%)	568	0/2 (0.00%)	0
Weight decreased ^† 1	51/529 (9.64%)	52	63/534 (11.80%)	75	0/2 (0.00%)	0
White blood cell count decreased ^† 1	141/529 (26.65%)	740	127/534 (23.78%)	616	0/2 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite ^† 1	141/529 (26.65%)	185	151/534 (28.28%)	206	1/2 (50.00%)	2
Hyperglycaemia ^† 1	36/529 (6.81%)	58	40/534 (7.49%)	51	0/2 (0.00%)	0
Hyperkalaemia ^† 1	35/529 (6.62%)	78	29/534 (5.43%)	35	0/2 (0.00%)	0
Hypoalbuminaemia ^† 1	38/529 (7.18%)	52	49/534 (9.18%)	67	0/2 (0.00%)	0
Hypokalaemia ^† 1	48/529 (9.07%)	67	67/534 (12.55%)	92	0/2 (0.00%)	0
Hypomagnesaemia ^† 1	79/529 (14.93%)	148	79/534 (14.79%)	139	0/2 (0.00%)	0
Hyponatraemia ^† 1	51/529 (9.64%)	86	49/534 (9.18%)	59	0/2 (0.00%)	0
Fluid retention ^† 1	1/529 (0.19%)	1	1/534 (0.19%)	1	1/2 (50.00%)	1
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	39/529 (7.37%)	45	41/534 (7.68%)	50	0/2 (0.00%)	0
Back pain ^† 1	53/529 (10.02%)	65	72/534 (13.48%)	77	0/2 (0.00%)	0
Myalgia ^† 1	27/529 (5.10%)	36	30/534 (5.62%)	33	0/2 (0.00%)	0
Pain in extremity ^† 1	28/529 (5.29%)	35	22/534 (4.12%)	24	0/2 (0.00%)	0
Nervous system disorders
Dizziness ^† 1	32/529 (6.05%)	44	50/534 (9.36%)	55	1/2 (50.00%)	1
Dysgeusia ^† 1	31/529 (5.86%)	34	32/534 (5.99%)	34	0/2 (0.00%)	0
Headache ^† 1	53/529 (10.02%)	79	45/534 (8.43%)	53	0/2 (0.00%)	0
Neuropathy peripheral ^† 1	21/529 (3.97%)	23	29/534 (5.43%)	31	0/2 (0.00%)	0
Peripheral sensory neuropathy ^† 1	31/529 (5.86%)	33	29/534 (5.43%)	30	0/2 (0.00%)	0
Psychiatric disorders
Insomnia ^† 1	41/529 (7.75%)	46	41/534 (7.68%)	45	0/2 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	36/529 (6.81%)	42	37/534 (6.93%)	43	0/2 (0.00%)	0
Dyspnoea ^† 1	51/529 (9.64%)	59	51/534 (9.55%)	56	0/2 (0.00%)	0
Skin and subcutaneous tissue disorders
Alopecia ^† 1	55/529 (10.40%)	58	68/534 (12.73%)	71	0/2 (0.00%)	0
Pruritus ^† 1	77/529 (14.56%)	106	51/534 (9.55%)	60	1/2 (50.00%)	1
Rash ^† 1	88/529 (16.64%)	113	49/534 (9.18%)	64	0/2 (0.00%)	0
Vascular disorders
Hypertension ^† 1	34/529 (6.43%)	40	37/534 (6.93%)	60	0/2 (0.00%)	0
1 Term from vocabulary, MedDRA 25.1 † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Senior Vice President, Global Clinical Development
Organization:	Merck Sharp & Dohme LLC
Phone:	1-800-672-6372
EMail:	ClinicalTrialsDisclosure@merck.com

Publications of Results:

Kelley RK, Ueno M, Yoo C, Finn RS, Furuse J, Ren Z, Yau T, Klumpen HJ, Chan SL, Ozaka M, Verslype C, Bouattour M, Park JO, Barajas O, Pelzer U, Valle JW, Yu L, Malhotra U, Siegel AB, Edeline J, Vogel A; KEYNOTE-966 Investigators. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 Jun 3;401(10391):1853-1865. doi: 10.1016/S0140-6736(23)00727-4. Epub 2023 Apr 16. Erratum In: Lancet. 2023 Sep 16;402(10406):964. Lancet. 2024 Mar 23;403(10432):1140.

Layout table for additonal information

Responsible Party:	Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:	NCT04003636
Other Study ID Numbers:	3475-966 MK-3475-966 ( Other Identifier: Merck ) KEYNOTE-966 ( Other Identifier: Merck ) 195007 ( Registry Identifier: JAPIC-CTI ) 2019-000944-82 ( EudraCT Number )
First Submitted:	June 28, 2019
First Posted:	July 1, 2019
Results First Submitted:	December 6, 2023
Results First Posted:	December 22, 2023
Last Update Posted:	March 5, 2024

To Top