Study of Pembrolizumab (MK-3475) or Placebo Given With Be... | NCT03062358

ID	Type	Description	Link
MK-3475-394	Other Identifier	MSD

Label	Type	Description	Intervention Names
pembrolizumab + BSC	Experimental	Participants receive pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.	Biological: pembrolizumab Other: best supportive care (BSC)
placebo + BSC	Placebo Comparator	Participants receive placebo by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.	Drug: placebo Other: best supportive care (BSC)

Name	Type	Description	Arm Group Labels	Other Names
pembrolizumab	Biological	Administered as an intravenous (IV) infusion every 3 weeks (Q3W)	pembrolizumab + BSC

Measure	Description	Time Frame
Overall Survival (OS)	OS is the time from randomization to death due to any cause, based on the Kaplan-Meier method for censored data.	Up to approximately 4 years

Measure	Description	Time Frame
Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	PFS is the time from randomization to first documented disease progression or death due to any cause per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) based on the Kaplan-Meier method for censored data.	Up to approximately 4 years

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Has a HCC diagnosis confirmed by radiology, histology, or cytology (fibrolamellar, and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible)
Has Barcelona Clinic Liver Cancer (BCLC) Stage C disease or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy and not amenable to a curative treatment approach.
Has a Child-Pugh A liver score within 7 days prior to first dose of study medication
Has a life expectancy of >3 months
Has at least one measurable lesion based on RECIST version 1.1 as determined by investigator.
Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 7 days prior to receiving the first dose of study medication.
Has documented objective radiographic progression during or after treatment with sorafenib or oxaliplatin-based chemotherapy, or else intolerance to sorafenib or oxaliplatin-based chemotherapy
Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study therapy
Female and male participants of reproductive potential must agree to use adequate contraception starting from the first dose of study medication, throughout the study period, and for up to 120 days after the last dose of study medication

Exclusion Criteria:

Is currently participating or has participated in a study with an investigational agent or using an investigational device within 4 weeks of the first dose of study medication
Has received sorafenib or oxaliplatin-based chemotherapy within 14 days of first dose of study medication
Has had esophageal or gastric variceal bleeding within the last 6 months
Has clinically apparent ascites on physical examination
Has portal vein invasion at the main portal branch (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging
Has had clinically diagnosed hepatic encephalopathy in the last 6 months
Has had a solid organ or hematologic transplant
Has had prior systemic therapy for HCC in the advanced (incurable) setting other than sorafenib or oxaliplatin-based chemotherapy, prior to start of study medication
Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
Has received locoregional therapy to liver (transcatheter chemoembolization [TACE], transcatheter embolization [TAE], hepatic arterial infusion [HAI], radiation, radioembolization, or ablation) within 4 weeks prior to the first dose of study medication
Has had major surgery to liver or other site within 4 weeks prior to the first dose of study medication
Has had a minor surgery ≤7 days prior to the first dose of study medication
Has not recovered adequately (i.e., Grade ≤1 or baseline) from the toxicity and/or complications from any intervention prior to study start
Has a diagnosed additional malignancy within 3 years prior to first dose of study medication with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cancers
Has a known history of, or any evidence of, central nervous system (CNS) metastases and/or carcinomatous meningitis
Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
Has an active infection requiring systemic therapy
Is pregnant or breast feeding or expecting to conceive or father starting from the first dose of study medication, throughout the study period, and for up to 120 days after the last dose of study medication
Has received prior immunotherapy with an anti-Programmed Cell Death Receptor 1 (PD-1), Programmed Cell Death Receptor Ligand 1 (anti-PD-L1), or anti-Programmed Cell Death Receptor Ligand 2 (PD-L2) or has previously participated in clinical studies with pembrolizumab
Has a known history of human immunodeficiency virus (HIV)
Has untreated active Hepatitis B
Has Hepatitis C in which participants received therapy for HCV <4 weeks prior to receiving pembrolizumab
Has received a live vaccine within 30 days prior to the first dose of study therapy

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Anhui Provincial Hospital ( Site 0032)		Hefei	Anhui	230001	China
The First Affiliated Hospital of Anhui Medical University ( Site 0005)

PubMed Identifier	Type	Citation	Retractions
36455168	Background	Qin S, Chen Z, Fang W, Ren Z, Xu R, Ryoo BY, Meng Z, Bai Y, Chen X, Liu X, Xiao J, Ho GF, Mao Y, Wang X, Ying J, Li J, Zhong W, Zhou Y, Siegel AB, Hao C. Pembrolizumab Versus Placebo as Second-Line Therapy in Patients From Asia With Advanced Hepatocellular Carcinoma: A Randomized, Double-Blind, Phase III Trial. J Clin Oncol. 2023 Mar 1;41(7):1434-1443. doi: 10.1200/JCO.22.00620. Epub 2022 Dec 1.
40486134

Label	URL
Merck Clinical Trials Information	View source

ID	Title	Description
FG000	Pembrolizumab + BSC	Participants received 200 mg pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus best supportive care (BSC).
FG001	Placebo + BSC

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 3, 2022	Sep 11, 2025

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Overall Survival (OS)

OS is the time from randomization to death due to any cause, based on the Kaplan-Meier method for censored data.

All randomized participants based on the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Up to approximately 4 years

ID	Title	Description
OG000	Pembrolizumab + BSC	Participants received 200 mg pembrolizumab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.
OG001	Placebo + BSC	Participants received placebo by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.

Units	Counts
Participants	OG000300 OG001153

Title

Denominators

Categories

Title	Measurements
	OG00014.6(12.6 to 18.0) OG00113.0(10.5 to 15.1)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		One-sided p-value	Stratified by macrovascular invasion, α-Fetoprotein and region with all cells that correspond to macrovascular invasion=Yes combined	0.0180	Log-rank test	Hazard Ratio (HR)	0.79			2-Sided	95	0.63	0.99			Based on Cox regression model with Efron's method of tie handling with treatment as a covariate		Superiority		Stratified by macrovascular invasion (Yes vs. No), α-Fetoprotein (ng/mL) (< 200 vs. ≥ 200) and region (China vs. ex-China) with all cells that correspond to macrovascular invasion=Yes combined.

Secondary

Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

PFS is the time from randomization to first documented disease progression or death due to any cause per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) based on the Kaplan-Meier method for censored data.

All randomized participants based on the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Up to approximately 4 years

ID	Title	Description
OG000	Pembrolizumab + BSC	Participants received 200 mg pembrolizumab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.
OG001	Placebo + BSC	Participants received placebo by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.

Units	Counts
Participants	OG000

Secondary

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

ORR is the percentage of participants who achieve complete response (CR) or partial response (PR) with confirmation per RECIST 1.1 by BICR. CR is the disappearance of all target lesions; PR is at least a 30% decrease in the sum of diameters of target lesions.

All randomized participants based on the treatment group to which they were randomized.

Posted

Number

95% Confidence Interval

Percentage of participants

Up to approximately 4 years

ID	Title	Description
OG000	Pembrolizumab + BSC	Participants received 200 mg pembrolizumab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.
OG001	Placebo + BSC	Participants received placebo by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.

Units	Counts
Participants	OG000

Secondary

Duration Of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

DOR is the time from first documented evidence of CR or PR per RECIST 1.1 by BICR until disease progression per RECIST 1.1 by BICR or death, based on Kaplan-Meier method for censored data. CR is the disappearance of all target lesions; PR is at least a 30% decrease in the sum of diameters of target lesions.

All randomized participants with CR or PR.

Posted

Median

Full Range

Months

Up to approximately 4 years

ID	Title	Description
OG000	Pembrolizumab + BSC	Participants received 200 mg pembrolizumab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.
OG001	Placebo + BSC	Participants received placebo by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.

Units	Counts
Participants	OG000

Secondary

Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

DCR is the percentage of participants who achieve CR, PR, or stable disease (SD) for ≥5 weeks prior to evidence of disease progression per RECIST 1.1 by BICR. CR is the disappearance of all target lesions; PR is at least a 30% decrease in the sum of diameters of target lesions.

All randomized participants based on the treatment group to which they were randomized, who achieved CR, PR, or SD for ≥5 weeks prior to evidence of disease progression.

Posted

Number

95% Confidence Interval

Percentage of participants

Up to approximately 4 years

ID	Title	Description
OG000	Pembrolizumab + BSC	Participants received 200 mg pembrolizumab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.
OG001	Placebo + BSC	Participants received placebo by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.

Units	Counts
Participants

Secondary

Time To Progression (TTP) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

TTP is the time from randomization to first documented disease progression per RECIST 1.1 by BICR, based on Kaplan-Meier method for censored data.

All randomized participants based on the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Up to approximately 4 years

ID	Title	Description
OG000	Pembrolizumab + BSC	Participants received 200 mg pembrolizumab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.
OG001	Placebo + BSC	Participants received placebo by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.

Units	Counts
Participants	OG000

Secondary

Number of Participants Who Experienced At Least One Adverse Event (AE)

An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy.

Randomized participants who received at least 1 dose of study intervention.

Posted

Count of Participants

Participants

Up to approximately 30 months.

ID	Title	Description
OG000	Pembrolizumab + BSC	Participants received 200 mg pembrolizumab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.
OG001	Placebo + BSC	Participants received placebo by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.

Units	Counts
Participants	OG000

Secondary

Number of Participants Who Discontinued Study Treatment Due to an AE

Randomized participants who received at least 1 dose of study intervention.

Posted

Count of Participants

Participants

Up to approximately 27 months.

ID	Title	Description
OG000	Pembrolizumab + BSC	Participants received 200 mg pembrolizumab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.
OG001	Placebo + BSC	Participants received placebo by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0012 events2 affected153 at risk EG0020 events0 affected12 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Coronary artery disease	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Prinzmetal angina	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Hypophysitis	Endocrine disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Ascites	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0006 events6 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0003 events3 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Gastritis	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Gastritis haemorrhagic	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Gastroduodenal ulcer	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0012 events2 affected153 at risk EG0020 events0 affected12 at risk
Nausea	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Oesophageal varices haemorrhage	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0006 events6 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Vomiting	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Chest discomfort	General disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Death	General disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
General physical health deterioration	General disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Pain	General disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Pyrexia	General disorders	MedDRA 27.1	Systematic Assessment	EG0004 events3 affected299 at risk EG0012 events2 affected153 at risk EG0020 events0 affected12 at risk
Swelling	General disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Acute hepatic failure	Hepatobiliary disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Autoimmune hepatitis	Hepatobiliary disorders	MedDRA 27.1	Systematic Assessment	EG0004 events4 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Biloma	Hepatobiliary disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Cholecystitis chronic	Hepatobiliary disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Dilatation intrahepatic duct acquired	Hepatobiliary disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Hepatic pain	Hepatobiliary disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Abdominal infection	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Dengue fever	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Diarrhoea infectious	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Epiglottitis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Epstein-Barr virus infection	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Febrile infection	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Gastroenteritis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Hepatitis E	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Infection	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Infectious pleural effusion	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Influenza	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Laryngopharyngitis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Liver abscess	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Peritonitis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Pneumonia	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0006 events6 affected299 at risk EG0013 events3 affected153 at risk EG0021 events1 affected12 at risk
Pneumonia fungal	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Post procedural infection	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Sepsis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Soft tissue infection	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Hand fracture	Injury, poisoning and procedural complications	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Alanine aminotransferase increased	Investigations	MedDRA 27.1	Systematic Assessment	EG0005 events5 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 27.1	Systematic Assessment	EG0008 events8 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Blood bilirubin increased	Investigations	MedDRA 27.1	Systematic Assessment	EG00011 events11 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Hepatitis B DNA increased	Investigations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Platelet count decreased	Investigations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Hypoproteinaemia	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Tumour associated fever	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.1	Systematic Assessment	EG0003 events2 affected299 at risk EG0012 events2 affected153 at risk EG0020 events0 affected12 at risk
Cerebral infarction	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Hepatic encephalopathy	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0003 events3 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Spinal cord compression	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Completed suicide	Psychiatric disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Immune-mediated nephritis	Renal and urinary disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Proteinuria	Renal and urinary disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Stress urinary incontinence	Renal and urinary disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0012 events1 affected153 at risk EG0020 events0 affected12 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0003 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0012 events1 affected153 at risk EG0020 events0 affected12 at risk
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0011 events1 affected153 at risk EG0020 events0 affected12 at risk
Dermatitis bullous	Skin and subcutaneous tissue disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected299 at risk EG0010 events0 affected153 at risk EG0020 events0 affected12 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG00055 events45 affected299 at risk EG00117 events16 affected153 at risk EG0022 events1 affected12 at risk
Bradycardia	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0010 events0 affected153 at risk EG0021 events1 affected12 at risk
Hyperthyroidism	Endocrine disorders	MedDRA 27.1	Systematic Assessment	EG00016 events16 affected299 at risk EG0014 events3 affected153 at risk EG0020 events0 affected12 at risk
Hypothyroidism	Endocrine disorders	MedDRA 27.1	Systematic Assessment	EG00035 events29 affected299 at risk EG00113 events11 affected153 at risk EG0020 events0 affected12 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG00018 events17 affected299 at risk EG0014 events4 affected153 at risk EG0020 events0 affected12 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG00026 events20 affected299 at risk EG00112 events12 affected153 at risk EG0020 events0 affected12 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG00020 events17 affected299 at risk EG0015 events4 affected153 at risk EG0020 events0 affected12 at risk
Ascites	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG00016 events15 affected299 at risk EG0015 events5 affected153 at risk EG0020 events0 affected12 at risk
Constipation	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG00029 events27 affected299 at risk EG00114 events10 affected153 at risk EG0020 events0 affected12 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG00076 events47 affected299 at risk EG00120 events14 affected153 at risk EG0020 events0 affected12 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0007 events6 affected299 at risk EG0014 events4 affected153 at risk EG0021 events1 affected12 at risk
Nausea	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG00024 events22 affected299 at risk EG0018 events8 affected153 at risk EG0020 events0 affected12 at risk
Vomiting	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG00025 events19 affected299 at risk EG00111 events10 affected153 at risk EG0020 events0 affected12 at risk
Asthenia	General disorders	MedDRA 27.1	Systematic Assessment	EG00022 events18 affected299 at risk EG00113 events11 affected153 at risk EG0020 events0 affected12 at risk
Fatigue	General disorders	MedDRA 27.1	Systematic Assessment	EG00020 events19 affected299 at risk EG00110 events9 affected153 at risk EG0020 events0 affected12 at risk
Malaise	General disorders	MedDRA 27.1	Systematic Assessment	EG00014 events12 affected299 at risk EG00110 events10 affected153 at risk EG0020 events0 affected12 at risk
Pyrexia	General disorders	MedDRA 27.1	Systematic Assessment	EG00070 events53 affected299 at risk EG00134 events21 affected153 at risk EG0020 events0 affected12 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 27.1	Systematic Assessment	EG00016 events14 affected299 at risk EG0018 events8 affected153 at risk EG0020 events0 affected12 at risk
COVID-19	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0010 events0 affected153 at risk EG0021 events1 affected12 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG00037 events32 affected299 at risk EG00112 events10 affected153 at risk EG0020 events0 affected12 at risk
Alanine aminotransferase increased	Investigations	MedDRA 27.1	Systematic Assessment	EG000138 events90 affected299 at risk EG00147 events36 affected153 at risk EG0027 events5 affected12 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 27.1	Systematic Assessment	EG000162 events107 affected299 at risk EG00159 events45 affected153 at risk EG0027 events5 affected12 at risk
Bilirubin conjugated increased	Investigations	MedDRA 27.1	Systematic Assessment	EG00026 events20 affected299 at risk EG0017 events7 affected153 at risk EG0020 events0 affected12 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 27.1	Systematic Assessment	EG00060 events43 affected299 at risk EG00119 events15 affected153 at risk EG0022 events2 affected12 at risk
Blood bilirubin increased	Investigations	MedDRA 27.1	Systematic Assessment	EG000142 events83 affected299 at risk EG00148 events40 affected153 at risk EG0021 events1 affected12 at risk
Blood creatinine increased	Investigations	MedDRA 27.1	Systematic Assessment	EG00013 events10 affected299 at risk EG0014 events4 affected153 at risk EG0021 events1 affected12 at risk
Blood glucose increased	Investigations	MedDRA 27.1	Systematic Assessment	EG00013 events9 affected299 at risk EG0014 events3 affected153 at risk EG0021 events1 affected12 at risk
Blood lactate dehydrogenase increased	Investigations	MedDRA 27.1	Systematic Assessment	EG00018 events15 affected299 at risk EG0018 events5 affected153 at risk EG0020 events0 affected12 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 27.1	Systematic Assessment	EG00062 events54 affected299 at risk EG00125 events23 affected153 at risk EG0023 events3 affected12 at risk
Hepatitis B DNA increased	Investigations	MedDRA 27.1	Systematic Assessment	EG00025 events15 affected299 at risk EG0017 events5 affected153 at risk EG0020 events0 affected12 at risk
Lymphocyte count decreased	Investigations	MedDRA 27.1	Systematic Assessment	EG00041 events30 affected299 at risk EG00111 events10 affected153 at risk EG0020 events0 affected12 at risk
Neutrophil count decreased	Investigations	MedDRA 27.1	Systematic Assessment	EG00098 events41 affected299 at risk EG00125 events17 affected153 at risk EG0020 events0 affected12 at risk
Platelet count decreased	Investigations	MedDRA 27.1	Systematic Assessment	EG000134 events65 affected299 at risk EG00134 events25 affected153 at risk EG0020 events0 affected12 at risk
Weight decreased	Investigations	MedDRA 27.1	Systematic Assessment	EG00026 events24 affected299 at risk EG0016 events6 affected153 at risk EG0020 events0 affected12 at risk
White blood cell count decreased	Investigations	MedDRA 27.1	Systematic Assessment	EG000128 events51 affected299 at risk EG00133 events21 affected153 at risk EG0021 events1 affected12 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG00050 events44 affected299 at risk EG00118 events14 affected153 at risk EG0020 events0 affected12 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG00028 events17 affected299 at risk EG0012 events2 affected153 at risk EG0020 events0 affected12 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG00019 events12 affected299 at risk EG0012 events2 affected153 at risk EG0021 events1 affected12 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG00046 events36 affected299 at risk EG00114 events13 affected153 at risk EG0023 events2 affected12 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG00024 events17 affected299 at risk EG00112 events8 affected153 at risk EG0021 events1 affected12 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG00023 events19 affected299 at risk EG0018 events7 affected153 at risk EG0020 events0 affected12 at risk
Hypoproteinaemia	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG00023 events17 affected299 at risk EG00112 events9 affected153 at risk EG0020 events0 affected12 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG00028 events26 affected299 at risk EG00111 events9 affected153 at risk EG0020 events0 affected12 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0002 events1 affected299 at risk EG0010 events0 affected153 at risk EG0021 events1 affected12 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG00020 events17 affected299 at risk EG00116 events12 affected153 at risk EG0021 events1 affected12 at risk
Insomnia	Psychiatric disorders	MedDRA 27.1	Systematic Assessment	EG00020 events20 affected299 at risk EG0014 events4 affected153 at risk EG0020 events0 affected12 at risk
Hypertonic bladder	Renal and urinary disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected299 at risk EG0010 events0 affected153 at risk EG0021 events1 affected12 at risk
Proteinuria	Renal and urinary disorders	MedDRA 27.1	Systematic Assessment	EG00033 events31 affected299 at risk EG00110 events10 affected153 at risk EG0022 events2 affected12 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG00044 events33 affected299 at risk EG00116 events13 affected153 at risk EG0020 events0 affected12 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected299 at risk EG0010 events0 affected153 at risk EG0021 events1 affected12 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 27.1	Systematic Assessment	EG00049 events35 affected299 at risk EG0016 events6 affected153 at risk EG0020 events0 affected12 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 27.1	Systematic Assessment	EG00054 events44 affected299 at risk EG0018 events8 affected153 at risk EG0020 events0 affected12 at risk
Hypertension	Vascular disorders	MedDRA 27.1	Systematic Assessment	EG00022 events18 affected299 at risk EG0017 events7 affected153 at risk EG0020 events0 affected12 at risk

ID	Term
D006528	Carcinoma, Hepatocellular
C565324	Parkinson Disease 4, Autosomal Dominant Lewy Body

ID	Term
D000230	Adenocarcinoma
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008113	Liver Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D004066	Digestive System Diseases
D008107	Liver Diseases

ID	Title	Description
BG000	Pembrolizumab + BSC	Participants received 200 mg pembrolizumab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.
BG001	Placebo + BSC	Participants received placebo by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pembrolizumab First Course	Participants received 200 mg pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.	263	300	76	299	272	299
EG001	Placebo First Course	Participants received placebo by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus BSC.	146	153	31	153	135	153
EG002	Pembrolizumab Second Course	Eligible participants randomized to the pembrolizumab first course who stopped pembrolizumab with stable disease (SD) or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year	8	12	1	12	12	12