Study of Pembrolizumab (MK-3475) or Placebo Given With Best Supportive Care in Asian Participants With Previously Treated Advanced Hepatocellular Carcinoma (MK-3475-394/KEYNOTE-394)

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 notamenable to locoregional therapy or refractory to locoregional therapy and notamenable 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 byinvestigator.

• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performedwithin 7 days prior to receiving the first dose of study medication.

• Has documented objective radiographic progression during or after treatment withsorafenib or oxaliplatin-based chemotherapy, or else intolerance to sorafenib oroxaliplatin-based chemotherapy

• Female participants of childbearing potential must have a negative urine or serumpregnancy test within 72 hours prior to receiving the first dose of study therapy

• Female and male participants of reproductive potential must agree to use adequatecontraception starting from the first dose of study medication, throughout the studyperiod, 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 investigationalagent or using an investigational device within 4 weeks of the first dose of studymedication

• Has received sorafenib or oxaliplatin-based chemotherapy within 14 days of firstdose 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, orcardiac 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 otherthan sorafenib or oxaliplatin-based chemotherapy, prior to start of study medication

• Has an active autoimmune disease that has required systemic treatment in the past 2years. Replacement therapy is not considered a form of systemic treatment.

• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or anyother form of immunosuppressive therapy within 7 days prior to the first dose ofstudy 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 studymedication

• Has had major surgery to liver or other site within 4 weeks prior to the first doseof 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/orcomplications from any intervention prior to study start

• Has a diagnosed additional malignancy within 3 years prior to first dose of studymedication with the exception of curatively treated basal cell carcinoma of theskin, 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) metastasesand/or carcinomatous meningitis

• Has a history of (non-infectious) pneumonitis that required steroids or currentpneumonitis

• Has an active infection requiring systemic therapy

• Is pregnant or breast feeding or expecting to conceive or father starting from thefirst dose of study medication, throughout the study period, and for up to 120 daysafter 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-ProgrammedCell Death Receptor Ligand 2 (PD-L2) or has previously participated in clinicalstudies 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 toreceiving pembrolizumab

• Has received a live vaccine within 30 days prior to the first dose of study therapy