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)
Condition: Carcinoma, Hepatocellular
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Intervention: pembrolizumab; placebo; best supportive care (BSC)
Intervention description: Administered as an intravenous (IV) infusion every 3 weeks (Q3W); Normal saline solution administered as an IV infusion Q3W; BSC will include pain management and management of other potential complications including ascites per local standards of care.
Intervention MeSH terms: Pembrolizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 453.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Programmed Cell Death Receptor 1 (PD-1); Programmed Cell Death Receptor Ligand 1 (PD-L1); Programmed Cell Death Receptor Ligand 2 (PD-L2); PD1; PD-1; PDL1; PD-L1; PDL2

Summary:

      The purpose of this study is to determine the efficacy and safety of pembrolizumab or placebo
      given with best supportive care (BSC) in Asian participants with previously systemically
      treated advanced hepatocellular carcinoma (HCC). The primary hypothesis of this study is that
      overall survival is prolonged in participants who receive pembrolizumab compared to those who
      receive placebo.
    

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