Phase 3, randomized KEYNOTE-240 study of pembrolizumab (Pembro) versus best supportive care (BSC) for second-line advanced hepatocellular carcinoma (HCC)

Abstract

Background: Sorafenib and oxaliplatin-based chemotherapy are standards of care for first-line HCC in several Asian countries. Because most HCC is driven by inflammation, the rationale to evaluate immunotherapy in patients (pts) with HCC is strong. The randomized, double-blind, placebo-controlled phase 3 KEYNOTE-240 study compares efficacy and safety of the anti-program med death 1 antibody pembro theta BSC versus placebo theta BSC in pts with previously treated advanced HCC. Trial design: Pts aged > 18 years with histologically or cytologically confirmed HCC (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes excluded), documented progression after stopping treatment with or intolerance to sorafenib, no previous systemic therapy for HCC other than sorafenib, disease not amenable to a curative treatment approach (eg, transplantation, surgery, or ablation), measurable dis-ease confirmed by central imaging vendor review per RECIST v1.1, Child-Pugh liver score A, ECOG performance status 0-1, adequate organ function, and predicted life expectancy >3 months are eligible. Pts will be randomly assigned 2:1 to receive pembro 200 mg or placebo every 3 weeks with BSC (given per local guidelines) for up to 35 cycles (2 years) or until disease progression, unacceptable toxicity, or investigator decision to withdraw. Randomization will be stratified by geographic region, presence of macrovascular invasion, and a-fetoprotein level. Response will be assessed every 6 weeks per RECIST v1.1 by central imaging vendor review. Adverse events (AEs) will be assessed throughout treatment and for 30 days thereafter (90 days for serious AEs). Primary end points are progression-free survival per RECIST v1.1 by central imaging vendor review and overall survival. Secondary end points include objective response rate, duration of response, disease control rate, and time to progression per RECIST v1.1 by central imaging vendor review, and evaluation of safety and tolerability. Planned enrollment in KEYNOTE-240 is 408 pts across 26 countries, including Hong Kong, Japan, Republic of Korea, Taiwan, and Thailand.