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

Abstract

Background: Sorafenib is the standard of care (SOC) for first-line HCC; however, there is no clear SOC after disease progression on or intolerance to sorafenib. Because most HCC is driven by inflammation, the rationale to evaluate immunotherapy in patients (pts) with this type of cancer is strong. The randomized, double-blind, placebo-controlled phase 3 KEYNOTE-240 study (ClinicalTrials.gov, NCT02702401) was designed to compare efficacy and safety of the anti-PD-1 antibody pembro + BSC vs placebo+ BSC in pts with previously treated advanced HCC. Trial design: Pts aged >=18 yearswith histologically or cytologically confirmedHCC(fibrolamellar andmixed hepatocellular/cholangiocarcinoma subtypes excluded), documented progression after stopping treatment with sorafenib or intolerance to sorafenib, no previous systemic therapy forHCC other than sorafenib, disease not amenable to a curative treatment approach (eg, transplantation, surgery, or ablation), measurable disease 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>3months are eligible. Pts will be randomly assigned 2:1 to receive pembro 200mg IVQ3W+ BSC or placeboQ3W+BSC for up to 35 cycles (~2 years) or until disease progression, unacceptable toxicity, or investigator decision. Randomization will be stratified by geographic region, presence ofmacrovascular invasion, and alpha-fetoprotein level. BSC will be provided by the investigator per local treatment practices. Response will be assessedQ6W 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) and graded perNCI CTCAE v4.0. Primary objectives are comparison of PFS per RECIST v1.1 by central imaging vendor review andOS between treatment arms. Secondary objectives are comparison ofORR, DOR,DCR, and TTP 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.