Pembrolizumab in patients with previously treated advanced hepatocellular carcinoma: Phase 2 KEYNOTE-224 study

Abstract

Background: Liver cancer is the second leading cause of cancer deaths worldwide. The tyrosine kinase inhibitor sorafenib is the standard of care for first‐line hepatocellular carcinoma (HCC), and there is currently no clear standard of care for second‐line HCC. Because most HCC is driven by inflammation, there is a strong rationale to evaluate immunotherapy in patients with this type of cancer. The single‐arm, multisite, phase 2 KEYNOTE‐224 study (ClinicalTrials.gov, NCT02702414) was designed to evaluate the efficacy and safety of the anti‐PD‐1 antibody pembrolizumab in patients with previously treated advanced HCC. Trial design: Approximately 100 patients will be enrolled. Inclusion criteria include age ≥18 years, histologically or cytologically confirmed diagnosis of HCC, documented objective radiographic progression after stopping treatment with sorafenib or intolerance to sorafenib, and disease not amenable to a curative treatment approach (eg, transplantation, surgery, or ablation). Patients must also have measurable disease confirmed by central imaging vendor per RECIST v1.1, Child‐Pugh liver score A, ECOG performance status 0‐1, and predicted life expectancy >3 months. Patients will be allocated to receive pembrolizumab 200 mg IV Q3W for up to 35 cycles (∼2 years) or until disease progression, unacceptable toxicity, or investigator decision. Response will be assessed every 9 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) and graded per NCI CTCAE v4.0. The primary end point is objective response rate per RECIST v1.1 by central imaging vendor review. Secondary end points are duration of response, disease control rate, time to progression, and progression‐free survival per RECIST v1.1 by central imaging vendor review; overall survival; and safety and tolerability.