Study of Pembrolizumab (MK-3475) as Monotherapy in Participants With Advanced Hepatocellular Carcinoma (MK-3475-224/KEYNOTE-224)

Summary

This is a efficacy and safety study of pembrolizumab (MK-3475, KEYTRUDA®) as monotherapy in participants with hepatocellular carcinoma (HCC) in two cohorts: participants with advanced HCC and with no curative option after disease progression on sorafenib or intolerance of sorafenib (Cohort 1) or who had not received treatment for systemic disease (Cohort 2). Study participants may receive pembrolizumab once every 3 weeks for up to 35 initial cycles (up to approximately 2 years) and a potential additional 17 cycles in a re-treatment phase (approximately an additional 1 year of treatment) . The primary objective of this study is to determine the Objective Response Rate (ORR) of pembrolizumab given as monotherapy in participants with HCC. Effective with Amendment 7: Upon study completion, participants are discontinued and may be enrolled in a pembrolizumab extension study, if available.

Timeline

Start

2016-05-31

Primary completion

2021-01-19

Completion

2023-09-29

Publications

• Chan SL, Finn RS, Edeline J, Ogasawara S, Knox JJ, Daniele B, Ryoo BY, Merle P, Bouattour M, Lim HY, Chao Y, Yau T, Haber BA, Malhotra U, Siegel AB, Liu CC, Kudo M, Cheng AL. Effect of pembrolizumab on viral hepatitis load and transaminases in advanced hepatocellular carcinoma. Ann Hepatol. 2026 Jan-Jun;31(1):102169. doi: 10.1016/j.aohep.2025.102169. Epub 2025 Dec 24.
• Zhou X, Cao J, Topatana W, Xie T, Chen T, Hu J, Li S, Juengpanic S, Lu Z, Zhang B, Wang K, Feng X, Shen J, Chen M. Evaluation of PD-L1 as a biomarker for immunotherapy for hepatocellular carcinoma: systematic review and meta-analysis. Immunotherapy. 2023 Apr;15(5):353-365. doi: 10.2217/imt-2022-0168. Epub 2023 Feb 27.
• Verset G, Borbath I, Karwal M, Verslype C, Van Vlierberghe H, Kardosh A, Zagonel V, Stal P, Sarker D, Palmer DH, Vogel A, Edeline J, Cattan S, Kudo M, Cheng AL, Ogasawara S, Daniele B, Chan SL, Knox JJ, Qin S, Siegel AB, Chisamore M, Hatogai K, Wang A, Finn RS, Zhu AX. Pembrolizumab Monotherapy for Previously Untreated Advanced Hepatocellular Carcinoma: Data from the Open-Label, Phase II KEYNOTE-224 Trial. Clin Cancer Res. 2022 Jun 13;28(12):2547-2554. doi: 10.1158/1078-0432.CCR-21-3807.
• Kudo M, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer DH, Verslype C, Zagonel V, Fartoux L, Vogel A, Sarker D, Verset G, Chan SL, Knox J, Daniele B, Yau T, Gurary EB, Siegel AB, Wang A, Cheng AL, Zhu AX; KEYNOTE-224 Investigators. Updated efficacy and safety of KEYNOTE-224: a phase II study of pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib. Eur J Cancer. 2022 May;167:1-12. doi: 10.1016/j.ejca.2022.02.009. Epub 2022 Mar 29.
• Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer D, Verslype C, Zagonel V, Fartoux L, Vogel A, Sarker D, Verset G, Chan SL, Knox J, Daniele B, Webber AL, Ebbinghaus SW, Ma J, Siegel AB, Cheng AL, Kudo M; KEYNOTE-224 investigators. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol. 2018 Jul;19(7):940-952. doi: 10.1016/S1470-2045(18)30351-6. Epub 2018 Jun 3.

Drugs

Indications