Pembrolizumab Monotherapy for Previously Untreated Advanced Hepatocellular Carcinoma: Data from the Open-Label, Phase II KEYNOTE-224 Trial

Gontran Verset, Ivan Borbath, Mark Karwal, Chris Verslype, Hans Van Vlierberghe, Adel Kardosh, Vittorina Zagonel, Per Stal, Debashis Sarker, Daniel H Palmer, Arndt Vogel, Julien Edeline, Stephane Cattan, Masatoshi Kudo, Ann-Lii Cheng, Sadahisa Ogasawara, Bruno Daniele, Stephen L Chan, Jennifer J Knox, Shukui Qin, Abby B Siegel, Michael Chisamore, Ken Hatogai, Anran Wang, Richard S Finn, Andrew X Zhu, Gontran Verset, Ivan Borbath, Mark Karwal, Chris Verslype, Hans Van Vlierberghe, Adel Kardosh, Vittorina Zagonel, Per Stal, Debashis Sarker, Daniel H Palmer, Arndt Vogel, Julien Edeline, Stephane Cattan, Masatoshi Kudo, Ann-Lii Cheng, Sadahisa Ogasawara, Bruno Daniele, Stephen L Chan, Jennifer J Knox, Shukui Qin, Abby B Siegel, Michael Chisamore, Ken Hatogai, Anran Wang, Richard S Finn, Andrew X Zhu

Abstract

Purpose: KEYNOTE-224 cohort 1 demonstrated that pembrolizumab was efficacious and tolerable in patients with advanced hepatocellular carcinoma (HCC) previously treated with sorafenib. We report results from KEYNOTE-224 (NCT02702414) cohort 2, which enrolled patients with advanced HCC and no prior systemic therapy.

Patients and methods: KEYNOTE-224 was an open-label, multicountry phase II trial. Eligible patients in cohort 2 had advanced HCC not amenable or refractory to locoregional therapy and not previously treated with systemic therapy. Patients received pembrolizumab 200 mg intravenously every 3 weeks for ≤2 years. Primary endpoint was objective response rate (ORR) by central imaging review per RECIST v1.1. Secondary endpoints included duration of response (DOR), disease control rate (DCR), time to progression (TTP), progression-free survival (PFS), overall survival (OS), and safety/tolerability.

Results: Between September 4, 2018, and February 20, 2019, 51 patients were allocated in cohort 2. The median time from the first dose to data cutoff (January 19, 2021) was 27 months (range, 23-29). ORR was 16% [95% confidence interval (CI), 7-29] and was similar across key subgroups. Median DOR was 16 months (range, 3-24+), and DCR was 57%. The median PFS was 4 months (95% CI, 2-8), and median TTP was 4 months (95% CI, 3-9). Median OS was 17 months (95% CI, 8-23). Grade ≥3 treatment-related adverse events occurred in 16% of patients.

Conclusions: In patients with advanced HCC with no prior systemic therapy, pembrolizumab provided durable antitumor activity, promising OS, and had a safety profile consistent with previous observations. These findings support further evaluation of pembrolizumab-based regimens for HCC.

Trial registration: ClinicalTrials.gov NCT03867084 NCT04246177 NCT02702414.

©2022 The Authors; Published by the American Association for Cancer Research.

Figures

Figure 1.
Figure 1.
Subgroup analyses of objective response. *All prespecified except the analyses by alcohol use.
Figure 2.
Figure 2.
Characteristics of tumor response to pembrolizumab. A, Best percentage change from baseline in target lesion in patients without viral etiology (green) and those with viral etiology (blue). Stars indicate patients with a confirmed response by central imaging review. B, Duration of study treatment and response in responders. Each horizontal line represents 1 patient. The end of the bar represents the dates of the last radiology imaging assessment.
Figure 3.
Figure 3.
Kaplan–Meier curves for PFS (A) and OS (B).

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