Pembrolizumab monotherapy for previously untreated advanced hepatocellular carcinoma: data from the open-label, phase 2 KEYNOTE-224 trial

Abstract Purpose:KEYNOTE-224 cohort 1 demonstrated that pembrolizumab was efficacious and tolerable in patients with advanced hepatocellular carcinoma (aHCC) previously treated with sorafenib. We report results from KEYNOTE-224 (NCT02702414) cohort 2, which enrolled patients with aHCC and no prior systemic therapy. Experimental Design:KEYNOTE-224 was an open-label, multi-country phase 2 trial. Eligible patients in cohort 2 had aHCC not amenable or refractory to locoregional therapy and not previously treated with systemic therapy. Patients received pembrolizumab 200 mg intravenously every three weeks for {less than or equal to}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 Sept 4, 2018 and Feb 20, 2019, 51 patients were allocated in cohort 2. The median time from the first dose to data cutoff (Jan 19, 2021) was 27 months (range, 23-29). ORR was 16% (95% 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 {greater than or equal to}3 treatment-related adverse events occurred in 16% of patients. Conclusions:In patients with aHCC 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.