A Phase 1b Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma: Extended Analysis of Study 116

Background: Treatment with lenvatinib (dosing for patients who weigh ≥60 kg was 12 mg/day; for patients who weigh <60 kg, the dose was 8 mg/day) plus pembrolizumab 200 mg once every 3 weeks demonstrated antitumor activity and a manageable safety profile in patients with first-line unresectable hepatocellular carcinoma (uHCC) in the open-label phase 1b Study 116/KEYNOTE-524 (primary analysis data cutoff date: October 31, 2019; median follow-up: 10.6 months). Objective: This analysis (updated data cutoff date: March 31, 2021) reports efficacy results from 17 months of additional follow-up time. Methods: 100 Patients with uHCC were included in the primary analysis (median follow-up: 27.6 months). Endpoints included overall survival (OS) and investigator-assessed progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) per modified RECIST. Landmark analyses of OS by best response at 3 and 9 months were performed. Pembrolizumab antidrug antibodies (ADAs) and concentrations were also measured (cutoff date: August 7, 2020). Results: ORR was 43.0% (95% CI 33.1% to 53.3%) and median DOR was 17.1 months (95% CI 6.9 to 19.3 months). Median PFS and OS were 9.3 months (95% CI 7.4 to 9.8 months) and 20.4 months (95% CI 14.4 to 25.9 months), respectively. No treatment-emergent ADAs were detected. Conclusion: Results show a sustained treatment effect with lenvatinib plus pembrolizumab in patients with uHCC in the first-line setting.