Phase 2 study of serplulimab with the bevacizumab biosimilar HLX04 in the first-line treatment of advanced hepatocellular carcinoma

INTRODUCTION: This study aimed to evaluate the safety and preliminary efficacy of serplulimab, a novel programmed death-1 inhibitor, with or without bevacizumab biosimilar HLX04 as first-line treatment in patients with advanced hepatocellular carcinoma. METHODS: This open-label, multicenter phase 2 study (clinicaltrials.gov identifier NCT03973112) was conducted in China and consisted of four treatment groups: group A (serplulimab 3 mg/kg plus HLX04 5 mg/kg, subsequent-line), group B (serplulimab 3 mg/kg plus HLX04 10 mg/kg, subsequent-line), group C (serplulimab 3 mg/kg, subsequent-line) and group D (serplulimab 3 mg/kg plus HLX04 10 mg/kg, first-line). Group D was the only group in which participants received the study treatment in the first-line setting. The primary endpoint was safety. RESULTS: Following previous report on groups A and B, results of group D are herein presented. As of February 7, 2023, 61 patients were enrolled and were followed up for a median of 25.5 months. Grade ≥ 3 treatment-emergent adverse events were reported by 29 (47.5%) patients. One patient died from adverse events that were considered related to study treatment. Among the patients with at least one post-baseline tumor assessment (n = 58), the objective response rate was 29.3% (95% CI: 18.1-42.7) as assessed by an independent radiological review committee (IRRC) per RECIST v1.1. IRRC-assessed median progression-free survival was 7.3 months (95% CI: 2.8-11.0), and median overall survival was 20.4 months (95% CI: 15.0-NE), respectively. CONCLUSION: Serplulimab combination therapy with HLX04 showed a manageable safety profile as well as preliminary efficacy in patients with advanced HCC in the first-line setting.