Effectiveness and safety of IBI310 combined with sintilimab versus sorafenib in the first-line treatment of advanced hepatocellular carcinoma (aHCC): A randomized, open-label, controlled, multicenter phase III clinical study.

4148 Background: Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have demonstrated efficacy in aHCC. Despite improved outcomes with PD-1/PD-L1 inhibitor-based regimens, prognosis remains poor and there is a continued unmet need for alternative therapies with long-term survival benefits. This study aimed to evaluate the effectiveness and safety of IBI310 (anti-CTLA-4 antibody) combined with sintilimab (anti-PD-1 antibody) in the first-line treatment of aHCC. Methods: Pts were randomized in a 2:1 ratio to IBI310+sintilimab group or sorafenib group. The experimental group received IBI310 3mg/kg intravenously (IV) and sintilimab 200 mg IV on day 1 of every 3 weeks. The control group received sorafenib 400 mg orally twice daily (BID) continuously until disease progression, intolerable toxicity, death or other protocol-specified discontinuation criteria. During the study, the IBI310 dose was adjusted to 1 mg/kg every 6 weeks. Primary end points included overall survival (OS) and objective response rate (ORR)assessed by the independent radiology review committee (IRRC) per RECIST v1.1. Secondary endpoint included progression-free survival (PFS), disease control rate (DCR), safety, etc. Results: As of August 2022, 344 patients were enrolled and allocated to Group 1 (G1, IBI310 3mg/kg + sintilimab, n=84), Group 2 (G2, modified-dose IBI310 1mg/kg + sintilimab, n=145) and Group 3 (G3, sorafenib, n=115). Overall, PFS and ORR improved with IBI310+sintilimab vs Sorafenib. The median OS in the primary endpoint was 44.0 months(G1), 36.1 months(G2) and 22.9 months(G3), respectively. Confirmed ORRs were significantly higher in the combination therapy groups (G1: 41.7%; G2: 22.1%) versus the control group (2.6%). Median PFS of three groups were 13.5 months(G1), 6.1 months(G2) and 2.8 months(G3), respectively. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 60.7% (G1), 34.7% (G2), and 35.1% (G3) of patients. Conclusions: Compared with sorafenib group, combination treatment of IBI310 + sintilimab as first-line treatment demonstrated survival benefits and a manageable safety profile in aHCC. Clinical trial information: NCT04720716 . Survival data. IBI310(3mg/kg)+Sintilimab(N=84) IBI310(1mg/kg)+Sintilimab(N=145) Sorafenib(N=115) mOS, m 44.0 36.1 22.9 Confirmed ORR, n(%) 35(41.7) 32(22.1) 3(2.6) mPFS, m 13.5 6.1 2.8