What question did this study set out to answer?

This study evaluates the effectiveness and safety of IBI310 combined with sintilimab compared to sorafenib in first-line treatment of advanced hepatocellular carcinoma.

May 29, 2026

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.

Key Points

This study evaluates the effectiveness and safety of IBI310 combined with sintilimab compared to sorafenib in first-line treatment of advanced hepatocellular carcinoma.
Patients were randomized in a 2:1 ratio to receive IBI310 + sintilimab or sorafenib.
The experimental group received IBI310 3mg/kg IV and sintilimab 200mg IV every 3 weeks; the control group received sorafenib 400mg orally BID until disease progression or intolerable toxicity.
Primary endpoints included overall survival and objective response rate assessed by independent reviewers.
Median overall survival was 44.0 months for IBI310 + sintilimab (G1), 36.1 months for modified IBI310 + sintilimab (G2), and 22.9 months for sorafenib (G3).
Confirmed objective response rates were significantly higher in the combination therapy groups (41.7% for G1, 22.1% for G2) than the control group (2.6%).
Median progression-free survival was 13.5 months for G1, 6.1 months for G2, and 2.8 months for G3.

Abstract

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

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