SHR-8068 plus adebrelimab and bevacizumab for advanced hepatocellular carcinoma (aHCC): A phase 1b/2 study.

作者：Lianxin Liu, Jiabei Wang, Tongsen Zheng, Yao Huang, Jiayin Yang, Jia Luo, Bihui Li, Jiansong Ji, Jie Ma, Qiang Xia, Jun Yao, Chaoliu Dai, Mafei Kang, Feixiang Wu, Chengsheng Zhang, Yabing Guo, Yaozhen Pan, Deyu Li, Yong Zha, Ying Sun · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.4093 · 被引用次数：1 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Colorectal Cancer Treatments and Studies、Liver physiology and pathology

4093 Background: Combination of an anti-PD-1/L1 antibody with an anti-angiogenic agent is currently the preferred 1L treatment for aHCC. Addition of a CTLA-4 inhibitor may further improve anti-tumor activity, with complementary immunostimulatory effects from CTLA-4 and PD-1/L1 blockade. We conducted a multicenter, open-label, phase 1b/2 trial (NCT05444088) to assess SHR-8068, a novel anti-CTLA-4 monoclonal antibody (mAb), combined with adebrelimab (A, anti-PD-L1 mAb) and bevacizumab (B) in patients (pts) with aHCC. Methods: Pts with or without prior treatment were enrolled (phase 1b: failed or refused standard therapy; phase 2: ≤1L systemic therapy, no immunotherapy [IO]). SHR-8068 was evaluated in 2 dosing regimens with AB: 1 mg/kg Q6W (Combo 1) or 4 mg/kg priming dose (Combo 2). An additional cohort evaluated AB alone (Combo 3). A was dosed at 20 mg/kg Q3W and B at 15 mg/kg Q3W for all regimens. Results: As of Oct 31, 2024, a total of 27, 53 and 21 pts received Combo 1, 2, and 3, respectively, across 2 study phases (overall: IO naïve, 97.0%; prior anti-angiogenic therapy, 32.7%); median follow-up was 16.7, 11.1 and 11.3 mo, respectively. In pts treated with Combo 2, the objective response rate (ORR) was 47.2% (25/53; 95% CI 33.3%–61.4%), with a median duration of response (DoR) of 12.7 mo (95% CI 5.8–NR). The median progression-free survival (PFS) was 8.7 mo (95% CI 5.5–11.6); median overall survival (OS) was not reached, with a 12-mo OS rate of 76.0% (95% CI 59.3%–86.6%). ...