这项多中心、开放标签、Ib/II 期研究旨在评估 cadonilimab（一种人源化四价双特异性抗体）联合乐伐替尼一线治疗晚期肝细胞癌 (aHCC) 的疗效和安全性。经组织学证实的 aHCC 患者接受包括每 2 周接受 6 mg/kg cadonilimab 加乐伐替尼（队列 A）或每 3 周接受 15 mg/kg cadonilimab 加乐伐替尼（队列 B）。主要终点是 RECIST v1.1 的客观缓解率 (ORR)，次要终点是安全性、无进展生存期 (PFS)、总生存期 (OS)、疾病控制率 (DCR)、缓解持续时间 (DoR)和反应时间 (TTR)。 共有 59 名患者入组（A 组 31 名，B 组 28 名）。截至数据截止日期（2023 年 7 月 28 日），中位随访时间为 27.4 个月。 A 组的 ORR 为 35.5%（95% CI：19.2，54.6），B 组的 ORR 为 35.7%（95% CI：18.6，55.9），中位 DoR 为 13.6 个月（95% CI：4.14，NE） ）和 13.67 个月（95% CI：3.52，NE）。中位 PFS 分别为 8.6 个月（95% CI：5.2，15.2）和 9.8 个月（95% CI：6.9，15.2）。队列 A 的中位 OS 为 27.1 个月（95% C：15.7，NE），而队列 B 未达到。66.1% 的患者报告了 ≥ 3 级治疗相关不良事件 (TRAE)，其中 TRAE 严重发生在 39.0% 的病例中。血小板计数减少 (47.5%)、蛋白尿 (45.8%)、高血压 (44.1%) 和白细胞计数 (44.1%) 是最常见的 TRAE。这种新型联合疗法显示出良好的疗效和可控制的毒性，可以提供一种选择在 aHCC 的一线环境中。[www.ClinicalTrials.gov], NCT04444167。版权所有 © 2023 Qiao, Han, Ye, Li, Shao, Bai, Xu, Sun, Wang, Wu, Huang, Song, Huang, Liu, Liu 、王、李、夏、白。

This multicenter, open-label, phase Ib/II study aimed to assess the efficacy and safety of cadonilimab, a humanized, tetravalent, bispecific antibody plus lenvatinib in first-line treatment of advanced hepatocellular carcinoma (aHCC).Patients with histologically confirmed aHCC were included to receive either 6 mg/kg cadonilimab every 2 weeks plus lenvatinib (cohort A) or 15 mg/kg cadonilimab every 3 weeks plus lenvatinib (cohort B). The primary endpoint was objective response rate (ORR) by RECIST v1.1, while the secondary endpoints were safety, progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DoR), and time to response (TTR).A total of 59 patients were enrolled (31 in cohort A and 28 in cohort B). The median follow-up time was 27.4 months as of the data cutoff date (July 28, 2023). The ORR in cohort A was 35.5% (95% CI: 19.2, 54.6) and that in cohort B was 35.7% (95% CI: 18.6, 55.9), and the median DoR was 13.6 months (95% CI: 4.14, NE) and 13.67 months (95% CI: 3.52, NE), respectively. The median PFS was 8.6 months (95% CI: 5.2, 15.2) and 9.8 months (95% CI: 6.9, 15.2), respectively. The median OS was 27.1 months (95% C: 15.7, NE) for cohort A, while it was not reached for cohort B. Grade ≥ 3 treatment-related adverse events (TRAEs) were reported in 66.1% of patients, with serious TRAEs occurring in 39.0% of cases. Decreased platelet count (47.5%), proteinuria (45.8%), hypertension (44.1%), and white blood cell count (44.1%) were the most common TRAEs.This novel combination therapy showed promising efficacy and manageable toxicity that could provide an option in first-line setting of aHCC.[www.ClinicalTrials.gov], NCT04444167.Copyright © 2023 Qiao, Han, Ye, Li, Shao, Bai, Xu, Sun, Wang, Wu, Huang, Song, Huang, Liu, Liu, Wang, Li, Xia and Bai.