■这个多中心,开放标签,Ib/II期研究旨在评估cadonilimab的疗效和安全性,一个人性化的,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)。
经组织学证实的aHCC患者每2周接受6mg/kgcadonilimab加乐伐替尼(队列A)或15mg/kgcadonilimab每3周加乐伐替尼(队列B)。主要终点是RECISTv1.1的客观缓解率(ORR),而次要终点是安全性,无进展生存期(PFS),总生存期(OS),疾病控制率(DCR),响应持续时间(DoR),响应时间(TTR)。
■共纳入59例患者(队列A31例,队列B28例)。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。队列A的ORR为35.5%(95%CI:19.2,54.6),队列B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),分别。中位PFS为8.6个月(95%CI:5.2,15.2)和9.8个月(95%CI:6.9,15.2),分别。队列A的中位OS为27.1个月(95%C:15.7,NE),而队列B未达到该水平。66.1%的患者报告了≥3级治疗相关不良事件(TRAEs),39.0%的病例发生严重TRAE。血小板计数减少(47.5%),蛋白尿(45.8%),高血压(44.1%),白细胞计数(44.1%)是最常见的TRAE。
■这种新型联合疗法显示出有希望的疗效和可控的毒性,可以在aHCC的一线设置中提供选择。
■[www.ClinicalTrials.gov],NCT04444167。
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.