Phase I study of Ori-C101, an armored GPC3-directed CAR-T, in patients with advanced hepatocellular carcinoma (HCC).

作者：Jia Fan, Jian Zhou, Xiaowu Huang, Qiang Gao, Jie-Yi Shi, Yifeng He, Zao‐Zhuo Shen, Wenwen Wang, Sidi Wei, Lan Gu, Zheng Li, Shanzhi Gu, Zhongwei Zhao, Rick Xu, Qian Zhang, Bin Li, Yu Tang, Xiaomin Ding, Xiaowen He · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.4084 · 被引用次数：5 · 研究领域：CAR-T cell therapy research

4084 Background: Previously, we reported the results of Ori-C101 from investigator initiated trial in China (ChiCTR1900028121). The data demonstrated that Ori-C101 owned a favorable safety profile and promising efficacy. Among 10 GPC3 + HCC patients (pts) treated with Ori-C101, 9 pts (90%) achieved disease control and 6 pts (60%) met partial response per RECIST 1.1. Two pts with PR attained progression-free survival of one and two years respectively, with an overall survival close to 3 years. These results implied that Ori-C101 potentially held significant clinical benefits. Subsequently, extensive optimizations and improvements in the manufacturing process were implemented to enhance its clinical efficacy and persistency. Hence, a multicenter registration study was launched in China (the BEACON study), and herein, we will present the preliminary results. Methods: This is an open-label, multi-center, dose-escalation (3+3 design) study. GPC3 + advanced HCC pts who failed at least 2 lines of systemic treatments received a single hepatic arterial infusion with a total dose of 0.9 to 6×10 8 CAR-T cells. Primary endpoints are rate of dose-limiting toxicities (DLTs) and safety with the aim to determine a recommended phase II dose (RP2D). Secondary endpoints are cellular kinetics, overall response rate by investigator assessment, duration of response, overall survival and overall safety. Results: As of Dec 17th, 2024, a total of 10 eligible pts received Ori-C101 infusion at 3 dose l...