Safety and efficacy of IBI389, an anti-CLDN18.2/CD3 bispecific antibody, in patients with advanced pancreatic ductal adenocarcinoma: Preliminary results from a phase 1 study.

作者：Jihui Hao, Zheng Li, Dai Ruihong, Ying Jieer, Qi Xu, Liwei Wang, Yongdong Jin, Ying Zhao, Yueyin Pan, Lulu Liu, Jun Zhang, Yuping Sun, Zuoxing Niu, Jun Yao, Dong Hua, Mingjun Zhang, Dai Guang-hai, Yulong Zhang, Hui Zhou, Feng Bi · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco.2024.42.16_suppl.4011 · 被引用次数：19 · 研究领域：Pancreatic and Hepatic Oncology Research、Monoclonal and Polyclonal Antibodies Research、Neuroendocrine Tumor Research Advances

4011 Background: CLDN18.2 expression has been observed in various solid tumors. In pancreatic ductal adenocarcinoma (PDAC), positive CLDN18.2 expression was reported in nearly 60% patients (pts), indicating its potential as a novel target for anti-tumor therapy. IBI389 is an anti-CLDN18.2/CD3 bispecific antibody that induces immune synapse formations by linking CD3 molecules in T-cell receptor complexes and CLDN18.2 antigens on the membrane of tumor cells. Herein, we report preliminary result from a phase I study to evaluate safety and efficacy of IBI389 in pts with PDAC. Methods: EligibleCLDN18.2-positivepts with locally advanced, refractory or metastaticPDAC who failed or were intolerant to standard treatments were enrolled. IBI389 monotherapy was intravenously administered at 6 dose levels (5-600 µg/kg, Q3W or Q2W) during the 2-stage dose escalation and the dose expansion. In dose levels ≥ 30 µg/kg, the step-up dosing strategy with priming dose of 3 to 10 µg/kg was applied. The primary objective was safety. Secondary objective was efficacy assessed by investigator per RECIST v1.1 including objective response rate (ORR) and disease control rate (DCR). Results: As of January 9, 2024, a total of 64 CLDN18.2-positive PDAC pts were enrolled (males: 64.1%, females:35.9%, median age: 60.0 years, stage IV: 84.4%). All patients received prior therapy with a median of 2 lines (range: 1 to 5). Treatment-related adverse events (TRAEs) occurred in 62 (96.9%) pts including 35 (54.7%) pt...