Claudin18.2 (CLDN18.2) expression and efficacy in pancreatic ductal adenocarcinoma (PDAC): Results from a phase I dose expansion cohort evaluating IBI343.

作者：Xianjun Yu, Jieer Ying, Enxiao Li, Aiping Zhou, Yuping Sun, Jinbo Yue, Jian Ruan, Jian Zhang, Lin Shen, Juan Du, Andrea Tazbirkova, Jia Liu, Yanru Qin, Michelle Frances Morris, Zhihua Li, Meili Sun, Yueyin Pan, Jun Zhang, Yingmei Guo, Hui Zhou · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.4017 · 被引用次数：10 · 研究领域：Pancreatic and Hepatic Oncology Research、Barrier Structure and Function Studies、Metabolism, Diabetes, and Cancer

4017 Background: CLDN18.2 is highly expressed in nearly 60% of PDAC cases. Yet to date, there are no approved targeted therapies and prognoses for these patients (pts) remain poor. IBI343, consisting of an anti-CLDN18.2 Fc silenced monoclonal antibody and the topoisomerase I inhibitor, exatecan, is the first CLDN18.2 antibody-drug conjugate to have shown encouraging efficacy in PDAC. Here, we report results from a phase 1 study (NCT05458219) in pts with PDAC treated with IBI343 by CLDN18.2 expression status (≥60% vs < 60%). Methods: Eligible pts with advanced PDAC and moderate to high expression of CLDN18.2 (defined as immunohistochemistry [IHC] membrane staining intensity ≥2 in ≥40% of tumor cells by IHC VENTANA CLDN18 [43-14A] Assay) who failed or were intolerant to standard treatment were enrolled. IBI343 was administered every 3 weeks at multiple dose levels (1, 3, 4.5, 6, 8, and 10 mg/kg). Endpoints included safety, objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) per RECIST v1.1, and overall survival (OS). Results: As of December 27, 2024, 83 pts from China and Australia were enrolled. 44 and 12 pts with CLDN18.2 expression ≥1 in ≥60% (+) and < 60% (-) of tumor cells, respectively, received IBI343 at 6mg/kg in the dose expansion phase (median age, 60 and 64 years; male, 54.5% and 66.7%; received prior treatments ≥2L, 61.4% and 83.3%). Among all treated pts (n = 83), treatment-emergent adverse ev...