Efficacy and safety of XNW27011, a Claudin 18.2 targeting antibody drug conjugate with topoisomerase 1 inhibitor payload, in patients with Claudin 18.2 positive gastric/gastroesophageal junction cancer: Results from ongoing phase I/II study.

作者：Jinming Yu, Yuping Sun, Tianshu Liu, Zengqing Guo, Jieer Ying, Meili Sun, Qing Wen, Zhenyang Liu, Yongchang Zhang, Jing Xia, Fangling Ning, Lixin Wan, Jingdong Zhang, Ting Deng, Jun Zhao, Jianguo Li, Qifeng Shi, Hui Zhao · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.3034 · 被引用次数：6 · 研究领域：HER2/EGFR in Cancer Research、Pancreatic and Hepatic Oncology Research、Gastric Cancer Management and Outcomes

3034 Background: CLDN18.2 is a clinically validated target for cancer treatment. XNW27011 is a CLDN18.2 targeted ADC conjugated with a novel topoisomerase 1inhibitor (topo1i). Dose-escalation study of XNW27011 demonstrated favorable safety, pharmacokinetics, and promising preliminary efficacy in advanced solid tumors. Here we report the results of XNW27011 in CLDN18.2+ GC/GEJC pts from ongoing expansion cohorts. Methods: Pts with CLDN18.2+ (TC≥5%, IHC ≥ 2+), advanced/metastatic solid tumors progressed on standard therapy and an ECOG PS of 0-2 are eligible to be enrolled in dose expansion cohorts. Pts received XNW27011 iv infusion Q3W at doses of 2.4, 3.0 and 3.6 mg/kg. 1 st endpoint is ORR, 2 nd endpoints include safety, other efficacy parameters, PK, ADA, and correlation between CLDN18.2 expression and efficacy. Results: As of Dec 28 th , 2024, a total of 116 pts with CLDN18.2+ solid tumors including 84 GC/GEJC pts were enrolled in expansion cohorts at doses of 2.4 mg/kg, 3.0 mg/kg and 3.6 mg/kg, with median age of 59 years, median lines of prior treatment 2, 80.2% received checkpoint inhibitors and 18.6% topo1i-containing therapies. The most common any grade TEAE (≥ 20%) in all patients were nausea, vomiting, anemia, appetite ↓, WBC ↓, neutrophil ↓, asthenia, hypoalbuminemia, platelet ↓, body weight ↓, and hypokalemia. The most common ≥ G3 TEAEs (≥5%) were neutrophil ↓, WBC ↓, anemia, lymphocyte ↓, and asthenia. TEAEs leading to dose interruption at 2.4, 3.0 and 3.6 mg/kg w...