A phase 1/2 study of LM-302, an anti-claudin 18.2 (CLDN18.2) antibody-drug conjugate in patients with advanced gastric/gastroesophageal junction cancer.

作者：Chunmei Bai, Junli Xue, Yi Zheng, Meili Sun, Jieer Ying, Fuxiang Zhou, Yiyi Yu, Yuping Sun, Ligang Xing, Yanqiao Zhang, Jinhua Wen, Jianping Xiong, Heshui Wu, Xiuli Yang, Lixin Wan, Shiwei Guo, Rusen Zhao, Zhizhen Zhu, Zhihua Gong, Jin Li · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco.2024.42.16_suppl.3028 · 被引用次数：17 · 研究领域：Cell Adhesion Molecules Research、Angiogenesis and VEGF in Cancer、Barrier Structure and Function Studies

3028 Background: LM-302 is a novel and potent MMAE antibody-drug conjugate (ADC) targeting CLDN18.2, which is highly expressed in gastric/gastroesophageal junction (GEJ), pancreatic, and biliary tract cancers. Preclinical studies of LM-302 have demonstrated compelling anti-tumor activity in multiple CLDN18.2-positive cell-lines and xenograft models. Methods: This phase 1/2 study included dose escalation phase and dose expansion phase. In the dose escalation phase, eligible patients received LM-302 once every three weeks (0.2-2.8 mg/kg Q3W), and once every two weeks (1.8-2.0 mg/kg Q2W) to evaluate the safety, tolerability, and pharmacokinetics. In the dose expansion phase, CLDN18.2-positive patients received LM-302 at recommended phase 2 doses of 2.4 mg/kg Q3W or 1.8 mg/kg Q2W to evaluate the efficacy and safety. The primary endpoints included dose-limiting toxicity (DLT) and adverse events (AEs) in phase 1, and objective response rate (ORR) in phase 2. Here we report the results from safety analysis of LM-302 and efficacy data in gastric/GEJ cancer. Results: As of September 23, 2023, 135 patients received LM-302 treatment and the median prior lines of systemic therapy were 2 (range 1-4). In phase 1 and 2, most common TRAEs were white blood cell decreased (51.9%), neutrophil count decreased (51.1%), anaemia (38.5%), vomiting (36.3%), and nausea (34.1%). The most frequent grade ≥3 TRAEs were neutrophil count decreased (22.2%) and white blood cell decreased (17.8%). In phase 2 d...