A phase 1 trial of claudin 18.2-specific antibody-drug conjugate CMG901 in patients with advanced gastric/gastroesophageal junction cancer.

作者：Rui‐Hua Xu, Dan‐Yun Ruan, Dong‐Sheng Zhang, Furong Liu, Suxia Luo, Zhixiang Zhuang, Zhen-Ning Wang, Funan Liu, Yanqiao Zhang, Jianwei Yang, Zhendong Chen, Yongsheng Wang, Junye Wang, Xiaohua Liang, Xiaojie Wu, Yulong Zheng, Jian Liu, Xi Shi, Wei Liu, Bo Chen · 发表于：Journal of Clinical Oncology · 年份：2023 · DOI：10.1200/jco.2023.41.36_suppl.434420 · 被引用次数：22 · 研究领域：Barrier Structure and Function Studies、Cell Adhesion Molecules Research、Caveolin-1 and cellular processes

434420 Background: Claudin 18.2 (CLDN18.2) is a promising therapeutic target for advanced gastric/gastroesophageal junction (G/GEJ) cancer. CMG901, a potential first-in-class CLDN18.2-targeted antibody-drug conjugate carrying monomethyl auristatin E (MMAE), has demonstrated potent anti-tumor activity in preclinical studies. Methods: This phase 1 trial included a dose-escalation phase (part A; 0.3-3.4 mg/kg) and a dose-expansion phase (part B; 2.2, 2.6, and 3.0 mg/kg) to evaluate safety, tolerability, and anti-tumor activity of CMG901 in patients (pts) with advanced G/GEJ cancer and other solid tumors. CLDN18.2 expression was not required for study entry in part A, but CLDN18.2 expression of ≥2+ membrane staining intensity in ≥5% tumor cells was required for G/GEJ cancer in part B. CMG901 was administrated intravenously every 3 weeks until disease progression or unacceptable toxicity. Primary endpoints were safety/tolerability and maximum tolerated dose (MTD) for part A, and objective response rate (ORR, per RECIST v1.1) and recommended phase 2 dose in part B. Here we present the G/GEJ cancer data from this ongoing trial. Results: MTD was not reached during dose escalation. As of July 24, 2023, 113 G/GEJ cancer pts received CMG901 at doses of 2.2-3.0 mg/kg (6 pts from part A and 107 pts from part B). The median prior lines of systemic therapy were 2 (range 1-6). Most common TEAEs were anaemia (62.8%), vomiting (57.5%), and hypoalbuminaemia (57.5%). Neutrophil count decreased (...