European journal of cancer (Oxford, England : 1990) · 2025
Tecotabart vedotin in Claudin 18.2-positive advanced gastric/gastroesophageal junction cancer: A Bayesian phase 1/2 clinical trial.
СтатьяКлиническое исследование I фазыКлиническое исследование II фазыМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Bai Chunmei, Zheng Yi, Sun Meili, Ying Jieer, Zhou Fuxiang, Yu Yiyi, Xing Ligang, Zhang Yanqiao, Wen Jinhua, Wu Heshui, Yang Xiuli, Wan Lixin, Guo Shiwei, Zhao Rusen, Zhu Zhizhen, Shen Wei, Wang Qi, Gu Shanzhi, Wu Hao, Chen Weichang, Xia Jin, Zhao Jun, Dong Xiaofang, Lou Wenhui, Jiang Kuirong, Zhang Zhiye, Chen Xiaobing, Fu Deliang, Chen Youshan, Wang Baoqing, Liu Jiaxin, Ji Yuan, Yuan Shijie, Li Yuan, Gong Zhihua, Fei Da, Qin Xia, Qin Crystal, Li Jin
Аннотация
BACKGROUND: Tecotabart vedotin (LM-302) is a novel antibody-drug conjugate (ADC) targeting CLDN18.2, a promising therapeutic target in gastrointestinal cancers. This phase 1/2 study evaluated the safety, pharmacokinetics, immunogenicity, and preliminary anti-tumor activity of tecotabart vedotin in patients with advanced solid tumors, with a focus on CLDN18.2-positive gastric/gastroesophageal junction (G/GEJ) cancer.
METHODS: This open-label, multicenter study utilized a Bayesian adaptive design. Phase 1 enrolled patients with advanced solid tumors; phase 2 focused on CLDN18.2-positive G/GEJ, pancreatic, biliary tract cancer, or gastrointestinal tumors with low to moderate CLDN18.2 expression. Tecotabart vedotin was administered at 0.2-2.8 mg/kg every 3 weeks (Q3W) or 1.8-2.0 mg/kg every 2 weeks (Q2W). Primary endpoints included dose-limiting toxicities (DLTs) and safety in phase 1, and objective response rate (ORR) in phase 2. Secondary endpoints included safety, pharmacokinetics, immunogenicity, and other anti-tumor activity outcomes.
RESULTS: Overall, 153 patients received tecotabart vedotin (phase 1: 38; phase 2: 115). DLTs occurred in 5 patients at higher dose levels. The maximum tolerated dose was 2.4 mg/kg Q3W; recommended phase 2 doses were 1.8 mg/kg Q2W and 2.4 mg/kg Q3W. Among 52 evaluable patients with CLDN18.2-positive G/GEJ cancer receiving 1.8 mg/kg Q2W, ORR was 32.7 % (95 % confidence interval [CI] 20.3-47.1), with median progression-free survival of 4.9 months (95 % CI 2.7-6.9), and overall survival of 10.9 months (95 % CI 9.1-17.1). Adverse events were manageable and consistent with monomethyl auristatin E-based ADCs.
CONCLUSIONS: Tecotabart vedotin demonstrated encouraging anti-tumor activity and manageable safety in CLDN18.2-positive G/GEJ cancer, supporting further clinical development in gastrointestinal malignancies.
METHODS: This open-label, multicenter study utilized a Bayesian adaptive design. Phase 1 enrolled patients with advanced solid tumors; phase 2 focused on CLDN18.2-positive G/GEJ, pancreatic, biliary tract cancer, or gastrointestinal tumors with low to moderate CLDN18.2 expression. Tecotabart vedotin was administered at 0.2-2.8 mg/kg every 3 weeks (Q3W) or 1.8-2.0 mg/kg every 2 weeks (Q2W). Primary endpoints included dose-limiting toxicities (DLTs) and safety in phase 1, and objective response rate (ORR) in phase 2. Secondary endpoints included safety, pharmacokinetics, immunogenicity, and other anti-tumor activity outcomes.
RESULTS: Overall, 153 patients received tecotabart vedotin (phase 1: 38; phase 2: 115). DLTs occurred in 5 patients at higher dose levels. The maximum tolerated dose was 2.4 mg/kg Q3W; recommended phase 2 doses were 1.8 mg/kg Q2W and 2.4 mg/kg Q3W. Among 52 evaluable patients with CLDN18.2-positive G/GEJ cancer receiving 1.8 mg/kg Q2W, ORR was 32.7 % (95 % confidence interval [CI] 20.3-47.1), with median progression-free survival of 4.9 months (95 % CI 2.7-6.9), and overall survival of 10.9 months (95 % CI 9.1-17.1). Adverse events were manageable and consistent with monomethyl auristatin E-based ADCs.
CONCLUSIONS: Tecotabart vedotin demonstrated encouraging anti-tumor activity and manageable safety in CLDN18.2-positive G/GEJ cancer, supporting further clinical development in gastrointestinal malignancies.