Phase 1 study of SHR-1826, a c-MET–directed antibody-drug-conjugate (ADC), in advanced solid tumors.

作者：Yang Zhang, Longhua Sun, Shengxiang Ren, Feng Pan, Haibo Zhu, Qi Dang, Panwen Tian, Funan Liu, Lin Wu, Sanxing Guo, Yudong Su, Jun Zhang, Yong Wang, Kai Chen, Rui Meng, Ying Cheng, Yi Hu, Yijun Jia, Mingge Li, Rui-Hua Xu · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.106 · 被引用次数：5 · 研究领域：Radiopharmaceutical Chemistry and Applications、Medical Imaging Techniques and Applications

106 Background: MET alterations are key drivers of diverse oncogenic processes, including tumor invasion, growth, and metastasis, and are associated with poor prognosis. SHR-1826 is a novel ADC of a humanized c-MET-directed IgG2 monoclonal antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. We conducted a multi-center, first-in-human, phase 1 trial of SHR-1826 in advanced solid tumors, and here report preliminary results from the dose-escalation and expansion portions. Methods: Patients (pts) with advanced solid tumors harboring MET alterations (overexpression, amplification, or activating mutation) who had failed standard therapy or no available standard therapy, were enrolled. The study consisted of dose-escalation (i3+3 design), dose-expansion and efficacy-expansion phases, during which pts received SHR-1826 at 2.2–6.0 mg/kg, Q3W, iv. Primary objectives were to assess safety and tolerability. Results: As of Dec.5, 2024, 116 pts were enrolled and treated (NSCLC/CRC/GC/PC, n=72/32/10/2; median age, 59.2 yrs; ECOG PS 1, 87.9%; ≥3 lines of prior therapy, 44.0%; median c-MET H-score, 163 [range 9-300]). During dose-escalation, 1 DLT was observed at 6.0 mg/kg (grade 3 febrile neutropenia). Grade ≥3 TRAEs were reported in 56 (48.3%) pts, with the most common being decreased neutrophil count (32.8%), decreased white blood cell count (22.4%), anaemia (13.8%), and decreased platelet count (11.2%). Interstitial lung disease occurred in ...