A pivotal phase 2 single-arm study of glecirasib (JAB-21822) in patients with NSCLC harboring KRAS G12C mutation.

作者：Yuankai Shi, Jian Fang, Ligang Xing, Yu Yao, Jian Zhang, Lian Liu, Yongsheng Wang, Changlu Hu, Jianping Xiong, Zhihua Liu, Runxiang Yang, Zhen Wang, Enfeng Zhao, Mengzhao Wang, Yanqiu Zhao, Kejing Tang, Zhihua Li, Zhengbo Song · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco.2024.42.36_suppl.468214 · 被引用次数：20 · 研究领域：Protein Kinase Regulation and GTPase Signaling、Melanoma and MAPK Pathways、Protein Tyrosine Phosphatases

468214 Background: KRAS G12C mutation occurs in approximately 4% of non-small cell lung cancers (NSCLC) in China. Glecirasib (Jacobio, Beijing, PRC) is a potent and highly selective covalent oral inhibitor of KRAS G12C. Methods: This phase 2 single-arm study (NCT05009329) of glecirasib was conducted in China at 43 sites, enrolling participants with locally advanced or metastatic KRAS G12C mutated NSCLC. Subjects must have received prior platinum-based therapy and an immune checkpoint inhibitor (ICI) as well as appropriate targeted agents for any actionable mutations per local standards. Primary study objective is overall response rate (ORR) assessed by independent review committee (IRC). The secondary study objectives include duration of response (DOR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety. Here we report topline results from this pivotal study. Results: A total of 119 patients with NSCLC harboring KRAS G12C mutation were enrolled and treated with single agent glecirasib at 800mg daily (median follow up 10.4 months). The median age was 62 years, 79% was male and 21% was female, and 80.7% had ECOG PS 1. The prior lines of therapy include 1-3, with 94.1% (112/119) patients having received prior platinum-based therapy and ICI. Confirmed ORR was 47.9% (56/117; 95% CI, 38.5%-57.3%) and confirmed DCR was 86.3% (101/117; 95% CI, 78.7%-92%) assessed by IRC. Median PFS per IRC was 8.2 months (95% CI, 5.5 – 13.1), and median OS w...