Abstract CT246: Open-label, single-arm, multicenter, phase 2 trial of garsorasib in KRAS G12C-mutated non-small-cell lung cancer

作者：Ziming Li, Xiaomin Dang, Dingzhi Huang, Jin Shi, Weiwei Li, Jianhua Shi, Xicheng Wang, Yiping Zhang, Zhengbo Song, Junping Zhang, Wu Zhuang, Xuewen Liu, Liyan Jiang, Xiangjiao Meng, Mingfang Zhao, Jianying Zhou, Liangming Zhang, Pingli Wang, Hui Luo, Junquan Yang, Shundong Cang, Xiang Wang, Jing Wang, Jiuwei Cui, Yan Yu, Zhihong Zhang, Junguo Lu, Weihua Yang, Gaofeng Li, Jifeng Feng, Dongqing Lv, Lin Wu, Yong Fang, Yan Wang, Yanqiu Zhao, Baoshan Cao, Wei Zhu, Zhixiang Zhuang, Qingshan Li, Mingxi Wang, Huan Zhou, Xiaorong Dong, Sheng Hu, Jian Fang, Yihong Zhang, Wenjia Wang, Ziyong Xiang, Zhe Shi, Ling Zhang, Shun Lü · 发表于：Cancer Research · 年份：2024 · DOI：10.1158/1538-7445.am2024-ct246 · 被引用次数：4 · 研究领域：Lung Cancer Research Studies、Lung Cancer Treatments and Mutations、Cancer therapeutics and mechanisms

Abstract Background: Garsorasib (D-1553), a potent KRAS G12C inhibitor, has previously demonstrated promising anti-tumor activity in KRAS G12C-mutated non-small-cell lung cancer (NSCLC) in a phase 1 study. Here we present the efficacy and safety of garsorasib in a pivotal phase 2 study. Methods: In this open-label, multicenter, single-arm phase 2 study, patients received garsorasib 600 mg twice daily in 21-day cycles. Eligible criteria included patients with locally advanced or metastatic NSCLC harboring KRAS G12C mutation, who had disease progression after prior anti-PD-(L)1 therapy and platinum-based chemotherapy or intolerance to the above regimens due to toxicity, and had measurable tumor lesions according to the RECIST, v1.1. The primary end point was objective response rate (ORR) evaluated by independent review committee (IRC) per RECIST v1.1. The secondary end points included duration of response (DOR), disease control rate (DCR), time to response (TTR), progression-free survival (PFS), overall survival (OS), and safety. Results: As of November 17, 2023, 123 patients (108 [87.8%] male, median age 64 [range: 33-80], and 11.4%/88.6% ECOG PS 0/1) were enrolled and treated, with a median follow-up of 7.92 months (range, 0.7, 16.5) and a median duration of treatment of 6.24 months (range, 0.7, 15.9). At data cutoff date, 82 patients (66.7%) discontinued treatment, with disease progression (46 patients [37.4%]) being the most common reason. Among 123 patients, IRC confirmed-...