Gumarontinib in patients with non-small-cell lung cancer harbouring MET exon 14 skipping mutations: a multicentre, single-arm, open-label, phase 1b/2 trial

作者：Yongfeng Yu, Jianya Zhou, Xingya Li, Kōichi Goto, Xuhong Min, Kazumi Nishino, Jiuwei Cui, Lin Wu, Jun Sakakibara, Yongqian Shu, Xiaorong Dong, Lu Li, Yasuto Yoneshima, Chengzhi Zhou, Xiaoling Li, Yiping Zhang, Dingzhi Huang, Aimin Zang, Wei Zhang, Xiuwen Wang, Li Zhang, Chong Bai, Jian Fang, Lejie Cao, Yanqiu Zhao, Yan Yu, Meiqi Shi, Diansheng Zhong, Fugen Li, Meng Li, Qiuxia Wu, Jun Zhou, Minghui Sun, Shun Lü · 发表于：EClinicalMedicine · 年份：2023 · DOI：10.1016/j.eclinm.2023.101952 · 被引用次数：56 · 研究领域：Lung Cancer Treatments and Mutations、Liver physiology and pathology、Fibroblast Growth Factor Research

Background: ex14-positive) NSCLC. Methods: ex14-positive NSCLC received oral gumarontinib 300 mg once daily in continuous 21-day cycles until disease progression, intolerable toxicity, or withdrawal of consent. Eligible patients had failed one or two prior lines of therapy (not including a MET inhibitor), were ineligible for/refused chemotherapy, and had no genetic alterations targetable with standard therapies. The primary endpoint was objective response rate in patients with a valid baseline tumour assessment, by blinded independent review. The study was registered at ClinicalTrials.gov (NCT04270591). Findings: ex14 status could not be confirmed by a central laboratory were excluded from the efficacy analysis. The objective response rate was 66% (95% CI 54-76) overall (n = 79), 71% (95% CI 55-83) in treatment-naïve patients (n = 44), and 60% (95% CI 42-76) in previously-treated patients (n = 35). The most common treatment-related adverse events (any grade) were oedema (67/84 patients, 80%) and hypoalbuminuria (32/84, 38%). Grade ≥3 treatment-emergent adverse events occurred in 45 (54%) patients. Treatment-related adverse events leading to permanent discontinuation occurred in 8% (7/84) of patients. Interpretation: ex14-positive NSCLC when used in first line or later. Funding: Haihe Biopharma Co., Ltd. Supported in part by grants from the National Science and Technology Major Project of China for "Clinical Research of Gumarontinib, a highly selective MET inhibitor" (2018ZX09...