Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of YK-029A in Treatment-Naive Patients With Advanced NSCLC Harboring EGFR Exon 20 Insertion Mutations: A Phase 1 Trial

作者：Jianchun Duan, Lin Wu, Kunyu Yang, Jun Zhao, Yanqiu Zhao, Xiumei Dai, Mingjun Li, Yanyan Xie, Yu Yao, Mingfang Zhao, Chengzhi Zhou, Xiubao Ren, Zhe Liu, Yueyin Pan, Yuping Li, Baogang Liu, Ying Cheng, Liyun Miao, Qitao Yu, Zhihong Zhang, Xiaoqing Liu, Jiuwei Cui, Yu Zhang, Li Zhang, Xiaoyan Li, Xiaoling Li, Bo Shen, Bi Chen, Shan Zeng, Bin Li, Yanping Hu, Lin Li, Rong Wu, Qibin Song, Jie Wang · 发表于：Journal of Thoracic Oncology · 年份：2023 · DOI：10.1016/j.jtho.2023.09.1449 · 被引用次数：16 · 研究领域：Lung Cancer Treatments and Mutations、Cancer Immunotherapy and Biomarkers、Melanoma and MAPK Pathways

INTRODUCTION: Treatment options for treatment-naive patients with advanced NSCLC harboring EGFR exon 20 insertion (ex20ins) mutations are limited. This study evaluated the safety, tolerability, and pharmacokinetics of YK-029A, a third-generation EGFR tyrosine kinase inhibitor, and the preliminary efficacy of YK-029A in treatment-naive patients with EGFR ex20ins mutation. METHODS: This multicenter, dose-escalation, and dose-expansion phase 1 clinical trial enrolled patients with NSCLC harboring EGFR mutations. During the dose-escalation phase, YK-029A was orally administered using the traditional 3+3 principle at 50, 100, 150, 200, and 250 mg/d. In the dose-expansion phase, treatment-naive patients with EGFR ex20ins mutations were enrolled and administered YK-029A 200 mg/d. The primary end point was safety and tolerability. RESULTS: The safety analysis included 108 patients. No dose-limiting toxicity was observed, and the maximum tolerated dose was not reached. The most common treatment-emergent adverse events were anemia (50.9%), diarrhea (49.1%), and rash (34.3%). There was minimal drug accumulation after multiple doses. A total of 28 treatment-naive patients with EGFR ex20ins mutations were enrolled in the dose-expansion and 26 were included in the efficacy analysis. According to the independent review committee evaluation, the objective response rate was 73.1% (95% confidence interval: 52.21%-88.43%), and the disease control rate was 92.3% (95% confidence interval: 74.87%-...