Iruplinalkib (WX-0593) Versus Crizotinib in ALK TKI-Naive Locally Advanced or Metastatic ALK-Positive NSCLC: Interim Analysis of a Randomized, Open-Label, Phase 3 Study (INSPIRE)

作者：Yuankai Shi, Jianhua Chen, Runxiang Yang, Hongbo Wu, Zhehai Wang, Weihua Yang, Jiuwei Cui, Yiping Zhang, Chunling Liu, Ying Cheng, Yunpeng Liu, Jinlu Shan, Donglin Wang, Lei Yang, Chang-Lu Hu, Jian Zhao, Ranhua Cao, Bangxian Tan, Ke Xu, Meimei Si, Hui Li, Ruifeng Mao, Lingyan Li, Xiaoyan Kang, Lin Wang · 发表于：Journal of Thoracic Oncology · 年份：2024 · DOI：10.1016/j.jtho.2024.01.013 · 被引用次数：43 · 研究领域：Lung Cancer Treatments and Mutations、Lung Cancer Research Studies、Colorectal Cancer Treatments and Studies

INTRODUCTION: Iruplinalkib (WX-0593) is a new-generation, potent ALK tyrosine kinase inhibitor (TKI) that has been found to have systemic and central nervous system (CNS) efficacy in ALK-positive NSCLC. We compared the efficacy and safety of iruplinalkib with crizotinib in patients with ALK TKI-naive, locally advanced or metastatic ALK-positive NSCLC. METHODS: In this open-label, randomized, multicenter, phase 3 study, patients with ALK-positive NSCLC were randomly assigned to receive iruplinalkib 180 mg once daily (7-d run-in at 60 mg once daily) or crizotinib 250 mg twice daily. The primary end point was progression-free survival (PFS) assessed by Independent Review Committee (IRC) per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included PFS by investigator, objective response rate (ORR), time to response, duration of response, intracranial ORR and time to CNS progression by IRC and investigator, overall survival, and safety. An interim analysis was planned after approximately 70% (134 events) of all 192 expected PFS events assessed by IRC were observed. Efficacy was analyzed in the intention-to-treat population. Safety was assessed in the safety population, which included all randomized patients who received at least one dose of the study drugs. This study is registered with Center for Drug Evaluation of China National Medical Products Administration (CTR20191231) and Clinicaltrials.gov (NCT04632758). RESULTS: From September 4, 2019, to D...