Repotrectinib in ROS1 Fusion–Positive Non–Small-Cell Lung Cancer

作者：Alexander Drilon, D. Ross Camidge, W. Marston Linehan, Sang‐We Kim, Benjamin Solomon, Rafał Dziadziuszko, Benjamin Besse, Kōichi Goto, Adrianus J. de Langen, Jürgen Wolf, Ki Hyeong Lee, Sanjay Popat, Christoph Springfeld, Misako Nagasaka, Enriqueta Felip, Nong Yang, Vamsidhar Velcheti, Shun Lü, Steven Kao, Christophe Dooms, Matthew Krebs, Wenxiu Yao, Muhammad Shaalan Beg, Xiufeng Hu, Denis Moro‐Sibilot, Parneet Cheema, Shanna Stopatschinskaja, Minal Mehta, Denise Trone, Armin Graber, Gregory E. Sims, Yong Yuan, Byoung Chul Cho · 发表于：New England Journal of Medicine · 年份：2024 · DOI：10.1056/nejmoa2302299 · 被引用次数：222 · 研究领域：Lung Cancer Treatments and Mutations、Lung Cancer Research Studies、Lung Cancer Diagnosis and Treatment

The early-generation ROS1 tyrosine kinase inhibitors (TKIs) that are approved for the treatment of ROS1 fusion–positive non–small-cell lung cancer (NSCLC) have antitumor activity, but resistance develops in tumors, and intracranial activity is suboptimal. Repotrectinib is a next-generation ROS1 TKI with preclinical activity against ROS1 fusion–positive cancers, including those with resistance mutations such as ROS1 G2032R. Download a PDF of the Research Summary. In this registrational phase 1–2 trial, we assessed the efficacy and safety of repotrectinib in patients with advanced solid tumors, including ROS1 fusion–positive NSCLC. The primary efficacy end point in the phase 2 trial was confirmed objective response; efficacy analyses included patients from phase 1 and phase 2. Duration of response, progression-free survival, and safety were secondary end points in phase 2. On the basis of results from the phase 1 trial, the recommended phase 2 dose of repotrectinib was 160 mg daily for 14 days, followed by 160 mg twice daily. Response occurred in 56 of the 71 patients (79%; 95% confidence interval [CI], 68 to 88) with ROS1 fusion–positive NSCLC who had not previously received a ROS1 TKI; the median duration of response was 34.1 months (95% CI, 25.6 to could not be estimated), and median progression-free survival was 35.7 months (95% CI, 27.4 to could not be estimated). Response occurred in 21 of the 56 patients (38%; 95% CI, 25 to 52) with ROS1 fusion–positive NSCLC who had pre...