An Effective New Tyrosine Kinase Inhibitor for ROS1 Fusion-Positive Non–Small-Cell Lung Cancer

ROS1 fusions occur in 2% of non–small-cell lung cancers (NSCLCs) and represent a targetable oncogene. Although two highly active ROS1 tyrosine kinase inhibitors (TKIs), crizotinib and entrectinib, have been available for years, resistance inevitably develops — often via on-target ROS1 mutations such as G2032R — and they have limited central nervous system efficacy; this there is a need for more effective therapies.

In this international, industry-sponsored, phase 1–2 trial, investigators assessed the efficacy and safety of repotrectinib in patients with ROS1 fusion-positive NSCLC. Repotrectinib is a next-generation ROS1 and NTRK TKI that was designed to inhibit both wild type and G2032R-mutant ROS1 and to have significant central nervous sys…