Jideytro (zidesamtinib) for previously treated ros1-positive non-small cell lung cancer: a new era in post-tki therapy.

Abstract

ROS1-positive non-small cell lung cancer (NSCLC) is a distinct oncogene-driven subtype that commonly affects younger, never-smokers and frequently develops central nervous system metastases and kinase-domain resistance mutations. Although first- and second-generation ROS1 tyrosine kinase inhibitors (TKIs) have improved outcomes, most patients eventually progress after treatment. On 22 July 2026, the U.S. Food and Drug Administration approved Jideytro (zidesamtinib) for adults with locally advanced or metastatic ROS1-positive NSCLC previously treated with a ROS1 TKI. Zidesamtinib is a selective, brain-penetrant, macrocyclic ROS1 inhibitor that spares tropomyosin receptor kinase (TRK) signaling while maintaining activity against diverse resistance mutations, including G2032R. In the pivotal ARROS-1 trial, it produced durable responses in heavily pretreated patients, including those with brain metastases, with low treatment discontinuation. Although prospective comparisons with crizotinib, entrectinib, repotrectinib, and taletrectinib are needed, zidesamtinib represents an important addition to post-TKI therapy for ROS1-positive NSCLC.