Zidesamtinib: First Approval.

Zidesamtinib (Jideytro™) is a brain-penetrant, selective small-molecule inhibitor of ROS1 being developed by Nuvalent (a subsidiary of GSK) for the treatment of advanced ROS1-positive non-small cell lung cancer (NSCLC) and other solid tumours. ROS1 fusions are oncogenic drivers in a range of cancers and are identified in approximately 1-2% of NSCLCs. Zidesamtinib potently inhibits diverse ROS1 fusion proteins and clinically relevant ROS1 resistance mutations. Further, zidesamtinib has been shown to induce intracranial tumour regression in xenograft models. Supported by findings from the phase I/II ARROS-1 trial, in July 2026, zidesamtinib was approved in the USA for use in the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC who received a prior ROS1 kinase inhibitor. This article summarises the milestones in the development of zidesamtinib leading to this first approval for advanced ROS1-positive NSCLC.