Nuvalent reports ARROS-1 data showing zidesamtinib activity in heavily pretreated ROS1-positive NSCLC, with FDA review underway and PDUFA decision expected in September 2026
Written By: Nikita Jha, BPharm
Reviewed By: Pharmacally Editorial Team
Nuvalent reported new clinical and preclinical data for its investigational ROS1-selective inhibitor zidesamtinib at the American Association for Cancer Research (AACR) Annual Meeting 2026, highlighting activity in heavily pretreated patients with ROS1-positive non-small cell lung cancer (NSCLC). The findings add to the company’s growing evidence base for zidesamtinib as a potential treatment option after prior ROS1-targeted therapy.
The U.S. Food and Drug Administration has accepted the New Drug Application for zidesamtinib in patients with advanced ROS1-positive NSCLC who have received at least one prior ROS1 tyrosine kinase inhibitor (TKI). The application has a Prescription Drug User Fee Act target action date of September 18, 2026, and Nuvalent anticipates a potential U.S. launch later in 2026.
Clinical results from the Phase 1/2 ARROS-1 trial (NCT05118789) showed meaningful activity in a heavily pretreated population, including patients previously treated with repotrectinib or taletrectinib. Objective response rates were 41% and 47%, respectively, with responses also observed in tumors harboring the ROS1 G2032R resistance mutation, where response rates reached up to 67%.
The median duration of response was 15.7 months in the repotrectinib-pretreated group. Zidesamtinib also demonstrated intracranial activity, with response rates of 44% and 71% in the respective pretreated groups, and complete responses were reported in patients with central nervous system disease.
Safety findings remained consistent with earlier reports, with low rates of dose reductions and treatment discontinuations and no TRK-related neurologic adverse events. Nuvalent said the strong enrolment in ARROS-1 reflects investigator interest and supports the continued unmet need in ROS1-positive NSCLC.
Preclinical data also suggested that zidesamtinib achieved greater brain penetration and more durable intracranial tumor control than repotrectinib and taletrectinib in ROS1 G2032R models, including continued activity after progression on earlier-line therapy. While these findings support the drug’s design as a brain-penetrant, ROS1-selective inhibitor, preclinical results do not by themselves establish clinical benefit.
Zidesamtinib is designed to inhibit ROS1 while avoiding tropomyosin receptor kinase (TRK), a feature that may help reduce neurologic adverse events associated with dual TRK/ROS1 inhibitors.
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About the Writer
Nikita Jha BPharm is a pharmacy graduate with expertise in clinical research, pharmacovigilance, and medical writing. In her words, she is passionate about translating complex scientific data into clear, accurate healthcare communications that advance drug safety and patient care.