FDA approves zidesamtinib for previously treated ROS1-positive non-small cell lung cancer

Approval of the drug, based on Phase I/II ARROS-1 trial data, arrived ahead of its target action date.

The FDA has approved zidesamtinib (Jideytro; GSK, London, UK) for adults with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) who have previously received a ROS1 kinase inhibitor. The approval arrived ahead of the drug’s original target action date of September 18, 2026, and followed earlier FDA Breakthrough Therapy and Orphan Drug designations. Zidesamtinib was acquired by GSK through its recently completed acquisition of Nuvalent, Inc.

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NSCLC is the most common form of lung cancer and may be characterized by specific genetic alterations, including changes involving ALK, ROS1, or HER2. ROS1-positive NSCLC can metastasize to the central nervous system, and resistance mutations and disease progression in the brain remain important challenges following treatment with a ROS1 inhibitor. According to GSK, approximately 50,000 people worldwide are diagnosed with ROS1-positive NSCLC each year, often nonsmokers in their 40s and 50s who may receive treatment over several years.

Zidesamtinib is an oral kinase inhibitor designed to combine high selectivity for ROS1, broad coverage of ROS1 resistance mutations, and blood–brain barrier penetration intended to address disease in the brain.

The approval was based on the global, single-arm Phase I/II ARROS-1 trial (NCT05118789), which evaluated zidesamtinib in patients with advanced or metastatic ROS1-positive NSCLC who had previously received a ROS1 inhibitor. Among 117 patients included in the efficacy analysis, the objective response rate was 44% (95% CI, 34–53%). Among responders, the estimated duration-of-response rates at six and 12 months were 82% and 69%, respectively. Responses were also observed in patients with brain metastases and ROS1 resistance mutations, according to GSK. Zidesamtinib continues to be evaluated in ARROS-1, including in patients who have not previously received a ROS1 inhibitor.

In the pooled safety population of 446 patients, the most common adverse reactions, occurring in at least 15% of patients, were edema, peripheral neuropathy, constipation, fatigue, and dyspnea. The US prescribing information also includes warnings and precautions concerning central nervous system adverse reactions, QTc prolongation, interstitial lung disease/pneumonitis, skeletal fractures, myalgia with creatine phosphokinase elevation, pancreatic toxicity, and embryo–fetal toxicity.

“The responses observed in ARROS-1, including in heavily pre-treated patients, represent meaningful progress for people living with this disease,” said Alexander Drilon, MD, an ARROS-1 trial investigator and Chief of the Early Development Service at Memorial Sloan Kettering Cancer Center. Dr Drilon disclosed serving as a consultant to and/or receiving expense reimbursements from Nuvalent, Inc.

Jideytro is GSK’s first approved medicine in lung cancer. The company is advancing other assets acquired from Nuvalent, including neladalkib for ALK-altered NSCLC, which is currently under FDA review with a target decision date of November 27, 2026, and NVL-330, an investigational treatment for HER2-altered NSCLC.

References

1. Jideytro (zidesamtinib) prescribing information. GSK. 2026.
2. GSK. Jideytro (zidesamtinib) approved in the US for previously treated ROS1-positive non-small cell lung cancer. Press release. July 22, 2026.
3. A Study of Zidesamtinib (NVL-520) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ROS1 Rearrangement (ARROS-1). ClinicalTrials.gov identifier: NCT05118789.