Zidesamtinib approved in the US for previously treated ROS1-positive non-small cell lung cancer

A 44% response rate after a prior ROS1 inhibitor

ARROS-1 enrols patients with advanced ROS1-positive NSCLC and other ROS1-positive solid tumours. The approval rests on the 117 of them with NSCLC who had already been treated with a ROS1 inhibitor. In that population GSK reported an objective response rate of 44%, with a 95% confidence interval of 34% to 53%. Duration of response rates were 82% at six months and 69% at 12 months.

GSK stated that zidesamtinib continues to be studied in ARROS-1, including in first-line treatment for patients who have not previously received a ROS1 inhibitor. The registry still lists the trial as recruiting, with an estimated enrolment of 359 participants, on a record last verified in 2025.

Responses in the brain and against resistance mutations, but no figures for either

GSK noted that NSCLC often spreads to the central nervous system. The company stated that the responses seen in ARROS-1 included patients with brain metastases and patients with ROS1 resistance mutations, and described zidesamtinib as designed to combine target selectivity, broad coverage of ROS1 resistance mutations and blood-brain barrier penetration. Response rates specific to either group were not given in the announcement.

Alexander Drilon, an ARROS-1 investigator and Chief of the Early Development Service at Memorial Sloan Kettering Cancer Center, set the result against those problems. GSK disclosed in the same announcement that he has served as a consultant to Nuvalent and has received expense reimbursements from the company:

“Despite advances in treatment, resistance mutations, disease progression in the brain and treatment-related adverse events continue to create challenges for patients. The responses observed in ARROS-1, including in heavily pre-treated patients, represent meaningful progress for people living with this disease.”Alexander Drilon, MD, ARROS-1 trial investigator and Chief of the Early Development Service, Memorial Sloan Kettering Cancer Center

Oedema and peripheral neuropathy among the reactions reported in at least 15%

In a pooled safety population of 446 patients, GSK stated that the adverse reactions occurring in at least 15% included oedema, peripheral neuropathy, constipation, fatigue and dyspnoea, and did not present the list as exhaustive. The announcement gave no severity grading, no discontinuation rates and no dose-modification rates. GSK stated that the US prescribing information would be published on the manufacturer’s site.

The Nuvalent programmes behind GSK’s first lung cancer medicine

Zidesamtinib reached GSK through the Nuvalent acquisition, announced as complete a week before the approval. Two further Nuvalent candidates are named in the announcement: neladalkib (NVL-655) for ALK-altered NSCLC, under FDA review with a target decision date of 27 November 2026, and NVL-330, an investigational treatment for HER2-altered NSCLC. GSK is separately developing risvutatug rezetecan, a B7-H3-targeted antibody-drug conjugate licensed from Hansoh Pharma, which reported positive phase III results in relapsed small-cell lung cancer in a Chinese patient population earlier in July.

GSK put the annual worldwide incidence of ROS1-positive NSCLC at approximately 50,000, and described the patients as often non-smokers in their 40s and 50s who may remain on treatment for several years.