The US Food and Drug Administration has approved Jideytro (zidesamtinib) for adults with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) who have previously received a ROS1 kinase inhibitor. GSK announced the decision on 23 July, ahead of a target action date the company had listed as 18 September 2026.
It is GSK’s first approved medicine in lung cancer, a portfolio the company has historically built around blood and women’s cancers. The asset came through GSK’s acquisition of Nuvalent, which closed on 15 July, meaning the drug moved from an acquired pipeline programme to a marketed product within about a week.
The clinical problem
ROS1 fusions drive a small share of NSCLC, on the order of 1–2% of cases, or an estimated 50,000 diagnoses worldwide each year, according to figures GSK cites. Patients skew younger and are frequently non-smokers, and many remain on targeted therapy for extended periods.
Two failure modes have shaped development in the class. Acquired kinase-domain mutations account for a substantial proportion of progression on earlier ROS1 inhibitors, with the G2032R solvent-front substitution the most commonly reported. The central nervous system is also a frequent site of relapse. Separately, several agents active against ROS1 also inhibit TRK, which published work has linked to neurologic adverse effects that can become dose-limiting.
Zidesamtinib was designed around those three constraints: coverage of ROS1 resistance mutations, brain penetration, and ROS1 selectivity that spares TRK. It is worth noting that the comparative case for the TRK-sparing design rests largely on preclinical work, mutagenesis screens and intracranial xenograft models published by the drug’s developers, rather than head-to-head clinical trials against repotrectinib, taletrectinib or entrectinib. No such comparative trials have been reported.
What the data show, and what they don’t
The approval is based on ARROS-1, a global single-arm phase I/II trial. In the 117 previously treated ROS1-positive NSCLC patients supporting the label, GSK reports an objective response rate of 44% (95% CI: 34–53%), with 82% and 69% of responders still in response at six and twelve months respectively.
Reported subgroup data indicate responses in patients with G2032R-mutant disease and in those with intracranial disease, the populations the molecule was designed for. Numbers reported across trial disclosures and the label have varied somewhat by data cut, so readers should treat the prescribing information as the authoritative source.
The structural caveats matter. ARROS-1 is single-arm and open-label, with no randomised comparator; response rate and duration are not survival endpoints, and cross-trial comparisons with other ROS1 inhibitors are not reliable evidence of superiority. The most common adverse reactions in the pooled safety population of 446 patients were oedema, peripheral neuropathy, constipation, fatigue and dyspnoea, per the company. Zidesamtinib continues to be evaluated in ARROS-1, including in patients who have not previously received a ROS1 inhibitor, the setting that would test whether it displaces current first-line options.
All efficacy and safety figures above are as reported by GSK and in the US prescribing information; independent analyses of the full dataset are not yet available.
Company positioning
In GSK’s announcement, chief scientific officer Tony Wood framed the speed of the approval as evidence for the company’s strategy of acquiring assets with validated targets. Trial investigator Alexander Drilon, MD, of Memorial Sloan Kettering Cancer Center, described the responses in pre-treated patients as meaningful progress against resistance and brain progression.
The approval is one piece of a broader lung cancer push. Neladalkib (NVL-655) for ALK-altered NSCLC is under FDA review with a decision date of 27 November 2026, and NVL-330 targets HER2-altered disease at an earlier stage, both from the Nuvalent portfolio. GSK is separately advancing risvutatug rezetecan (Ris-Rez), 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 China patient population earlier this month.
Whether that adds up to a durable franchise will depend on the November ALK decision and on how zidesamtinib performs in the first-line setting, where the comparative bar is considerably higher than in the pre-treated population covered by this label.
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Written by: Semiramida Nina Markosyan, Editor, OncoDaily Canada