Jideytro (zidesamtinib): FDA approval, pivotal trial and safety
Approved
Type
New molecular entity · Oral
FDA-approved use
To treat adults with locally advanced or metastatic ROS1-positive non-small cell lung cancer after receiving a ROS1 kinase inhibitorWording from FDA's list of novel approvals.
FDA review
Standard reviewOrphan drug
Company
Nuvalent
Application
NDA 220185
Specialty
Oncology
At a glance
Jideytro (zidesamtinib) is a kinase inhibitor approved on July 22, 2026 for adults with locally advanced or metastatic ROS1-positive non-small cell lung cancer who have already received a ROS1 kinase inhibitor. In the single-arm ARROS-1 trial, 44% of 117 previously treated patients had a confirmed response (95% CI 34 to 53). The main safety concerns are CNS effects, QTc prolongation, interstitial lung disease, fractures, CPK elevation and pancreatic toxicity.
What it is and how it works
Zidesamtinib inhibits the ROS1 tyrosine kinase, including ROS1 resistance mutations such as G2032R. It also inhibits ALK and, to a lesser degree, TRK kinases in biochemical assays. In preclinical models it was active against ROS1 fusion tumors, including intracranial disease. Its distinguishing feature is activity after earlier ROS1 inhibitors have failed, including after resistance mutations have emerged.
Multicenter, single-arm, open-label, multi-cohort phase 1/2 trial. Tumor response was assessed by blinded independent central review.
Patients
117 adults with previously treated locally advanced or metastatic ROS1-positive NSCLC, ECOG performance status 1 or lower, and measurable disease. 49% had CNS metastases. Half had received one prior ROS1 inhibitor and half had received two or more. 52% had prior platinum chemotherapy.
Compared with
None (single arm).
Primary endpoint
Confirmed overall response rate and duration of response by RECIST v1.1 per blinded independent central review.
Result
Confirmed response rate was 44% (95% CI 34 to 53), with complete response in 0.9%. Duration of response ranged from 1.9 to 28.5+ months. Response lasted at least 6 months in 82% and at least 12 months in 69%.
Other results
With one prior ROS1 inhibitor, response rate was 49% (95% CI 36 to 63). With two or more, it was 38% (95% CI 26 to 52). In 50 patients with measurable CNS metastases, intracranial response was 48% (95% CI 34 to 63), with complete response in 22%. Responses occurred in 21 of 42 patients (50%) with ROS1 resistance mutations and in 14 of 26 (54%) with G2032R.
Safety in the trial
In 446 patients in the pooled safety population, the most common adverse reactions were edema (38%), peripheral neuropathy (25%), constipation (17%), fatigue (16%) and dyspnea (15%). CNS adverse reactions occurred in 25%, and 2.5% were Grade 3 or 4. Grade 3 or 4 increased lipase occurred in 8%.
How does Jideytro (zidesamtinib) compare with the alternatives (Lorlatinib, Repotrectinib, Taletrectinib) for adults with locally advanced or metastatic ROS1-positive non-small cell lung cancer after receiving a ROS1 kinase inhibitor? Summarize head-to-head and indirect evidence, efficacy, safety and where each fits, with citations.
There is no boxed warning. Warnings cover CNS adverse reactions (dizziness, ataxia, cognitive and psychiatric disorders), QTc prolongation, interstitial lung disease or pneumonitis, skeletal fractures, myalgia with CPK elevation, pancreatic toxicity and embryo-fetal toxicity. In the pooled safety population of 446 patients, CNS reactions occurred in 25%, and 2.5% were Grade 3 or 4. The most common adverse reactions were edema, peripheral neuropathy, constipation, fatigue and dyspnea. The most common Grade 3 or 4 laboratory abnormalities were increased lipase, CPK and triglycerides, decreased lymphocytes and decreased hemoglobin. ECGs, electrolytes, amylase, lipase and CPK should be monitored.
What it competes with
ROS1-positive NSCLC is treated with ROS1 tyrosine kinase inhibitors, with chemotherapy and immunotherapy used in some settings. After progression on a first ROS1 inhibitor, options include another ROS1 inhibitor or chemotherapy.
LorlatinibALK/ROS1 inhibitor with intracranial activity, used after earlier ROS1 inhibitors.
RepotrectinibROS1 and TRK inhibitor designed to overcome some resistance mutations, including solvent front mutations.
TaletrectinibROS1 inhibitor with activity in both TKI-naive and pretreated disease.
Platinum-based chemotherapyStandard cytotoxic option, often with pemetrexed, when targeted therapy options are exhausted.
Bottom line for clinicians
Jideytro is for adults with ROS1-positive NSCLC that has progressed after a ROS1 kinase inhibitor, including patients with brain metastases or resistance mutations. The evidence comes from a single-arm trial with no comparator, so response and duration data cannot be compared directly with other agents. Weigh baseline and ongoing monitoring needs, especially CNS effects, QTc, lipase and CPK.
Dosing, contraindications and full warnings are in the prescribing information.
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Last updated October 28, 2026 by 2 Minute Medicine.
For healthcare professionals. A summary of public FDA documents and published trials, not medical advice. Check the full prescribing information before prescribing.
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