FDA Approves Zidesamtinib in Pretreated ROS1+ NSCLC

The FDA has approved zidesamtinib (Jideytro) for adult patients with locally advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC) who received a prior ROS1 kinase inhibitor.¹

The approval is supported by data from the phase 1/2 ARROS-1 trial (NCT05118789). Findings from the study revealed that the confirmed overall response rate (ORR) was 44% (95% CI, 34%-53%) in the overall population (n = 117), including a complete response (CR) rate of 0.9%.^1,2 The 6- and 12-month duration of response (DOR) rates were 82% and 69%, respectively.

“The rapid progression of [zidesamtinib] from development to approval reflects both the strength of the underlying science and the urgent need for additional effective and tolerable treatments for ROS1-positive lung cancer,” Tony Wood, chief scientific officer of GSK, stated in a news release.¹ “Today's approval provides an important new option for these patients and supports our strategy to acquire assets with validated targets that could meaningfully improve standards of care.”

How was ARROS-1 designed?

ARROS-1 was a multicenter, single-arm, open-label, multi-cohort trial that enrolled patients with ROS1-positive locally advanced or metastatic NSCLC.² Patients were also required to have an ECOG performance status of 0 or 1 and measurable disease per RECIST 1.1 criteria. Those with asymptomatic, stable intracranial metastases were eligible.

The primary end point in phase 2 of the study was ORR.³ Secondary end points included safety, DOR, clinical benefit rate, time to response, progression-free survival, time to response, overall survival, and pharmacokinetic measures.

What were the additional efficacy and safety data?

Among patients who received 1 prior ROS1 TKI (n = 59), the ORR was 49% (95% CI, 36%-63%).² Patients who received at least 2 prior ROS1 TKIs (n = 58) achieved an ORR of 38% (95% CI, 26%-52%).

In patients with measurable central nervous system metastases at baseline who had not received radiation therapy to the brain within 2 months prior to study entry (n = 50), the ORR was 48% (95% CI, 34%-63%), including a CR rate of 22%. Responses were reported in 21 of the 42 patients (50%) with ROS1 resistance mutations.

“Despite advances in treatment, resistance mutations, disease progression in the brain and treatment-related adverse effects [AEs] continue to create challenges for patients,” Alexander Drilon, MD, the chief of the Early Drug Development Service and the Carol Bassok Lowenstein Chair at Memorial Sloan Kettering Cancer Center in New York, New York, added in the news release.¹ “The responses observed in ARROS-1, including in heavily pre-treated patients, represent meaningful progress for people living with this disease.”

In terms of safety (n = 432), serious AEs were reported in 22% of patients.² Fatal AEs occurred at a rate of 2.3%, and treatment discontinuation due to AEs was also reported in 2.3% of patients. The most common any-grade AEs included edema (38%), peripheral neuropathy (25%), and constipation (17%).

"For patients, the goal is not just more time, but quality time to live life as normally as possible while on treatment,” Janet Freeman-Daily, co-founder and president of The ROS1ders, said in the news release.¹ "The ROS1-positive community is deeply invested in advancing care with treatments that are effective and tolerable. Today's approval gives patients and their doctors an important new option and represents meaningful progress for our community."

References

1. Jideytro (zidesamtinib) approved in the US for previously treated ROS1-positive non-small cell lung cancer. News release. GSK. July 22, 2026. Accessed July 22, 2026. https://www.gsk.com/en-gb/media/press-releases/jideytro-zidesamtinib-approved-in-the-us-for-previously-treated-ros1-positive-non-small-cell-lung-cancer/?linkId=100000431854785
2. Jideytro. Prescribing information. GSK. 2026. Accessed July 22, 2026. https://nuvalent.com/pdfs/jideytro-full-prescribing-information.pdf
3. A study of zidesamtinib (NVL-520) in patients with advanced NSCLC and other solid tumors harboring ROS1 rearrangement (ARROS-1). ClinicalTrials.gov. Updated October 24, 2025. Accessed July 22, 2026. https://clinicaltrials.gov/study/NCT05118789