Frontline Activity Seen With Zidesamtinib in ROS1+ NSCLC

Zidesamtinib (Jideytro) demonstrated a high objective response rate (ORR) in patients with previously untreated ROS1-positive non–small cell lung cancer (NSCLC), according to registrational data from the phase 1/2 ARROS-1 trial (NCT05118789).¹

Zidesamtinib recently received FDA approval in July 2026 for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC who have received a prior ROS1 tyrosine kinase inhibitor (TKI), also supported by ARROS-1.² The new findings, presented at the 2026 World Conference on Lung Cancer (WCLC), will support a planned supplemental new drug application (sNDA) to the FDA seeking to expand the agent into the first-line setting.

At a median follow-up of 15.2 months, among the 94 TKI-naive patients included in the analysis, the ORR was 94% (95% CI, 87%-98%), with a complete response rate of 15%. The progression-free survival at 12 months was 90%, while median PFS remained unreached.

“Patients with ROS1-positive NSCLC may receive treatment for many years while continuing to work, care for their families and live their daily lives. They need treatments that provide lasting control of their disease, including in the brain, while limiting [adverse] effects and treatment disruption,” Alexander Drilon, MD, chief of the early drug development service at Memorial Sloan Kettering Cancer Center and ARROS-1 primary investigator, stated in a news release.¹ “The durable responses and low rates of treatment discontinuation observed in ARROS-1 represent encouraging progress toward addressing these long-term treatment needs.”

ARROS-1: Background and Design

The ARROS-1 study is a global, single-arm, first-in-human phase 1/2 trial evaluating zidesamtinib across lines of therapy in patients with ROS1-positive NSCLC.³ The phase 2 cohort included patients with locally advanced or metastatic disease who had not previously received a ROS1 TKI. Patients could have received up to 1 prior line of chemotherapy and/or immunotherapy.

Across the study, 532 patients with ROS1-positive NSCLC received zidesamtinib at a dose of 100 mg once daily, including 183 patients receiving their first TKI-targeted treatment. For the efficacy analysis presented at WCLC, patients had measurable disease by blinded independent central review and had initiated treatment by June 15, 2025, allowing for at least 9 months of follow-up for duration of response.

Additional Findings: Intracranial Activity and Safety Profile

The study also showed activity against disease involving the brain. Among the 10 patients with measurable brain metastases at baseline, all 10 responded to zidesamtinib (100%; 95% CI, 69%-100%). Seven patients (70%) achieved complete clearance of detectable brain tumors. At 12 months, 78% of these patients maintained an intracranial response.

No central nervous system (CNS) progression events were observed among patients who did not have brain metastases at baseline. The intracranial findings are particularly relevant to the potential use of zidesamtinib earlier in the treatment course, given that CNS disease was present in a subset of patients enrolled in the trial.

The efficacy findings were accompanied by low rates of treatment discontinuation, consistent with prior reports. Most treatment-related adverse events (TRAEs) were low grade, with the most common including peripheral edema, weight increase, increased blood creatine phosphokinase, dysgeusia, and increased aspartate aminotransferase levels.

REFERENCES

1. GSK presents positive registrational data to potentially expand Jideytro (zidesamtinib) to first-line ROS1-positive non-small cell lung cancer. News release. GSK. September 13, 2026. Accessed September 14, 2026. https://tinyurl.com/2m8wktmm

2. FDA approves zidesamtinib for ROS1-positive non-small cell lung cancer. News release. United States Food and Drug Administration. July 22, 2026. Accessed September 14, 2026. https://tinyurl.com/4hvxnrb6

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 September 14, 2026. https://clinicaltrials.gov/study/NCT05118789