ARROS-1 Trial Supports Zidesamtinib in TKI-Naive Patients With Advanced ROS1-Positive NSCLC
By: Julia Cipriano, MS, CMPP
Posted: Thursday, November 5, 2026
In an analysis of the global, first-in-human phase I/II ARROS-1 trial, zidesamtinib demonstrated clinically meaningful activity in tyrosine kinase inhibitor (TKI)-naive patients with ROS1-positive non–small cell lung cancer (NSCLC) and a safety profile consistent with previous reports, according to Alexander Drilon, MD, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical Center, New York, and colleagues. The findings, presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC; Abstract PL03.06), support further investigation of this ROS1 TKI in earlier lines of therapy.
Zidesamtinib was approved by the U.S. Food and Drug Administration based on earlier ARROS-1 findings in patients with locally advanced or metastatic ROS1-positive NSCLC previously treated with at least one ROS1 TKI. Of the 532 patients who received zidesamtinib at 100 mg once daily in the single-arm trial, 183 were TKI-naive. The current efficacy analysis focused on 94 evaluable patients in the phase II TKI-naive cohort, of whom 27% had received prior chemotherapy and 17% had received prior immunotherapy, with up to one prior line permitted; baseline central nervous system metastases were present in 17%.
The objective response rate was 93%, with 94% and 86% of responses maintained at 9 and 12 months, respectively. Intracranial responses were observed in all 10 patients included in the intracranial response analysis, with a complete response rate of 70%; the intracranial duration-of-response rates were 100% at 9 months and 78% at 12 months. Median progression-free survival was not reached, with 9- and 12-month progression-free survival rates of 95% and 90%, respectively.
Across the overall study population, the most common treatment-related adverse events were peripheral edema (34%; grade ≥ 3: 0.6%), weight gain (18%; grade ≥ 3: 4%), increased blood creatine phosphokinase (18%; grade ≥ 3: 3%), dysgeusia (17%; grade ≥ 3: 0%), and increased aspartate aminotransferase (15%; grade ≥ 3: 1%). Treatment-related adverse events led to dose reductions in 11% of patients and treatment discontinuation in 1%.
Disclosure: No information regarding conflicts of interest was provided.
