New results from the global Phase I/II ARROS-1 trial showed clinically meaningful activity with zidesamtinib in patients with advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) who had not previously received a tyrosine kinase inhibitor (TKI). The findings were presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC).
Among 94 efficacy-evaluable TKI-naive patients, the objective response rate by blinded independent central review was 94% (88 of 94 patients). The nine-month duration-of-response rate was 94%, and the 12-month duration-of-response rate was 86%.
Zidesamtinib also demonstrated substantial intracranial activity. Among 10 evaluable patients with central nervous system metastases, the intracranial objective response rate was 100%, including a 70% intracranial complete response rate. The nine-month intracranial duration-of-response rate was 100%, and the 12-month rate was 78%.
The global, single-arm, first-in-human ARROS-1 trial included a Phase II cohort of patients with locally advanced or metastatic ROS1-positive NSCLC who were naive to TKI therapy. Up to one prior line of chemotherapy and/or immunotherapy was permitted. Patients received zidesamtinib 100 mg once daily.
Across all lines of therapy, 532 patients with ROS1-positive NSCLC received zidesamtinib 100 mg once daily, including 183 who were TKI-naive. The study population was geographically diverse, with 35% of patients enrolled in the Asia-Pacific region, 33% in Europe and 32% in North America.
The most common treatment-related adverse events occurring in at least 15% of patients were peripheral edema (34%), increased weight (18%), increased blood creatine phosphokinase (18%), dysgeusia (17%) and increased aspartate aminotransferase (15%). Treatment-related adverse events led to dose reductions in 11% of patients and treatment discontinuation in 1%.
Zidesamtinib demonstrated clinically meaningful activity in TKI-naive patients with ROS1-positive NSCLC, with a safety profile consistent with previous reports and low rates of dose reduction and discontinuation. The findings support continued investigation of zidesamtinib in earlier lines of therapy."
Alexander Drilon, M.D., Memorial Sloan Kettering Cancer Center and Weill Cornell Medical Center, New York City
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