ARROS-1 Trial Reports 94% Blinded ORR for Zidesamtinib in TKI-Naive ROS1-Positive NSCLC

The ARROS-1 study permitted up to one prior chemotherapy or immunotherapy line and enrolled a geographically balanced population across Asia-Pacific, Europe, and North America. In the TKI-naive cohort the nine-month duration-of-response rate reached 94% while the twelve-month rate was 86%. Among ten patients with measurable CNS metastases the intracranial objective response rate was 100% with a 70% complete response rate, suggesting meaningful blood-brain barrier penetration not uniformly achieved by earlier ROS1 inhibitors.

Existing first-line options such as entrectinib and repotrectinib report objective response rates of 67-79% in similar populations with shorter intracranial durability in some series. Zidesamtinib’s low rates of dose reduction (11%) and discontinuation (1%) contrast with higher toxicity-driven attrition seen in some comparator agents, yet the absence of a randomized control arm prevents direct attribution of these differences to the drug itself rather than patient selection.

The single-arm design and conference presentation without peer-reviewed publication limit causal inference and leave progression-free survival and overall survival immature. Ongoing phase 3 evaluation against current standards will be required to establish whether the observed response depth and CNS activity translate into clinically meaningful survival gains or quality-of-life improvements.

Next steps include maturation of survival endpoints and initiation of randomized trials in both TKI-naive and pretreated settings to quantify comparative efficacy and long-term safety.