Dr Drilon on the ARROS-1 Trial Data With Zidesamtinib in ROS1+ NSCLC

"All 10 patients responded to therapy. In fact, 7 out of the 10 had a complete response to therapy. [This] really underscores that the drug works well in the CNS."

Alexander Drilon, MD, chief of the Early Drug Development Service and the Carol Bassok Lowenstein Chair at Memorial Sloan Kettering Cancer Center, discussed efficacy and safety data from the phase 1/2 ARROS-1 trial (NCT05118789) evaluating the ROS1 tyrosine kinase inhibitor (TKI) zidesamtinib (Jideytro) in patients with TKI-naive, advanced/metastatic ROS1-positive non–small cell lung cancer (NSCLC), presented at the 2026 IASLC World Conference on Lung Cancer.

Zidesamtinib, already FDA approved for TKI-pretreated ROS1-positive NSCLC, was designed to spare TRK inhibition while maximizing coverage of ROS1 fusions, ROS1 resistance mutations, and central nervous system (CNS) disease, Drilon explained. The TKI-naive efficacy population comprised 94 patients with measurable disease by blinded independent central review (BICR); the cohort skewed toward a younger median age, female sex, and never-smoking status, and 17% had baseline brain metastases, Drilon noted, adding that roughly one-quarter (27%) of patients had received prior chemotherapy with or without immunotherapy.

By BICR, the objective response rate was 94% (n = 88 of 94; 95% CI, 87%-98%), including a 15% complete response rate, according to Drilon. Median duration of response (DOR) and progression-free survival (PFS) had not been reached, but the 12-month DOR and PFS rates were 86% (95% CI, 75%-92%) and 90% (95% CI, 81%-95%), respectively, he said. Among 10 patients evaluable for intracranial response, all responded, including 7 complete responses, and no CNS progression events occurred among patients who entered the trial without baseline brain metastases, Drilon reported.

In the 532-patient safety population, the most common treatment-related adverse effects included peripheral edema (any grade, 42%; grade ≥3, 1%), increased creatine phosphokinase (any grade, 23%; grade ≥3, 5%), constipation (any grade, 23%; grade ≥3, <1%), transaminase elevations, and weight gain (any grade, 22%; grade ≥3, 7%), the majority low grade, Drilon said. Dose reductions due to treatment-emergent adverse effects occurred in 12% of patients and discontinuations in 4%, a profile he characterized as favorable.