2 Clarke Drive
Suite 100
Cranbury, NJ 08512
© 2025 MJH Life Sciences™ and OncLive - Clinical Oncology News, Cancer Expert Insights. All rights reserved.
Will the FDA approve zidesamtinib for ROS1-positive advanced non–small cell lung cancer after a prior TKI?
The FDA has accepted a new drug application (NDA) seeking the approval of zidesamtinib, for the treatment of adult patients with locally advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC) who received at least 1 prior ROS1 TKI.1
The regulatory agency assigned a Prescription Drug User Fee Act target action date of September 18, 2026.
The NDA is supported by data from the phase 1/2 ARROS-1 trial (NCT05118789). Findings presented at the IASLC 2025 World Conference on Lung Cancer showed that patients who received any prior treatment with a ROS1 TKI with or without chemotherapy (n = 117) achieved an overall response rate (ORR) of 44% (95% CI, 34%-53%), including a complete response (CR) rate of 1%.2 In patients who received only 1 prior ROS1 TKI in the form of crizotinib or entrectinib, with or without chemotherapy (n = 55), experienced an ORR of 51% (95% CI, 37%-65%) and a CR rate of 2%. In patients who received at least 2 prior ROS1 TKIs with or without chemotherapy (n = 58), the ORR was 38% (95% CI, 26%-52%).
ARROS-1 was a global, first-in-human trial evaluating zidesamtinib in patients with advanced ROS1-positive solid tumors (n = 514), including NSCLC. The pivotal safety population (n = 432) including patients with ROS1-positive advanced NSCLC who were treated with the agent at 100 mg once daily. The pivotal efficacy population was comprised of patients with ROS1 TKI–pretreated NSCLC who had measurable disease per blinded independent central review (BICR).
During phase 1, zidesamtinib was evaluated at daily doses ranging from 25 mg to 150 mg. After 100 mg once per day was identified as the recommended phase 2 dose, it was further examined in patients with ROS1-positive NSCLC who were naïve to a ROS1 TKI or pretreated with at least 1 ROS1 TKI, and in patients with other ROS1-positive advanced solid tumors, irrespective of prior ROS1 TKI exposure.
ORR per RECIST 1.1 criteria as assessed by BICR served as the primary end point in phase 2. Secondary end points included duration of response (DOR), time to next treatment, clinical benefit rate, progression-free survival (PFS), and overall survival.
Findings also showed that among patients with NSCLC who received at least 1 prior ROS1 TKI, the 6-, 12-, and 18-month DOR rates were 84% (95% CI, 71%-92%), 78% (95% CI, 62%-88%), and 62% (95% CI, 28%-84%), respectively. In patients who received 1 prior ROS1 TKI, these rates were all 93% (95% CI, 74%-98%).
In the group that received any prior ROS1 TKI treatment, the 6-, 12-, and 18-month PFS rates were 57% (95% CI, 47%-66%), 48% (95% CI, 38%-57%), and 40% (95% CI, 24%-55%), respectively. In the population that received 1 prior ROS1 TKI, these respective rates were 70% (95% CI, 56%-81%), 68% (95% CI, 53%-79%), and 68% (95% CI, 53%-79%).
Regarding safety, treatment-emergent adverse effects (TEAEs) led to dose reductions in 10% of patients (n = 432) and treatment discontinuation in 2% of patients. The most common TEAEs reported in at least 15% of patients included peripheral edema (any-grade, 36%; grade ≥3, 0.7%), constipation (17%; 0%), increased blood creatine phosphokinase levels (16%; 3.5%), fatigue (16%; 0.7%), and dyspnea (15%; 3.0%).
Related Content:
