Clinical Summary: 

• Design/Population: The phase 1/2 ARROS-1 trial evaluated zidesamtinib in patients with locally advanced or metastatic ROS1-positive advanced non-small cell lung cancer who had not previously received a ROS1 tyrosine kinase inhibitor. Prior chemotherapy and/or immunotherapy was permitted. 
• Key Outcomes: Zidesamtinib produced a 93% objective response rate, with most responses remaining ongoing at 1 year. Among patients with measurable baseline central nervous system metastases, intracranial response was 100%, including a 70% intracranial complete response rate. 
• Clinical Relevance: The high systemic response rate, durable responses, and intracranial activity support further evaluation of zidesamtinib in earlier lines of treatment for ROS1-positive non-small cell lung cancer, including patients with central nervous system involvement. 

Results from the phase 1/2 ARROS-1 trial demonstrated that zidesamtinib shows clinically meaningful systemic and intracranial activity in tyrosine kinase inhibitor (TKI)-naïve patients with advanced or metastatic ROS1-positive advanced non-small cell lung cancer (NSCLC). 

These results were presented by Alexander Drilon, MD, Memorial Sloan Kettering Cancer Center, New York, New York, in a plenary session at the World Conference on Lung Cancer. 

In the phase 2 cohort of this single-arm, first-in-human trial, researchers enrolled patients who had not previously received a ROS1 TKI to receive 100 mg of once daily zidesamtinib. Patients who received up to 1 prior line of chemotherapy and/or immunotherapy were included in trial enrollment. 

A key end point was objective response rate (ORR), as assessed via blinded independent central review. Other key end points included duration of response, progression-free survival (PFS), intracranial ORR, and safety.

Overall, 532 patients with ROS1-positive NSCLC received zidesamtinib across lines of therapy, including 183 who were TKI-naïve. The efficacy analysis included 94 TKI-naïve patients with measurable disease.

At analysis, zidesamtinib produced an ORR of 93%, with responses observed in 87 of 94 evaluable patients. Nine-month duration of response was 94% and 12-month duration of response was 86%. 

Zidesamtinib also demonstrated intracranial activity among patients with measurable central nervous system disease. Intracranial ORR was 100% among 10 evaluable patients, including a 70% intracranial complete response rate. Intracranial duration of response was 100% at 9 months and 78% at 12 months. 

Safety was evaluated across 532 patients who received 100 mg of once daily zidesamtinib across lines of therapy. The most common treatment-related adverse events occurring in at least 15% of patients included peripheral edema (34%), increased weight (18%), increased blood creatine phosphokinase (18%), dysgeusia (17%), and increased aspartate aminotransferase (15%). Events of grade ≥3 included peripheral edema (0.6%), increased weight (4%), increased blood creatine phosphokinase (3%), and increased aspartate aminotransferase (1%). 

The findings demonstrate high systemic response rates with zidesamtinib in TKI-naïve ROS1-positive NSCLC, together with notable activity in patients with measurable central nervous system metastases. The reported durability of systemic and intracranial responses provides additional support for evaluating zidesamtinib earlier in the treatment course.

Source: 

Drilon A, De Langen AJ, Besse B, et al. Zidesamtinib in TKI-naive patients with advanced/metastatic ROS1+ NSCLC: ARROS-1 efficacy and safety data. Presented at the World Conference on Lung Cancer; September 12-15, 2026; Seoul, South Korea. Abstract PL03.06.