Dr Pennell on the Significance of the FDA Approval of Taletrectinib for ROS1+ NSCLC

"This is an exciting advance. Although it represents a pretty rare subgroup of people with non–small cell lung cancer, [ROS1-positive disease is] still one of the major subgroups of oncogene-driven subtypes of lung cancer."

Nathan A. Pennell, MD, PhD, an associate professor in the Department of Medicine and director of the Lung Cancer Medical Oncology Program at the Taussig Cancer Institute of Cleveland Clinic, discussed the significance of the FDA approval of taletrectinib (Ibtrozi) for ROS1-positive non–small cell lung cancer (NSCLC).

On June 11, 2025, the FDA approved taletractinib for the treatment of patients with locally advanced or metastatic, ROS1-positive NSCLC, based on findings from the phase 2 TRUST-I (NCT04395677) and TRUST-II (NCT04919811) trials. Findings supporting the approval showed that treatment-naive patients treated with taletrectinib achieved an overall response rate (ORR) of 90% (95% CI, 83%-95%) in TRUST-I (n = 103) and 85% (95% CI, 73%-93%) in TRUST-II (n = 54). In these respective patient populations, the 12-month duration of response (DOR) rates were 72% and 63%.

In patients previously treated with a ROS1 TKI, the ORRs were 52% (95% CI, 39%-64%) in TRUST-I (n = 66) and 62% (95% CI, 46%-75%) in TRUST-II (n = 47). The 6-month DOR rates were 74% and 83%, respectively.

According to Pennell, ROS1-positive NSCLC represents a distinct molecular subtype for which treatment advancements have been limited by resistance mechanisms and adverse effect profiles of earlier TKIs. He noted that although ROS1-targeted therapies have existed for over a decade, each has faced trade-offs in safety or durability. In contrast, taletrectinib demonstrated durability and safety across both treatment-naive and pretreated populations, he said.

Ultimately, Pennell explained that the FDA approval of taletrectinib could position this agent as a best-in-class ROS1 inhibitor with the potential to improve long-term disease control and minimize toxicity in this molecularly defined NSCLC population.