Dr Nagasaka on the Importance of Taletrectinib for the ROS1+ NSCLC Treatment Paradigm

"[The FDA approval of taletrectinib] gives patients another option for treatment, which is really important. The drug has good coverage against a broad spectrum of ROS1 [mutations], excellent brain penetration, and a reasonable toxicity profile."

Misako Nagasaka, MD, PhD, an oncologist and associate professor in the Division of Hematology and Oncology, Medicine at University of California Irvine School of Medicine, discussed the importance of the FDA approval of taletrectinib (Ibtrozi) for the treatment of patients with locally advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC), as well as the efficacy data that supported this decision.

The FDA approval, granted on June 11, 2025, was based on findings from the phase 2 TRUST-I (NCT04395677) and TRUST-II (NCT04919811) trials. Both trials evaluated taletrectinib in patients with ROS1-positive NSCLC and used similar eligibility criteria, though they differed in geographic scope, Nagasaka noted. TRUST-I enrolled patients exclusively in China, while TRUST-II was a global study. In both studies, patients had to have locally advanced or metastatic ROS1-positive NSCLC and were stratified based on prior treatment status—either TKI-naive or previously treated with a ROS1 TKI.

In treatment-naive patients, the confirmed overall response rate (ORR) was 90% (95% CI, 83%-95%) in TRUST-I and 85% (95% CI, 73%-93%) in TRUST-II. Among patients who had received prior ROS1-targeted therapy, the ORR was 52% (95% CI, 39%-64%) in TRUST-I and 62% (95% CI, 46%-75%) in TRUST-II. These findings highlight the drug’s robust antitumor activity in both treatment-naive and previously treated settings, Nagasaka said.

Nagasaka noted that the approval of taletrectinib provides a meaningful new option for patients, particularly those who have progressed on prior TKIs. Taletrectinib demonstrated activity against a broad range of ROS1 mutations, including the treatment-resistant ROS1 G2032R mutation, and showed excellent central nervous system (CNS) penetration—an important consideration given the risk of brain metastases in this patient population. In terms of safety, the drug exhibited a favorable toxicity profile, with gastrointestinal adverse effects such as nausea being the most commonly reported but generally resolving within the first few months of therapy, she detailed.

Overall, the availability of taletrectinib expands the treatment landscape for patients with ROS1-positive NSCLC and addresses a clear unmet need, especially in the setting of resistance to prior ROS1-targeted agents, Nagasaka concluded.