Taletrectinib Approval Expands Options in Advanced/Metastatic ROS1+ NSCLC

Following the FDA approval of taletrectinib (Ibtrozi) for patients with locally advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC), CancerNetwork^® spoke with Jorge Nieva, MD, about how this regulatory decision may impact the treatment paradigm for this disease.

The approval was supported by findings from the phase 2 TRUST-I trial (NCT04395677) and the phase 2 TRUST-II trial (NCT04919811). The total efficacy population included 157 patients who had no prior treatment with a ROS1 tyrosine kinase inhibitor (TKI) and 113 who were previously treated with a ROS1 TKI.

Topline results showed an objective response rate (ORR) of 90% (95% CI, 83%-95%) in TRUST-I and 85% (95% CI, 73%-93%) in TRUST-II among patients who had no prior treatment. Of those with pretreated disease, the respective ORRs were 52% (95% CI, 39%-64%) and 62% (95% CI, 46%-75%) in each study population.

According to Nieva, an associate professor of clinical medicine at the Keck School of Medicine of the University of Southern California, taletrectinib may offer advantages over other therapies in the ROS1-positive metastatic NSCLC space based on its improved central nervous system (CNS) toxicity profile and “excellent” response and progression-free survival data. He stated that taletrectinib would become the go-to first-line agent in his practice. Additionally, he discussed strategies for mitigating toxicities related to taletrectinib such as nausea and diarrhea, and highlighted the need for additional research to improve immunotherapy options in NSCLC.

“I’m very happy that we have choices for patients, and I’m very happy that we have such a wide variety of drugs, but we still need to do better, and we need to find better ways of using these agents because they’re still not cures for the majority of patients,” Nieva stated. “While these drugs can be helpful at debulking tumors, we still need to do a lot more work [to do] on making this a disease of the past for those patients who have it.”

Reference

FDA approves taletrectinib for ROS1-positive non-small cell lung cancer. News release. FDA. June 11, 2025. Accessed July 8, 2025. https://tinyurl.com/yc4f379m