Taletrectinib is Suitable for First- and Second-Line ROS1+ NSCLC

In the wake of taletrectinib’s (Ibtrozi) approval in ROS1-positive non–small cell lung cancer (NSCLC), CancerNetwork® spoke with Jorge Nieva, MD, about how this change in the landscape might affect his practice.1

The FDA’s approval of taletrectinib was supported by results from the phase 2 TRUST-I (NCT04395677) and TRUST-II (NCT04919811) trials. As one of the investigators on the TRUST-II trial, Nieva, an associate professor of clinical medicine at the Keck School of Medicine of the University of Southern California, already had experience utilizing the agent.2

He stated that this was going to become his go-to first-line drug in this indication, not just because he’s comfortable with it, but because it can also be used in the second-line setting following treatment with entrectinib (Rozlytek), repotrectinib (Augtyro), and crizotinib (Xalkori).

Now with 4 approved agents in ROS1-positive NSCLC, Nieva expressed that he is glad for all the advancements that have been made, though there is still more work to be done, particularly in the aim for a cure.

Transcript:

This is going to be the go-to first-line drug in my practice. I had the opportunity to participate in the clinical trials with this agent. For all oncologists, the more you use a drug, the more you’re comfortable with managing its toxicity and the more comfortable you are with understanding what’s to come for our patient population and counseling them on what they can expect. It’s a drug that I’m very comfortable with, and it is a drug I’ll likely use primarily in the first-line setting.

For patients who were treated with other agents, if they had received entrectinib or some other agent in the past, then they certainly can use this drug in the second line. The good news for patients is that we now have choices, and we have very good drugs for ROS1 disease, including taletrectinib, repotrectinib, and entrectinib, and even crizotinib is a good drug in many parts of the world where they may not have access to some of the newer agents. 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 most patients. While these drugs can be helpful at debulking tumors, we still need to do a lot more work on making this a disease of the past for those patients who have it.

Reference

1. FDA approves taletrectinib for ROS1-positive non-small cell lung cancer. News release. FDA. June 11, 2025. Accessed June 23, 2025. https://tinyurl.com/yc4f379m
2. Nagasaka M, Ohe Y, Zhou C, et al. TRUST-II: a global phase II study of taletrectinib in ROS1-positive non-small-cell lung cancer and other solid tumors. Future Oncology, 19(2), 123–135. doi:10.2217/fon-2022-1059