The FDA has cleared a supplemental new drug application (sNDA) for taletrectinib (Ibtrozi), updating the label with new duration of response (DOR) data in TKI-naive patients with locally advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC); the decision comes 4 months ahead of the Prescription Drug User Fee Act date.1
The decision incorporates an additional 14 months of follow-up from the phase 2 TRUST-I (NCT04395677) and TRUST-II (NCT04919811) studies.2,3 The updated label denotes that at a median follow-up of 51 months, the median DOR was 49.7 months (95% CI, 41.3-not reached [NR]) in TRUST-I TKI-naive patients (n = 103).2
FDA Clears sNDA for Taletrectinib With Updated DOR in TKI-Naive ROS1+ NSCLC: Top Takeaways
- The FDA cleared a sNDA for taletrectinib (Ibtrozi), updating the label with longer-term duration of response (DOR) data in TKI-naive patients with advanced ROS1-positive non–small cell lung cancer.
- The decision comes 4 months ahead of the Prescription Drug User Fee Act date.
- FDA labeling now reports a 49.7-month median DOR in TKI-naive patients with advanced ROS1+ NSCLC enrolled in TRUST-I, with a 51-month median follow-up.
"This approval is a significant milestone for Ibtrozi because this data is now part of the FDA-approved label, something physicians and patients can turn to directly," David Hung, MD, founder, president, and chief executive officer of Nuvation Bio, stated in a news release.1 "A median [DOR] of more than 4 years—the longest median DOR reported for an FDA-approved ROS1 TKI—is a remarkable outcome for people living with ROS1+ NSCLC, and having it in the label means something real for patients: a clearer sense of how long they might expect to stay on treatment, and more confidence in what that path could look like at a moment when a new diagnosis can feel overwhelming. It also gives physicians additional evidence to support using Ibtrozi early in a patient's care, when that choice matters most."
The regulatory agency previously approved taletrectinib for use in patients with locally advanced or metastatic ROS1-positive NSCLC in June 2025, based on earlier data from the trials.4,5 In treatment-naive patients enrolled in TRUST-I (n = 103) and TRUST-II (n = 54), the objective response rates (ORRs) were 90% (95% CI, 83%-95%) and 85% (95% CI, 73%-93%), respectively. In ROS1 TKI–pretreated patients enrolled in TRUST-I (n = 66) and TRUST-II (n = 47), the respective ORRs were 52% (95% CI, 39%-64%) and 62% (95% CI, 46%-75%). At the time of the decision, Joel Neal, MD, PhD, and Christian Rolfo, MD, PhD, spoke to the significance of the taletrectinib approval for OncLive On Air.6
How were TRUST-I and TRUST-II designed?
The single-arm, multicenter, open-label, trials included patients with histologically confirmed, locally advanced or metastatic, ROS1-positive NSCLC who had an ECOG performance status no higher than 1 and measurable disease by RECIST 1.1 criteria.3 Patients with locally advanced disease could enroll irrespective of prior exposure to chemotherapy. Participants were given oral taletrectinib at a once daily dose of 600 mg. The key efficacy objectives were ORR and DOR by RECIST criteria and blinded independent central review (BICR) assessment.
What were the patient and disease characteristics of those enrolled in TRUST-I and TRUST-II?
The median patient age of those enrolled in TRUST-I who had no prior exposure to ROS1 TKIs (n = 103) was 56 years (range, 26-78). All of these patients were Asian, and 55% were female. Most of these patients were never smokers (73%), had an ECOG performance status of 1 (81%), and had metastatic disease at baseline (91%). The majority of patients had adenocarcinoma (95%). Seventeen percent of patients had central nervous system (CNS) metastases by BICR. Lastly, 19% of patients previously received platinum-based chemotherapy for advanced disease.
