FDA Approves Taletrectinib for Locally Advanced or Metastatic ROS1+ NSCLC

The FDA has approved taletrectinib (Ibtrozi) for the treatment of 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 is supported by findings from the phase 2 TRUST-I (NCT04395677) and TRUST-II (NCT04919811) studies, with a median follow-up of 51 months in TRUST-I and an additional 14 months of data from the collective studies.^2,3

The median duration of response (DOR) was 49.7 months (95% CI, 41.3-not reached [NR]) in TRUST-I TKI-naive patients (n = 103).² The DOR rates at 24, 36, and 48 months were 76.0%, 65.1%, and 55.4%, respectively. For TKI-naive patients enrolled in TRUST-II (n = 54), the median DOR was NR (95% CI, 20.6-NR).³

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%).

"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."

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.

Among those enrolled in TRUST-II who were naive to ROS1 TKIs (n = 54), the median patient age was 57 years (range, 27-82). In this group, 65% were Asian, 56% were female, and 50% were never smokers. More than half of patients had an ECOG performance status of 1 (61%), and most had baseline metastatic disease (91%); 98% had adenocarcinoma. A little more than one-third had CNS metastases by BICR (35%), and 19% previously received platinum-based chemotherapy.

References

1. Nuvation Bio announces FDA approval of supplemental new drug application for IBTROZI® (taletrectinib) with updated duration of response in TKI-Naïve advanced ROS1-positive non-small cell lung cancer. News release. Nuvation Bio. September 17, 2026. Accessed September 17, 2026. https://investors.nuvationbio.com/news/news-details/2026/Nuvation-Bio-Announces-FDA-Approval-of-Supplemental-New-Drug-Application-for-IBTROZI-taletrectinib-with-Updated-Duration-of-Response-in-TKI-Nave-Advanced-ROS1-Positive-Non-Small-Cell-Lung-Cancer/default.aspx
2. Li W, Zhang Y, Fan H, et al. Long-term efficacy and safety of taletrectinib in patients with ROS1+ non–small cell lung cancer: Results from the phase II TRUST-I study. J Clin Oncol. 2026;44(18):1670-1675. doi:10.1200/JCO-26-00434
3. Ibtrovi. Prescribing information. Nuvation Bio, Inc.; 2026. Accessed September 17, 2026. https://ibtrozi-pi.com/IBTROZI_taletrectinib-prescribing-information.pdf
4. FDA approves taletrectinib for ROS1-positive non-small cell lung cancer. FDA. June 11, 2025. Accessed September 17, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-taletrectinib-ros1-positive-non-small-cell-lung-cancer
5. U.S. Food and Drug Administration approves Nuvation Bio’s Ibtrozi (taletrectinib), a next-generation oral treatment for advanced ROS1-positive non-small cell lung cancer. News release. Nuvation Bio. June 11, 2025. Accessed September 17, 2026. https://investors.nuvationbio.com/news/news-details/2025/U-S--Food-and-Drug-Administration-Approves-Nuvation-Bios-IBTROZI-taletrectinib-a-Next-Generation-Oral-Treatment-for-Advanced-ROS1-Positive-Non-Small-Cell-Lung-Cancer/default.aspx