FDA Approves sNDA for Taletrectinib With Updated DOR Data in ROS1+ NSCLC

The FDA has approved a supplemental new drug application (sNDA) for taletrectinib (Ibtrozi), updating the drug's label with longer-term duration of response (DOR) data in tyrosine kinase inhibitor (TKI)-naive patients with advanced ROS1-positive (ROS1+) non–small cell lung cancer (NSCLC).¹ The updated label reflects a median DOR of 49.7 months among TKI-naive patients enrolled in the phase 2 TRUST-I study (NCT04395677), based on a median follow-up of 51 months—more than 4 years of sustained clinical benefit.

The approval, which arrived 4 months ahead of the drug's target action date, incorporates an additional 14 months of follow-up from the pivotal TRUST-I and TRUST-II (NCT04919811) studies as of an August 2025 data cutoff. Many patients remained on treatment for extended periods with a continued response, some for multiple years, the company reported. The data were also presented at the American Association for Cancer Research (AACR) Annual Meeting 2026 and published simultaneously in the Journal of Clinical Oncology.²

Safety Profile Unaffected

The label update did not change the safety sections of the prescribing information, and no new safety signals emerged with the additional follow-up.¹ Taletrectinib's label continues to carry warnings for hepatotoxicity, interstitial lung disease/pneumonitis, QTc interval prolongation, hyperuricemia, myalgia with creatine phosphokinase elevation, skeletal fractures, and embryo-fetal toxicity. The most frequently reported adverse reactions (≥20%) remain diarrhea, nausea, vomiting, dizziness, rash, constipation, and fatigue.

"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," said David Hung, M.D., Founder, President, and Chief Executive Officer of Nuvation Bio. "A median duration of response of more than four 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."

Prior Regulatory History

Taletrectinib, an oral, CNS-active, selective ROS1 inhibitor, first received full FDA approval in June 2025 for adult patients with locally advanced or metastatic ROS1+ NSCLC across lines of therapy, following priority review and breakthrough therapy designations for both TKI-naive and TKI-pretreated disease.¹ Nuvation Bio and its partner, Eisai, are separately pursuing approval in Europe and the United Kingdom: the European Medicines Agency validated a marketing authorization application for full approval consideration in March 2026, and the UK Medicines and Healthcare products Regulatory Agency validated an application in June 2026.

Ongoing Clinical Development

Beyond TRUST-I and TRUST-II, Nuvation Bio is conducting 2 additional registrational studies of taletrectinib. TRUST-III (NCT06564324) is a confirmatory, randomized phase 3 study comparing taletrectinib vs crizotinib in 194 patients with advanced ROS1+ NSCLC in China who have not previously received a ROS1 TKI. TRUST-IV (NCT07154706) is a placebo-controlled phase 3 study of taletrectinib as adjuvant treatment in approximately 180 patients with resected early-stage ROS1+ NSCLC across the US, Canada, Europe, Japan, and China; its primary end point is investigator-assessed disease-free survival, with a primary completion date estimated for 2030.

REFERENCES

1. Nuvation Bio announces FDA approval of supplemental New Drug Application for IBTROZI (taletrectinib) with updated duration of response in TKI-naive advanced ROS1-positive non-small cell lung cancer. News release. Nuvation Bio. September 16, 2026. Accessed September 17, 2026. https://tinyurl.com/2jjz25s4

2. Bazhenova L, et al. TRUST I/II: updated pooled efficacy outcomes of taletrectinib in TKI-naive ROS1+ non-small cell lung cancer. Presented at: American Association for Cancer Research (AACR) Annual Meeting; 2026. Abstract CT300.