FDA approves taletrectinib for ROS1-positive non-small cell lung cancer

Regulatory approval: On June 11, 2025, the FDA approved taletrectinib (Ibtrozi; Nuvation Bio) for adults with locally advanced or metastatic ROS1-positive non-small cell lung cancer. Approval was based on two multicenter, single-arm, open-label trials (TRUST-I and TRUST-II) assessing confirmed ORR and DOR by blinded independent central review (RECIST v1.1) in ROS1 TKI–naïve and ROS1 TKI–pretreated patients. Labeling includes multiple warnings, and the recommended dose is 600 mg orally once daily on an empty stomach.

FDA approval (June 11, 2025)

The FDA approved taletrectinib (Ibtrozi; Nuvation Bio Inc.), a kinase inhibitor, for adults with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).

Evidence base

Efficacy was evaluated in two multicenter, single-arm, open-label trials: TRUST-I (NCT04395677) and TRUST-II (NCT04919811). Patients had locally advanced or metastatic ROS1-positive NSCLC and were either ROS1 TKI–naïve (n=157 total: 103 TRUST-I; 54 TRUST-II) or previously treated with one prior ROS1 TKI (n=113 total: 66 TRUST-I; 47 TRUST-II). Patients may have received prior chemotherapy for advanced disease.

Primary outcomes were confirmed overall response rate (ORR) and duration of response (DOR) by blinded independent central review per RECIST v1.1:

  • TKI–naïve: ORR 90% (95% CI 83–95) in TRUST-I; 85% (95% CI 73–93) in TRUST-II; DOR ≥12 months in 72% and 63% of responders, respectively.
  • TKI-pretreated: ORR 52% (95% CI 39–64) in TRUST-I; 62% (95% CI 46–75) in TRUST-II; DOR ≥6 months in 74% and 83% of responders, respectively.

Safety and dosing

Label warnings/precautions include hepatotoxicity, ILD/pneumonitis, QTc prolongation, hyperuricemia, myalgia with CPK elevation, skeletal fractures, and embryo-fetal toxicity. Recommended dose: 600 mg orally once daily on an empty stomach until progression or unacceptable toxicity.

The application received priority review, breakthrough designation, and orphan drug designation. Full prescribing information is expected on Drugs@FDA.

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