Taletrectinib Approved for ROS1-Positive Non–Small Cell Lung Cancer
Expert Perspectives · Lyn Brook · 2025-06-13
The FDA has granted approval to the kinase inhibitor taletrectinib (Ibtrozi™, Nuvation Bio Inc.) for the treatment of adults with locally advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC).
Why This Approval Matters
The approval of taletrectinib provides a new targeted treatment option for patients with ROS1-positive NSCLC, a subset of lung cancer with limited therapeutic choices. This decision expands the arsenal of kinase inhibitors available to clinicians, offering hope for improved outcomes in both treatment-naive and previously treated patients.
Breaking Down the TRUST-I and TRUST-II Trials
Efficacy was evaluated in two multicenter, single-arm, open-label clinical trials: TRUST-I (NCT04395677) and TRUST-II (NCT04919811). The studies enrolled 157 adults—103 in TRUST-I and 54 in TRUST-II—with locally advanced or metastatic, ROS1-positive NSCLC, who were naive to ROS1 tyrosine kinase inhibitor (TKI) therapy; and 113 patients—66 in TRUST-I and 47 in TRUST-II—who had received one prior ROS1 TKI. Some patients had also received prior chemotherapy for advanced disease.
The major efficacy outcome measures were confirmed overall response rate (ORR) and duration of response (DOR), as determined by blinded independent central review according to RECIST v1.1.
Key Efficacy Results:
- Treatment-naive patients:
- The ORR was 90% in TRUST-I and 85% in TRUST-II.
- 72% of responders in TRUST-I and 63% in TRUST-II had a DOR ≥12 months.
- TKI-pretreated patients:
- The ORR was 52% in TRUST-I and 62% in TRUST-II.
- 74% of responders in TRUST-I and 83% in TRUST-II had a DOR ≥6 months.
Managing Adverse Events
The prescribing information for taletrectinib includes warnings and precautions for hepatotoxicity, interstitial lung disease/pneumonitis, QTc interval prolongation, hyperuricemia, myalgia with creatine phosphokinase elevation, skeletal fractures, and embryo-fetal toxicity.
Clinical Implications and Future Outlook
“Taletrectinib continues to show high and durable overall responses, prolonged progression-free survival, robust activity against intracranial lesions and acquired resistance mutations including G2032R, and a favorable safety profile with a low incidence of neurologic treatment-emergent adverse events,” wrote Wei Li, MD, of the Department of Medical Oncology at Shanghai Pulmonary Hospital of Tongji University School of Medicine, and colleagues, in their published results of the TRUST-I trial.
Dosing and Administration
The recommended dose of taletrectinib is 600 mg orally once daily, administered on an empty stomach, defined as no food intake at least two hours before and two hours after dosing. Treatment should continue until disease progression or unacceptable toxicity.