FDA Approves Repotrectinib for Patients With Advanced or Metastatic ROS1-Positive Non-Small Cell Lung Cancer

On November 15, 2023, the US Food and Drug Administration (FDA) approved repotrectinib for patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).

This approval was based on results from the global, multicenter, single-arm, open-label, multi-cohort, phase 1/2, TRIDENT-1 study. In this study, investigators enrolled 71 patients who were ROS1 tyrosine kinase inhibitor (TKI)-naïve who had previously received ≤1 lines of platinum-based chemotherapy and/or immunotherapy; and 56 patients who underwent 1 prior line of ROS1 TKI therapy who did not undergo any prior lines of platinum-based chemotherapy or immunotherapy. Repotrectinib was administered once daily at a dose of 160 mg for 14 days, with or without food followed by 160 mg repotrectinib twice daily until disease progression or unacceptable toxicity. The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR), according to RECIST v1.1 assessed by blinded independent central review. 

At the time of analysis, confirmed ORR was 78% in TKI-naïve arm and 38% in the ROS1 TKI-treated arm. Median DOR was 34.1 months and 14.8 months, respectively. Following TKI therapy, responses were observed in intracranial lesions among patients with measurable central nervous system metastases and resistance mutations. The most common adverse reactions, occurring in >20% of patients, included dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, ataxia, fatigue, cognitive disorders, and muscular weakness. 

The recommended dose is 160 mg of oral repotrectinib once daily with or without food for 14 days followed by 160 mg of repotrectinib twice daily until disease progression or unacceptable toxicity. 

This is the first FDA approval for patients with ROS1-positive NSCLC previously treated with a TKI inhibitor in addition to patients who are TKI-naïve.

Source:

FDA approves repotrectinib for ROS1-positive non-small cell lung cancer. Published November 16, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-repotrectinib-ros1-positive-non-small-cell-lung-cancer