On November 15, 2023, the U.S. Food and Drug Administration (FDA) approved repotrectinib (Augtyro™) for locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC). This is the first FDA approval for treatment of patients with ROS1-positive NSCLC who have previously received a ROS1 tyrosine kinase inhibitor (TKI), in addition to patients who are TKI naïve.

FDA update

Approval was based on TRIDENT-1, a global, multicenter, single-arm, open-label, multicohort clinical trial (NCT03093116) that included patients with ROS1-positive locally advanced or metastatic NSCLC. Efficacy was evaluated in 71 ROS1 TKI-naïve patients who received up to one prior line of platinum-based chemotherapy or immunotherapy and 56 patients who received one prior ROS1 TKI with no prior platinum-based chemotherapy or immunotherapy.

The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR), according to RECIST v1.1 as assessed by blinded independent central review. Confirmed ORR was 79% (95% CI = 68, 88) in the ROS1 TKI naïve group and 38% (95% CI = 25, 52) in patients who had prior treatment with a ROS1 inhibitor, and median DOR was 34.1 months (95% CI = 25.6, not evaluable) and 14.8 months (95% CI = 7.6, not evaluable), respectively. The researchers observed responses in intracranial lesions in patients with measurable central nervous system metastases and in patients with resistance variants following TKI therapy.

The most common adverse reactions reported in more than 20% of patients were dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, ataxia, fatigue, cognitive disorders, and muscular weakness.

The recommended repotrectinib dose is 160 mg orally once daily with or without food for 14 days, then increased to 160 mg twice daily, until patients experience disease progression or unacceptable toxicity.

View the full prescribing information for repotrectinib.

FDA’s review used the Assessment Aid, a voluntary submission from the applicant to facilitate the assessment. The application was granted priority review, breakthrough designation, and fast-track designation. FDA-expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient investigational new drug applications for oncology products, healthcare professionals may contact the Oncology Center of Excellence’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.