FDA Grants Accelerated Approval to Repotrectinib for Adult and Pediatric Patients With NRTK Gene Fusion-Positive Solid Tumors

On June 13, 2024, the US Food and Drug Administration (FDA) granted accelerated approval to repotrectinib for adult and pediatric patients 12 years and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, are locally advanced or metastatic, or where surgical resection is likely to result in severe morbidity, and that have progressed following treatment or have no satisfactory alternative therapy. This approval was based on results from the phase 1/2 TRIDENT-1 study. 

In this single-arm, open-label, multi-cohort study, 88 adult patients with locally advanced or metastatic NTRK gene fusion-positive solid tumors who either received a prior TRK tyrosine-kinase inhibitor (TKI; n = 48) or were TKI-naive (n = 40) received 160 mg of repotrectinib once daily for 14 days followed by 160 mg twice daily until disease progression or unacceptable toxicity. All patients were assessed for central nervous lesions at baseline and patients with symptomatic brain metastases were excluded. Tumor assessments were performed every 8 weeks. The major efficacy outcome measures included overall response rate (ORR) and duration of response (DOR) as assessed by blinded independent central review. 

At analysis, confirmed ORR was 58% in the TKI-naive arm and 50% in the TKI-pretreated arm. Median DOR was not estimable in the TKI-naive arm and 9.9 months in the TKI-pretreated arm. The most common adverse reactions occurring in >20% of patients included dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia, cognitive impairment, muscular weakness, and nausea. 

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

Source: 

FDA grants accelerated approval to repotrectinib for adult and pediatric patients with NTRK gene fusion-positive solid tumors. Published online: June 13, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-repotrectinib-adult-and-pediatric-patients-ntrk-gene-fusion-positive