FDA Approves Repotrectinib for NTRK Gene Fusion-Positive Solid Tumors

FDA Approves Repotrectinib for NTRK Gene Fusion-Positive Solid Tumors

The FDA has granted accelerated approval to repotrectinib (Augtyro) for the treatment of adult and pediatric patients aged 12 years and older with NTRK gene fusion-positive solid tumors, either locally advanced or metastatic, or tumors for which surgical resection may result in severe morbidity, and whose disease progressed after treatment with no satisfactory alternative therapy.

This approval was based on findings from the TRIDENT-1 trial (NCT03093116). In this multicenter, single-arm, open-label, multi-cohort trial, the efficacy of repotrectinib was assessed in 88 adult patients with locally advanced or metastatic NTRK gene fusion-positive solid tumors who were either previously treated with TRK tyrosine kinase inhibitor (n = 48) or naïve to the therapy (n = 40). All patients in this trial were assessed for central nervous lesions at baseline, and those with symptomatic brain metastases were excluded. Researchers performed tumor assessments every 8 weeks.

The major efficacy outcome measures for the TRIDENT-1 trial were overall response rate (ORR) and duration of response (DOR), which was assessed by blinded independent central review using RECIST v1.1.

The tyrosine kinase inhibitor-naïve group had a confirmed ORR of 58% (95% CI, 41%-73%) and 50% (95% CI, 35%-65%) in the pretreated group. The median DOR was not estimable (NE; 95% CI, NE-NE) in patients naïve to tyrosine kinase inhibitors compared with 9.9 months (95% CI, 7.4-13.0) in those pretreated with the therapy.

The most common adverse reactions, occurring in at least 20% of patients, included dysgeusia, dizziness, constipation, peripheral neuropathy, fatigue, dyspnea, cognitive impairment, ataxia, nausea, and muscular weakness.

According to the notice from the FDA, the recommended dose for repotrectinib is 160 mg orally once per day for 14 days, with an increase to 160 mg twice per day with or without food, until unacceptable toxicity or disease progression.

Reference

FDA grants accelerated approval to repotrectinib for adult and pediatric patients with NTRK gene fusion-positive solid tumors. News release. FDA. June 13, 2024. Accessed 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