FDA grants accelerated approval to repotrectinib for adult and pediatric patients with NTRK gene fusion-positive solid tumors
Regulatory approval: On June 13, 2024, the FDA granted accelerated approval to repotrectinib (AUGTYRO) for adults and pediatric patients aged ≥12 years with NTRK gene fusion–positive solid tumors that are locally advanced/metastatic or where surgery would likely cause severe morbidity, and that have progressed after treatment or have no satisfactory alternative therapy. Approval was supported by the single-arm TRIDENT-1 trial, reporting confirmed ORR of 58% in TRK TKI–naïve and 50% in TRK TKI–pretreated patients.
FDA accelerated approval (June 13, 2024)
The US FDA granted accelerated approval to repotrectinib (AUGTYRO; Bristol-Myers Squibb) for adult and pediatric patients aged ≥12 years with NTRK gene fusion–positive solid tumors that 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.
Supporting evidence
Efficacy and safety were evaluated in TRIDENT-1 (NCT03093116), a multicenter, single-arm, open-label, multi-cohort trial including 88 adults with locally advanced or metastatic NTRK fusion–positive solid tumors: TRK TKI–pretreated (n=48) and TKI-naïve (n=40). Patients were assessed for CNS lesions at baseline; symptomatic brain metastases were excluded. Tumor assessments occurred every 8 weeks.
Primary efficacy endpoints were overall response rate (ORR) and duration of response (DOR) by RECIST v1.1 per blinded independent central review. Confirmed ORR was 58% (95% CI 41–73) in the TKI-naïve group and 50% (95% CI 35–65) in the TKI-pretreated group. Median DOR was not estimable in TKI-naïve patients and 9.9 months (95% CI 7.4–13.0) in TKI-pretreated patients.
Safety and dosing (label)
Common adverse reactions (>20%) included dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia, cognitive impairment, muscular weakness, and nausea. Recommended dosing: 160 mg orally once daily for 14 days, then 160 mg twice daily, with or without food, until progression or unacceptable toxicity.