On June 13, the U.S. Food and Drug Administration (FDA) granted accelerated approval to repotrectinib (Augtyro) for adult and pediatric patients aged 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.
TRIDENT-1
Efficacy was evaluated in TRIDENT-1 (ClinicalTrials.gov identifier NCT03093116), a multicenter, single-arm, open-label, multicohort trial in 88 adult patients with locally advanced or metastatic NTRK gene fusion–positive solid tumors who had either received a prior TRK tyrosine kinase inhibitor (TKI, n = 48) or were TKI-naive (n = 40). 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 were overall response rate and duration of response according to Response Evaluation Criteria in Solid Tumors version 1.1 as assessed by blinded independent central review. Confirmed overall response rate in the TKI-naive group was 58% (95% confidence internal [CI] = 41%–73%) and 50% (95% CI = 35%–65%) in the TKI-pretreated group. Median duration of response was not estimable (95% CI = not evaluable to not evaluable) in the TKI-naïve group and 9.9 months (95% CI = 7.4–13.0 months) in the TKI-pretreated group.
The most common adverse reactions (occurring in > 20% of patients receiving repotrectinib) were dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia, cognitive impairment, muscular weakness, and nausea.
The recommended repotrectinib dose is 160 mg orally once daily for 14 days, then increased to 160 mg twice daily with or without food, until disease progression or unacceptable toxicity.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Priority Review, Fast Track designation, Breakthrough Therapy designation, and Orphan Drug designation.
