On June 13, 2024, the U.S. Food and Drug Administration granted accelerated approval to repotrectinib (Augtyro) for adult and pediatric patients aged 12 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.

FDA update

Efficacy was evaluated in TRIDENT-1 (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 either received a prior TRK tyrosine kinase inhibitor (TKI) (n = 48) or were TKI-naïve (n = 40). All patients were assessed for central nervous lesions at baseline, and patients with symptomatic brain metastases were excluded. Researchers performed tumor assessments every eight weeks throughout the study.

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 in the TKI-naïve group was 58% (95% CI = 41, 73) and 50% (95% CI = 35, 65) in the TKI-pretreated group. Median DOR was not estimable (NE) (95% CI = NE, NE) in the TKI-naïve group and 9.9 months (95% CI = 7.4, 13.0) in the TKI-pretreated group.

The most common adverse reactions reported in more than 20% of patients are 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 patients experience disease progression or unacceptable toxicity. View the full prescribing information for repotrectinib.

The applicant used the Assessment Aid to facilitate FDA’s review. FDA granted the granted priority review, fast track designation, breakthrough therapy designation, and orphan drug designation. FDA’s 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 applications for investigational oncology products, healthcare professionals may contact the Oncology Center of Excellence’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.