Repotrectinib Granted Accelerated Approval for NTRK Gene Fusion–Positive Solid Tumors

Matthew Hadfield, DO

The FDA has granted accelerated approval to repotrectinib (Augtyro™, Bristol Myers Squibb) for adult and pediatric patients ≥12 years of age with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion 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.

Why it matters: “The accelerated FDA approval of the NTRK-targeted therapy repotrectinib represents another significant success story in the push to bring targeted therapeutic options to patients with cancer,” wrote Matthew Hadfield, DO, a Medical Oncology Fellow at Brown University and Fellows Forum Member at Oncology Data Advisor.

What they studied: Efficacy was assessed in the TRIDENT-1 trial (NCT03093116), a phase 1/2, single-arm, open-label, multi-cohort study of 88 patients, 48 of which had locally advanced or metastatic NTRK gene fusion–positive solid tumors who had either received a prior TRK tyrosine kinase inhibitor (TKI) and 40 of which were TKI-naive. Patients were excluded if they had symptomatic brain metastases. All patients were assessed for central nervous system (CNS) lesions at baseline and received a tumor assessment every eight weeks.

The primary efficacy outcomes measured were overall response rate and duration of response, according to RECIST v1.1 as assessed by Blinded Independent Central Review (BICR).

What they found: In the TKI-naive cohort, repotrectinib produced a confirmed overall response rate of 58%. The TKI-pretreated cohort endured a confirmed overall response rate of 50%. The median duration of response was not evaluable in the TKI-naive cohort and was 9.9 months in the TKI-pretreated cohort.

Adverse events: The most common adverse events experienced by >20% of patients receiving repotrectinib were dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia, cognitive impairment, muscular weakness, and nausea.

Conclusion: “This approval will undoubtedly bring another treatment option to the armamentarium for patients with NTRK fusions who have no other options with regards to therapy,” concluded Dr. Hadfield. “This approval is a win for patients and further evidence of the paradigm shift and success of tissue-agnostic clinical trials leading to approvals.”

Instructions: The recommended dosage is 160 mg of repotrectinib orally, once daily for 14 days, then increased to 160 mg twice daily with or without food, until disease progression or unacceptable toxicity.

For More Information

Drilon A, Camidge DR, Lin JJ, et al (2024). Repotrectinib in ROS1 fusion-positive non-small-cell lung cancer. N Engl J Med, 390(2):118-131. DOI:10.1056/NEJMoa2302299

Augtyro™ (repotrectinib) prescribing information (2024). Bristol Myers Squibb Company. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/218213s001lbl.pdf

Clinicaltrials.gov (2024). A study of repotrectinib (TPX-0005) in patients with advanced solid tumors harboring ALK, ROS1, or NTRK1-3 rearrangements (TRIDENT-1). NLM identifier: NCT03093116.

US Food and Drug Administration (2024). FDA grants accelerated approval to repotrectinib for adult and pediatric patients with NTRK gene fusion-positive solid tumors. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-repotrectinib-adult-and-pediatric-patients-ntrk-gene-fusion-positive

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