The FDA has granted accelerated approval to repotrectinib for the treatment of adult and pediatric patients aged 12 years and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion. This approval targets patients with locally advanced or metastatic tumors, or those for whom surgical resection would likely result in severe morbidity, and who have either progressed following prior treatment or have no satisfactory alternative therapies.
The efficacy of repotrectinib was demonstrated in the TRIDENT-1 trial, a multicenter, single-arm, open-label, multi-cohort study that involved 88 adult patients with locally advanced or metastatic NTRK gene fusion-positive solid tumors. Among these participants, 48 had previously received a TRK tyrosine kinase inhibitor (TKI), while 40 were TKI-naïve. Baseline assessments for central nervous system (CNS) lesions were conducted, with symptomatic brain metastases being an exclusion criterion. Tumor assessments were performed every eight weeks.
The primary efficacy outcomes measured were the overall response rate (ORR) and the duration of response (DOR) according to RECIST v1.1 criteria, as assessed by blinded independent central review. The results revealed a confirmed ORR of 58% in the TKI-naïve group and 50% in the TKI-pretreated group. The median DOR was not estimable in the TKI-naïve group, while it was 9.9 months in the TKI-pretreated group.
Common adverse reactions experienced by more than 20% of patients included dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia (lack of muscle control), cognitive impairment, muscular weakness, and nausea.
This accelerated approval of repotrectinib offers a new therapeutic option where previously there were limited alternatives. This decision underscores the ongoing efforts to bring innovative treatments to patients with challenging and rare cancers.
References:
- https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-repotrectinib-adult-and-pediatric-patients-ntrk-gene-fusion-positive
Viktor Grünwald
