Repotrectinib Approved for Adults and Children with NTRK-mutated Cancer

The targeted therapy Repotrectinib was approved for solid tumors with certain NTRK mutations, regardless of where the tumors originated. 

The U.S. Food and Drug Administration (FDA) has granted accelerated approval to repotrectinib (Augtyro) for adult and pediatric patients aged 12 years or older with solid tumors that are locally advanced, metastatic, or ineligible for surgical removal; have progressed after prior treatment or have no other available treatment options; and harbor NTRK gene fusions. 

Repotrectinib was approved to treat solid tumors with certain gene mutations. 

In rare instances, a portion of one of the three NTRK genes breaks away and fuses to another gene, increasing the cancer-promoting activity of NTRK. Repotrectinib is a targeted therapy that treats cancers with NTRK gene fusions by inhibiting NTRK activity. The unique chemical design of repotrectinib might enable it to effectively treat tumors that are resistant to previously approved NTRK inhibitors. 

Repotrectinib’s approval was based on results from TRIDENT-1, a multicenter, single-arm, open-label, multicohort phase I/II clinical trial that enrolled 88 adult patients with locally advanced or metastatic solid tumors that harbored NTRK gene fusions.  

Among 48 patients who had received prior treatment with an NTRK inhibitor, 50% experienced a response to repotrectinib, and the responses persisted for a median of 9.9 months. Among the 40 patients who had not been previously treated with an NTRK inhibitor, 58% experienced a response; the median duration of response was not estimable. 

The recommended dose of repotrectinib is 160 mg once daily for 14 days, then 160 mg twice daily until disease progression or unacceptable toxicity. 

In normal cells, NTRK genes activate cellular proliferation in response to certain growth signals, but fusion of an NTRK gene with another gene can hyperactivate NTRK, leading to unregulated cellular proliferation that results in cancer. NTRK gene fusions are found in less than 1% of adult cancers and between 0.44% and 3.33% of pediatric cancers.  

The FDA rendered its decision on June 13, 2024. Accelerated approval means that continued approval may be contingent upon a confirmatory trial.