Repotrectinib

Indication. Repotrectinib is indicated for adult and pediatric patients with an NTRK gene fusion and solid tumors that are locally advanced or metastatic for which surgical resection may cause severe morbidity.

Evidence. FDA approval was based on data from TRIDENT-1 (NCT03093116), a multicenter, single-arm, open-label, multicohort trial.[6-8][Level of evidence C3]

Efficacy. In 88 adult patients with locally advanced or metastatic NTRK gene fusion–positive solid tumors, the overall response rate was 58% (95% CI, 41%–73%) for patients who had not received prior NTRK tyrosine kinase inhibitors (TKIs) (n = 40) and 50% (95% CI, 35%–65%) for patients who had previously received NTRK TKIs (n = 48). The median duration of response was not estimable in the TKI-naïve group and was 9.9 months (95% CI, 7.4–13.0) in the TKI-pretreated group. The median follow-up was 24.0 months.[6,8]

Identification of biomarker. NTRK gene fusion status was prospectively determined at local laboratories using NGS, Sanger sequencing, reverse transcription–polymerase chain reaction, or FISH. Not all NTRK variants are gene fusions. Repotrectinib has not shown clinical efficacy in patients with nonfusion NTRK variants.