Repotrectinib in NTRK fusion-positive advanced solid tumors

New data from the phase 1/ 2 trial TRIDENT-1, recently published on Nature Medicine, showed durable systemic and intracranial responses with generally low-grade adverse events in patients with NTRK fusion-positive advanced solid tumors.

TRIDENT-1 is a registrational phase 1/2 trial assessing repotrectinib, a next-generation ROS1/TRK tyrosine kinase inhibitor, in adults with advanced solid tumors, including NTRK-positive disease. A total of 565 patients were enrolled and treated with at least one dose of repotrectinib for safety analysis; 120 patients with NTRK+ locally advanced or metastatic solid tumors who started treatment with repotrectinib at any dose were analyzed for efficacy. After a follow-up up to 25.7 months, the response rate was 59% in the tyrosine kinase inhibitors-naive population with a progression-free survival of 30.3 months; in patients pretreated with tyrosine kinase inhibitors, response rate was 48% and progression-free survival was 7.4 months; in pretreated patients with NTRK mutations response rate was 53%. Intracranial responses were observed in two of three tyrosine kinase inhibitors-naive patients and in four of six tyrosine kinase inhibitors-pretreated patients with measurable intracranial disease at baseline. Most treatment-related adverse events were low grade, the most common being dizziness (57%). «Repotrectinib showed durable clinical activity in adult patients with NTRK-positive solid tumors, including in patients with previous tyrosine kinase inhibitors treatment, with or without intracranial disease», authors say. «This evidence supports repotrectinib as a new treatment option for patients with NTRK-positive solid tumors. Looking forward, studies with longer follow-up and larger patient populations will help understand how response durability translates to overall survival as well as ascertain the ideal treatment sequence».