A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements

Overview

• In the registrational phase 1-2 TRIDENT-1 trial, the recommended dose was 160 mg daily for 14 days then 160 mg twice daily. Response occurred in 56 of 71 ROS1 inhibitor-naive patients with ROS1 fusion-positive non-small-cell lung cancer (79 percent, 95 percent confidence interval 68 to 88), with median duration of response 34.1 months and median progression-free survival 35.7 months; in 21 of 56 patients who had had one ROS1 inhibitor and no chemotherapy (38 percent, 25 to 52), median duration of response was 14.8 months and progression-free survival 9.0 months; and in 10 of 17 patients with ROS1 G2032R (59 percent, 33 to 82). Among 426 patients treated at the phase 2 dose the commonest treatment-related events were dizziness (58 percent), dysgeusia (50 percent) and paraesthesia (30 percent), with 3 percent discontinuing (New England Journal of Medicine 2024).