biostudies-literatureUnknown32(2)Besse BEarly-generation TRK tyrosine kinase inhibitors (TKIs) approved for treating NTRK fusion-positive (NTRK⁺) solid tumors provide clinical benefit; however, resistance emerges. Repotrectinib is a next-generation ROS1/TRK TKI with a compact macrocyclic structure designed to improve durability of response. TRIDENT-1 is a registrational phase 1/2 trial assessing repotrectinib, a next-generation ROS1/TRK TKI, in adults with advanced solid tumors, including NTRK⁺ disease. The primary endpoint was confirmed objective response; secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival and safety. Median follow-up ranged between 21.3 months and 25.7 months. In the TKI-naive cohort (n = 51; 95% confidence interval (CI)), the responNature medicine682-689https://www.ebi.ac.uk/biostudies/studies/S-EPMC12920079biostudies-literatureRepotrectinib in NTRK fusion-positive advanced solid tumors: a phase 1/2 trial.PMC12920079Kollengode KYang HPopat SCalvet CYLin JJYang NSolomon BJSpringfeld CLim DWTHong JYBazhenova LHammell ABde Langen AJKim DWGoto KNagasaka MBaik CSMoreno VHervieu AWolf JDrilon ABesse BXu YYuan YfalseRepotrectinib in NTRK fusion-positive advanced solid tumors: a phase 1/2 trial.Early-generation TRK tyrosine kinase inhibitors (TKIs) approved for treating NTRK fusion-positive (NTRK⁺) solid tumors provide clinical benefit; however, resistance emerges. Repotrectinib is a next-generation ROS1/TRK TKI with a compact macrocyclic structure designed to improve durability of response. TRIDENT-1 is a registrational phase 1/2 trial assessing repotrectinib, a next-generation ROS1/TRK TKI, in adults with advanced solid tumors, including NTRK⁺ disease. The primary endpoint was confirmed objective response; secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival and safety. Median follow-up ranged between 21.3 months and 25.7 months. In the TKI-naive cohort (n = 51; 95% confidence interval (CI)), the respon2026-01-01T00:00:00Z2026 Feb2026-07-16T15:11:00.988Z2026-07-09T11:03:02.069ZS-EPMC129200794163937910.1038/s41591-025-04079-7