Journal Article

DKFZ-2026-00289

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Repotrectinib in NTRK fusion-positive advanced solid tumors: a phase 1/2 trial.

Besse, B. ; Lin, J. J. ; Bazhenova, L. ; Goto, K. ; de Langen, A. J. ; Kim, D.-W. ; Wolf, J. ; Springfeld, C.DKFZ* ; Popat, S. ; Lim, D. W. T. ; Nagasaka, M. ; Hong, J. Y. ; Baik, C. S. ; Hervieu, A. ; Moreno, V. ; Yang, N. ; Kollengode, K. ; Yang, H. ; Xu, Y. ; Calvet, C. Y. ; Yuan, Y. ; Hammell, A. B. ; Drilon, A. ; Solomon, B. J.

2026
Springer Nature [New York, NY]

Abstract: 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 response rate was 59% (44-72); the median DOR was not estimable (NE); and the median PFS was 30.3 months (9.0-NE). In the TKI-pretreated cohort (n = 69; 95% CI), the response rate was 48% (36-60); the median DOR was 9.8 months (7.4-13.0); and the median PFS was 7.4 months (3.9-9.7). Of 30 TKI-pretreated patients with NTRK solvent front mutations, 16 had a response (53%; 95% CI: 34-72). Intracranial responses were observed in two of three TKI-naive patients and in four of six TKI-pretreated patients with measurable intracranial disease at baseline. Among all treated patients (n = 565), the most common any-grade treatment-related adverse event (TRAE) was dizziness (57%); most TRAEs were low grade; and 4% discontinued repotrectinib due to a TRAE. Here repotrectinib demonstrated durable systemic and intracranial responses with generally low-grade adverse events in patients with NTRK+ solid tumors, including those with previous TRK TKI treatment and solvent front mutations. These results support the use of repotrectinib to treat patients with NTRK+ solid tumors. ClinicalTrials.gov identifier: NCT03093116 .

Note: #NCTZFB9# / epub

---

Contributing Institute(s):

1. Koordinierungsstelle NCT Heidelberg (HD02)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 80 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---