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Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism
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Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism

Published on: July 28, 2017

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Repotrectinib in NTRK fusion-positive advanced solid tumors: a phase 1/2 trial

Benjamin Besse1, Jessica J Lin2, Lyudmila Bazhenova3

  • 1Paris-Saclay University, Gustave Roussy Cancer Center, Villejuif, France. Benjamin.BESSE@gustaveroussy.fr.

Nature Medicine
|February 4, 2026
PubMed

Insights

Repotrectinib, a next-generation tyrosine kinase inhibitor (TKI), shows durable responses in NTRK fusion-positive solid tumors. This TKI is effective even in patients previously treated with TKIs and those with specific mutations, demonstrating a favorable safety profile.

Area of Science:

  • Oncology
  • Pharmacology
  • Genetics

Background:

  • Early-generation TRK tyrosine kinase inhibitors (TKIs) offer clinical benefits for NTRK fusion-positive (NTRK+) solid tumors but are limited by emerging resistance.
  • Repotrectinib is a next-generation ROS1/TRK TKI engineered with a macrocyclic structure to enhance response durability.

Purpose of the Study:

  • To assess the efficacy and safety of repotrectinib in adult patients with advanced solid tumors, specifically focusing on NTRK+ disease.
  • To evaluate repotrectinib's performance in both TKI-naive and TKI-pretreated patient populations, including those with specific NTRK solvent front mutations.

Main Methods:

  • The TRIDENT-1 trial (Phase 1/2, NCT03093116) evaluated repotrectinib in patients with advanced solid tumors, including NTRK+ disease.
  • Primary endpoint: confirmed objective response rate. Secondary endpoints: duration of response (DOR), progression-free survival (PFS), overall survival, and safety.
  • Patients were stratified into TKI-naive and TKI-pretreated cohorts, with subgroup analyses for solvent front mutations and intracranial disease.

Main Results:

  • In TKI-naive patients (n=51), response rate was 59% (95% CI: 44-72) with a median PFS of 30.3 months (9.0-NE).
  • In TKI-pretreated patients (n=69), response rate was 48% (95% CI: 36-60) with a median DOR of 9.8 months (7.4-13.0) and median PFS of 7.4 months (3.9-9.7).
  • Of 30 TKI-pretreated patients with NTRK solvent front mutations, 16 responded (53%; 95% CI: 34-72). Intracranial responses were observed in both cohorts.

Conclusions:

  • Repotrectinib demonstrated durable systemic and intracranial responses in patients with NTRK+ solid tumors, including those with prior TRK TKI treatment and solvent front mutations.
  • The treatment-related adverse events were generally low-grade, with a low discontinuation rate (4%), supporting repotrectinib's favorable safety profile.
  • These findings support repotrectinib as a valuable therapeutic option for patients diagnosed with NTRK fusion-positive solid tumors.

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