# TRIDENT-1: repotrectinib in ROS1 fusion-positive non-small-cell lung cancer

Source: https://onco.cc/key-papers/paper-trident-1-repotrectinib-nejm-2024/  
OnCo record `paper-trident-1-repotrectinib-nejm-2024` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The next-generation ROS1 and TRK inhibitor repotrectinib shrank tumours in almost four in five untreated patients with ROS1-positive lung cancer, kept the disease under control for nearly three years, and worked in about four in ten patients after crizotinib including those with the resistant G2032R mutation.

## Summary

Phase 1/2 study of 171 patients with ROS1 fusion-positive non-small-cell lung cancer treated with repotrectinib, including 71 who had not received a ROS1 inhibitor and 56 previously treated with one.

In ROS1 inhibitor-naive patients, objective response was 79 percent with median progression-free survival 35.7 months; in patients after one prior ROS1 inhibitor without chemotherapy, response was 38 percent with median progression-free survival 9.0 months, and 59 percent of G2032R-mutant tumours responded. Dizziness was the most frequent side effect.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: New England Journal of Medicine
- Year: 2024
- DOI: 10.1056/NEJMoa2302299
- Authors: Drilon A, Camidge DR, Lin JJ, et al.
- Findings: ROS1 inhibitor-naive: objective response 79 percent; median progression-free survival 35.7 months.; After one prior ROS1 inhibitor: objective response 38 percent; 59 percent in G2032R-mutant tumours.
- What it means: Repotrectinib is a preferred first-line ROS1 inhibitor because of its durability and coverage of resistance mutations, and it is also approved for NTRK fusion-positive tumours after prior TRK inhibitors.
- Caveats: Single-arm; dizziness in about 60 percent and dysgeusia in half.; No randomised comparison with crizotinib or entrectinib.

## Sources

- N Engl J Med 2024: https://doi.org/10.1056/NEJMoa2302299
- PubMed: https://pubmed.ncbi.nlm.nih.gov/38197815/

## Connected records

- cancers: [NTRK fusion-positive non-small-cell lung cancer](https://onco.cc/cancers/ntrk-fusion-nsclc/), [ROS1-positive non-small-cell lung cancer](https://onco.cc/cancers/ros1-positive-nsclc/)
- drugs: [Repotrectinib](https://onco.cc/drugs/repotrectinib/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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