{"entity":{"id":"paper-trident-1-repotrectinib-nejm-2024","kind":"paper","name":"TRIDENT-1: repotrectinib in ROS1 fusion-positive non-small-cell lung cancer","aka":[],"tldr":"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.\n\nIn 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.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2024","url":"https://doi.org/10.1056/NEJMoa2302299"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/38197815/"}],"tags":[],"related":[],"cancers":["ntrk-fusion-nsclc","ros1-positive-nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["repotrectinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2024,"doi":"10.1056/NEJMoa2302299","pmid":"38197815","authors":"Drilon A, Camidge DR, Lin JJ, et al.","paperType":"observational","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."],"whatItMeans":"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."],"changedPractice":true,"participants":171},"route":"/key-papers/paper-trident-1-repotrectinib-nejm-2024/","neighbours":{"cancer":[{"id":"ntrk-fusion-nsclc","kind":"cancer","name":"NTRK fusion-positive non-small-cell lung cancer","route":"/cancers/ntrk-fusion-nsclc/"},{"id":"ros1-positive-nsclc","kind":"cancer","name":"ROS1-positive non-small-cell lung cancer","route":"/cancers/ros1-positive-nsclc/"}],"drug":[{"id":"repotrectinib","kind":"drug","name":"Repotrectinib","route":"/drugs/repotrectinib/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}