{"entity":{"id":"repotrectinib","kind":"drug","name":"Repotrectinib","aka":[],"tldr":"A ROS1 and NTRK pill that also works after other ROS1 drugs fail, with dizziness as its signature side effect.","summary":"Repotrectinib is a compact macrocyclic ROS1 and TRK inhibitor whose small size lets it bind kinases carrying solvent-front mutations such as ROS1 G2032R, the usual escape route from crizotinib and entrectinib. It is used in ROS1-positive non-small-cell lung cancer both in patients who have never had a ROS1 drug and in those whose disease has progressed on one, and in NTRK-fusion solid tumours of any type. In TRIDENT-1 the response rate was 79% in TKI-naive and 38% in TKI-pretreated ROS1-positive NSCLC. It was approved in November 2023 for ROS1 and June 2024 for NTRK fusions (tumour-agnostic). Dizziness and other neurological effects from TRK inhibition are its signature toxicity, and zidesamtinib (2026) offers a TRK-sparing alternative with fewer neurologic effects. In short, it is the ROS1 pill that still works after other ROS1 drugs fail.","status":"approved","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Repotrectinib","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Repotrectinib"}],"tags":[],"related":["ros1-fusion"],"cancers":["nsclc","ros1-positive-nsclc","ntrk-fusion-nsclc"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["ros1","ntrk"],"drugs":["zidesamtinib"],"companies":["bms"],"institutions":[],"pathways":[],"terms":[],"trials":["nct04094610","nct03093116","nct06140836"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Augtyro","modality":"Small-molecule kinase inhibitor (ROS1 / NTRK)","mechanism":"Compact macrocyclic ROS1/TRK inhibitor active against solvent-front mutations.","approvals":[{"region":"US","year":2023,"indication":"ROS1+ locally advanced or metastatic NSCLC"},{"region":"US","year":2024,"indication":"NTRK-fusion solid tumours (tumour-agnostic)"},{"region":"EU","year":2025,"indication":"ROS1+ NSCLC; NTRK+ solid tumours; 13 Jan 2025 (conditional)","note":"Conditional marketing authorisation"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[{"date":"2024-06-13","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint; the confirmatory requirement was still open 2.3 years later, when the FDA's table was read.","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-repotrectinib-adult-and-pediatric-patients-ntrk-gene-fusion-positive","indication":"Treatment of adult and pediatric patients 12 years of age and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, are locally advanced or metastatic where surgical resection is likely results in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy"}]},"route":"/drugs/repotrectinib/","neighbours":{"biomarker":[{"id":"ntrk-fusion","kind":"biomarker","name":"NTRK1/2/3 gene fusion","route":"/biomarkers/ntrk-fusion/"},{"id":"ros1-fusion","kind":"biomarker","name":"ROS1 fusion (ROS1-positive)","route":"/biomarkers/ros1-fusion/"}],"cancer":[{"id":"inflammatory-myofibroblastic-tumour","kind":"cancer","name":"Inflammatory myofibroblastic tumour (IMT)","route":"/cancers/inflammatory-myofibroblastic-tumour/"},{"id":"kras-wild-type-pdac","kind":"cancer","name":"KRAS wild-type pancreatic ductal adenocarcinoma","route":"/cancers/kras-wild-type-pdac/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"ntrk-fusion-nsclc","kind":"cancer","name":"NTRK fusion-positive non-small-cell lung cancer","route":"/cancers/ntrk-fusion-nsclc/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"ros1-positive-nsclc","kind":"cancer","name":"ROS1-positive non-small-cell lung cancer","route":"/cancers/ros1-positive-nsclc/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"ntrk","kind":"target","name":"NTRK","route":"/targets/ntrk/"},{"id":"ros1","kind":"target","name":"ROS1","route":"/targets/ros1/"}],"drug":[{"id":"zidesamtinib","kind":"drug","name":"Zidesamtinib","route":"/drugs/zidesamtinib/"}],"company":[{"id":"bms","kind":"company","name":"Bristol Myers Squibb","route":"/companies/bms/"},{"id":"zai-lab","kind":"company","name":"Zai Lab","route":"/companies/zai-lab/"}],"trial":[{"id":"nct03093116","kind":"trial","name":"A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements","route":"/trials/nct03093116/"},{"id":"nct04094610","kind":"trial","name":"A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations","route":"/trials/nct04094610/"},{"id":"nct06140836","kind":"trial","name":"A Study of Repotrectinib Versus Crizotinib in Participants With Locally Advanced or Metastatic Tyrosine Kinase Inhibitor (TKI)-naïve ROS1-positive Non-Small Cell Lung Cancer (NSCLC) (TRIDENT-3)","route":"/trials/nct06140836/"},{"id":"profile-1001-ros1","kind":"trial","name":"PROFILE 1001 ROS1 expansion cohort","route":"/trials/profile-1001-ros1/"},{"id":"nct06315010","kind":"trial","name":"Repotrectinib in ROS1-positive Non-small Cell Lung Cancer Patients With Active Brain Metastasis","route":"/trials/nct06315010/"}],"person":[{"id":"alexander-drilon","kind":"person","name":"Alexander Drilon","route":"/people/alexander-drilon/"},{"id":"kim-dong-wan","kind":"person","name":"Dong-Wan Kim","route":"/people/kim-dong-wan/"}],"paper":[{"id":"paper-trident-1-repotrectinib-nejm-2024","kind":"paper","name":"TRIDENT-1: repotrectinib in ROS1 fusion-positive non-small-cell lung cancer","route":"/key-papers/paper-trident-1-repotrectinib-nejm-2024/"}],"pathway":[{"id":"thyroid-cancer-signalling","kind":"pathway","name":"Thyroid cancer (KEGG map)","route":"/pathways/thyroid-cancer-signalling/"}]}}