{"entity":{"id":"entrectinib","kind":"drug","name":"Entrectinib","aka":[],"tldr":"Entrectinib (Rozlytrek) is a pill for NTRK-fusion cancers and ROS1 lung cancer that reaches brain metastases.","summary":"Entrectinib is a multikinase inhibitor of TRKA, TRKB, TRKC, ROS1 and ALK that was designed to cross the blood-brain barrier. It is a tumour-agnostic drug for solid tumours with NTRK gene fusions, which occur across salivary gland tumours, sarcomas, colorectal cancer and many other types, and for ROS1-positive metastatic NSCLC. An integrated analysis of STARTRK-2, STARTRK-1 and ALKA showed a 57% response rate in NTRK-fusion tumours and 77% in ROS1-positive NSCLC, with activity against brain metastases. Japan approved it in June 2019 for NTRK-fusion tumours, the US in August 2019 for both indications and the EU in 2020; the paediatric label was extended in 2023 to infants from one month of age. Weight gain, dizziness, cognitive effects and cardiac failure are class-related TRK toxicities. Entrectinib treats cancers by their fusion gene rather than their organ of origin.","status":"approved","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Entrectinib","links":[{"label":"Label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=entrectinib"},{"label":"NICE TA1118: entrectinib for NTRK fusion-positive solid tumours, terminated appraisal (7 January 2026)","url":"https://www.nice.org.uk/guidance/ta1118"},{"label":"NICE TA644 (12 August 2020), replaced","url":"https://www.nice.org.uk/guidance/ta644"},{"label":"EMA Rozlytrek product page","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/rozlytrek"},{"label":"NICE TA643: entrectinib for treating ROS1-positive advanced non-small-cell lung cancer","url":"https://www.nice.org.uk/guidance/ta643"}],"tags":["gap-fill"],"related":["ros1-fusion","ntrk-fusion"],"cancers":["nsclc","salivary-gland","sarcoma","colorectal","ros1-positive-nsclc","ntrk-fusion-nsclc","pancreatic","kras-wild-type-pdac","lung-cancer"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["ntrk","ros1","alk"],"drugs":[],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":["tumour-agnostic","gene-fusion","blood-brain-barrier"],"trials":["nct05170204","nct02568267","nct04302025","nct04603807","nct02650401","profile-1001-ros1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Pancreatic cancer: entrectinib's tumour-agnostic NTRK indication (FDA accelerated approval; EU marketing authorisation 31 July 2020) applies to the rare NTRK fusion-positive pancreatic tumours, but in England the Cancer Drugs Fund route closed with the terminated TA1118 in January 2026, leaving larotrectinib (TA630) as the funded option."],"brand":"Rozlytrek","modality":"Small-molecule TRK/ROS1/ALK TKI (CNS-penetrant)","mechanism":"Multikinase inhibitor of TRKA/B/C, ROS1 and ALK designed to cross the blood-brain barrier.","approvals":[{"region":"JP","year":2019,"indication":"NTRK fusion solid tumours"},{"region":"US","year":2019,"indication":"ROS1-positive metastatic NSCLC; NTRK fusion solid tumours (≥12 years, extended to ≥1 month 2023)"},{"region":"EU","year":2020,"indication":"Same"},{"region":"UK","year":2020,"indication":"NTRK fusion-positive solid tumours: NICE TA644 (12 August 2020) recommended entrectinib within the Cancer Drugs Fund; it was replaced by TA1118 (terminated appraisal, 7 January 2026) because the company did not make a submission, and only people already on treatment continue","note":"https://www.nice.org.uk/guidance/terminated/ta1118"},{"region":"England (NICE)","year":2020,"indication":"NTRK fusion-positive solid tumours, including colorectal cancer","note":"TA644, published 12 August 2020, withdrawn: replaced by TA1118, which NICE terminated on 7 January 2026 with no complete evidence submission. People already treated through the Cancer Drugs Fund may continue."},{"region":"England (NICE)","year":2020,"indication":"ROS1-positive advanced non-small-cell lung cancer in patients who have not had a ROS1 inhibitor","note":"TA643, published 12 August 2020, subject to the commercial arrangement. This is a separate appraisal from the tumour-agnostic NTRK guidance."}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[{"date":"2019-08-15","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint; the confirmatory requirement was still open 7.1 years later, when the FDA's table was read.","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-pediatric-indication-entrectinib-and-approves-new-pellet-formulation","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 without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy . *"},{"date":"2023-10-20","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint; the confirmatory requirement was still open 2.9 years later, when the FDA's table was read.","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-pediatric-indication-entrectinib-and-approves-new-pellet-formulation","indication":"Formulation: Adult and pediatric patients older than 1 month of age with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation as detected by an FDA-approved test, are metastatic or where surgical resection is likely to result in severe morbidity and have progressed following treatment or have no satisfactory alternative therapy ."}]},"route":"/drugs/entrectinib/","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":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"},{"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":"metastatic-cancer","kind":"cancer","name":"Metastatic cancer (cancer that has spread)","route":"/cancers/metastatic-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":"paediatric-high-grade-glioma","kind":"cancer","name":"Paediatric high-grade glioma (excluding diffuse midline glioma)","route":"/cancers/paediatric-high-grade-glioma/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"papillary-thyroid-cancer","kind":"cancer","name":"Papillary thyroid cancer","route":"/cancers/papillary-thyroid-cancer/"},{"id":"ros1-positive-nsclc","kind":"cancer","name":"ROS1-positive non-small-cell lung cancer","route":"/cancers/ros1-positive-nsclc/"},{"id":"salivary-gland","kind":"cancer","name":"Salivary gland cancers","route":"/cancers/salivary-gland/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"},{"id":"secretory-carcinoma-breast","kind":"cancer","name":"Secretory carcinoma of the breast","route":"/cancers/secretory-carcinoma-breast/"},{"id":"uterine-sarcoma","kind":"cancer","name":"Uterine sarcoma","route":"/cancers/uterine-sarcoma/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"alk","kind":"target","name":"ALK","route":"/targets/alk/"},{"id":"ntrk","kind":"target","name":"NTRK","route":"/targets/ntrk/"},{"id":"ros1","kind":"target","name":"ROS1","route":"/targets/ros1/"}],"company":[{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"term":[{"id":"blood-brain-barrier","kind":"term","name":"Blood-brain barrier (BBB)","route":"/terms/blood-brain-barrier/"},{"id":"colorectal-uk-drug-access","kind":"term","name":"Colorectal cancer drugs in England: what NICE has recommended","route":"/terms/colorectal-uk-drug-access/"},{"id":"gene-fusion","kind":"term","name":"Gene fusion","route":"/terms/gene-fusion/"},{"id":"lung-uk-drug-access","kind":"term","name":"Lung cancer drugs in England: what NICE has recommended","route":"/terms/lung-uk-drug-access/"},{"id":"pancreatic-cancer-uk-drug-access","kind":"term","name":"Pancreatic cancer drugs in England: NICE appraisals and the Cancer Drugs Fund (September 2026)","route":"/terms/pancreatic-cancer-uk-drug-access/"},{"id":"tumour-agnostic","kind":"term","name":"Tumour-agnostic (tissue-agnostic) approval","route":"/terms/tumour-agnostic/"}],"trial":[{"id":"nct05170204","kind":"trial","name":"A Study Evaluating the Efficacy and Safety of Multiple Therapies in Cohorts of Participants With Locally Advanced, Unresectable, Stage III Non-Small C","route":"/trials/nct05170204/"},{"id":"nct04302025","kind":"trial","name":"A Study of Multiple Therapies in Biomarker-selected Participants With Resectable Stages IB-III Non-small Cell Lung Cancer (NSCLC)","route":"/trials/nct04302025/"},{"id":"nct04603807","kind":"trial","name":"A Study to Compare the Efficacy and Safety of Entrectinib and Crizotinib in Participants With Advanced or Metastatic ROS1 Non-small Cell Lung Cancer (NSCLC) With and Without Central Nervous System (CNS) Metastases","route":"/trials/nct04603807/"},{"id":"nct02568267","kind":"trial","name":"Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangeme","route":"/trials/nct02568267/"},{"id":"cupisco","kind":"trial","name":"CUPISCO","route":"/trials/cupisco/"},{"id":"determine-trial","kind":"trial","name":"DETERMINE","route":"/trials/determine-trial/"},{"id":"profile-1001-ros1","kind":"trial","name":"PROFILE 1001 ROS1 expansion cohort","route":"/trials/profile-1001-ros1/"},{"id":"nct02650401","kind":"trial","name":"Study Of Entrectinib (Rxdx-101) in Children and Adolescents With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options","route":"/trials/nct02650401/"},{"id":"nct04589845","kind":"trial","name":"Tumor-agnostic Precision Immuno-oncology and Somatic Targeting Rational for You (TAPISTRY) Platform Study","route":"/trials/nct04589845/"}],"paper":[{"id":"paper-doebele-entrectinib-ntrk-lancet-oncol-2020","kind":"paper","name":"Entrectinib in NTRK fusion-positive solid tumours: integrated analysis of three trials","route":"/key-papers/paper-doebele-entrectinib-ntrk-lancet-oncol-2020/"},{"id":"paper-drilon-entrectinib-ros1-lancet-oncol-2020","kind":"paper","name":"Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three trials","route":"/key-papers/paper-drilon-entrectinib-ros1-lancet-oncol-2020/"},{"id":"paper-asco-metastatic-pancreatic-cancer-guideline-update-jco-2020","kind":"paper","name":"Metastatic Pancreatic Cancer: ASCO Guideline 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