{"entity":{"id":"larotrectinib","kind":"drug","name":"Larotrectinib","aka":[],"tldr":"The first drug approved for a gene fusion regardless of where the cancer started; it works in about 75% of NTRK-fusion cancers, from infant fibrosarcoma to salivary and thyroid cancers.","summary":"Drilon (NEJM 2018): 75% response across 17 tumour types; approved November 2018 as the second tumour-agnostic approval (after pembrolizumab MSI-H). Long durability (median DOR >40 months in updates); resistance via NTRK solvent-front mutations (G595R) addressed by repotrectinib and next-generation TRK inhibitors. Paediatric formulation.","status":"approved","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Larotrectinib","links":[{"label":"Drilon 2018 (NEJM)","url":"https://doi.org/10.1056/NEJMoa1714448"},{"label":"Label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=larotrectinib"},{"label":"NICE TA630: larotrectinib for NTRK fusion-positive solid tumours, Cancer Drugs Fund (27 May 2020)","url":"https://www.nice.org.uk/guidance/ta630"},{"label":"EMA Vitrakvi product page","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/vitrakvi"}],"tags":["gap-fill"],"related":["ntrk-fusion"],"cancers":["salivary-gland","thyroid","colorectal","nsclc","sarcoma","pancreatic","kras-wild-type-pdac","ntrk-fusion-nsclc"],"sections":[],"technologies":["kinase-inhibitors","cgp"],"targets":["ntrk"],"drugs":[],"companies":["bayer"],"institutions":[],"pathways":[],"terms":["tumour-agnostic","gene-fusion"],"trials":["nct02637687"],"people":[],"bottlenecks":[],"keyPapers":["paper-oreilly-hechtman-ntrk-fusion-pancreatic-larotrectinib-ann-oncol-2019"],"journals":[],"dependsOn":[],"notes":["Pancreatic cancer: NTRK fusions are rare drivers of KRAS wild-type pancreatic cancer; NICE NG85 (1.9.11) points to TA630, which makes larotrectinib available through the Cancer Drugs Fund while more data are collected. EU marketing authorisation 19 September 2019 (Vitrakvi)."],"brand":"Vitrakvi","modality":"Small-molecule pan-TRK inhibitor (first generation)","mechanism":"Highly selective ATP-competitive inhibitor of TRKA/B/C (NTRK1/2/3) fusion kinases.","approvals":[{"region":"US","year":2018,"indication":"Solid tumours with NTRK gene fusion without known acquired resistance mutation, metastatic or unresectable, adults and children"},{"region":"EU","year":2019,"indication":"Same"},{"region":"UK","year":2020,"indication":"NTRK fusion-positive solid tumours in adults and children, locally advanced or metastatic or where surgery would cause severe morbidity, with no satisfactory treatment options: NICE TA630 (27 May 2020) recommends it within the Cancer Drugs Fund under a managed access agreement","note":"https://www.nice.org.uk/guidance/ta630"},{"region":"England (NICE)","year":2020,"indication":"NTRK fusion-positive solid tumours, including colorectal cancer","note":"TA630, published 27 May 2020: recommended for use within the Cancer Drugs Fund only, under a managed access agreement, where there is no satisfactory treatment option."}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[{"date":"2018-11-26","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint, with a confirmatory trial required.","source":"https://www.fda.gov/drugs/fda-approves-larotrectinib-solid-tumors-ntrk-gene-fusions-0","indication":"Treatment of adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine 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 no satisfactory alternative treatments or that have progressed following treatment"},{"date":"2018-11-26","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint, with a confirmatory trial required.","source":"https://www.fda.gov/drugs/fda-approves-larotrectinib-solid-tumors-ntrk-gene-fusions-0","indication":"Formation: Treatment of adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine 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 no satisfactory alternative treatments or that have progressed following treatment"},{"date":"2025-04-09","type":"conversion","region":"US","note":"Confirmed: the accelerated approval of 2018 converted to traditional approval 6.4 years after it was granted.","source":"https://www.fda.gov/drugs/fda-approves-larotrectinib-solid-tumors-ntrk-gene-fusions-0","indication":"Treatment of adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine 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 no satisfactory alternative treatments or that have progressed following treatment"},{"date":"2025-04-09","type":"conversion","region":"US","note":"Confirmed: the accelerated approval of 2018 converted to traditional approval 6.4 years after it was granted.","source":"https://www.fda.gov/drugs/fda-approves-larotrectinib-solid-tumors-ntrk-gene-fusions-0","indication":"Formation: Treatment of adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine 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 no satisfactory alternative treatments or that have progressed following treatment"}]},"route":"/drugs/larotrectinib/","neighbours":{"biomarker":[{"id":"ntrk-fusion","kind":"biomarker","name":"NTRK1/2/3 gene fusion","route":"/biomarkers/ntrk-fusion/"}],"cancer":[{"id":"ampullary","kind":"cancer","name":"Ampullary cancer (ampulla of Vater)","route":"/cancers/ampullary/"},{"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":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal 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(APEC1621)","route":"/trials/pediatric-match/"},{"id":"nci-match","kind":"trial","name":"NCI-MATCH (EAY131)","route":"/trials/nci-match/"},{"id":"nct05725200","kind":"trial","name":"Study to Investigate Outcome of Individualized Treatment in Patients With Metastatic Colorectal Cancer","route":"/trials/nct05725200/"}],"paper":[{"id":"paper-drilon-larotrectinib-nejm-2018","kind":"paper","name":"Larotrectinib in TRK fusion-positive cancers in adults and children","route":"/key-papers/paper-drilon-larotrectinib-nejm-2018/"},{"id":"paper-asco-metastatic-pancreatic-cancer-guideline-update-jco-2020","kind":"paper","name":"Metastatic Pancreatic Cancer: ASCO Guideline Update","route":"/key-papers/paper-asco-metastatic-pancreatic-cancer-guideline-update-jco-2020/"},{"id":"paper-oreilly-hechtman-ntrk-fusion-pancreatic-larotrectinib-ann-oncol-2019","kind":"paper","name":"Tumour response to TRK inhibition in a patient with pancreatic adenocarcinoma harbouring an NTRK gene 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