{"entity":{"id":"ntrk-fusion","kind":"biomarker","name":"NTRK1/2/3 gene fusion","aka":["NTRK fusion","NTRK gene fusion","TRK fusion","NTRK1 fusion","NTRK2 fusion","NTRK3 fusion","ETV6-NTRK3","ETV6::NTRK3","TRK fusion cancer","NTRK"],"tldr":"An NTRK fusion joins one of three TRK kinase genes to a partner and drives cancers from infant fibrosarcoma to salivary and thyroid tumours, rare in common cancers but near-universal in a few rare ones. Larotrectinib, entrectinib and repotrectinib are approved for it regardless of tumour type.","summary":"NTRK1, NTRK2 and NTRK3 fusions (ETV6::NTRK3 in secretory carcinomas and infantile fibrosarcoma, LMNA::NTRK1 and TPM3::NTRK1 elsewhere) are best detected by RNA sequencing; DNA panels miss some NTRK2 and NTRK3 events because of long introns, and pan-TRK immunohistochemistry is a screen that needs molecular confirmation. Larotrectinib (2018) and entrectinib (2019) are labelled tumour-agnostically for solid tumours with an NTRK gene fusion without a known acquired resistance mutation, metastatic or where surgery would cause severe morbidity, with no satisfactory alternative or after progression; repotrectinib (2024) for NTRK fusion-positive solid tumours. FoundationOne CDx and Liquid CDx and TruSight Oncology Comprehensive are the listed companion diagnostics.","asOf":"2026-09-23","links":[{"label":"VITRAKVI prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0c8ca614-58b2-4aa4-83d3-0387a8f782fd"},{"label":"Rozlytrek prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c7c71b0c-2549-4495-86b6-c2807fa54908"}],"tags":["biomarker","fusion"],"related":["ret-fusion","ros1-fusion","alk-fusion"],"cancers":["metastatic-cancer","sarcoma","thyroid","salivary-gland","colorectal","nsclc","pancreatic","kras-wild-type-pdac","gallbladder","biliary-tract-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":["larotrectinib","entrectinib","repotrectinib","foundationone-cdx","trusight-oncology-comprehensive"],"companies":[],"institutions":[],"pathways":[],"terms":["gene-fusion","tumour-agnostic","tki-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-oreilly-hechtman-ntrk-fusion-pancreatic-larotrectinib-ann-oncol-2019","paper-philip-kras-wild-type-pancreatic-ccr-2022","paper-giraldo-gallbladder-msk-impact-ccr-2022","paper-cowzer-biliary-targeted-therapy-determinants-ccr-2026"],"journals":[],"dependsOn":[],"notes":["Pancreatic ductal adenocarcinoma: NTRK fusions in about 0.4%, enriched in KRAS wild-type disease; the published pancreatic case responded to larotrectinib for six months under the tumour-agnostic approval before acquiring resistance (O'Reilly and Hechtman 2019).","Colorectal cancer: NTRK1 and NTRK3 fusions in about 0.2 to 0.3% of tumours (cBioPortal), enriched in RAS and BRAF wild-type, mismatch repair deficient, right-sided disease. The threshold is the presence of a fusion on an RNA-based or fusion-capable DNA assay, and the approvals (larotrectinib, entrectinib) are tumour-agnostic.","Gallbladder cancer: one LMNA::NTRK1 fusion patient among 233 (about 0.4%) in cBioPortal gbc_mskcc_2022; NTRK1 fusions were among the actionable findings (Giraldo 2022) and NTRK-driven biliary tumours retained the driver at progression (Cowzer 2026). RNA-based testing is needed because DNA panels miss some NTRK2 and NTRK3 events.","Lung cancer: about 0.2% of adenocarcinomas by structural-variant calling (cBioPortal), covered by tumour-agnostic approvals rather than a lung indication. NTRK point mutations are common on exome panels and are passengers, so only a fusion assay gives an actionable result."],"target":"ntrk","measurement":"sequencing-variant","scoringRule":{"text":"An in-frame fusion involving the kinase domain of NTRK1, NTRK2 or NTRK3 detected by RNA or DNA sequencing (pan-TRK IHC as a screen only), without a known acquired resistance mutation.","quote":"NTRK1, NTRK2 and NTRK3 fusions","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools","sourceLabel":"FDA: List of FDA-Authorized Companion Diagnostic Devices"},"thresholds":[{"value":"NTRK gene fusion without a known acquired resistance mutation","drugId":"larotrectinib","cancerId":"metastatic-cancer","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0c8ca614-58b2-4aa4-83d3-0387a8f782fd","quote":"VITRAKVI is indicated for the 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.","status":"current"},{"value":"NTRK gene fusion in tumour or plasma","drugId":"entrectinib","cancerId":"metastatic-cancer","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c7c71b0c-2549-4495-86b6-c2807fa54908","quote":"Select patients for treatment of locally advanced or metastatic solid tumors with ROZLYTREK based on the presence of a NTRK gene fusion in tumor or plasma specimens","status":"current"}],"tests":["foundationone-cdx","foundationone-liquid-cdx","trusight-oncology-comprehensive","tempus-xt","caris-mi-profile","oncoextra"],"assays":["foundationone-cdx-panel","foundationone-liquid-cdx"],"companionDiagnostics":[{"device":"FoundationOne CDx","maker":"Foundation Medicine","companyId":"foundation-medicine","drugs":["larotrectinib"],"indication":"Solid Tumors - Tissue","pma":"P170019/S017 (10/23/2020)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"FoundationOne CDx","maker":"Foundation Medicine","companyId":"foundation-medicine","drugs":["entrectinib"],"indication":"Solid Tumors - Tissue","pma":"P170019/S014 (06/07/2022)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"FoundationOne Liquid CDx","maker":"Foundation Medicine","companyId":"foundation-medicine","drugs":["entrectinib"],"indication":"Solid Tumors - Plasma","pma":"P190032/S004 (12/22/2022)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"TruSight Oncology Comprehensive","maker":"Illumina","companyId":"illumina","drugs":["larotrectinib"],"indication":"Solid Tumors - Tissue","pma":"P230011 (08/21/2024)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"}],"forPatient":"If your tumour carries an NTRK fusion, a TRK tablet (larotrectinib, entrectinib or repotrectinib) is on label whatever the type of cancer, once it has spread or cannot be removed without serious harm, and responses are frequent and often long. Ask whether the test included RNA sequencing, because DNA-only panels can miss these fusions."},"route":"/biomarkers/ntrk-fusion/","neighbours":{"biomarker":[{"id":"alk-fusion","kind":"biomarker","name":"ALK fusion (ALK-positive)","route":"/biomarkers/alk-fusion/"},{"id":"nrg1-fusion","kind":"biomarker","name":"NRG1 gene fusion","route":"/biomarkers/nrg1-fusion/"},{"id":"ret-fusion","kind":"biomarker","name":"RET fusion and RET mutation","route":"/biomarkers/ret-fusion/"},{"id":"ros1-fusion","kind":"biomarker","name":"ROS1 fusion (ROS1-positive)","route":"/biomarkers/ros1-fusion/"}],"cancer":[{"id":"biliary-tract-cancer","kind":"cancer","name":"Biliary tract cancer (all types)","route":"/cancers/biliary-tract-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"},{"id":"kras-wild-type-pdac","kind":"cancer","name":"KRAS wild-type pancreatic ductal adenocarcinoma","route":"/cancers/kras-wild-type-pdac/"},{"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":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"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":"thyroid","kind":"cancer","name":"Thyroid cancer","route":"/cancers/thyroid/"}],"drug":[{"id":"entrectinib","kind":"drug","name":"Entrectinib","route":"/drugs/entrectinib/"},{"id":"foundationone-cdx","kind":"drug","name":"FoundationOne CDx / Liquid CDx","route":"/drugs/foundationone-cdx/"},{"id":"larotrectinib","kind":"drug","name":"Larotrectinib","route":"/drugs/larotrectinib/"},{"id":"repotrectinib","kind":"drug","name":"Repotrectinib","route":"/drugs/repotrectinib/"},{"id":"trusight-oncology-comprehensive","kind":"drug","name":"TruSight Oncology Comprehensive","route":"/drugs/trusight-oncology-comprehensive/"}],"term":[{"id":"gene-fusion","kind":"term","name":"Gene fusion","route":"/terms/gene-fusion/"},{"id":"tumour-agnostic","kind":"term","name":"Tumour-agnostic (tissue-agnostic) approval","route":"/terms/tumour-agnostic/"},{"id":"tki-term","kind":"term","name":"Tyrosine kinase inhibitor (TKI)","route":"/terms/tki-term/"}],"paper":[{"id":"paper-giraldo-gallbladder-msk-impact-ccr-2022","kind":"paper","name":"Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention","route":"/key-papers/paper-giraldo-gallbladder-msk-impact-ccr-2022/"},{"id":"paper-cowzer-biliary-targeted-therapy-determinants-ccr-2026","kind":"paper","name":"Molecular and clinical determinants of targeted therapy treatment in biliary tract cancer","route":"/key-papers/paper-cowzer-biliary-targeted-therapy-determinants-ccr-2026/"},{"id":"paper-philip-kras-wild-type-pancreatic-ccr-2022","kind":"paper","name":"Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma","route":"/key-papers/paper-philip-kras-wild-type-pancreatic-ccr-2022/"},{"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 fusion","route":"/key-papers/paper-oreilly-hechtman-ntrk-fusion-pancreatic-larotrectinib-ann-oncol-2019/"}],"target":[{"id":"ntrk","kind":"target","name":"NTRK","route":"/targets/ntrk/"}]}}