{"entity":{"id":"vemurafenib","kind":"drug","name":"Vemurafenib","aka":[],"tldr":"Vemurafenib was the first BRAF inhibitor (2011); it shrank melanomas in weeks and proved that a single mutation could be drugged in a solid tumour.","summary":"BRIM-3: OS benefit versus dacarbazine in BRAF V600E melanoma; approved August 2011 alongside ipilimumab in the same year that transformed the disease. Now used with cobimetinib (coBRIM) or displaced by encorafenib-binimetinib and dabrafenib-trametinib. Also approved for Erdheim-Chester disease. Photosensitivity, arthralgia, and cutaneous squamous cell carcinomas (from paradoxical MAPK activation in RAS-mutant keratinocytes) are characteristic.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Vemurafenib","links":[{"label":"BRIM-3, NEJM 2011","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1103782"}],"tags":[],"related":["braf-v600e"],"cancers":["melanoma","braf-v600-melanoma","advanced-melanoma","colorectal","braf-v600e-colorectal"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["braf"],"drugs":[],"companies":["roche-genentech"],"institutions":[],"pathways":["ras-mapk"],"terms":[],"trials":["columbus","nct04302025","swog-s1406"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["In colorectal cancer vemurafenib alone is almost inactive because BRAF blockade causes feedback activation of EGFR. SWOG S1406 added it to irinotecan and cetuximab in previously treated BRAF V600E disease and improved progression-free survival (hazard ratio 0.50, p=0.001) and response (17 against 4 percent), the proof of principle that BEACON CRC and BREAKWATER turned into approved encorafenib-based regimens."],"brand":"Zelboraf","modality":"Small-molecule kinase inhibitor (BRAF V600)","mechanism":"ATP-competitive inhibitor of BRAF V600 monomers; paradoxically activates wild-type RAF dimers, hence MEK partnering.","approvals":[{"region":"US","year":2011,"indication":"Unresectable or metastatic BRAF V600E melanoma"},{"region":"US","year":2017,"indication":"Erdheim-Chester disease with BRAF V600 mutation"}],"mechanismSteps":["Vemurafenib enters the cell and binds the ATP pocket of mutant BRAF V600E","MEK and ERK phosphorylation fall within hours","Proliferation stops and apoptosis follows in BRAF-addicted melanoma cells","In RAS-active normal cells, drug-bound BRAF dimerises with CRAF and paradoxically boosts signalling, causing skin squamous lesions","Resistance emerges via NRAS mutation, BRAF splice variants, or MEK mutations, restoring ERK output"],"dosing":{"route":"Oral","schedule":"960 mg twice daily continuously","modifications":"Dose reduction for grade 2-3 rash, arthralgia, photosensitivity, QT prolongation","monitoring":"Dermatology exams for squamous cell carcinoma; ECG; liver enzymes","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/202429s019lbl.pdf"},"toxicity":[{"event":"Cutaneous squamous cell carcinoma / keratoacanthoma","anyGradePct":24,"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa1103782","note":"BRIM-3 vemurafenib arm"},{"event":"Arthralgia","anyGradePct":53,"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa1103782"},{"event":"Photosensitivity","anyGradePct":33,"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa1103782"}],"access":[],"regulatoryEvents":[{"date":"2011-08-17","type":"approval","region":"US","note":"Approved with the cobas BRAF V600 companion test, the first melanoma targeted therapy"},{"date":"2015-11-10","type":"approval","region":"US","note":"Cobimetinib approved in combination (coBRIM)"}]},"route":"/drugs/vemurafenib/","neighbours":{"biomarker":[{"id":"braf-v600e","kind":"biomarker","name":"BRAF V600E (and V600K)","route":"/biomarkers/braf-v600e/"}],"cancer":[{"id":"advanced-melanoma","kind":"cancer","name":"Advanced melanoma (unresectable stage III and stage IV)","route":"/cancers/advanced-melanoma/"},{"id":"braf-v600-melanoma","kind":"cancer","name":"BRAF V600-mutant melanoma","route":"/cancers/braf-v600-melanoma/"},{"id":"braf-v600e-colorectal","kind":"cancer","name":"BRAF V600E-mutant colorectal cancer","route":"/cancers/braf-v600e-colorectal/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"craniopharyngioma","kind":"cancer","name":"Craniopharyngioma","route":"/cancers/craniopharyngioma/"},{"id":"erdheim-chester-disease","kind":"cancer","name":"Erdheim-Chester disease","route":"/cancers/erdheim-chester-disease/"},{"id":"histiocytoses","kind":"cancer","name":"Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms","route":"/cancers/histiocytoses/"},{"id":"hairy-cell-leukemia","kind":"cancer","name":"Hairy cell leukaemia","route":"/cancers/hairy-cell-leukemia/"},{"id":"langerhans-cell-histiocytosis","kind":"cancer","name":"Langerhans cell histiocytosis (LCH)","route":"/cancers/langerhans-cell-histiocytosis/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"lch-multisystem","kind":"cancer","name":"Multisystem Langerhans cell histiocytosis (with or without risk-organ involvement)","route":"/cancers/lch-multisystem/"},{"id":"lch-single-system","kind":"cancer","name":"Single-system Langerhans cell histiocytosis (bone, skin or one other organ)","route":"/cancers/lch-single-system/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"}],"company":[{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"pathway":[{"id":"melanoma-signalling","kind":"pathway","name":"Melanoma (KEGG map)","route":"/pathways/melanoma-signalling/"},{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"trial":[{"id":"nct02050321","kind":"trial","name":"A Phase II Study of Vemurafenib Combined With Acitretin in Patients With Advanced Melanoma","route":"/trials/nct02050321/"},{"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":"cobrim","kind":"trial","name":"coBRIM","route":"/trials/cobrim/"},{"id":"columbus","kind":"trial","name":"COLUMBUS","route":"/trials/columbus/"},{"id":"cupisco","kind":"trial","name":"CUPISCO","route":"/trials/cupisco/"},{"id":"determine-trial","kind":"trial","name":"DETERMINE","route":"/trials/determine-trial/"},{"id":"nct05768178","kind":"trial","name":"DETERMINE Trial Treatment Arm 05: Vemurafenib in Combination With Cobimetinib in Adult Patients With BRAF Positive Cancers.","route":"/trials/nct05768178/"},{"id":"imspire150","kind":"trial","name":"IMspire150","route":"/trials/imspire150/"},{"id":"mypathway","kind":"trial","name":"MyPathway","route":"/trials/mypathway/"},{"id":"pediatric-match","kind":"trial","name":"NCI-COG Pediatric MATCH (APEC1621)","route":"/trials/pediatric-match/"},{"id":"swog-s1406","kind":"trial","name":"SWOG S1406","route":"/trials/swog-s1406/"},{"id":"tapur","kind":"trial","name":"TAPUR (Targeted Agent and Profiling Utilization Registry)","route":"/trials/tapur/"}],"drug":[{"id":"cobimetinib","kind":"drug","name":"Cobimetinib","route":"/drugs/cobimetinib/"}],"person":[{"id":"mcarthur-grant","kind":"person","name":"Grant McArthur","route":"/people/mcarthur-grant/"},{"id":"keith-flaherty","kind":"person","name":"Keith T. Flaherty","route":"/people/keith-flaherty/"}],"paper":[{"id":"paper-chapman-vemurafenib-nejm-2011","kind":"paper","name":"BRIM-3: improved survival with vemurafenib in melanoma with BRAF V600E mutation","route":"/key-papers/paper-chapman-vemurafenib-nejm-2011/"},{"id":"paper-columbus-lancet-oncol-2018","kind":"paper","name":"COLUMBUS: encorafenib plus binimetinib versus vemurafenib or encorafenib in BRAF-mutant melanoma","route":"/key-papers/paper-columbus-lancet-oncol-2018/"},{"id":"paper-erdheim-chester-disease-consensus-recommendations-blood-2020","kind":"paper","name":"Erdheim-Chester disease: consensus recommendations for evaluation, diagnosis and treatment in the molecular era","route":"/key-papers/paper-erdheim-chester-disease-consensus-recommendations-blood-2020/"},{"id":"paper-ve-basket-vemurafenib-erdheim-chester-lch-jama-oncol-2018","kind":"paper","name":"VE-BASKET: vemurafenib for BRAF V600-mutant Erdheim-Chester disease and Langerhans cell histiocytosis","route":"/key-papers/paper-ve-basket-vemurafenib-erdheim-chester-lch-jama-oncol-2018/"},{"id":"paper-donadieu-vemurafenib-refractory-multisystem-lch-jco-2019","kind":"paper","name":"Vemurafenib for refractory multisystem Langerhans cell histiocytosis in children: an international observational study","route":"/key-papers/paper-donadieu-vemurafenib-refractory-multisystem-lch-jco-2019/"}],"term":[{"id":"braf-v600-mutation","kind":"term","name":"BRAF V600E mutation","route":"/terms/braf-v600-mutation/"}]}}