{"entity":{"id":"binimetinib","kind":"drug","name":"Binimetinib","aka":[],"tldr":"Binimetinib is the MEK inhibitor partnered with encorafenib; blocking the next step in the same relay stops the tumour rerouting around the BRAF block.","summary":"Binimetinib is an allosteric, ATP-non-competitive inhibitor of MEK1 and MEK2, the kinases immediately downstream of BRAF; blocking the next step in the relay stops the tumour rerouting around a BRAF inhibitor. It is given at 45 mg twice daily with encorafenib 450 mg once daily for BRAF V600E/K melanoma (approved June 2018 on COLUMBUS) and BRAF V600E metastatic NSCLC (2023). COLUMBUS showed median PFS of 14.9 versus 7.3 months for vemurafenib (HR 0.54) and median OS of 33.6 months, with less pyrexia than dabrafenib-trametinib. Class effects are retinopathy (serous retinal detachment), CK elevation, left-ventricular dysfunction, rash and diarrhoea, so eye examinations, echocardiograms and CK monitoring are recommended. Whether BRAF/MEK doublets or immunotherapy should come first in BRAF-mutant melanoma remains debated. For a newcomer, binimetinib is the MEK half of the encorafenib pair.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Binimetinib","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Binimetinib"}],"tags":[],"related":[],"cancers":["melanoma","nsclc","braf-v600e-nsclc","braf-v600-melanoma","advanced-melanoma"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["braf"],"drugs":["encorafenib"],"companies":["pfizer"],"institutions":[],"pathways":["ras-mapk"],"terms":["ocular-toxicity"],"trials":["columbus","nct05270044","nct04657991","nct03947385","nct05195632"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Mektovi","modality":"Small-molecule kinase inhibitor (MEK1/2)","mechanism":"Allosteric, ATP-non-competitive MEK1/2 inhibitor.","approvals":[{"region":"US","year":2018,"indication":"BRAF V600E/K melanoma with encorafenib"},{"region":"US","year":2023,"indication":"BRAF V600E metastatic NSCLC with encorafenib"}],"mechanismSteps":["Binds MEK1/2 outside the ATP site and locks them in an inactive conformation","ERK phosphorylation falls even if RAF activity rebounds","Combined with a BRAF inhibitor, blocks the paradoxical activation that causes squamous skin lesions and delays resistance"],"dosing":{"route":"Oral","schedule":"45 mg twice daily with encorafenib 450 mg once daily","modifications":"Hold for retinopathy, LVEF drop, CK rise","monitoring":"Ophthalmology at baseline and for symptoms; echocardiogram; CK","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/210498s009lbl.pdf"},"toxicity":[],"access":[],"regulatoryEvents":[{"date":"2018-06-27","type":"approval","region":"US","note":"Encorafenib + binimetinib approved for BRAF V600 melanoma"}]},"route":"/drugs/binimetinib/","neighbours":{"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":"braf-v600e-nsclc","kind":"cancer","name":"BRAF V600E-mutant non-small-cell lung cancer","route":"/cancers/braf-v600e-nsclc/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"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/"}],"drug":[{"id":"encorafenib","kind":"drug","name":"Encorafenib","route":"/drugs/encorafenib/"}],"company":[{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"},{"id":"pierre-fabre","kind":"company","name":"Pierre Fabre","route":"/companies/pierre-fabre/"}],"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/"}],"term":[{"id":"ocular-toxicity","kind":"term","name":"Ocular toxicity (keratopathy, blurred vision)","route":"/terms/ocular-toxicity/"}],"trial":[{"id":"nct04657991","kind":"trial","name":"A Clinical Trial of Three Study Medicines (Encorafenib, Binimetinib, and Pembrolizumab) in Patients With Advanced or Metastatic Melanoma","route":"/trials/nct04657991/"},{"id":"nct05270044","kind":"trial","name":"Adjuvant Encorafenib and Binimetinib in High-risk Stage II Melanoma With a BRAF Mutation.","route":"/trials/nct05270044/"},{"id":"beacon-crc","kind":"trial","name":"BEACON CRC","route":"/trials/beacon-crc/"},{"id":"columbus","kind":"trial","name":"COLUMBUS","route":"/trials/columbus/"},{"id":"combomatch-binimetinib-folfox","kind":"trial","name":"ComboMATCH: FOLFOX with or without binimetinib in second-line biliary tract cancer with MAPK pathway alterations","route":"/trials/combomatch-binimetinib-folfox/"},{"id":"nct03803553","kind":"trial","name":"Identification and Treatment Of Micrometastatic Disease in Stage III Colon Cancer","route":"/trials/nct03803553/"},{"id":"nci-match","kind":"trial","name":"NCI-MATCH (EAY131)","route":"/trials/nci-match/"},{"id":"pharos","kind":"trial","name":"PHAROS","route":"/trials/pharos/"},{"id":"nct05195632","kind":"trial","name":"Phase II Study Investigating the Combination of Encorafenib and Binimetinib in BRAF V600E Mutated Chinese Patients With Metastatic Non-Small Cell Lung","route":"/trials/nct05195632/"},{"id":"nct03947385","kind":"trial","name":"Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions","route":"/trials/nct03947385/"}],"paper":[{"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-kopetz-beacon-encorafenib-braf-colorectal-nejm-2019","kind":"paper","name":"Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer (BEACON CRC)","route":"/key-papers/paper-kopetz-beacon-encorafenib-braf-colorectal-nejm-2019/"},{"id":"paper-pharos-encorafenib-binimetinib-riely-jco-2023","kind":"paper","name":"PHAROS: encorafenib plus binimetinib in BRAF V600E-mutant metastatic non-small-cell lung cancer","route":"/key-papers/paper-pharos-encorafenib-binimetinib-riely-jco-2023/"}],"biomarker":[{"id":"braf-v600e","kind":"biomarker","name":"BRAF V600E (and V600K)","route":"/biomarkers/braf-v600e/"}]}}