{"entity":{"id":"encorafenib","kind":"drug","name":"Encorafenib","aka":[],"tldr":"Encorafenib is a BRAF inhibitor that, with cetuximab and chemotherapy, became first-line standard for BRAF-mutant colorectal cancer in 2026.","summary":"Encorafenib is an ATP-competitive BRAF V600 inhibitor with a long target residence time, giving sustained pathway suppression. It is used with binimetinib in BRAF V600 melanoma (COLUMBUS, approved 2018), with cetuximab in previously treated BRAF V600E colorectal cancer (BEACON, 2020), and with cetuximab plus FOLFOX first line for BRAF V600E metastatic colorectal cancer after BREAKWATER (accelerated approval December 2024, full approval 2026 with an overall survival benefit); it is also used with binimetinib in BRAF V600E NSCLC. In colorectal cancer the EGFR antibody is essential because BRAF blockade alone triggers feedback reactivation through EGFR. Dosing is 450 mg daily with binimetinib or 300 mg daily with cetuximab; new primary skin cancers are a class risk. For a newcomer: the BRAF drug that finally worked in bowel cancer once paired with the right partners.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Encorafenib","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Encorafenib"},{"label":"NICE TA668: encorafenib plus cetuximab for previously treated BRAF V600E metastatic colorectal cancer","url":"https://www.nice.org.uk/guidance/ta668"},{"label":"EMA Braftovi","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/braftovi"},{"label":"FDA oncology approval notifications","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancerhematologic-malignancies-approval-notifications"}],"tags":[],"related":["braf-v600e"],"cancers":["colorectal","melanoma","nsclc","braf-v600e-colorectal","braf-v600e-nsclc","braf-v600-melanoma","advanced-melanoma"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["braf","egfr"],"drugs":[],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":[],"trials":["nct05270044","nct04657991","nct05217446","nct05195632","swog-s1406"],"people":[],"bottlenecks":[],"keyPapers":["paper-venderbosch-mmr-braf-metastatic-colorectal-pooled-ccr-2014","paper-jones-non-v600-braf-colorectal-jco-2017"],"journals":[],"dependsOn":[],"notes":["Colorectal cancer biomarkers: the threshold is BRAF V600E specifically, present in 6 to 18% of tumours by cohort and 8.2% of first-line metastatic patients. Non-V600 BRAF mutations, 22% of all BRAF mutations found on sequencing, are not covered: they signal differently and carry a median overall survival of 60.7 months rather than 11.4 (Jones 2017)."],"brand":"Braftovi","modality":"Small-molecule kinase inhibitor (BRAF)","mechanism":"ATP-competitive BRAF V600 inhibitor with long target residence time.","approvals":[{"region":"US","year":2018,"indication":"BRAF V600 melanoma with binimetinib"},{"region":"US","year":2020,"indication":"BRAF V600E mCRC with cetuximab, previously treated"},{"region":"US","year":2026,"indication":"First-line BRAF V600E mCRC with cetuximab and chemotherapy"},{"region":"US","year":2024,"indication":"Metastatic colorectal cancer with a BRAF V600E mutation, with cetuximab and mFOLFOX6, previously untreated","note":"Accelerated approval on 20 December 2024 on BREAKWATER."},{"region":"US","year":2026,"indication":"Metastatic colorectal cancer with a BRAF V600E mutation","note":"Traditional approval granted 24 February 2026, converting the accelerated approval."},{"region":"EU","year":2018,"indication":"BRAF V600E-mutant metastatic colorectal cancer, with cetuximab","note":"Braftovi marketing authorisation issued 19 September 2018; the EMA product page lists metastatic colorectal cancer with the BRAF V600E mutation among its uses alongside melanoma and non-small-cell lung cancer."},{"region":"England (NICE)","year":2021,"indication":"BRAF V600E mutation-positive metastatic colorectal cancer after previous systemic treatment, with cetuximab","note":"TA668, published 6 January 2021, subject to the commercial arrangements. There is no NICE recommendation for the first-line triplet with chemotherapy."}],"mechanismSteps":["Oral drug is absorbed and reaches the tumour","Binds the ATP pocket (or allosteric site) of BRAF V600E","Phosphorylation of downstream substrates stops","Long target residence time; paired with MEK or EGFR blockade to prevent pathway reactivation","Oncogene-addicted cells arrest and undergo apoptosis"],"dosing":{"route":"Oral","schedule":"450 mg once daily with binimetinib (melanoma); 300 mg once daily with cetuximab ± FOLFOX (colorectal)","modifications":"Reduce for uveitis, QTc, hepatotoxicity","monitoring":"Dermatologic exams (new primary skin cancers), ECG, LFTs, eye exams","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},"toxicity":[{"event":"Fatigue"},{"event":"Nausea"},{"event":"Diarrhoea"},{"event":"Vomiting"},{"event":"Arthralgia"},{"event":"Rash"},{"event":"Dermatologic reactions"},{"event":"New primary cutaneous malignancies"}],"access":[{"country":"US","reimbursement":"Medicare Part D (oral); commercial plans per formulary, often with prior authorisation","assistance":"https://www.pfizeroncologytogether.com","source":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files","asOf":"2026-09-06"},{"country":"UK","reimbursement":"NICE: recommended with binimetinib in BRAF V600 melanoma (TA562) and with cetuximab in BRAF V600E CRC (TA668)","source":"https://www.nice.org.uk/guidance/published?ngt=Technology%20appraisal%20guidance","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2018-06-27","type":"approval","region":"US","note":"BRAF V600 melanoma with binimetinib (COLUMBUS)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2020-04-08","type":"approval","region":"US","note":"BRAF V600E metastatic CRC with cetuximab after prior therapy (BEACON)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2023-10-11","type":"approval","region":"US","note":"BRAF V600E NSCLC with binimetinib","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2024-12-20","type":"accelerated-approval","region":"US","note":"First-line BRAF V600E mCRC with cetuximab and mFOLFOX6 (BREAKWATER, accelerated)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications","indication":"In combination with cetuximab and mFOLFOX6, for the treatment of patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation, as detected by an FDA-approved test"},{"date":"2026-Q1","type":"approval","region":"US","note":"Full approval in first-line BRAF V600E mCRC with OS benefit","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2026-02-24","type":"conversion","region":"US","note":"Confirmed: the accelerated approval of 2024 converted to traditional approval 1.2 years after it was granted.","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-encorafenib-cetuximab-and-mfolfox6-metastatic-colorectal-cancer-braf","indication":"In combination with cetuximab and mFOLFOX6, for the treatment of patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation, as detected by an FDA-approved test"}]},"route":"/drugs/encorafenib/","neighbours":{"biomarker":[{"id":"braf-v600e","kind":"biomarker","name":"BRAF V600E (and V600K)","route":"/biomarkers/braf-v600e/"},{"id":"ras-wild-type","kind":"biomarker","name":"RAS wild-type (extended KRAS and NRAS testing)","route":"/biomarkers/ras-wild-type/"}],"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":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"early-onset-colorectal","kind":"cancer","name":"Early-onset colorectal cancer (under 50)","route":"/cancers/early-onset-colorectal/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"colorectal-serrated-adenocarcinoma","kind":"cancer","name":"Serrated adenocarcinoma of the colon and rectum","route":"/cancers/colorectal-serrated-adenocarcinoma/"}],"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/"},{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"}],"company":[{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"},{"id":"pierre-fabre","kind":"company","name":"Pierre Fabre","route":"/companies/pierre-fabre/"}],"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":"nct05217446","kind":"trial","name":"A Study of Encorafenib Plus Cetuximab Taken Together With Pembrolizumab Compared to Pembrolizumab Alone in People With Previously Untreated Metastatic","route":"/trials/nct05217446/"},{"id":"nct07178717","kind":"trial","name":"A Study to Characterize Encorafenib Plus Cetuximab as Rechallenge Treatment for BRAF V600E-mutant Metastatic Colorectal Cancer Patients After Previous Therapy W","route":"/trials/nct07178717/"},{"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":"breakwater","kind":"trial","name":"BREAKWATER","route":"/trials/breakwater/"},{"id":"columbus","kind":"trial","name":"COLUMBUS","route":"/trials/columbus/"},{"id":"nct06411600","kind":"trial","name":"Combination Therapy for BRAF-V600E Metastatic CRCm","route":"/trials/nct06411600/"},{"id":"nct03803553","kind":"trial","name":"Identification and Treatment Of Micrometastatic Disease in Stage III Colon Cancer","route":"/trials/nct03803553/"},{"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":"nct05725200","kind":"trial","name":"Study to Investigate Outcome of Individualized Treatment in Patients With 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Ascierto","route":"/people/paolo-ascierto/"},{"id":"reinhard-dummer","kind":"person","name":"Reinhard Dummer","route":"/people/reinhard-dummer/"},{"id":"rene-bernards","kind":"person","name":"René Bernards","route":"/people/rene-bernards/"},{"id":"ryan-corcoran","kind":"person","name":"Ryan B. Corcoran","route":"/people/ryan-corcoran/"},{"id":"scott-kopetz","kind":"person","name":"Scott Kopetz","route":"/people/scott-kopetz/"},{"id":"sherry-lansing","kind":"person","name":"Sherry Lansing","route":"/people/sherry-lansing/"}],"idea":[{"id":"idea-bio1-drug-holiday-resensitisation","kind":"idea","name":"Pause a failed drug so the tumour becomes sensitive to it again","route":"/ideas/idea-bio1-drug-holiday-resensitisation/"}]}}