# Encorafenib

Source: https://onco.cc/drugs/encorafenib/  
OnCo record `encorafenib` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-04
- Brand: Braftovi
- Modality: Small-molecule kinase inhibitor (BRAF)
- Mechanism: ATP-competitive BRAF V600 inhibitor with long target residence time.
- Approvals: US 2018: BRAF V600 melanoma with binimetinib; US 2020: BRAF V600E mCRC with cetuximab, previously treated; US 2026: First-line BRAF V600E mCRC with cetuximab and chemotherapy; US 2024: Metastatic colorectal cancer with a BRAF V600E mutation, with cetuximab and mFOLFOX6, previously untreated; US 2026: Metastatic colorectal cancer with a BRAF V600E mutation; EU 2018: BRAF V600E-mutant metastatic colorectal cancer, with cetuximab; England (NICE) 2021: BRAF V600E mutation-positive metastatic colorectal cancer after previous systemic treatment, with cetuximab
- Dosing: Oral; 450 mg once daily with binimetinib (melanoma); 300 mg once daily with cetuximab ± FOLFOX (colorectal)

## 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).

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Encorafenib
- FDA label (DailyMed): https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Encorafenib
- NICE TA668: encorafenib plus cetuximab for previously treated BRAF V600E metastatic colorectal cancer: https://www.nice.org.uk/guidance/ta668
- EMA Braftovi: https://www.ema.europa.eu/en/medicines/human/EPAR/braftovi
- FDA oncology approval notifications: https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancerhematologic-malignancies-approval-notifications

## Connected records

- biomarkers: [BRAF V600E (and V600K)](https://onco.cc/biomarkers/braf-v600e/), [RAS wild-type (extended KRAS and NRAS testing)](https://onco.cc/biomarkers/ras-wild-type/)
- cancers: [Advanced melanoma (unresectable stage III and stage IV)](https://onco.cc/cancers/advanced-melanoma/), [BRAF V600-mutant melanoma](https://onco.cc/cancers/braf-v600-melanoma/), [BRAF V600E-mutant colorectal cancer](https://onco.cc/cancers/braf-v600e-colorectal/), [BRAF V600E-mutant non-small-cell lung cancer](https://onco.cc/cancers/braf-v600e-nsclc/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Early-onset colorectal cancer (under 50)](https://onco.cc/cancers/early-onset-colorectal/), [Melanoma](https://onco.cc/cancers/melanoma/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Serrated adenocarcinoma of the colon and rectum](https://onco.cc/cancers/colorectal-serrated-adenocarcinoma/)
- technologies: [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [BRAF](https://onco.cc/targets/braf/), [EGFR](https://onco.cc/targets/egfr/)
- companies: [Pfizer (incl. Seagen)](https://onco.cc/companies/pfizer/), [Pierre Fabre](https://onco.cc/companies/pierre-fabre/)
- trials: [A Clinical Trial of Three Study Medicines (Encorafenib, Binimetinib, and Pembrolizumab) in Patients With Advanced or Metastatic Melanoma](https://onco.cc/trials/nct04657991/), [A Study of Encorafenib Plus Cetuximab Taken Together With Pembrolizumab Compared to Pembrolizumab Alone in People With Previously Untreated Metastatic](https://onco.cc/trials/nct05217446/), [A Study to Characterize Encorafenib Plus Cetuximab as Rechallenge Treatment for BRAF V600E-mutant Metastatic Colorectal Cancer Patients After Previous Therapy W](https://onco.cc/trials/nct07178717/), [Adjuvant Encorafenib and Binimetinib in High-risk Stage II Melanoma With a BRAF Mutation.](https://onco.cc/trials/nct05270044/), [BEACON CRC](https://onco.cc/trials/beacon-crc/), [BREAKWATER](https://onco.cc/trials/breakwater/), [COLUMBUS](https://onco.cc/trials/columbus/), [Combination Therapy for BRAF-V600E Metastatic CRCm](https://onco.cc/trials/nct06411600/), [Identification and Treatment Of Micrometastatic Disease in Stage III Colon Cancer](https://onco.cc/trials/nct03803553/), [PHAROS](https://onco.cc/trials/pharos/), [Phase II Study Investigating the Combination of Encorafenib and Binimetinib in BRAF V600E Mutated Chinese Patients With Metastatic Non-Small Cell Lung](https://onco.cc/trials/nct05195632/), [Study to Investigate Outcome of Individualized Treatment in Patients With Metastatic Colorectal Cancer](https://onco.cc/trials/nct05725200/), [SWOG S1406](https://onco.cc/trials/swog-s1406/), [Testing the Use of BRAF-Targeted Therapy After Surgery and Usual Chemotherapy for BRAF-Mutated Colon Cancer](https://onco.cc/trials/nct05710406/)
- key papers: [BREAKWATER: encorafenib plus cetuximab with chemotherapy as first treatment for BRAF V600E-mutated colorectal cancer](https://onco.cc/key-papers/paper-breakwater-nejm-2025/), [COLUMBUS: encorafenib plus binimetinib versus vemurafenib or encorafenib in BRAF-mutant melanoma](https://onco.cc/key-papers/paper-columbus-lancet-oncol-2018/), [Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer (BEACON CRC)](https://onco.cc/key-papers/paper-kopetz-beacon-encorafenib-braf-colorectal-nejm-2019/), [Mismatch repair status and BRAF mutation status in metastatic colorectal cancer: a pooled analysis of the CAIRO, CAIRO2, COIN and FOCUS studies](https://onco.cc/key-papers/paper-venderbosch-mmr-braf-metastatic-colorectal-pooled-ccr-2014/), [Non-V600 BRAF mutations define a clinically distinct molecular subtype of metastatic colorectal cancer](https://onco.cc/key-papers/paper-jones-non-v600-braf-colorectal-jco-2017/), [PHAROS: encorafenib plus binimetinib in BRAF V600E-mutant metastatic non-small-cell lung cancer](https://onco.cc/key-papers/paper-pharos-encorafenib-binimetinib-riely-jco-2023/)
- drugs: [Binimetinib](https://onco.cc/drugs/binimetinib/), [therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF)](https://onco.cc/drugs/therascreen-cdx/)
- pairings: [BRAF inhibitor + MEK inhibitor](https://onco.cc/pairings/braf-plus-mek/), [Immunotherapy first, then BRAF/MEK (BRAF-mutant melanoma)](https://onco.cc/pairings/io-first-then-braf-mek/)
- roadmaps: [Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation](https://onco.cc/roadmaps/colorectal-roadmap/)
- terms: [Colorectal cancer drugs in England: what NICE has recommended](https://onco.cc/terms/colorectal-uk-drug-access/)
- institutions: [Vall d'Hebron University Hospital / VHIO](https://onco.cc/institutions/vall-dhebron/)
- pathways: [Colorectal cancer (KEGG map)](https://onco.cc/pathways/colorectal-cancer-signalling/), [Melanoma (KEGG map)](https://onco.cc/pathways/melanoma-signalling/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- people: [Elena Élez](https://onco.cc/people/elena-elez/), [Josep Tabernero](https://onco.cc/people/josep-tabernero/), [Paolo A. Ascierto](https://onco.cc/people/paolo-ascierto/), [Reinhard Dummer](https://onco.cc/people/reinhard-dummer/), [René Bernards](https://onco.cc/people/rene-bernards/), [Ryan B. Corcoran](https://onco.cc/people/ryan-corcoran/), [Scott Kopetz](https://onco.cc/people/scott-kopetz/), [Sherry Lansing](https://onco.cc/people/sherry-lansing/)
- ideas: [Pause a failed drug so the tumour becomes sensitive to it again](https://onco.cc/ideas/idea-bio1-drug-holiday-resensitisation/)

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