{"entity":{"id":"beacon-crc","kind":"trial","name":"BEACON CRC","aka":[],"tldr":"BEACON was the first trial to show that blocking BRAF works in bowel cancer once the escape route through EGFR is blocked too: encorafenib with cetuximab lengthened life and shrank ten times as many tumours as chemotherapy.","summary":"BEACON CRC randomised 665 patients with BRAF V600E-mutant metastatic colorectal cancer that had progressed after one or two regimens to encorafenib, binimetinib and cetuximab (triplet), encorafenib and cetuximab (doublet), or investigator-choice irinotecan or FOLFIRI with cetuximab. Earlier BRAF inhibitor monotherapy had failed in this disease because loss of BRAF signalling releases feedback activation of EGFR, which the antibody blocks.\n\nIn the updated analysis median overall survival was 9.3 months with the triplet and 9.3 months with the doublet against 5.9 months with control; confirmed response rates were 27 percent, 20 percent and 2 percent. The MEK inhibitor added toxicity without a survival gain, so the doublet became the regimen taken forward.\n\nThe FDA approved encorafenib with cetuximab for previously treated BRAF V600E colorectal cancer in April 2020, the first targeted therapy for this subtype, and BREAKWATER then moved the doublet, with FOLFOX, into first-line treatment.","status":"positive","asOf":"2026-09-17","links":[{"label":"ClinicalTrials.gov NCT02928224","url":"https://clinicaltrials.gov/study/NCT02928224"},{"label":"New England Journal of Medicine 2019","url":"https://doi.org/10.1056/NEJMoa1908075"},{"label":"Journal of Clinical Oncology 2021 (updated survival)","url":"https://doi.org/10.1200/JCO.20.02088"}],"tags":[],"related":[],"cancers":["colorectal","braf-v600e-colorectal"],"sections":[],"technologies":["kinase-inhibitors","monoclonal-antibody"],"targets":["braf","egfr","mek"],"drugs":["encorafenib","binimetinib","cetuximab","folfiri","irinotecan"],"companies":["pfizer"],"institutions":[],"pathways":["ras-mapk"],"terms":[],"trials":[],"people":["scott-kopetz","josep-tabernero","elena-elez"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02928224","phase":"3","setting":"BRAF V600E-mutant metastatic colorectal cancer after one or two prior lines: encorafenib plus cetuximab with or without binimetinib, versus irinotecan-based chemotherapy plus cetuximab","sponsor":"Pfizer (Array BioPharma)","result":"Median overall survival 9.3 months (encorafenib-cetuximab, with or without binimetinib) vs 5.9 months (chemotherapy plus cetuximab); response rate 20% (doublet) vs 2%.","yearReported":2019,"enrolled":665,"outcomes":[{"endpoint":"Overall survival (updated analysis)","primary":true,"unit":"months","arms":[{"name":"Encorafenib + binimetinib + cetuximab","n":224,"value":9.3},{"name":"Encorafenib + cetuximab","n":220,"value":9.3},{"name":"Chemotherapy + cetuximab","n":221,"value":5.9}],"source":"https://doi.org/10.1200/JCO.20.02088"},{"endpoint":"Confirmed objective response rate","unit":"%","arms":[{"name":"Encorafenib + binimetinib + cetuximab","n":224,"value":27},{"name":"Encorafenib + cetuximab","n":220,"value":20},{"name":"Chemotherapy + cetuximab","n":221,"value":2}],"source":"https://doi.org/10.1200/JCO.20.02088"}],"replication":"BREAKWATER replicated the biology in first line with a larger survival gain; the earlier SWOG S1406 trial had shown the same EGFR-feedback rationale with vemurafenib, irinotecan and cetuximab."},"route":"/trials/beacon-crc/","neighbours":{"cancer":[{"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/"}],"technology":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"},{"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/"},{"id":"mek","kind":"target","name":"MEK1/2","route":"/targets/mek/"}],"drug":[{"id":"binimetinib","kind":"drug","name":"Binimetinib","route":"/drugs/binimetinib/"},{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"},{"id":"encorafenib","kind":"drug","name":"Encorafenib","route":"/drugs/encorafenib/"},{"id":"folfiri","kind":"drug","name":"FOLFIRI (5-FU, leucovorin, irinotecan)","route":"/drugs/folfiri/"},{"id":"irinotecan","kind":"drug","name":"Irinotecan (and liposomal irinotecan)","route":"/drugs/irinotecan/"}],"company":[{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"person":[{"id":"elena-elez","kind":"person","name":"Elena Élez","route":"/people/elena-elez/"},{"id":"josep-tabernero","kind":"person","name":"Josep Tabernero","route":"/people/josep-tabernero/"},{"id":"scott-kopetz","kind":"person","name":"Scott Kopetz","route":"/people/scott-kopetz/"}]}}