{"entity":{"id":"cobrim","kind":"trial","name":"coBRIM","aka":[],"tldr":"coBRIM showed that adding cobimetinib to vemurafenib gives people with BRAF-mutant melanoma about five more months before the disease grows and about five more months of life.","summary":"coBRIM randomised 495 patients with untreated BRAF V600 metastatic melanoma to vemurafenib with cobimetinib or vemurafenib with placebo. It was the second phase 3 trial of a BRAF plus MEK doublet and used the first approved BRAF inhibitor as its backbone.\n\nMedian progression-free survival was 12.3 months with the combination against 7.2 months (hazard ratio 0.58) in the updated analysis (Lancet Oncology 2016), and median overall survival 22.3 months against 17.4 months (hazard ratio 0.70). Serous retinopathy, raised creatine kinase and photosensitivity were the notable toxicities; secondary skin cancers were less frequent than with vemurafenib alone.\n\nThe result led to approval of cobimetinib in late 2015 and, with COMBI-d and COMBI-v, settled that the doublet rather than a single BRAF inhibitor is the standard. The vemurafenib-cobimetinib backbone was later used in IMspire150 to test the addition of atezolizumab.","status":"positive","asOf":"2026-09-17","links":[{"label":"ClinicalTrials.gov NCT01689519","url":"https://clinicaltrials.gov/study/NCT01689519"},{"label":"NEJM 2014","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1408868"},{"label":"Updated analysis, Lancet Oncology 2016","url":"https://doi.org/10.1016/S1470-2045(16)30122-X"}],"tags":[],"related":[],"cancers":["braf-v600-melanoma","advanced-melanoma","melanoma"],"sections":[],"technologies":[],"targets":["braf","mek"],"drugs":["vemurafenib","cobimetinib"],"companies":[],"institutions":[],"pathways":["ras-mapk"],"terms":[],"trials":[],"people":["james-larkin","paolo-ascierto"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT01689519","phase":"3","setting":"Untreated unresectable or metastatic BRAF V600-mutant melanoma: vemurafenib plus cobimetinib versus vemurafenib plus placebo","sponsor":"Genentech / Roche","result":"Median progression-free survival 12.3 vs 7.2 months (HR 0.58); median overall survival 22.3 vs 17.4 months (HR 0.70).","yearReported":2014,"enrolled":495,"outcomes":[{"endpoint":"Progression-free survival","primary":true,"unit":"months","arms":[{"name":"Vemurafenib + cobimetinib","n":247,"value":12.3},{"name":"Vemurafenib + placebo","n":248,"value":7.2}],"hr":0.58,"source":"https://doi.org/10.1016/S1470-2045(16)30122-X"},{"endpoint":"Overall survival","unit":"months","arms":[{"name":"Vemurafenib + cobimetinib","n":247,"value":22.3},{"name":"Vemurafenib + placebo","n":248,"value":17.4}],"hr":0.7,"source":"https://doi.org/10.1016/S1470-2045(16)30122-X"}],"replication":"COMBI-d and COMBI-v (dabrafenib-trametinib) and COLUMBUS (encorafenib-binimetinib) found the same class effect."},"route":"/trials/cobrim/","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":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"}],"target":[{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"},{"id":"mek","kind":"target","name":"MEK1/2","route":"/targets/mek/"}],"drug":[{"id":"cobimetinib","kind":"drug","name":"Cobimetinib","route":"/drugs/cobimetinib/"},{"id":"vemurafenib","kind":"drug","name":"Vemurafenib","route":"/drugs/vemurafenib/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"person":[{"id":"james-larkin","kind":"person","name":"James Larkin","route":"/people/james-larkin/"},{"id":"paolo-ascierto","kind":"person","name":"Paolo A. Ascierto","route":"/people/paolo-ascierto/"}]}}