{"entity":{"id":"brf113928","kind":"trial","name":"BRF113928 cohort C (dabrafenib with trametinib, untreated BRAF V600E)","aka":["BRF113928"],"tldr":"Thirty-six patients showed that the melanoma combination of a BRAF and a MEK drug also works in the small slice of lung cancers with the same mutation.","summary":"BRAF V600E occurs in 1 to 2 percent of lung adenocarcinomas. BRF113928 was a sequentially enrolled multicohort study: cohort A gave dabrafenib alone in previously treated disease, cohort B gave dabrafenib with trametinib in previously treated disease, and cohort C, reported in 2017, gave the combination to 36 previously untreated patients at 19 centres in eight countries.\n\nThe investigator-assessed confirmed objective response rate was 64 percent (23 of 36, 95 percent confidence interval 46 to 79), with two complete responses (6 percent) and 21 partial responses (58 percent). Every patient had at least one adverse event and 69 percent had a grade 3 or worse event; pyrexia is the characteristic problem with this combination.\n\nThe FDA granted the combination full approval for BRAF V600E-mutant metastatic non-small-cell lung cancer in 2017 on cohorts B and C. In England NICE TA898 (14 June 2023) recommends dabrafenib with trametinib only as first-line treatment of advanced disease, subject to the commercial arrangement; NICE TA1150 (6 May 2026) added encorafenib with binimetinib, again first line only, so a patient who has already had chemotherapy is not funded for either.","status":"positive","asOf":"2026-09-25","links":[{"label":"ClinicalTrials.gov NCT01336634","url":"https://clinicaltrials.gov/study/NCT01336634"},{"label":"BRF113928 cohort C (Lancet Oncology 2017)","url":"https://doi.org/10.1016/S1470-2045(17)30679-4"},{"label":"NICE TA898: dabrafenib plus trametinib for BRAF V600 mutation-positive advanced non-small-cell lung cancer","url":"https://www.nice.org.uk/guidance/ta898"}],"tags":[],"related":[],"cancers":["braf-v600e-nsclc"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["braf"],"drugs":["dabrafenib","trametinib","dabrafenib-trametinib"],"companies":["novartis"],"institutions":[],"pathways":["ras-mapk"],"terms":["braf-v600-mutation","driver-mutation"],"trials":["pharos"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT01336634","phase":"2","setting":"Previously untreated metastatic BRAF V600E-mutant non-small-cell lung cancer: dabrafenib 150 mg twice daily with trametinib 2 mg daily, single arm, with investigator-assessed objective response as the primary endpoint","sponsor":"GlaxoSmithKline, later Novartis","result":"Confirmed objective response 64 percent (23 of 36), with 6 percent complete responses; grade 3 or worse adverse events in 69 percent.","yearReported":2017,"enrolled":36,"enrolledBasis":"treated","enrolledNote":"36 previously untreated patients were enrolled into cohort C; the registry enrolment figure covers all three cohorts of the study.","outcomes":[{"endpoint":"Objective response rate (investigator assessed, untreated cohort)","primary":true,"unit":"%","arms":[{"name":"Dabrafenib with trametinib","n":36,"value":64}],"ci":[46,79],"source":"https://doi.org/10.1016/S1470-2045(17)30679-4"}],"replication":"PHAROS reproduced the effect with encorafenib and binimetinib in both untreated and previously treated BRAF V600E-mutant disease."},"route":"/trials/brf113928/","neighbours":{"cancer":[{"id":"braf-v600e-nsclc","kind":"cancer","name":"BRAF V600E-mutant non-small-cell lung cancer","route":"/cancers/braf-v600e-nsclc/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"}],"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":"dabrafenib","kind":"drug","name":"Dabrafenib","route":"/drugs/dabrafenib/"},{"id":"dabrafenib-trametinib","kind":"drug","name":"Dabrafenib + trametinib","route":"/drugs/dabrafenib-trametinib/"},{"id":"trametinib","kind":"drug","name":"Trametinib","route":"/drugs/trametinib/"}],"company":[{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"term":[{"id":"braf-v600-mutation","kind":"term","name":"BRAF V600E mutation","route":"/terms/braf-v600-mutation/"},{"id":"driver-mutation","kind":"term","name":"Driver mutation","route":"/terms/driver-mutation/"}],"trial":[{"id":"pharos","kind":"trial","name":"PHAROS","route":"/trials/pharos/"}]}}