{"entity":{"id":"trametinib","kind":"drug","name":"Trametinib","aka":[],"tldr":"Trametinib (Mekinist) blocks MEK, the protein one step below BRAF in the growth-signal chain. Paired with dabrafenib it treats BRAF-mutant melanoma, lung, thyroid and other cancers, including brain tumours in children.","summary":"Trametinib was approved by the FDA in May 2013 as a single agent for BRAF V600E or V600K metastatic melanoma (METRIC: progression-free survival superior to chemotherapy) and in January 2014 in combination with dabrafenib, the pairing that became standard after COMBI-d and COMBI-v. All later indications are with dabrafenib: adjuvant stage III melanoma (COMBI-AD), BRAF V600E metastatic NSCLC, anaplastic thyroid cancer, tumour-agnostic BRAF V600E solid tumours and paediatric low-grade glioma with an oral solution (2023). The EU authorised Mekinist in 2014. Rash, diarrhoea, reduced ejection fraction, retinal vein occlusion and central serous retinopathy are the MEK-class toxicities; pyrexia dominates the combination.","status":"approved","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Trametinib","links":[{"label":"US label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=trametinib"},{"label":"NCI drug page","url":"https://www.cancer.gov/about-cancer/treatment/drugs/trametinib"},{"label":"EPAR","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/mekinist"}],"tags":["nci-list"],"related":["dabrafenib","dabrafenib-trametinib","braf-v600e"],"cancers":["melanoma","nsclc","thyroid","anaplastic-thyroid-cancer","low-grade-serous-ovarian-cancer","paediatric-low-grade-glioma","paediatric-high-grade-glioma","braf-v600e-nsclc","braf-v600-melanoma","stage-iii-melanoma"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["mek"],"drugs":[],"companies":["novartis"],"institutions":[],"pathways":["ras-mapk"],"terms":[],"trials":["combi-ad","nct04940052","nct05372354","nct05358249","nct04417621","nct03899155","nct05874414"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Mekinist","modality":"Small-molecule allosteric MEK1/2 inhibitor","mechanism":"Reversible, non-ATP-competitive inhibitor of MEK1 and MEK2 kinase activity and activation, blocking ERK phosphorylation downstream of BRAF.","approvals":[{"region":"US","year":2013,"indication":"BRAF V600E/K unresectable or metastatic melanoma (single agent)"},{"region":"US","year":2014,"indication":"With dabrafenib: metastatic melanoma; later adjuvant melanoma, NSCLC, anaplastic thyroid cancer, tumour-agnostic BRAF V600E solid tumours, paediatric low-grade glioma"},{"region":"EU","year":2014,"indication":"BRAF V600 melanoma alone or with dabrafenib; later NSCLC and adjuvant melanoma"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[{"date":"2014-01-08","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint, with a confirmatory trial required.","indication":"In combination with dabrafenib for unresectable or metastatic melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test"},{"date":"2015-11-20","type":"conversion","region":"US","note":"Confirmed: the accelerated approval of 2014 converted to traditional approval 1.9 years after it was granted.","indication":"In combination with dabrafenib for unresectable or metastatic melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test"},{"date":"2022-06-22","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint; the confirmatory requirement was still open 4.2 years later, when the FDA's table was read.","source":"https://www.fda.gov#endnote2","indication":"In combination with dabrafenib for adult and pediatric patients 6 years of age and older with unresectable or metastatic solid tumors with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options *"}]},"route":"/drugs/trametinib/","neighbours":{"drug":[{"id":"dabrafenib","kind":"drug","name":"Dabrafenib","route":"/drugs/dabrafenib/"},{"id":"dabrafenib-trametinib","kind":"drug","name":"Dabrafenib + 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melanoma","route":"/cancers/conjunctival-melanoma/"},{"id":"low-grade-serous-ovarian-cancer","kind":"cancer","name":"Low-grade serous ovarian cancer","route":"/cancers/low-grade-serous-ovarian-cancer/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"metastatic-cancer","kind":"cancer","name":"Metastatic cancer (cancer that has spread)","route":"/cancers/metastatic-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"optic-pathway-glioma","kind":"cancer","name":"Optic pathway glioma","route":"/cancers/optic-pathway-glioma/"},{"id":"paediatric-high-grade-glioma","kind":"cancer","name":"Paediatric high-grade glioma (excluding diffuse midline glioma)","route":"/cancers/paediatric-high-grade-glioma/"},{"id":"paediatric-low-grade-glioma","kind":"cancer","name":"Paediatric low-grade glioma","route":"/cancers/paediatric-low-grade-glioma/"},{"id":"papillary-thyroid-cancer","kind":"cancer","name":"Papillary thyroid cancer","route":"/cancers/papillary-thyroid-cancer/"},{"id":"stage-iii-melanoma","kind":"cancer","name":"Stage III melanoma (after surgery)","route":"/cancers/stage-iii-melanoma/"},{"id":"thyroid","kind":"cancer","name":"Thyroid cancer","route":"/cancers/thyroid/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"mek","kind":"target","name":"MEK1/2","route":"/targets/mek/"}],"company":[{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"}],"pathway":[{"id":"choline-metabolism-in-cancer","kind":"pathway","name":"Choline metabolism in cancer","route":"/pathways/choline-metabolism-in-cancer/"},{"id":"glioma-signalling","kind":"pathway","name":"Glioma (KEGG map)","route":"/pathways/glioma-signalling/"},{"id":"melanoma-signalling","kind":"pathway","name":"Melanoma (KEGG map)","route":"/pathways/melanoma-signalling/"},{"id":"nsclc-signalling","kind":"pathway","name":"Non-small cell lung cancer (KEGG map)","route":"/pathways/nsclc-signalling/"},{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"},{"id":"thyroid-cancer-signalling","kind":"pathway","name":"Thyroid cancer (KEGG map)","route":"/pathways/thyroid-cancer-signalling/"}],"trial":[{"id":"nct05372354","kind":"trial","name":"A Study to Evaluate Safety, Drug Levels and Effectiveness of CC-92480 (BMS-986348) in Combination With Other Treatments in Participants With Relapsed ","route":"/trials/nct05372354/"},{"id":"brf113928","kind":"trial","name":"BRF113928 cohort C (dabrafenib with trametinib, untreated BRAF V600E)","route":"/trials/brf113928/"},{"id":"combi-ad","kind":"trial","name":"COMBI-AD","route":"/trials/combi-ad/"},{"id":"combi-d","kind":"trial","name":"COMBI-d","route":"/trials/combi-d/"},{"id":"nct05874414","kind":"trial","name":"Combination of GNS561 and Trametinib in Patients With Advanced KRAS Mutated Cholangiocarcinoma","route":"/trials/nct05874414/"},{"id":"nct07440290","kind":"trial","name":"DETERMINE Trial Treatment Arm 07: Dabrafenib in Combination With Trametinib in Adult, Paediatric and Teenage/Young Adult Patients With BRAF V600 Mutation-Positi","route":"/trials/nct07440290/"},{"id":"nct03784014","kind":"trial","name":"Molecular Profiling of Advanced Soft-tissue Sarcomas","route":"/trials/nct03784014/"},{"id":"nci-match","kind":"trial","name":"NCI-MATCH (EAY131)","route":"/trials/nci-match/"},{"id":"nct03899155","kind":"trial","name":"Pan Tumor Rollover Study","route":"/trials/nct03899155/"},{"id":"nct05358249","kind":"trial","name":"Platform Study of JDQ443 in Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation","route":"/trials/nct05358249/"},{"id":"roar","kind":"trial","name":"ROAR (Rare Oncology Agnostic Research) basket: BRAF V600E biliary tract cancer cohort","route":"/trials/roar/"},{"id":"nct07468071","kind":"trial","name":"Rollover Study for Participants Who Have Been Treated With and Are Continuing to Benefit From Opnurasib as a Single Agent or in Combination With Other","route":"/trials/nct07468071/"},{"id":"nct04940052","kind":"trial","name":"Study of Efficacy and Safety of Dabrafenib in Combination With Trametinib in Previously Treated Patients With Metastatic, Radio-active Iodine Refracto","route":"/trials/nct04940052/"},{"id":"nct04417621","kind":"trial","name":"Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma","route":"/trials/nct04417621/"},{"id":"nct06456138","kind":"trial","name":"Trametinib Plus Anlotinib Combined With Tislelizumab in KRAS-mutant NSCLC","route":"/trials/nct06456138/"},{"id":"nct05275374","kind":"trial","name":"XP-102 and XP-102 in Combination With Trametinib in Advanced Solid Tumor Patients With a BRAF V600 Mutation","route":"/trials/nct05275374/"}],"paper":[{"id":"paper-combi-ad-nejm-2017","kind":"paper","name":"COMBI-AD: adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma","route":"/key-papers/paper-combi-ad-nejm-2017/"},{"id":"paper-combi-d-long-lancet-2015","kind":"paper","name":"COMBI-d: dabrafenib and trametinib versus dabrafenib alone for BRAF V600-mutant melanoma","route":"/key-papers/paper-combi-d-long-lancet-2015/"},{"id":"paper-subbiah-dabrafenib-trametinib-atc-jco-2018","kind":"paper","name":"Dabrafenib and trametinib in BRAF V600E-mutant anaplastic thyroid cancer 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glioma","route":"/key-papers/paper-hargrave-dabrafenib-trametinib-paediatric-hgg-jco-2023/"},{"id":"paper-dreamseq-jco-2023","kind":"paper","name":"DREAMseq (ECOG-ACRIN EA6134): sequencing dabrafenib-trametinib and nivolumab-ipilimumab in BRAF-mutant metastatic melanoma","route":"/key-papers/paper-dreamseq-jco-2023/"},{"id":"paper-gog-281-trametinib-lgsoc-gershenson-lancet-2022","kind":"paper","name":"GOG 281/LOGS: trametinib versus standard of care in recurrent low-grade serous ovarian cancer","route":"/key-papers/paper-gog-281-trametinib-lgsoc-gershenson-lancet-2022/"}]}}