# Trametinib

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

## TL;DR

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.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-10
- Tags: nci-list
- 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: US 2013: BRAF V600E/K unresectable or metastatic melanoma (single agent); US 2014: With dabrafenib: metastatic melanoma; later adjuvant melanoma, NSCLC, anaplastic thyroid cancer, tumour-agnostic BRAF V600E solid tumours, paediatric low-grade glioma; EU 2014: BRAF V600 melanoma alone or with dabrafenib; later NSCLC and adjuvant melanoma

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Trametinib
- US label (DailyMed): https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=trametinib
- NCI drug page: https://www.cancer.gov/about-cancer/treatment/drugs/trametinib
- EPAR: https://www.ema.europa.eu/en/medicines/human/EPAR/mekinist

## Connected records

- drugs: [Dabrafenib](https://onco.cc/drugs/dabrafenib/), [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [Selumetinib](https://onco.cc/drugs/selumetinib/)
- biomarkers: [BRAF class II and class III mutations (non-V600)](https://onco.cc/biomarkers/braf-class-ii-iii/), [BRAF V600E (and V600K)](https://onco.cc/biomarkers/braf-v600e/)
- cancers: [Anaplastic thyroid cancer](https://onco.cc/cancers/anaplastic-thyroid-cancer/), [BRAF V600-mutant melanoma](https://onco.cc/cancers/braf-v600-melanoma/), [BRAF V600E-mutant non-small-cell lung cancer](https://onco.cc/cancers/braf-v600e-nsclc/), [Brain and spinal cord tumours (all types)](https://onco.cc/cancers/brain-tumours/), [Conjunctival melanoma](https://onco.cc/cancers/conjunctival-melanoma/), [Low-grade serous ovarian cancer](https://onco.cc/cancers/low-grade-serous-ovarian-cancer/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Melanoma](https://onco.cc/cancers/melanoma/), [Metastatic cancer (cancer that has spread)](https://onco.cc/cancers/metastatic-cancer/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Optic pathway glioma](https://onco.cc/cancers/optic-pathway-glioma/), [Paediatric high-grade glioma (excluding diffuse midline glioma)](https://onco.cc/cancers/paediatric-high-grade-glioma/), [Paediatric low-grade glioma](https://onco.cc/cancers/paediatric-low-grade-glioma/), [Papillary thyroid cancer](https://onco.cc/cancers/papillary-thyroid-cancer/), [Stage III melanoma (after surgery)](https://onco.cc/cancers/stage-iii-melanoma/), [Thyroid cancer](https://onco.cc/cancers/thyroid/)
- technologies: [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [MEK1/2](https://onco.cc/targets/mek/)
- companies: [Novartis](https://onco.cc/companies/novartis/)
- pathways: [Choline metabolism in cancer](https://onco.cc/pathways/choline-metabolism-in-cancer/), [Glioma (KEGG map)](https://onco.cc/pathways/glioma-signalling/), [Melanoma (KEGG map)](https://onco.cc/pathways/melanoma-signalling/), [Non-small cell lung cancer (KEGG map)](https://onco.cc/pathways/nsclc-signalling/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/), [Thyroid cancer (KEGG map)](https://onco.cc/pathways/thyroid-cancer-signalling/)
- trials: [A Study to Evaluate Safety, Drug Levels and Effectiveness of CC-92480 (BMS-986348) in Combination With Other Treatments in Participants With Relapsed ](https://onco.cc/trials/nct05372354/), [BRF113928 cohort C (dabrafenib with trametinib, untreated BRAF V600E)](https://onco.cc/trials/brf113928/), [COMBI-AD](https://onco.cc/trials/combi-ad/), [COMBI-d](https://onco.cc/trials/combi-d/), [Combination of GNS561 and Trametinib in Patients With Advanced KRAS Mutated Cholangiocarcinoma](https://onco.cc/trials/nct05874414/), [DETERMINE Trial Treatment Arm 07: Dabrafenib in Combination With Trametinib in Adult, Paediatric and Teenage/Young Adult Patients With BRAF V600 Mutation-Positi](https://onco.cc/trials/nct07440290/), [Molecular Profiling of Advanced Soft-tissue Sarcomas](https://onco.cc/trials/nct03784014/), [NCI-MATCH (EAY131)](https://onco.cc/trials/nci-match/), [Pan Tumor Rollover Study](https://onco.cc/trials/nct03899155/), [Platform Study of JDQ443 in Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation](https://onco.cc/trials/nct05358249/), [ROAR (Rare Oncology Agnostic Research) basket: BRAF V600E biliary tract cancer cohort](https://onco.cc/trials/roar/), [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](https://onco.cc/trials/nct07468071/), [Study of Efficacy and Safety of Dabrafenib in Combination With Trametinib in Previously Treated Patients With Metastatic, Radio-active Iodine Refracto](https://onco.cc/trials/nct04940052/), [Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma](https://onco.cc/trials/nct04417621/), [Trametinib Plus Anlotinib Combined With Tislelizumab in KRAS-mutant NSCLC](https://onco.cc/trials/nct06456138/), [XP-102 and XP-102 in Combination With Trametinib in Advanced Solid Tumor Patients With a BRAF V600 Mutation](https://onco.cc/trials/nct05275374/)
- key papers: [COMBI-AD: adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma](https://onco.cc/key-papers/paper-combi-ad-nejm-2017/), [COMBI-d: dabrafenib and trametinib versus dabrafenib alone for BRAF V600-mutant melanoma](https://onco.cc/key-papers/paper-combi-d-long-lancet-2015/), [Dabrafenib and trametinib in BRAF V600E-mutant anaplastic thyroid cancer (ROAR)](https://onco.cc/key-papers/paper-subbiah-dabrafenib-trametinib-atc-jco-2018/), [Dabrafenib plus trametinib in previously treated BRAF V600E-mutant metastatic non-small-cell lung cancer](https://onco.cc/key-papers/paper-planchard-dabrafenib-trametinib-braf-nsclc-lancet-oncol-2016/), [Dabrafenib plus trametinib in previously untreated BRAF V600E-mutant metastatic non-small-cell lung cancer](https://onco.cc/key-papers/paper-planchard-dabrafenib-trametinib-first-line-lancet-oncol-2017/), [Dabrafenib plus trametinib in relapsed or refractory BRAF V600-mutant paediatric high-grade glioma](https://onco.cc/key-papers/paper-hargrave-dabrafenib-trametinib-paediatric-hgg-jco-2023/), [DREAMseq (ECOG-ACRIN EA6134): sequencing dabrafenib-trametinib and nivolumab-ipilimumab in BRAF-mutant metastatic melanoma](https://onco.cc/key-papers/paper-dreamseq-jco-2023/), [GOG 281/LOGS: trametinib versus standard of care in recurrent low-grade serous ovarian cancer](https://onco.cc/key-papers/paper-gog-281-trametinib-lgsoc-gershenson-lancet-2022/)

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