Trametinib
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.
Overview
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.
- AmivantamabApproved
- CamizestrantApproved
- Comprehensive genomic profilingStandard of care
- Liquid biopsy (ctDNA)Standard of care
- LorlatinibApproved
- MRD / molecular residual disease testingEstablished
- ADC payload neutralisersPhase 1
- BGB-16673Phase 3
- Bispecific ADCPhase 3
- BRUIN CLL-321Positive
- CaDAnCe-304Recruiting
- CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)Active
- A clone report from blood at every treatment cycle
- A fast route to the matched drug when it is licensed for another cancer
- A multi-cancer platform trial of adaptive (dose-holiday) therapy
- A national rapid research autopsy network for end-stage cancer
- A standard evolvability score for every tumour
- A standing platform trial that assigns treatment by how the tumour escaped
Background: ADC sequencing, Antigen escape (antigen loss, lineage switch), BCG-unresponsive, Castration-resistant prostate cancer (CRPC), Circulating tumour DNA (ctDNA). Also on OnCo: Resistance atlas: how tumours escape and what closes the route · Lines of therapy.
Approvals
| Region | Year | Indication |
|---|---|---|
| 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 |
Trials
topRecruiting now (live from ClinicalTrials.gov)
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Landmark trials in OnCo
Latest papers
topQuery for this drug: (TITLE:"Trametinib" OR ABSTRACT:"Trametinib" OR TITLE:"Mekinist" OR ABSTRACT:"Mekinist") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Trametinib, not a curated reading list.
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