Trametinib: first global approval

Drugs. 2013 Jul;73(11):1245-54. doi: 10.1007/s40265-013-0096-1.


Trametinib is an orally bioavailable mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor with antineoplastic activity. The compound specifically binds to MEK1 and MEK2, resulting in inhibition of growth factor-mediated cell signalling and cellular proliferation in various cancers. Originally developed by Japan Tobacco, GlaxoSmithKline has licensed exclusive worldwide rights to the compound and conducted development in a number of different cancer types. Trametinib, as a monotherapy, has been approved in the US for the treatment of unresectable or metastatic malignant melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test. The compound, as a monotherapy, has also been submitted for regulatory review in the EU for BRAF mutation-positive malignant melanoma, and is in phase III development in Europe, Argentina, Canada and Oceania. Phase II development is underway for pancreatic cancer, non-small cell lung cancer and relapsed or refractory leukaemias. GlaxoSmithKline is also developing trametinib for use in combination with dabrafenib in BRAF V600 mutation-positive metastatic cutaneous melanoma; the combination is at the preregistration stage in the EU and a phase III clinical programme is underway worldwide. Phase II development for this combination is also underway in colorectal cancer. Several phase I trials have also been initiated to evaluate trametinib in combination with other drugs for the treatment of various solid tumours and haematological malignancies. A paediatric oral solution formulation has been assessed against the oral tablet formulation in a phase I trial. This article summarizes the milestones in the development of trametinib leading to this first approval for unresectable or metastatic BRAF mutation-positive malignant melanoma.

MeSH terms

  • Clinical Trials as Topic
  • Drug Approval
  • Humans
  • MAP Kinase Kinase 1 / antagonists & inhibitors
  • MAP Kinase Kinase 2 / antagonists & inhibitors
  • Melanoma / drug therapy*
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyridones / therapeutic use*
  • Pyrimidinones / therapeutic use*
  • Skin Neoplasms


  • Protein Kinase Inhibitors
  • Pyridones
  • Pyrimidinones
  • trametinib
  • MAP Kinase Kinase 1
  • MAP Kinase Kinase 2

Supplementary concepts

  • Melanoma, Cutaneous Malignant