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Trametinib: First Global Approval

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Abstract

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.

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Authors and Affiliations

  1. Adis R & D Insight, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, 0754, Auckland, New Zealand

    Cameron J. M. Wright

  2. Adis, Auckland, New Zealand

    Paul L. McCormack

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  2. Paul L. McCormack
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Correspondence to Cameron J. M. Wright.

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This profile has been extracted and modified from the Adis R&D Insight drug pipeline database. Adis R&D Insight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch.

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Wright, C.J.M., McCormack, P.L. Trametinib: First Global Approval. Drugs 73, 1245–1254 (2013). https://doi.org/10.1007/s40265-013-0096-1

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