Trametinib

Generic Name: Trametinib

Brand Names: Mekinist, Spexotras

Drug Type: Small Molecule

Chemical Formula: C_₂₆H_₂₃FIN_₅O_₄

CAS Number: 871700-17-3

Unique Ingredient Identifier: 33E86K87QN

Background: Trametinib is an orally bioavailable mitogen-activated extracellular signal-regulated kinase 1 (MEK1) and MEK2 inhibitor. It was first approved by the FDA in May 2013 for the treatment of melanoma. It was later approved by Health Canada on July 18, 2013 and by the European Commission on June 30, 2014. Trametinib is currently approved to treat a variety of cancers with BRAF mutations, such as non-small cell lung cancer and thyroid cancer, as monotherapy or in combination with dabrafenib, a BRAF inhibitor, for improved therapeutic efficacy. Originally developed by Japan Tobacco, trametinib was initially investigated for treating inflammation, but further studies for this indication were not pursued.

Indication: Trametinib is indicated as monotherapy for the treatment of BRAF-inhibitor treatment-naïve patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations.

It is used in combination with dabrafenib for the:

In the US, BRAF V600E or V600K mutations must be detected by an FDA-approved test. Trametinib is not indicated for the treatment of patients with colorectal cancer because of known intrinsic resistance to BRAF inhibition.

Associated Conditions: Advanced Non-Small Cell Lung Cancer (NSCLC), Locally Advanced Anaplastic Thyroid Cancer, Low-Grade Glioma, Melanoma, Metastatic Anaplastic Thyroid Cancer, Metastatic Melanoma, Metastatic Non-Small Cell Lung Cancer, Stage III Melanoma, Unresectable Melanoma, Unresectable or Metastatic Solid Tumors

Clinical Trials

A Study Comparing Trametinib and Dabrafenib Combination Therapy to Dabrafenib Monotherapy in Subjects With BRAF-mutant Melanoma

Phase 3

Completed

Conditions: Melanoma

Interventions: Drug: Dabrafenib
Drug: Trametinib
Drug: Trametinib placebo

First Posted Date: 2012-04-25

Last Posted Date: 2021-02-17

Lead Sponsor: Novartis Pharmaceuticals

Target Recruit Count: 423

Registration Number: NCT01584648

Locations: 🇬🇧
Novartis Investigative Site, Preston, United Kingdom

GSK1120212 in Surgically Resectable Oral Cavity Squamous Cell Cancer

Phase 2

Completed

Conditions: Neoplasms, Oral
Mouth Neoplasms

Interventions: Drug: GSK1120212

First Posted Date: 2012-03-14

Last Posted Date: 2016-12-26

Lead Sponsor: Washington University School of Medicine

Target Recruit Count: 20

Registration Number: NCT01553851

Locations: 🇺🇸
Washington University School of Medicine, St. Louis, Missouri, United States

A Study of the Safety and Activity of the MEK Inhibitor Given Together With the AKT Inhibitor to Patients With Multiple Myeloma or Solid Tumor Cancers

Phase 1

Completed

Conditions: Cancer

Interventions: Drug: GSK1120212
Drug: GSK2110183

First Posted Date: 2011-11-22

Last Posted Date: 2017-11-13

Lead Sponsor: GlaxoSmithKline

Target Recruit Count: 335

Registration Number: NCT01476137

Locations: 🇺🇸
GSK Investigational Site, San Antonio, Texas, United States

Defining the Triple Negative Breast Cancer Kinome Response to GSK1120212

Early Phase 1

Completed

Conditions: Breast Cancer

Interventions: Drug: GSK1120212

First Posted Date: 2011-11-08

Last Posted Date: 2020-09-02

Lead Sponsor: UNC Lineberger Comprehensive Cancer Center

Target Recruit Count: 15

Registration Number: NCT01467310

Locations: 🇺🇸
Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, United States

Phase 1 Study of Pazopanib With GSK1120212 in Advanced Solid Tumors, Enriched With Patients With Differentiated Thyroid Cancer, Soft-tissue Sarcoma, and Cholangiocarcinoma

Phase 1

Completed

Conditions: Solid Tumors
Thyroid Cancer
Soft-tissue Sarcoma
Cholangiocarcinoma

Interventions: Drug: Pazopanib
Drug: GSK1120212

First Posted Date: 2011-09-22

Last Posted Date: 2018-08-29

Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Target Recruit Count: 89

Registration Number: NCT01438554

Locations: 🇺🇸
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, United States
🇺🇸
MD Anderson Cancer Center, Houston, Texas, United States