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Chemical compound From Wikipedia, the free encyclopedia
Binimetinib, sold under the brand name Mektovi, is an anti-cancer medication used to treat various cancers.[4] Binimetinib is a selective inhibitor of MEK, a central kinase in the tumor-promoting MAPK pathway.[5] Inappropriate activation of the pathway has been shown to occur in many cancers.[5] In June 2018 it was approved by the FDA in combination with encorafenib for the treatment of patients with unresectable or metastatic BRAF V600E or V600K mutation-positive melanoma.[6][7] In October 2023, it was approved by the FDA for treatment of NSCLC with a BRAF V600E mutation in combination with encorafenib.[8] It was developed by Array Biopharma.
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| Trade names | Mektovi |
| Other names | MEK162, ARRY-162, ARRY-438162 |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a618041 |
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| Drug class | Antineoplastic agent |
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| ECHA InfoCard | 100.167.617 |
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| Formula | C17H15BrF2N4O3 |
| Molar mass | 441.233 g·mol−1 |
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Binimetinib is an orally available inhibitor of mitogen-activated protein kinase kinase (MEK), or more specifically, a MAP2K inhibitor.[9] MEK is part of the RAS pathway, which is involved in cell proliferation and survival. MEK is upregulated in many forms of cancer.[10] Binimetinib, uncompetitive with ATP, binds to and inhibits the activity of MEK1/2 kinase, which has been shown to regulate several key cellular activities including proliferation, survival, and angiogenesis.[11] MEK1/2 are dual-specificity threonine/tyrosine kinases that play key roles in the activation of the RAS/RAF/MEK/ERK pathway and are often upregulated in a variety of tumor cell types.[12] Inhibition of MEK1/2 prevents the activation of MEK1/2 dependent effector proteins and transcription factors, which may result in the inhibition of growth factor-mediated cell signaling.[13] As demonstrated in preclinical studies, this may eventually lead to an inhibition of tumor cell proliferation and an inhibition in production of various inflammatory cytokines including interleukin-1, -6 and tumor necrosis factor.[13]
In 2015, it was in phase III clinical trials for ovarian cancer,[14] BRAF mutant melanoma,[15] and NRAS Q61 mutant melanoma.[16]
In December 2015, the company announced that the mutant-NRAS melanoma trial was successful.[17] In the trial, those receiving binimetinib had a median progression-free survival of 2.8 months versus 1.5 months for those on the standard dacarbazine treatment.[18] NDA submitted Jun 2016,[19] and the FDA should decide by 30 June 2017.[20]
In April 2016, it was reported that the phase III trial for low-grade ovarian cancer was terminated due to lack of efficacy.[21]
In 2017, the FDA informed Array Biopharma that the phase III trial data was not sufficient and the New Drug Application was withdrawn.[22]
In June 2018, it was approved for the treatment of certain melanomas by the U.S. Food and Drug Administration (FDA) in combination with encorafenib.[6] The FDA approved binimetinib based primarily on evidence from one clinical trial (NCT01909453) of 383 patients with BRAF V600 mutation-positive melanoma that was advanced or could not be removed by surgery.[7] The trial was conducted at 162 sites in Europe, North America, and various countries around the world.[7]
In October 2023, the US Food and Drug Administration approved encorafenib with binimetinib for adults with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation, as detected by an FDA-approved test.[8]
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