|DB11967||Binimetinib||Binimetinib, also known as _Mektovi_, is a potent is a potent and selective oral mitogen-activated protein kinase 1/2 (MEK 1/2) inhibitor which is combined with [Encorafenib] [A34275],[L3335].
On June 27, 2018, the Food and Drug Administration approved the combination of [Encorafenib] and binimetinib (BRAFTOVI and MEKTOVI, from Array BioPharma Inc.) in combination for patients with unresectable or metastatic melanoma with the BRAF V600E or V600K mutations, as detected by an FDA-approved test [L3335].|
|DB05239||Cobimetinib||Cobimetinib is an orally active, potent and highly selective small molecule inhibiting mitogen-activated protein kinase kinase 1 (MAP2K1 or MEK1), and central components of the RAS/RAF/MEK/ERK signal transduction pathway. It has been approved in Switzerland and the US, in combination with vemurafenib for the treatment of patients with unresectable or metastatic BRAF V600 mutation-positive melanoma.|
|DB08912||Dabrafenib||Dabrafenib mesylate (Tafinlar) is a reversible ATP-competitive kinase inhibitor and targets the MAPK pathway. It was approved on May 29, 2013 for the treatment of melanoma [L2718].
In May 2018, Tafinlar (dabrafenib) and Mekinist ([DB08911]) in combination have been approved to treat anaplastic thyroid cancer caused by an abnormal BRAF V600E gene [L2714].|
|DB11718||Encorafenib||Encorafenib, also known as _BRAFTOVI_, is a kinase inhibitor. Encorafenib inhibits BRAF gene, which encodes for B-raf protein, which is a proto-oncogene involved in various genetic mutations [FDA label]. This protein plays a role in regulating the MAP kinase/ERK signaling pathway, which impacts cell division, differentiation, and secretion. Mutations in this gene, most frequently the V600E mutation, are the most commonly identified cancer-causing mutations in melanoma, and have been isolated in various other cancers as well, including non-Hodgkin lymphoma, colorectal cancer, thyroid carcinoma, non-small cell lung carcinoma, hairy cell leukemia and adenocarcinoma of the lung [L3344].
On June 27, 2018, the Food and Drug Administration approved encorafenib and [Binimetinib] (BRAFTOVI and MEKTOVI, Array BioPharma Inc.) in combination for patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test [FDA label].|
|DB06186||Ipilimumab||Ipilimumab is a monoclonal antibody, more specifically a fully humanized IgG1 antibody produced in mammalian cell culture, to the cytotoxic T lymphocyte antigen-4 (CTLA-4) which activates antitumor immunity by inhibiting this major checkpoint.[A35065, A35080] This antineoplastic agent was developed by Bristol-Myers Squibb and Medarex and FDA approved on March 25, 2011, for the treatment of melanoma.[L3581] On October 2015, the FDA approved expanded the indications for Ipilimumab, allowing it to be used to reduce the risk of relapsed skin cancer after surgery.[L3582] On July 11, 2018, the FDA approved an additional indication for the combination of low dose ipilimumab and [nivolumab] for the treatment of previously treated microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) metastatic colorectal cancer.[L3590]|
|DB09035||Nivolumab||Nivolumab is a fully humanized IgG4 antibody targeting the immune checkpoint programmed death receptor-1 (PD-1). This molecule was produced entirely on mice and grafted onto human kappa and IgG4 Fc region with the mutation _S228P_ for additional stability and reduced variability.[A35203] It is developed by Bristol Myers Squibb and originally FDA approved on December 22, 2014. Since this approval, nivolumab has been approved for a variety of other uses related to cancer therapy. On 2017, was notably approved for the treatment of hepatocellular carcinoma[L3632] and on July 11, 2018, the FDA approved this agent in combination with low doses of [ipilimumab] for the treatment of MSI-H/dMMR metastatic colorectal cancer.[L3611]|
|DB09037||Pembrolizumab||Pembrolizumab is a highly selective IgG4-kappa humanized monoclonal antibody against PD-1 receptor. It was generated by grafting the variable sequences of a very high-affinity mouse antihuman PD-1 antibody onto a human IgG4-kappa isotype with the containing a stabilizing S228P Fc mutation.[A18829] It contains 32 cysteine residues and the complete folded molecule includes 4 disulfide linkages as interchain bonds and 23 interchain bonds.[F136] It was developed by Merck & Co and firstly approved for the treatment of metastatic malignant melanoma. This is the first approved therapy against PD-1.[A7624] It was approved firstly by the FDA on September 4, 2014.[L2954] Its approval in melanoma was extended to several countries such as Australia, Israel, Korea, Macau, the European Union and the United Arab Emirates.[A33350] On June 12, 2018, Pembrolizumab was approved for the treatment of cervical cancer under the status of accelerated approval.[L2955]|
|DB08911||Trametinib||Trametinib dimethyl sulfoxide is a kinase inhibitor. Each 1-mg tablet contains 1.127 mg trametinib dimethyl sulfoxide equivalent to 1 mg of trametinib non-solvated parent. FDA approved on May 29, 2013 [L2727].
The U.S. Food and Drug Administration approved [DB08912](Tafilnar) and Mekinist (trametinib), administered together, for the treatment of anaplastic thyroid cancer (ATC) that cannot be removed by surgery or has spread to other parts of the body (metastatic), and has a type of abnormal gene, BRAF V600E (BRAF V600E mutation-positive) [L2726].
Thyroid cancer is a disease in which cancer cells form in the tissues of the thyroid. Anaplastic thyroid cancer is a rare, aggressive type of thyroid cancer. The National Institutes of Health (NIH) estimates there will be 53,990 new cases of thyroid cancer and an estimated 2,060 deaths from the disease in the United States in 2018. Anaplastic thyroid cancer accounts for approximately 1 to 2 percent of all thyroid cancers [L2726].|
|DB08881||Vemurafenib||Vemurafenib is a competitive kinase inhibitor with activity against BRAF kinase with mutations like V600E.[A31269] It exerts its function by binding to the ATP-binding domain of the mutant BRAF.[A31270] Vemurafenib was co-developed by Roche and Plexxikon and it obtained its FDA approval on August 17, 2011, under the company Hoffmann La Roche. After approval, Roche in collaboration with Genentech launched a broad development program. [L1012]|