|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].|
|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 human IgG4 monoclonal antibody that acts as an immunomodulator by blocking ligand activation of programmed cell death 1 (PD-1) receptor on T cells. It is indicated for use in patients with unresectable (cannot be surgically removed) or metastatic melanoma who no longer respond to other drugs. Nivolumab is administered as an intravenous infusion over 60 minutes every 2 weeks.|
|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]|