Unresectable Melanoma

DrugDrug NameDrug Description
DB05239CobimetinibCobimetinib 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.
DB08912DabrafenibDabrafenib 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].
DB06186IpilimumabIpilimumab 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]
DB09035NivolumabNivolumab 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.
DB09037PembrolizumabPembrolizumab 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]
DB08911TrametinibTrametinib 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].
DB08881VemurafenibVemurafenib 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]
DrugDrug NameTargetType
DB05239CobimetinibDual specificity mitogen-activated protein kinase kinase 1target
DB05239CobimetinibMultidrug resistance protein 1enzyme
DB05239CobimetinibSolute carrier organic anion transporter family member 1B1transporter
DB05239CobimetinibSolute carrier organic anion transporter family member 1B3transporter
DB05239CobimetinibATP-binding cassette sub-family G member 2transporter
DB08912DabrafenibCytochrome P450 3A4enzyme
DB08912DabrafenibCytochrome P450 2C8enzyme
DB08912DabrafenibMultidrug resistance protein 1transporter
DB08912DabrafenibATP-binding cassette sub-family G member 2transporter
DB08912DabrafenibSolute carrier organic anion transporter family member 1B1transporter
DB08912DabrafenibSolute carrier organic anion transporter family member 1B3transporter
DB08912DabrafenibSolute carrier family 22 member 6transporter
DB08912DabrafenibSolute carrier family 22 member 8transporter
DB08912DabrafenibSerine/threonine-protein kinase B-raftarget
DB08912DabrafenibRAF proto-oncogene serine/threonine-protein kinasetarget
DB08912DabrafenibSerine/threonine-protein kinase SIK1target
DB08912DabrafenibSerine/threonine-protein kinase Nek11target
DB08912DabrafenibLIM domain kinase 1target
DB06186IpilimumabCytotoxic T-lymphocyte protein 4target
DB09035NivolumabProgrammed cell death protein 1target
DB09037PembrolizumabProgrammed cell death protein 1target
DB08911TrametinibCytochrome P450 2C8enzyme
DB08911TrametinibCytochrome P450 3A4enzyme
DB08911TrametinibDual specificity mitogen-activated protein kinase kinase 1target
DB08911TrametinibDual specificity mitogen-activated protein kinase kinase 2target
DB08881VemurafenibSerum albumincarrier
DB08881VemurafenibAlpha-1-acid glycoprotein 1carrier
DB08881VemurafenibCytochrome P450 1A2enzyme
DB08881VemurafenibCytochrome P450 2D6enzyme
DB08881VemurafenibCytochrome P450 3A4enzyme
DB08881VemurafenibSerine/threonine-protein kinase B-raftarget
DB08881VemurafenibMultidrug resistance-associated protein 1transporter
DB08881VemurafenibATP-binding cassette sub-family G member 2transporter
DrugDrug NamePhaseStatusCount
DB08912Dabrafenib2Active Not Recruiting1
DB06186Ipilimumab2Active Not Recruiting1
DB09035Nivolumab2Active Not Recruiting1
DB01229Paclitaxel2Active Not Recruiting1
DB06589Pazopanib2Active Not Recruiting1