MCS110 With BRAF/MEK Inhibition in Patients With Melanoma

This research study is studying a combination of targeted therapies as a possible treatment for advanced melanoma that was found to have a BRAF V600E or BRAF V600K genetic mutation. The interventions involved in this study are: * MCS110 * Dabrafenib * Trametinib

This is a Phase I/II clinical trial. A Phase I clinical trial tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational intervention to use for further studies. "Investigational" means that the intervention is being studied. The FDA (the U.S. Food and Drug Administration) has not approved MSC110 as a treatment for any disease. The FDA has approved dabrafenib and trametinib as treatment options for this disease. Dabrafenib and trametinib attack different proteins that promote the growth of cancerous cells. These two treatments work in cancers with a mutation in the BRAF gene which alters a protein signaling pathway in cancer cells. The BRAF mutation status will be confirmed during this trial by review or procedure in order to make sure this clinical trial is right for the participant. Dabrafenib is a BRAF inhibitor that works by preventing altered BRAF proteins from stimulating the growth of the melanoma cancer cells. Trametinib works by blocking a protein related to BRAF called MEK that has been known to stimulate cells that also promote melanoma growth. In order to participate in the study, the participant disease needs to be tested positive for a mutation (a permanent change in the DNA sequence of a gene) of the BRAF gene that belongs to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous. Once the BRAF gene is mutated, the normal functioning of the BRAF protein may be changed. It is normal for patients with a BRAF mutation to receive these types of inhibitor therapies at some point in their treatment. MCS110 is a colony-stimulating factor-1 (CSF-1) inhibitor. It is a human monoclonal antibody which binds CSF-1. A monoclonal antibody is a type of protein made in the laboratory that can locate and bind to substances in the body, including tumor cells. MCS110 is being developed as a treatment for patients with advanced cancer. In this research study, the investigators are adding MCS110 to the treatment with dabrafenib and trametinib at the time when the participant's disease is growing despite these medications. The hope is that MCS110 will enhance how the cancer will respond to dabrafenib and trametinib and overcome any resistance to these medications that has developed. In previous laboratory studies performed by treating melanoma cancer cells with a CSF-1R (CSF-1 Receptor which interacts with the CSF-1 protien) inhibitor and a BRAF inhibitor, it was found that the CSF-1R inhibitor was successful in increasing efficacy.