This research study is a Phase I clinical trial, which tests the safety of an investigational personalized neoantigen vaccine consisting of personalized neoantigen peptides and Hiltonol® (NeoVax) plus Montanide® in combination with Nivolumab and Ipilimumab. The study also intends to define the appropriate dose of investigational Ipilimumab administered subcutaneously (under the skin) to use for further studies. Investigational means that the combination is being studied.~The FDA (the U.S. Food and Drug Administration) has not approved personalized neoantigen peptides, Hiltonol® or Montanide® a as a treatment for any disease. It is an investigational drug being developed for use in the treatment of metastatic melanoma.~The FDA has approved Nivolumab (Opdivo®) and Ipilimumab (Yervoy™) as a treatment option for this disease.~The FDA has approved Ipilimumab administered intravenously as a treatment option for this disease.~The FDA has not approved Ipilimumab administered subcutaneously (under the skin) as a treatment for any disease.~The purpose of this study is to determine if it is possible to administer safely a personalized neoantigen vaccine (NeoVax) + Montanide in combination with Ipilimumab and Nivolumab against melanoma by using information gained from specific characteristics of melanoma.~It is known that melanoma cancers have mutations (changes in genetic material) that are specific to an individual patient and tumor. These mutations can cause the tumor cells to produce proteins that appear very different from the body's own cells. It is possible that these proteins used in a vaccine may induce strong immune responses, which may help the body fight any tumor cells that could cause the melanoma to come back in the future.~Melanoma cells will be obtained either by tumor surgery or tumor biopsy. The genetic material contained in the melanoma cells will be examined for the presence of tumor-specific mutations. This information will be used to prepare small protein fragments, which are called peptides. The vaccine will consist of up to 20 of these peptides mixed with two drugs that activate the immune system called Poly-ICLC (Hiltonol®) and Montanide®.~Poly-ICLC (also called Hiltonol) binds proteins on the surface of certain immune cells to make it appear as if a virus is present. When the cells detect the vaccine, they think it is a virus and turn on the immune system. Poly-ICLC is a compound that has been used to help the body in its fight against cancer. Poly-ICLC will be mixed with neoantigen peptides to create the personalized neoantigen vaccine (NeoVax). Poly-ICLC is an investigational drug, meaning the FDA has not approved it as a treatment for any disease.~Montanide® is an activator of immunity that enhances response to vaccination through slow release of the peptides from the injection site and its ability to create an inflammation and stimulate the recruitment of specific cells of the participant's immune system.~Montanide® will be mixed with the personalized neoantigen vaccine product and administered as an injection given underneath the skin.~Ipilimumab and Nivolumab are antibodies that prevent cancer cells from suppressing immune response so that the body can attack and kill the cancer.~An antibody is a common type of protein produced by the body that the immune system (a system that defends the body against potentially harmful particles) uses to find and destroy foreign molecules (particles not typically found in the body) such as bacteria and viruses. Antibodies can also be produced in the laboratory for use in treating patients. There are now several approved antibodies for the therapy of cancer and other diseases.~In this research study, the investigators are looking at the effectiveness (how well the drug works), safety, and tolerability of the Personalized NeoAntigen Cancer Vaccine plus Montanide® combined with Ipilimumab and Nivolumab.
This research study is studying a new type of personalized neoantigen vaccine (NeoVax) plus Montanide® in combination with Ipilimumab (Yervoy™) and Nivolumab (Opdivo®) as a possible treatment for melanoma.~The drugs involved in this study are:~Personalized Neoantigen Vaccine~Poly-ICLC (Hiltonol®)~Montanide®~Ipilimumab (Yervoy™)~Nivolumab (Opdivo®)