Phase 1 Study of GRN-1201 in HLA-A*02 Subjects With Resected Melanoma

This is a study of an investigational cancer vaccine called GRN-1201. Treatment with the GRN-1201 vaccine is a type of immunotherapy. The goal of immunotherapy is to stimulate the body's immune system (white blood cells) to attack cancer cells and kill them. GRN-1201 consists of 4 different peptides (small parts of proteins) that are expressed by melanoma cells. The intent of treatment with GRN-1201 is to increase your body's immune response to melanoma. To further increase your body's immune response against tumor cells, the GRN-1201 vaccine will be mixed with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF, also known as sargramostim). GM-CSF is a man-made protein that helps stimulate the immune system and increase the response against the tumor cells. This is a phase I study which means that this will be the first time GRN-1201 is given in combination with GM-CSF to humans. It will be tested in a small number of people to evaluate its safety, find a safe dose, and identify side effects. The safety of GRN-1201 will be tested at three different doses; the GM-CSF dose will remain the same.

GRN-1201 is a novel HLA-A\*02-restricted multiple-peptide, therapeutic cancer vaccine, being developed by GreenPeptide for the treatment of melanoma because it can induce immune responses against tumor associated antigens (TAAs), particularly cytotoxic T cell (CTL) responses. Granulocyte-macrophage-colony-stimulating-factor (GM-CSF) (Leukine®, SanofiAventis) will be administered in combination with GRN-1201 as an immuno-adjuvant In contrast to advanced melanoma, treatment options in the adjuvant setting are limited. Surgical resection is the primary treatment of Stage IIb, IIc, and III melanoma patients. The rate of disease recurrence in patients with American Joint Committee on Cancer (AJCC) TNM Stage II (T2-4N0M0) and Stage III (TanyN+M0) disease ranges between 20 -60%, with 5-year overall survival between 45 - 70%. Thus, safe and effective treatment options to reduce the risk of recurrence are much needed. Considering their generally safe nature, peptide-based cancer vaccines would be ideal to address this unmet medical need. Patients with Stage IIb, IIc or III melanoma are, in general, healthy following local therapy. They are anticipated to maintain an immune system uncompromised by chemotherapy or disease burden. Further, they may have already developed immune response to TAAs targeted by GRN-1201, which may increase the probability of developing effective immune responses. It is conceivable that the combination of peptide vaccines with an immune checkpoint inhibitor, especially with a PD-1 pathway inhibitor, could enhance the efficacy of immunotherapy without increasing toxicity. Studies evaluating the combination of a melanoma vaccine with nivolumab in advanced melanoma \[14\] and resected high-risk metastatic melanoma patients \[15\] reported encouraging clinical outcome. The pre-clinical data suggest that GRN-1201 may have anti-tumor activity in the adjuvant setting or may enhance activity of other drugs such as checkpoint inhibitors in the adjuvant or metastatic disease setting, by enhancing immune responses against TAAs.