UV1 is a therapeutic cancer vaccine that has been explored in prostate and lung cancers, and in combination with ipilimumab in malignant melanoma. This study will explore the safety, tolerability and efficacy of UV1 administered with GM-CSF in melanoma patients who are also receiving pembrolizumab.

Key Inclusion Criteria:

1. Stage IIIB, IIIC or IV melanoma
2. Previously untreated and eligible for pembrolizumab treatment (prior treatment with BRAF and MEK inhibitors permitted) 3) Adequate blood, liver and kidney function 4) Consent to undergo tumor biopsies during the study

Exclusion Criteria:

1. Uveal or ocular malignant melanoma
2. History of hematologic or primary solid tumor malignancy with the exception of patients in remission for at least 5 years, as judged by the investigator are allowed
3. Prior systemic treatment for unresectable or metastatic melanoma. Exception: Prior treatment with BRAF and MEK inhibitors permitted. A washout period of at least 3-half-lives (median terminal half-life) prior to the first dose of trial treatment must have elapsed.
4. Prior therapy with an anti-CTLA4, anti-PD-1, anti-PD-L1, anti-PD-L2 agent or oncolytic virus.
5. Known hypersensitivity to GM-CSF
6. Women who are breastfeeding, pregnant or expect to be pregnant during the study through 6 months after the last dose
7. Men who plan to become a father during the study through 4 months after the last dose of study medication
8. Known history of, or any evidence of active, non-infectious pneumonitis
9. History of cardiac disease