Inclusion Criteria:

• Male or female patients at least 18 years of age at the time of signing the informed consent form (ICF).
• Histologically confirmed diagnosis of unresectable stage IIIB-D or unresectable stage IV malignant melanoma. Patient must have at least 1 measurable lesion at Screening according to the RECIST 1.1 criteria.  Note that lesions not measurable on a computed tomography (CT) scan or a magnetic resonance imaging (MRI) will be considered as non-measurable lesions.
• Eligible for combination treatment with nivolumab and ipilimumab.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function as indicated by the following laboratory values:
• Hematological
  • Absolute neutrophil count (ANC) ≥1,500/µL;
  • Platelet count ≥ 100 x 10^3 /µL;
  • Hemoglobin ≥ 9 g/dL; or ≥ 5.6 mmol/L.
• Renal
  • Creatinine ≤ 1.5 x upper limit of normal (ULN).
• Hepatic
  • Total bilirubin ≤1.5 x ULN; or
  • Direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 ULN;
  • Aspartate aminotransferase/ glutamic-oxaloacetic transaminase and alanine aminotransferase/glutamic-pyruvic transaminase ≤ 2.5 x ULN for patients without liver metastasis or ≤ 5 x ULN for patients with liver metastasis.
• Male patients who are sexually active with a female of childbearing potential must agree to use an adequate method of contraception prior to the first dose through 5 months after the last dose of UV1 vaccination, nivolumab, or ipilimumab, whichever is administered last. The recommended method is using a male condom.
• Women of childbearing potential (WOCBP) must have a negative urine or serum/plasma pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum/plasma pregnancy test will be performed. The serum/plasma pregnancy test must be negative for the patient to be eligible. 8. WOCBP (refer to Section 8.3.6) must use adequate contraception Adequate contraception must be maintained throughout the study, starting with the first dose through 5 months after the last dose of UV1 vaccination, nivolumab, or ipilimumab, whichever is administered last. The acceptable contraceptive methods for WOCBP included in the study are: Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable), Intrauterine device (IUD), Intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner (provided that the partner is the sole sexual partner of the WOCBP trial participant and that the vasectomized partner has received medical assessment of the surgical success), or sexual abstinence (if this is the preferred and usual lifestyle of the subject).
• Written informed consent prior to any study-specific procedures.

Exclusion Criteria:

• Previous non-melanoma malignancies unless curatively-treated and complete remission was achieved at least 2 years prior to randomization. Patients with prior curatively-treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or carcinoma in situ of the breast, or other in situ cancers are allowed irrespective of time passed since curative treatment. Patients with prior completely resected malignant melanoma are also allowed.
• Known brain metastases or leptomeningeal metastases. If a patient experiences neurological symptoms indicative of brain metastases, a brain MRI should be performed.
• Diagnosis of uveal or ocular melanoma.
• Known history or any evidence of active, non-infectious pneumonitis.
• History of New York Heart Association class 3-4 congestive heart failure or history of myocardial infarction within 6 months of starting study treatment.
• Active infection requiring systemic treatment.
• Diagnosis of immunodeficiency.
• Known history of severe hypersensitivity reactions to nivolumab, ipilimumab, sargramostim, or their excipients.
• Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies). No HIV testing is required unless mandated by local health authority.
• History of or active hepatitis B (hepatitis B surface antigen reactive) or active hepatitis C (hepatitis C virus antibody). Testing must be performed to determine eligibility.
• Systemic corticosteroid treatment (doses exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive treatment within 7 days prior to the first dose of induction therapy. Topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption) are allowed. Physiologic replacement doses of systemic corticosteroids, a brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions is permitted even with > 10 mg/day prednisone equivalents.
• Receipt of a live vaccine within 30 days prior to the start of induction therapy performed to determine eligibility.
• Women who are breastfeeding.
• Prior systemic treatment for unresectable stage IIIB-D or unresectable stage IV malignant melanoma. Prior systemic BRAF/MEK inhibitors or immunotherapy as neoadjuvant or adjuvant or other setting treatment of stage I-IIIA, resectable IIIB-D, or resectable IV if patient progressed earlier than 6 months after last dose of such treatment.
• Systemic corticosteroid treatment (doses exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive treatment within 7 days prior to the first dose of induction therapy. Topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption) are allowed. Physiologic replacement doses of systemic corticosteroids, a brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions is permitted even with >10 mg/day prednisone equivalents.
• Receipt of a live vaccine within 30 days prior to the start of induction therapy.
• Receipt of any other investigational therapy within 4 weeks of the first dose of study treatment.
• Any medical, psychological, or social condition that would make it difficult for the patient to participate in the study and comply with the study procedures, restrictions, and requirements.