UV1 Vaccination Plus Nivolumab and Ipilimumab in Treatment of Melanoma

Efficacy and Safety of UV1 Vaccination in Combination With Nivolumab and Ipilimumab as First Line Treatment of Patients With Unresectable or Metastatic Melanoma (INITIUM Study)

This is a randomized, open label study to investigate efficacy and safety of UV1 vaccination in combination with nivolumab and ipilimumab as first line treatment of adult patients with histologically confirmed unresectable metastatic melanoma.

This is a randomized, open label study to investigate efficacy and safety of UV1 vaccination in combination with nivolumab and ipilimumab as first line treatment of adult patients with histologically confirmed unresectable metastatic melanoma.

Patients in the experimental arm will receive 8 UV1 vaccinations over 4 cycles of nivolumab and ipilimumab. Patients in the control arm will receive 4 cycles of nivolumab and ipilimumab. Patients in both arms will start maintenance therapy 6 weeks after the last dose of induction therapy, nivolumab at a dose of 480 mg every 4 weeks.

All patients will be followed up until death or until the end of the study.

To support the Extended Exploratory Cohort of the study, an additional 20 patients at selected sites will be enrolled in a single arm UV1 cohort for collection of additional biological material. These patients are in addition to the 156 randomized patients in the main part of the study and will not be included in the main analysis of the study.

Inclusion Criteria:

1. Male or female patients at least 18 years of age at the time of signing the ICF.

2. Histologically confirmed diagnosis of unresectable stage IIIB D, or unresectable stage IV malignant melanoma.

3. Eligible for combination treatment with nivolumab and ipilimumab.

4. An ECOG performance status of 0 or 1.

5. Adequate organ function as indicated by the following laboratory values:

   Hematological

   1. Absolute neutrophil count ≥1,500/µL
   2. Platelet count ≥100 x 103/µL
   3. Hemoglobin ≥9 g/dL or ≥5.6 mmol/L Renal
   4. Creatinine ≤1.5 x upper limit of normal (ULN) Hepatic
   5. Total bilirubin ≤1.5 x ULN or direct bilirubin ≤ ULN for patients with total bilirubin levels >1.5 ULN
   6. Aspartate aminotransferase/serum glutamic oxaloacetic transaminase and alanine aminotransferase/serum glutamic pyruvic transaminase ≤2.5 x ULN for patients without liver metastasis or ≤5 x ULN for patients with liver metastasis.

6. Male patients who are sexually active with a female of childbearing potential must agree to use an adequate method of contraception.

7. Women of childbearing potential (WOCBP) must have a negative urine or serum/plasma pregnancy test.

8. WOCBP must use adequate contraception.

Exclusion Criteria:

1. 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.
2. Known brain metastases or leptomeningeal metastases. If a patient experiences neurological symptoms indicative of brain metastases, a brain MRI should be performed.
3. Diagnosis of uveal or ocular melanoma.
4. Known history or any evidence of active, non-infectious pneumonitis.
5. History of New York Heart Association class 3-4 congestive heart failure or history of myocardial infarction within 6 months of starting induction therapy.
6. Active infection requiring systemic treatment.
7. Diagnosis of immunodeficiency.
8. Known history of severe hypersensitivity reactions to nivolumab, ipilimumab, sargramostim, or their excipients.
9. Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
10. History of or active hepatitis B (hepatitis B surface antigen reactive) or active hepatitis C (hepatitis C virus antibody).
11. Women who are breastfeeding.
12. Prior systemic treatment for unresectable stage IIIB D or unresectable stage IV malignant melanoma.
13. 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.
14. Receipt of a live vaccine within 30 days prior to start of induction therapy.
15. Receipt of any other investigational treatment within 4 weeks of the first dose of induction therapy.
16. 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.