A Study of Varlilumab (Anti-CD27) and Ipilimumab and CDX-1401 in Patients With Unresectable Stage III or IV Melanoma

Key Inclusion Criteria: 1. Histologic diagnosis of melanoma. 2. Unresectable Stage III or IV disease 3. Documented progressive disease based on radiographic, clinical or pathologic assessment. 4. No more than three prior anticancer regimens (BRAF/MEK inhibitors, IL-2 or investigational agents) including no more than one chemotherapy-containing regimen for advanced (recurrent, locally advanced or metastic) disease. 5. Measurable disease. 6. Life expectancy ≥ 12 weeks. 7. If of childbearing potential (male or female), agrees to practice an effective form of contraception during study treatment and for at least 70 days following last treatment. 8. Availability of tumor tissue for central laboratory analyses. Key Exclusion Criteria: 1. Previous treatment with anti-CD27 antibody, ipilimumab or other anti-CTLA-4 targeted therapies. Previous therapy with other checkpoint blockers such as anti-PD-1 or anti-PD-L1 is acceptable, unless treatment was discontinued for intolerance. 2. For patients enrolled to Phase II Cohort B: Previous administration of vaccine therapy targeting NY-ESO-1. 3. BRAF/MEK inhibitors within 2 weeks prior to first dose of study treatment. 4. Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to first dose of study treatment. 5. Monoclonal based therapies within 4 weeks and all other immunotherapy within 2 weeks prior to first dose of study treatment. 6. Systemic radiation therapy within 4 weeks, focal radiotherapy within 2 weeks and radiopharmaceuticals (strontium, samarium) within 8 weeks prior to first dose of study treatment. 7. Ocular Melanoma 8. Other prior malignancy, except for adequately treated basal or squamous cell skin cancer or in situ cancers; or any other cancer from which the patient has been disease-free for at least 3 years. 9. Active, untreated central nervous system metastases. 10. Active autoimmune disease or documented history of autoimmune disease. 11. Active diverticulitis 12. Significant cardiovascular disease including CHF or poorly controlled hypertension.