Study of Combination of Ipilimumab and Nivolumab in Patients With Melanoma

Inclusion Criteria

• Be at least 16 years of age;
• Histologic diagnosis of resected Stages IIIB/IIIC/ IV melanoma, with no evidence of disease clinically and radiologically, and negative surgical margins. All melanomas regardless of primary site of disease will be allowed;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Prior chemotherapy or immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) must have been completed at least 4 weeks before study drug administration, and all adverse events have either returned to baseline or stabilized;
• Prior treated brain or meningeal metastases must be without magnetic resonance imaging (MRI) evidence of progression for at least 8 weeks and off immunosuppressive doses of systemic steroids (> 10 mg/day prednisone or equivalent) for at least 2 weeks before study drug administration;
• Prior systemic radiation therapy must have been completed at least 4 weeks before study drug administration. Prior focal radiotherapy completed at least 2 weeks before study drug administration. No radiopharmaceuticals (strontium, samarium) within 8 weeks before study drug administration;
• Immunosuppressive doses of systemic medications, such as steroids or absorbed topical steroids (doses > 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks before study drug administration;
• Completed nitrosourea treatment at least 6 weeks before administration of any study drug;
• Prior surgery that required general anesthesia must be completed at least 4 weeks before study drug administration. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before study drug administration and subjects should be recovered;
• Screening laboratory values must meet the following criteria:

white blood cells (WBCs) ≥ 2000 cells/μL

• neutrophils ≥ 1500 cells/μL
• platelets ≥ 100 x 103/μL
• hemoglobin ≥ 9.0 g/dL
• serum creatinine ≤ 2 mg/dL
• AST ≤ 2.5 x upper limit of normal (ULN) without, and ≤ 5 x ULN with hepatic metastasis
• ALT ≤ 2.5 x ULN without, and ≤ 5 x ULN with hepatic metastasis
• bilirubin ≤ 2 x ULN (except subjects with Gilbert's syndrome, who must have total bilirubin 35 mIU/mL;
• Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception.
• Subject must have read, understood, and provided written informed consent and HIPAA authorization after the nature of the study has been fully explained; and
• Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.

Exclusion Criteria

• Subjects who fulfill any of the following conditions at Screening will not be eligible for admission into the study:
• History of severe hypersensitivity reactions to other mAbs;
• Prior non-melanoma malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast;
• Subjects with any active autoimmune disease (Appendix 3) or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy;
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS);
• Positive tests for hepatitis B virus surface antigen (HBV SAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating active or chronic infection;
• Prior therapy with an