Study of the Combination of Anti-OX40 and Ipilimumab in Patients With Metastatic Melanoma

Inclusion Criteria: * Patients with unresectable or metastatic melanoma, for whom treatment with Ipilimumab is indicated * Radiologically measurable disease by immune-related Response Criteria * ECOG performance status of 0-1. * Anticipated lifespan greater than 12 weeks. * At the time of day 1 of the study, patients must be at least 3 weeks since surgery * At the time of day 1 of the study, patients with brain metastases must be asymptomatic and, at least 8 weeks without tumor progression after any whole brain radiotherapy, at least 4 weeks since craniotomy and resection or stereotactic radiosurgery, at least 3 weeks without new brain metastases as evidenced by MRI/CT * The following laboratory parameters must be within the ranges specified: Hemoglobin-≥ 9 g/dL, WBC-≥ 3.0 x 109/L, INR-≤ 1.5, Total Bilirubin-≤ 1.9 g/dL \& AST/ALT-≤ 3 x ULN * Have been informed of other treatment options. * At least 18 years. Able and willing to give valid written informed consent. Exclusion Criteria: * Any contraindications for ipilimumab/Yervoy®. * Prior exposure to ipilimumab/Yervoy® * Prior exposure to Anti-OX40 or a mouse monoclonal antibody. * History of severe allergic reactions to any unknown allergens or anti-OX40 Autoimmune disease except for autoimmune thyroiditis or vitiligo. * Unresolved immune related adverse events following prior biological therapy. * Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may be available. * Known immunodeficiency or HIV, Hepatitis B or Hepatitis C positivity. * Other serious illnesses (e.g., serious infections requiring antibiotics). * Participation in any other clinical trial involving another investigational agent within 4 weeks prior to day 1 of the study. * Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study. * Lack of availability for immunological and clinical follow-up assessments. * Women who are breast feeding or pregnant as evidenced by positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) done within 72 hours of first dosing. * Women of childbearing potential not using a medically acceptable means of contraception for the duration of the study. * Any condition that, in the clinical judgment of the treating physician, is likely to prevent the patient from complying with any aspect of the protocol or that may put the patient at unacceptable risk.