CLINICAL TRIAL / NCT01621490

Allocation:

     Part 1 and 2: Single Arm study

     Part 3 and 4: Randomized Controlled Trial

     Intervention Model:

     Part 1 and 2: Single group: Single arm study

     Part 3 and 4: Parallel: Participants are assigned to one of two or more groups in parallel for the duration of the study

     Minimum Age:

     Part 1: 18

     Part 2, 3 and 4: 16

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

        Part 1:

        Inclusion Criteria:

         - Men and women >18 years

         - Eastern Cooperative Oncology Group (ECOG) status = 0 to 1

         - Subjects with unresectable Stage III or IV melanoma who are either refractory or intolerant to, or have refused standard therapy for treatment of metastatic melanoma

         - Subject must have histologic or cytologic confirmation of advanced melanoma

         - Subjects must have at least one measurable lesion at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

         - Subjects must have at least 1 tumor site that can be biopsied at acceptable clinical risk and must consent to pre- and post-treatment biopsies

        Exclusion Criteria:

         - Active or progressing brain metastases

         - Other concomitant malignancies (with some exceptions per protocol)

         - Active or history of autoimmune disease

         - Positive test for human immunodeficiency virus (HIV) 1&2 or known acquired immunodeficiency syndrome (AIDS)

         - History of any hepatitis

         - Prior therapy with any antibody/drug that targets the T cell coregulatory proteins, including but not limited to, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40,and anti-CD40 antibodies. However, half the patients must have progressed on anti Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA4) monoclonal antibody therapy

        Part 2, 3 and 4:

        Inclusion Criteria

         - Men and women >16 years

         - Eastern Cooperative Oncology Group (ECOG) status = 0 to 1

         - Subjects with unresectable Stage III or IV melanoma who are either refractory or intolerant to, or have refused standard therapy for treatment of metastatic melanoma

         - Subjects must never received anti-CTLA4 therapy

         - Subjects must have histologic or cytologic confirmation of advanced melanoma

         - Subjects must have at least two measurable lesions at baseline by CT or MRI as per RECIST 1.1 criteria

         - Subjects must have at least 1 tumor site that can be biopsied at acceptable clinical risk and must consent to pre- and post-treatment biopsies

         - Subjects in Part 4 must have brain metastases

        Exclusion Criteria

         - Active or progressing brain metastases (except for Part 4 subjects)

         - Other concomitant malignancies (with some exceptions per protocol)

         - Active or history of autoimmune disease

         - Positive test for HIV 1&2 or known AIDS

         - History of any hepatitis

         - Prior therapy with any antibody/drug that targets the T cell coregulatory proteins, including but not limited to, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40,and anti-CD40 antibodies