PH 1 Biomarker Study of Nivolumab and Ipilimumab and Nivolumab in Combination With Ipilimumab in Advanced Melanoma

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