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

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