Phase 1 Biomarker Study of Anti-PD-1 in Advanced Melanoma

• Immunomodulatory effects of BMS-936558 as measured by changes from baseline in activated and memory T cells, interferon, interferon inducible factors, and CD4 and CD8 T cell infiltration [ Time Frame: Pre-dose day 1 ] [ Designated as safety issue: No ]
• Immunomodulatory effects of BMS-936558 as measured by changes from baseline in activated and memory T cells, interferon, interferon inducible factors, and CD4 and CD8 T cell infiltration [ Time Frame: Up to day 57 (Cycle 2 Day 1) ] [ Designated as safety issue: No ]

• Safety and tolerability of BMS-936558 as measured by the incidence of adverse events (AEs), serious AEs, death, and changes in vital signs [ Time Frame: Up to 14 weeks after last dose of study drug ] [ Designated as safety issue: Yes ]
• Safety and tolerability of BMS-936558 as measured by laboratory test abnormalities [ Time Frame: Every 2 weeks up to 14 weeks after last treatment ] [ Designated as safety issue: Yes ]
• Antitumor Activity of BMS-936558 as measured by the objective response rate (ORR), duration of response, and progression free survival (PFS) [ Time Frame: Every 8 weeks until confirmed disease progression and in follow-up if no progression ] [ Designated as safety issue: No ]
• Immunogenicity of BMS-936558 as measured by the frequency of subjects with at least one positive ADA assessment and the frequency of subjects who develop anti-drug antibodies (ADA) after a negative baseline assessment [ Time Frame: Day 1, Day 15, Day 43 of cycle 1, Day 1 of cycle 2, Day 15 of cycle 3, every 16 weeks after cycle 3 Up to 2 years, and at Follow-up visits 1 (49±3 days after last treatment) and Follow-up visit 2 (90-120 days since last treatment) ] [ Designated as safety issue: Yes ]
• Association between Programmed cell death ligand 1 (PD-L1) and clinical efficacy will be measured by PDL1 expression levels clinical activity (ORR, PFS) [ Time Frame: Pre-dose Up to Day 1 (screening) and Day 29 of cycle 1 ] [ Designated as safety issue: No ]
  Screening (day -7 to day 1 predose)

The purpose of this study is to evaluate pharmacodynamic changes of BMS-936558 treatment on the biomarkers measured in the peripheral blood and tumor tissues of subjects with advanced melanoma (unresectable or advanced).

• Advanced Melanoma
• Metastatic Melanoma

For additional information, please contact the BMS oncology clinical trial information service at 855-216-0126 or email MyCancerStudyConnect@emergingmed.com. Please visit www.BMSStudyConnect.com for more information on clinical trial participation.

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