Phase I Biomarker Study (BMS-936558)

• Safety and tolerability of BMS-936558 as measured by the incidence and severity of adverse events [ Time Frame: Assessed at a minimum of every 3 weeks up to 70 days following discontinuation of study drug (at progression of disease, toxicities requiring discontinuation, withdrawal of consent or study closure) ] [ Designated as safety issue: Yes ]
• Progression free survival in the BMS-936558 arms [ Time Frame: Progression free survival will be assessed in each individual treatment arm by tumor assessments every 6 weeks ] [ Designated as safety issue: No ]
• The tumor response rate in the BMS-936558 arms as assessed by the Investigator assessment of best overall response [ Time Frame: Up to 22 months after study start ] [ Designated as safety issue: No ]
  The tumor response rate will be assessed on all subjects at the time they discontinue study treatment by the Investigators assessment of best overall response for a subject
• Overall response rate for BMS-936558 as assessed by the number of subjects which demonstrate an objective response divided by the total number of treated subjects with measurable disease at baseline [ Time Frame: response rate will be assessed by tumor assessments every 6 weeks ] [ Designated as safety issue: No ]
• Disease control rate for BMS-936558 as measured by the number of subjects with an objective response + the number of subjects with stable disease divided by the total number of treated subjects with measurable disease at baseline [ Time Frame: disease control will be assessed by tumor assessments every 6 weeks ] [ Designated as safety issue: No ]
• Duration of objective response for BMS-936558 as measured by the time when the criteria for an objective response are first met until the date of documented disease progression or death [ Time Frame: Duration of response will be assessed by tumor assessments every 6 weeks ] [ Designated as safety issue: No ]
• Duration of stable disease for BMS-936558 as measured in subjects whose best overall response is stable disease as the time from baseline until the date of documented disease progression or death [ Time Frame: Duration of response will be assessed by tumor assessments every 6 weeks ] [ Designated as safety issue: No ]
• Immunogenicity of BMS-936558 as measured by the detection of human antibodies against BMS-936558 [ Time Frame: Serum sample collected at baseline, 12 weeks following initiation of study treatment; and during the first 2 follow-up visits in the follow-up phase ] [ Designated as safety issue: Yes ]

The purpose of this study is to evaluate the pharmacodynamic and biologic properties of BMS-936558 in subjects with metastatic renal cell carcinoma.

Intervention Model: Parallel Dose Comparison

• Drug: BMS-936558 (Anti-PD-1)
  Solution, Intravenous infusion, 0.3 mg/kg, Every 3 weeks, Indefinitely depending on response
• Drug: BMS-936558 (Anti-PD-1)
  Solution, Intravenous infusion, 2 mg/kg, Every 3 weeks, Indefinitely depending on response
• Drug: BMS-936558 (Anti-PD-1)
  Solution, Intravenous infusion, 10 mg/kg, Every 3 weeks, Indefinitely depending on response

• Experimental: Arm 1: BMS-936558
  Intervention: Drug: BMS-936558 (Anti-PD-1)
• Experimental: Arm 2: BMS-936558
  Intervention: Drug: BMS-936558 (Anti-PD-1)
• Experimental: Arm 3: BMS-936558
  Intervention: Drug: BMS-936558 (Anti-PD-1)
• Experimental: Arm 4: BMS-936558
  (treatment naive)
  Intervention: Drug: BMS-936558 (Anti-PD-1)

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:

• Women and men ≥ 18 years of age.
• Histologic confirmation of renal cell carcinoma with a clear cell component.
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST).
• Tumor sites that can be accessed for repeat biopsies at acceptable clinical risk.
• Previously treated subjects must have failed at least 1 prior anti-angiogenic agent and can have a maximum of 3 prior systemic treatments for renal cell cancer.
• Subjects in the treatment naive arm cannot have received prior systemic therapy for their renal cell carcinoma.

Exclusion Criteria:

• Active or progressing brain metastases.
• Active concomitant.
• Active or history of autoimmune disease.
• Active use of systemic corticosteroids.
• Prior therapy with Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA4), anti Programmed death-1 (anti-PD1), anti Programmed death ligand 1 (anti-PD-L1), anti Programmed death ligand 2 (anti-PD-L2), anti-CD137, anti-CD40, anti-OX40 antibodies.