PD-1 Alone or With Dendritic Cell/Renal Cell Carcinoma Fusion Cell Vaccine

• Number of participants with adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  To assess the toxicity associated with treating patients with metastatic RCC with CT-011 alone or CT-011 in conjunction iwth DC/RCC
• Response Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  To evaluate the complete and partial response rate following completing 4 cycles of CT-011 alone or CT-011 in conjunction with DC/RCC fusion vaccine.

• Immunologic Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  To evaluate immunologic response directed against RCC and tumor specific antigens following therapy with CT-011 alone or CT-011 in conjunction with DC/RCC fusion vaccine. Immunologic response will be characterized as peak response post-therapy and ongoing response at 3 and 6 months following treatment.
• Effect on Circulating Regulatory T cells [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  To evaluate the effect of CT-011 alone or in conjunction with DC/RCC fusions on circulating regulatory T cells and PD-1 expression by circulating and bone marrow derived T cells.
• Overall Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  To evaluate overall survival following treatment with CT-011 alone or CT-011 in conjunction with DC/RCC fusion vaccine.

• Immunologic Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  To evaluate immunologic response directed against RCC and tumor specific antigens following therapy with CT-011 alone or CT-011 in conjunction with DC/RCC fusion vaccine. Immunologic response will be characterized as peak response post-therapy and ongoing response at 3 and 6 months following treatment.
• Effect on Circulating Regulatory T cells [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  To evaluate the effecto of CT-011 alone or in conjunction with DC/RCC fusions on ciruclating regulatory T cells and PD-1 expression by circulating and bone marrow derived T cells.
• Overall Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  To evaluate overall survival following treatment with CT-011 alone or CT-011 in conjunction with DC/RCC fusion vaccine.

CT-011 is an investigational monoclonal antibody. Monoclonal antibodies are a type of drug that are known to target specific cells (in this case, cells in the immune system) The DC RCC Vaccine is agent that tries to help the immune system to recognize and fight against cancer cells.

The purpose of this research study is to determine the safety of CT-011 alone, and in combination with the Dendritic Cell Renal Cell Carcinoma (DC RCC) vaccine. The investigators are also trying to find out what effect the combination has on the disease, and on your immune system.

This study is divided into 2 groups. The first 22 subjects will be in Group 1 and will receive CT-011 only. The next 22 subjects will be in Group 2 and will receive CT-011 and the DC RCC vaccine.

Group 1: Subjects in this cohort are not required to have tumor resection (nephrectomy) to participate in this study. For subjects who are undergoing nephrectomy and for subjects undergoing resection for another metastasis, infusions of CT-011 will begin 21 to 35 days post-surgery. Subjects will receive 4 cycles of CT-011 therapy. Each cycle consists of a dose of CT-011 given on days 1, 14, and 28 intravenously.

For subjects who are not undergoing nephrectomy for standard of care therapy, infusions of CT-011 will begin 21 to 28 days following registration on the study. Subjects will receive a total of four cycles of CT-011 therapy. Each cycle consists of a dose of CT-011 given on days 1, 14, and 28 intravenously.

Group 2: Subjects in this cohort will have chosen to undergo a "debulking nephrectomy" (surgery to remove a tumor of the kidney, but not all of the cancer cells in your body) as a standard treatment for kidney cancer or have tumor lesions that are accessible (may be removed without major surgery) and are being removed to treat or diagnose their cancer. All subjects in this group will receive infusions of CT-011 21 to 35 days following tumor resection.

Subjects will receive a total of 4 cycles of CT-011 therapy. Each cycle consists of a dose of CT-011 given on days 1, 14, and 28. In addition they will receive a vaccination of the DC RCC vaccine on day 8 of each cycle.

• Drug: CT-011
  CT-011 at 3 mg/kg IV for 4 cycles of 6 weeks
• Biological: DC/RCC fusion vaccine
  Vaccination once per cycle on Day 8 of treatment cycles 2-4

• Active Comparator: CT-011
  CT-011 3 mg/kg for 4 cycles of 6 weeks
  Intervention: Drug: CT-011
• Active Comparator: CT-011 with DC/RCC fusion vaccine
  CT-011 with DC/RCC fusion vaccine for subjects undergoing nephrectomy, resection of tumor tissue, or aspiration of malignant effusion
  Interventions:

  • Drug: CT-011
  • Biological: DC/RCC fusion vaccine

Inclusion Criteria:

• Stage IV renal cancer
• Measurable disease
• Life expectancy > 3 months
• Adequate organ and marrow function

Exclusion Criteria:

• Clinical evidence of central nervous system (CNS) disease. Subjects with a history of treated brain metastasis must be stable with no evidence of disease for 3 months
• Clinically significant autoimmune disease
• HIV+
• Serious intercurrent illness such as infection requiring intravenous (IV) antibiotics, or significant cardiac disease characterized by significant arrhythmia, uncontrolled hypertension, unstable ischemic coronary disease or congestive heart failure
• Pregnant or lactating
• History of clinically significant venous thromboembolism (For Cohort 2)

• National Institutes of Health (NIH)
• National Cancer Institute (NCI)