Inclusion Criteria:
Histologically confirmed, locally advanced & surgically inoperable or metastatic renal cell carcinoma or malignant melanoma are eligible. Pre-treatment tumor samples, such as paraffin blocks or unstained slides, must be available for analyses.

Adult patients must have failed at least 1 prior therapy. Patients with renal cell carcinoma must have failed either sorafenib or sunitinib as 1 of their prior therapies. Other qualifying prior therapies include any medical, surgical, radiation or investigational approaches used for potential therapeutic benefit (but not for diagnostic purposes) in patients with advanced disease. Potential patients may not be eligible for curative intent treatment (e.g., potentially curative surgical resection or chemotherapy).

Age > or = 18 yrs

Expected survival > or =5 months

ECOG Performance Status 0 to 2.

Measurable disease as defined by RECIST

Laboratory:

At the time of enrollment, patients must be >4 wks since major surgery, radiotherapy, chemotherapy (> or =6 wks if they were treated with a nitrosourea, mitomycin, or monoclonal antibodies such as bevacizumab), immunotherapy, or biotherapy/targeted therapies and recovered from the toxicity of prior treatment to< or = Grade 1, exclusive of alopecia. Concurrent cancer therapy is not permitted. (In patients who received long acting agents, a treatment-free interval of 2 half-lives should be considered.)

Patients must be able to give written informed consent to participate. Patients may not be consented by a durable power of attorney.

Male and female patients of child-producing potential must agree to use effective contraception while enrolled on study and receiving the experimental drug, and for at least 3 months after the last treatment. Female patients of child-producing potential must have a negative serum pregnancy test.

Documentation of flu vaccination if enrolled during flu season (as defined by the availability of vaccine). Otherwise, patient should receive the current flu vaccine > or = 1 wk before beginning GC1008 therapy.

Exclusion Criteria:
Central nervous system (CNS) metastases, meningeal carcinomatosis, malignant seizures, or a disease that either causes or threatens neurologic compromise (e.g., unstable vertebral metastases).

History of ascites or pleural effusions, unless successfully treated, completely resolved, and the patient has not been treated for these conditions for >4 months.

Active thrombophlebitis, thromboembolism, hypercoagulability states, bleeding, or use of anti-coagulation therapy (including anti-platelet agents). Patients with a history of deep venous thrombosis may participate if successfully treated, completely resolved, and no treatment has been given for >4 months.

Hypercalcemia: Calcium >11.0 mg/dL (2.75 mmol/L) unresponsive or uncontrolled in response to standard therapy (e.g., bisphosphonates).

Pregnant or nursing women.

Patients diagnosed with another malignancy – unless following curative intent therapy, the patient has been disease free for at least 5 yrs and the probability of recurrence of the prior malignancy is <5%. Patients with curatively treated early stage squamous cell carcinoma of the skin, basal cell carcinoma of the skin, or cervical intraepithelial neoplasia (CIN) are eligible for this study.

Patients with an organ transplant, including those that have received an allogeneic bone marrow transplant.

Use of investigational agents within 4 wks prior to study enrollment (within 6 wks if the treatment was with a long-acting agent such as a monoclonal antibody).

Patients on immunosuppressive therapy

Significant or uncontrolled medical illness, such as congestive heart failure (CHF), myocardial infarction, symptomatic coronary artery disease, significant ventricular arrhythmias within the last 6 months, or significant pulmonary dysfunction. Patients with a remote history of asthma or active mild asthma may participate.

Active infection, including unexplained fever (temperature > 38.1 degrees C) or antibiotic therapy within 1 wk prior to enrollment.

Systemic autoimmune disease (e.g., systemic lupus erythematosus, active rheumatoid arthritis, etc.).

A known allergy to any component of GC1008.

Patients who, in the opinion of the Investigator, have significant medical or psychosocial problems that warrant exclusion.