Inclusion Criteria:

- Subject must have read, understood, and provided written informed consent and
authorization in compliance with the Health Insurance Portability and Accountability
Act (HIPAA) afer the nature of the study has been fully explained.

- Subject must be at least 18 years of age with a histologic diagnosis of unresectable
Stage III or IV malignant melanoma (may include mucosal melanoma). Subjects with
either stable or progressive malignancy will be permitted in the study.
Classification of stable or progressive disease, to be recorded for all subjects,
will be defined by the Response Evaluation Criteria in Solid Tumors (RECIST), as
detailed in Appendix 3 and determined since last melanoma treatment. Subjects must
have at least 1 site of measurable disease.

- At least 4 weeks since treatment (surgery, chemotherapy, radiation, or immuno-
therapy) for melanoma and recovered from any serious toxicity experienced during
treatment.

- Life expectancy of at least 18 weeks.

- Karnofsky Performance Status of at least 70%

- Screening laboratory values must meet the following criteria:

- WBC ≥2500/μL

- ANC ≥1500/μL

- Platelets ≥100 x 10'/μL

- Hematocrit ≥30%

- Hemoglobin ≥10 g/dL

- Creatinine ≤2 mg/dL

- AST ≤2 x ULN*

- Bilirubin ≤1.0 x ULN*, (except subjects with Gilbert's Syndrome, who must have a
total bilirubin less than 3.0 mg/dL)

- HIV negative

- HBsAg negative

- anti-HCV nonreactive. If reactive, subject must have a negative HCV RNA
qualitative PCR.

- Unless definitely attributable to disease.

Exclusion Criteria:

- Any prior malignancy except for the following: adequately treated basal or squamous
cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or any
other cancer from which the subject has been disease-free for at least 5 years

- History of autoimmune disease (including uveitis and autoimmune inflammatory eye
disease) prior to entrance into the study.

- Active infection requiring therapy, chronic active HBV or HCV, or confirmed
reactivity with HIV tests.

- Tetanus booster immunization within 2 months of initial screening procedures, or a
history of anaphylaxis or severe local reaction to the tetanus vaccine.

- Pregnant or nursing: it is not known what effect MDX-010 could have on the developing
immune system of the fetus or infant, therefore, exposure in utero or via breast milk
will not be allowed.

- Any underlying medical condition which, in the opinion of the principal investigator,
will make the administration of study drug hazardous or obscure the interpretation of
adverse events.

- Any concurrent medical condition requiring the use of systemic or topical
corticosteroids or the use of immunosuppressive agents (e.g. cyclosporine and its
analog, or chemotherapy agents). All corticosteroid use must have been discontinued
at least 4 weeks prior to trial entry.

- Prior treatment with MDX-010 or any other anti-CTLA-4 monoclonal antibody.

- Evidence or history of significant cardiac, pulmonary, hepatic, renal, psychiatric or
gastrointestinal disease that would make the administration of MDX-010 unsafe.

- Concurrent treatment with chemotherapy or other immunotherapy regimens (must be
completed at least 4 weeks before Screening).