Inclusion Criteria:

- Histologically confirmed metastatic melanoma

- Unresectable stage III or IV disease

- For unknown primary disease, diagnosis of metastatic disease by cytology FNA is
not acceptable

- Measurable disease

- No more than 1 prior investigational therapy or systemic therapeutic regimen*,
including any of the following:

- Chemotherapy

- Biological therapy

- Biochemotherapy

- Investigational treatment

- No CNS metastases

- ECOG performance status 0-1

- WBC ≥ 2,000/μL

- ANC ≥ 1,500/μL

- Platelet count ≥ 100,000/μL

- Hemoglobin ≥ 8 g/dL

- Creatinine ≤ 3.0 times upper limit of normal (ULN)

- AST and ALT ≤ 2.5 times ULN

- Bilirubin ≤ 3.0 times ULN (total bilirubin < 3.0 mg/dL for patients with Gilbert
syndrome)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for up to 12 weeks after
completion of study

- No HIV infection

- No active infection with hepatitis B virus

- No active or chronic infection with hepatitis C virus

- No other malignancy with the past 2 years except adequately treated and cured basal
cell or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ
of the cervix

- No history of autoimmune disease, including any of the following:

- Inflammatory bowel disease

- Symptomatic disease (e.g., rheumatoid arthritis, systemic progressive
sclerosis[scleroderma])

- Systemic lupus erythematosus

- Autoimmune vasculitis (e.g., Wegener granulomatosis)

- Motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome
and myasthenia gravis)

- Patients with a history of autoimmune thyroiditis are eligible if their current
thyroid disorder is treated and stable with replacement or other medical therapy

- No underlying medical or psychiatric condition that, in the opinion of the
investigator, will make the administration of study drug hazardous or obscure the
interpretation of adverse events, such as a condition associated with frequent
diarrhea

- No concurrent medical condition requiring the use of systemic steroids

- No other concurrent CTLA-4 inhibitor or agonist or CD137 agonist

- At least 4 weeks since prior and no concurrent therapy with any of the following:

- Aldesleukin (IL-2)

- Interferon

- Non-study immunotherapy regimens

- Cytotoxic chemotherapy

- Immunosuppressive agents

- Other investigational therapies

- Chronic use of systemic corticosteroids

- Concurrent inhaled or topical steroids allowed

- Concurrent physiologic replacement doses of corticosteroids allowed

- No prior non-oncology vaccine therapy for the prevention of infectious disease within
the past 28 days or after any dose of ipilimumab

- No prior ipilimumab, CD137agonist, or CTLA-4 inhibitor or agonist

- No other systemic or local anticancer medications