Inclusion Criteria:

1. Patients with measurable or evaluable unresectable, stage IV metastatic melanoma.
Either histologic or cytologic diagnosis is acceptable.

2. Eastern Cooperative Oncology Group (ECOG) performance status 0, or 1 (Appendix A.)

3. Age 18 years or above.

4. Laboratory values (performed within 28 days prior to enrollment) as follows:

- WBC ≥2000/microliter

- Absolute lymphocyte count >300/mm3

- Serum creatinine <1.5 X upper limit of laboratory normal

- Hgb >8g/dl (patients may be transfused to reach this level)

- Hct > 24%

- Platelets >100,000 cells/mm3

- Total bilirubin <1.5 X upper limit of laboratory normal, unless due to
Gilbert's disease

- AST (SGOT)/ALT (SGPT) <2.5 X upper limit of laboratory normal

- Alkaline phosphatase <2.5 X upper limit of laboratory normal

- HIV Negative

- Hepatitis B surface antigen Negative

- Hepatitis C antibody Negative

5. Women of childbearing potential must have a negative pregnancy test and must avoid
becoming pregnant while on treatment. Men must avoid fathering a child while on
treatment. This exclusion is required due to the unknown toxicities that anti-OX40
may have on the forming fetus, spermatogenesis or the nursing child. Also, because
pregnancy may impair immune function it may limit the treatment efficacy.

6. Ability to give informed consent and comply with the protocol. Patients with a
history of psychiatric illness must be judged able to understand fully the
investigational nature of the study and the risks associated with the therapy.

7. No active bleeding.

8. No clinical coagulopathy (INR <1.5, PT <16 seconds, PTT < 38 seconds).

9. Anticipated lifespan greater than 12 weeks.

10. Failed at least one prior medical therapy for metastatic melanoma.

Exclusion Criteria:

1. Active infection.

2. History of or active autoimmune disease.

3. Prior mouse monoclonal antibody treatment.

4. Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo
or fetus.

5. Need for chronic maintenance oral steroids.

6. Active brain metastatic disease. Treated brain metastases with surgery, gamma-knife
radiosurgery and/or whole brain radiation and stable for at least 4 weeks and off
steroids are eligible.

7. Any medical or psychiatric condition that in the opinion of the PI would preclude
compliance with study procedures.