A Phase I/II Open-Label Study of Ipilimumab and GM-CSF Administered to Unresectable Stage IIIC and Stage IV Melanoma Patients

Inclusion Criteria:

- Patients may be entered in the study only if they meet all of the following criteria.

1. Male or female patients ≥18 years of age;

2. Patients with histological confirmed melanoma (Stage IIIC or Stage IV, American
Joint Commission on Cancer);

3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2;

4. Life expectancy ≥3 months;

5. At least 1 site of radiographically measurable disease by immune-related
response criteria (irRC);

6. Adequate hematologic, renal, and liver function as defined by laboratory values
performed within 42 days prior to initiation of dosing:

- Absolute neutrophil count (ANC) ≥1.0 x 109/L;

- Platelet count ≥50 x 109/L;

- Hemoglobin ≥8 g/dL;

- Serum creatinine ≤3 x upper limit of normal (ULN)

- Total serum bilirubin ≤2 x ULN;

- Serum aspartate transaminase (AST/SGOT) or serum alanine transaminase
(ALT/SGPT) ≤2x ULN, and ≤3 x ULN if liver metastases are present.

7. Fertile males should use an effective method of contraception during treatment
and for at least 3 months after completion of treatment, as directed by their
physician;

8. Pre-menopausal females and females <2 years after the onset of menopause should
have a negative pregnancy test at Screening. Pre-menopausal females must agree
to use an acceptable method of birth control from the time of the negative
pregnancy test up to 90 days after the last dose of study drug. Females of
non-childbearing potential may be included if they are either surgically sterile
or have been postmenopausal for ≥1 year;

9. Before study entry, written informed consent must be obtained from the patient
prior to performing any study-related procedures.

Exclusion Criteria:

- Patients will not be entered in the study for any of the following:

1. Treatment with Denileukin Diftitox within 42 days prior to the start of
Ipilimumab;

2. Prior treatment with Ipilimumab;

3. Known hypersensitivity to Ipilimumab or any of its components

4. Received radiotherapy for non CNS disease within the 2 weeks prior to commencing
study treatment or have not recovered from side effects of all radiation-related
toxicities to Grade ≤1, except for alopecia;

5. Steroids within one week prior to initiation of Ipilimumab.

6. Pre-existing autoimmune colitis.

7. Patients with an allograft requiring immunosuppression;

8. Known positive human immunodeficiency virus (HIV)

9. Pregnant, breast-feeding, or refusing double barrier contraception, oral
contraceptives, or avoidance of pregnancy measures;

10. Have any other uncontrolled infection or medical condition that could interfere
with the conduct of the study.