NY-ESO-1 Vaccine in Combination With Ipilimumab in Patients With Unresectable or Metastatic Melanoma

Inclusion Criteria:

1. Patients with unresectable or metastatic melanoma, for whom treatment with ipilimumab was indicated as per ipilimumab/Yervoy® package insert (applicable for United States \[US\] sites) or product information (applicable for Australia site).
2. Radiologically measurable disease by irRC.
3. Tumor expression of NY-ESO-1 or LAGE-1 antigen by immunohistochemistry or reverse transcriptase-polymerase chain reaction (RT-PCR), or evidence of seropositivity to NY-ESO-1 or LAGE-1.
4. Willingness to provide at least one pre-and post-vaccination tumor biopsy sample.
5. Expected survival of at least 4 months.
6. At the time of Day 1 of the study, patients must have been at least 3 weeks since surgery.
7. At the time of Day 1 of the study, patients with brain metastases must have been asymptomatic and:

   * at least 8 weeks without tumor progression after any whole brain radiotherapy;
   * at least 4 weeks since craniotomy and resection or stereotactic radiosurgery;
   * at least 3 weeks without new brain metastases as evidenced by magnetic resonance imaging (MRI).
8. Eastern Cooperative Oncology Group performance status of 0 to 2.
9. Laboratory parameters for vital functions must have been in the normal range. Laboratory abnormalities that were not clinically significant were generally permitted, except for the following laboratory parameters, which must have been within the ranges specified:

   * hemoglobin: ≥ 10 g/dL;
   * neutrophil count: ≥ 1.5 x 10\^9/L;
   * lymphocyte count: ≥ lower limit of normal (LLN);
   * platelet count: ≥ 80 x 10\^9/L;
   * serum creatinine: ≤ 2 mg/dL;
   * serum bilirubin: ≤ 2 x upper limit of normal (ULN);
   * aspartate aminotransferase (AST)/alanine aminotransferase (ALT): ≤ 2 x ULN.
10. Had been informed of other treatment options.
11. Age ≥ 18 years.
12. Able and willing to give valid written informed consent.

Exclusion Criteria:

1. Any contraindications for ipilimumab/Yervoy® as per package insert (applicable for US sites) or product information (applicable for Australia site).
2. Prior exposure to NY-ESO-1 vaccine.
3. Active autoimmune disease, symptoms or conditions except for vitiligo, type I diabetes, treated thyroiditis, asymptomatic laboratory evidence of autoimmune disease (e.g., +antinuclear antibody \[ANA\], +rheumatoid factor \[RF\], antithyroglobulin antibodies), or mild arthritis requiring no therapy or manageable with nonsteroidal anti-inflammatory drugs (NSAIDs).
4. Unresolved immune-related adverse events following prior biological therapy.
5. Systemic treatment with high-dose corticosteroids (greater than prednisone 10 mg daily or equivalent).
6. Treatment with protocol-specified non-permitted concomitant therapies.
7. Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may have been available.
8. Myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, chest pain or shortness of breath with activity, or other heart conditions being treated by a doctor.
9. Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ.
10. Known immunodeficiency or human immunodeficiency virus positivity, active Hepatitis B or active Hepatitis C.
11. History of severe allergic reactions to vaccines or unknown allergens.
12. Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders).
13. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to Day 1 of the study.
14. Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study.
15. Lack of availability for immunological and clinical follow-up assessments.
16. Women who were breast feeding or pregnant as evidenced by positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) done within 14 days prior to first dosing and urine test within 72 hours prior to first dosing.
17. Women of childbearing potential not using a medically acceptable means of contraception for the duration of the study.
18. Any condition that, in the clinical judgment of the treating physician, was likely to prevent the patient from complying with any aspect of the protocol or that may have put the patient at unacceptable risk.