This was a Phase 1, open-label, fixed-dose study of immunization with the NY-ESO-1 protein combined with CpG 7909 as an adjuvant in patients with histopathologically confirmed, high-risk Stage D1 or advanced prostate cancer. The primary study objective was to assess the safety of NY-ESO-1 protein/CpG 7909 immunization, and the secondary objective was to evaluate the immunity induced by immunization.

Eligible patients received vaccinations consisting of the NY-ESO-1 protein (100 µg) combined with CpG 7909 (2.5 mg) administered intradermally every 3 weeks for 4 doses. Patients who demonstrated stable disease, minor response, partial response, or complete response at Week 13 may have continued to receive vaccinations until disease progression. In patients with mixed response, single progressive lesions may have been resected and vaccination may have been continued.

Safety was monitored continuously. Blood samples were obtained for clinical hematology, biochemistry and immune response assessments, including antinuclear antibody (ANA) and anti-dsDNA, NY-ESO-1 and/or LAGE-1 specific antibodies, and NY-ESO-1 specific cluster of differentiation (CD)4+ and CD8+ T cells.

A tumor sample, resected prior to immunization, was tested to determine NY-ESO-1 and/or LAGE-1 expression. Delayed-type hypersensitivity (DTH) testing was performed at baseline and on study.

Disease status was assessed at baseline and on study in patients with measurable disease.

Inclusion Criteria

Patients were eligible for enrollment if they fulfilled the following criteria:

1. High-risk Stage D1 or metastatic prostate cancer (D2), confirmed by review of histology.

2. Fully recovered from surgery.

3. Showed stable or progressive disease as assessed by X-ray, ultrasound, and/or computed tomography (CT) scans under hormonal and/or chemotherapeutic treatment, which had been administered for ≥ 3 months.

4. Any pretreatment with chemo- or radiotherapy must have been discontinued for ≥ 4 weeks prior to the first dose of study agent. Hormone therapy was allowed before and throughout the study.

5. Expected survival of ≥ 3 months.

6. Karnofsky performance status of ≥ 70%.

7. Within the last 2 weeks prior to study day 1, vital laboratory parameters should have been within the normal range, except for the following laboratory parameters, which should have been within the ranges specified:

   • Leukocytes > 3,000/µl.
   • Lymphocytes > 700/µl.
   • Platelets > 100,000/µl.
   • Serum creatinine < 2.5 mg/dL.
   • Alanine aminotransferase, aspartate aminotransferase, and total bilirubin < 2.5 x upper limit of normal.

8. Age ≥ 18 years.

9. Able to give valid written informed consent.

Exclusion Criteria

Patients were excluded from the study if they fulfilled any of the following criteria:

1. Clinically significant heart disease (i.e., New York Heart Association Class 3 congestive heart failure; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty within the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias).
2. Other serious illnesses, e.g., active infections requiring antibiotics, bleeding disorders.
3. Concomitant systemic treatment with corticosteroids. Topical or inhalational steroids were permitted.
4. Metastatic disease to the central nervous system.
5. Mental impairment, in the opinion of the Investigator, that may have compromised the ability to give informed consent and comply with the requirements of the study.
6. Lack of availability for immunological and clinical follow-up assessments.
7. Participation in chemotherapy, radiation therapy, or any other clinical trial involving another investigational agent within 4 weeks prior to first dosing.
8. Being a recipient of an organ or bone marrow allograft. Having an autoimmune disease other than vitiligo, such as, but not limited to, inflammatory bowel disease or multiple sclerosis.

The population comprises all enrolled patients.

All adverse events (AEs), regardless of causality to study drug, were documented from the first dose of study treatment through the final follow-up visit, for an AE collection period of up to 56 weeks for each patient.

AE documentation included onset/resolution dates, severity using the NCI CTCAE (version 3.0), seriousness, relationship to study drug, study drug action taken, treatment, and outcome. In summaries, preferred terms were counted only once per patient at the maximum reported grade.