Immunization With NY-ESO-1 Protein Combined With CpG 7909 in Patients With Prostate Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase 1 Study of Immunization With NY-ESO-1 Protein Combined With CpG 7909 in Patients With High-risk Stage D1 or Advanced Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Biological: NY-ESO-1 protein/CpG 7909


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients were eligible for enrollment if they fulfilled the following criteria: High-risk Stage D1 or metastatic prostate cancer (D2), confirmed by review of histology. Fully recovered from surgery. 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. 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. Expected survival of ≥ 3 months. Karnofsky performance status of ≥ 70%. 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. Age ≥ 18 years. Able to give valid written informed consent. Exclusion Criteria Patients were excluded from the study if they fulfilled any of the following criteria: 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). Other serious illnesses, e.g., active infections requiring antibiotics, bleeding disorders. Concomitant systemic treatment with corticosteroids. Topical or inhalational steroids were permitted. Metastatic disease to the central nervous system. 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. Lack of availability for immunological and clinical follow-up assessments. Participation in chemotherapy, radiation therapy, or any other clinical trial involving another investigational agent within 4 weeks prior to first dosing. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NY-ESO-1 protein + CpG 7909<br>Patients received immunization with intradermal injections of the NY-ESO-1 protein combined with CpG 7909. | Biological: NY-ESO-1 protein/CpG 7909<br>* Patients received vaccinations consisting of the NY-ESO-1 protein (100 µg) combined with CpG 7909 (2.5 mg) as an adjuvant administered intradermally every 3 weeks for 4 doses (i.e., 12-week cycle).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Treatment-emergent Adverse Events (TEAEs) | Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, as follows: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), and Grade 5 (fatal). Adverse events (AEs) were reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, performance status evaluations, and any other medically indicated assessments, including patient interviews, from the first dose of study treatment through the final follow-up visit. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment. | Up to 56 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Cellular Antibody Response to NY-ESO-1 | Assays to assess cluster of differentiation (CD)4+ and CD8+ antigen-specific responses were performed at baseline (within 14 days prior to the first vaccination) and during the vaccination period (Weeks 4, 10, 16, 22, and 28) by enzyme-linked immune absorbent spot (ELISPOT) assay. A positive response was considered if the number of spots in the peptide-exposed well was 2-fold or more higher than the number of spots in the unstimulated well, and if there was a minimum of 10 (after subtraction of background spots) peptide-specific spots/25.000 T cells or less if T-cell clones were used. | Up to 28 weeks | 
| Number of Patients With Humoral Antibody Response to NY-ESO-1 | Assays to assess NY-ESO-1 specific antibodies were performed at baseline (within 14 days prior to the first vaccination) and during the vaccination period (Weeks 4, 7, 10, 13, 16, 19, 22, 25, and 28). Sera were assessed over a range of dilutions from 1:100 to 1:400,000. Vaccine-induced antibodies were mapped with a panel of overlapping 20 mer peptides (25 μg/mL) spanning the whole protein sequence by enzyme-linked immunosorbent assay (ELISA). Immunoglobulin (Ig) subclasses G1 and G3 were determined by Western blot analysis using secondary antibody mouse anti-human IgG1/IgG3 at a dilution of 1:1000. | Up to 28 weeks | 
| Number of Patients With Best Tumor Response as Measured by the Response Evaluation Criteria in Solid Tumors (RECIST) | Appropriate imaging scans were performed at baseline (within 14 days prior to the first vaccination) and during the vaccination period (Weeks 13 and 28). Response was assessed using RECIST version 1.0 (Therasse et al, J Natl Cancer Inst 2000; 92:205-16). Per RECIST, target lesions are categorized as follows: complete response (CR): disappearance of all target lesions (no evaluable disease); partial response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; progressive disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; stable disease (SD): small changes that do not meet above criteria. | Up to 32 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NY-ESO-1 protein, immunization, advanced prostate cancer