Phase Ib Trial of Two Folate Binding Protein Peptide Vaccines (E39 and J65) in Breast and Ovarian Cancer Patients

The study is a prospective, randomized, non-blinded, single-center Phase Ib trial. Patients
will be identified that have a diagnosis of breast or ovarian cancer, have completed their
standard courses of therapy and are disease-free. They will be properly screened, counseled
and consented prior to enrollment. Once enrolled, each patient's blood will be tested for
HLA-A2 status (approximately 50% will be HLA-A2+). Additionally, their tumors will be tested
for FBP-expression and this information will be tracked for purposes of correlative science.

Patients who are HLA-A2+ will be stratified based on cancer diagnosis (breast versus
ovarian), then randomized by computer tables to one of three arms for the PVS. Each arm will
receive 6 monthly injections of peptide + GM-CSF. Arm A will receive six inoculations with
E39 peptide; arm B will receive three inoculations with E39 followed by three with J65; and
arm C will receive three inoculations with J65, followed by three of E39. Since J65 has not
been previously used in humans, a two week waiting period will be instituted between the
first and second patients enrolled in either Arm B or C. Immunologic data will be assessed at
1 month and 6 months (±2 wks) after the PVS, specifically ex vivo immunologic recognition of
E39 and J65 will be assessed by clonal expansion using a dextramer assay and the in vivo
response will be assessed by Delayed Type Hypersensitivity (DTH). Immunologic recognition of
E39 will be the primary endpoint, with recognition of J65 serving as an additional data
point. The 6 month post-PVS immunologic data will then be used to assess each patient for
significant residual immunity (SRI), defined as ≥2-fold increase in E39-specific CD8+ T-cells
from the pre-vaccination level. Patients will then be sorted into two groups: those with SRI
and those without. Patients within each group will then be randomized to receive one booster
of either J65 or E39. Each patient will return to clinic within 1-2 weeks of their 6mo
post-PVS visit to receive their single booster inoculation. This second randomization will
result in four groups: 1) patients with SRI receiving E39; 2) patients with SRI receiving
J65; 3) patients without SRI receiving E39; 4) patients without SRI receiving J65.
Immunologic data will then again be gathered at 1 month (±2 wks) and 6 months (±2 wks)
post-booster. This final immunologic data will be analyzed for differences between the four
groups. Additionally, toxicity data will be gathered.

Patients will be monitored closely for one hour after each inoculation with questioning,
serial exams, and vital signs every 15 minutes. Patients will then be asked to return to the
vaccine clinic 48-72 hours after each inoculation for questioning regarding any local or
systemic toxicity and to examine and measure the local reaction at the vaccination sites. The
graded toxicity scale (NCI Common Terminology Criteria for Adverse Events, v4.03) will be
utilized to assess local and systemic toxicity. GM-CSF dose reduction may be required if
>10cm of erythema and induration is seen at the injection site after any given inoculation.

Inclusion Criteria:

1. Patients must have breast or ovarian cancer

2. Patients must have completed primary breast or ovarian cancer therapy (i.e., surgery,
chemotherapy, immunotherapy and/or radiation therapy as appropriate per standard of
care for patient's specific cancer)

3. Patients must be without evidence of residual disease as assessed by their treatment
team

4. Patients must be either post-menopausal or surgically post-menopausal

5. Patients must be HLA-A2 positive

6. Patients must have a good performance status (ECOG<2)

Exclusion Criteria:

1. HLA-A2 negative patients

2. Currently receiving immunosuppressive therapy to include chemotherapy, steroids, or
methotrexate

3. In poor health (Karnofsky <60%, ECOG >2)

4. Total bilirubin >1.5, creatinine >2, hemoglobin <10, platelets <50,000, WBC <2,000

5. Active pulmonary disease requiring medication to include multiple inhalers

6. Of child-bearing age with intact reproductive organs

7. Involved in other experimental protocols (except with permission of the other study
PI)

8. History of autoimmune disease