Triple negative breast cancers (TNBCs) occur in approximately 20-25% of all patients with
breast cancer and are associated with a poor prognosis. Patients with TNBCs derive no
benefit from targeted therapies. Excluding those patients who demonstrate a pathologic
complete response following neoadjuvant chemotherapy, which is a minor fraction (i.e. 15%),
overall survival is only 45% at 7 years.
Following standard of care, there are windows of opportunity to further and safely treat
patients to prevent recurrence. Stimulating the immune system to produce T cells immunity
specific for tumor antigens may significantly delay recurrence and cure patients.
The proposed vaccine is intended to induce T cells to survey for the reemergence of TNBCs
and to prevent recurrence in the adjuvant setting. The vaccine strategy is antigen-specific
and targets the Folate Receptor Alpha (FR). FR is an ideal target because of its limited
expression in the healthy tissues and it high expression in 86% of TNBCs. Studies have shown
that it is a biologically important marker that is associated with poorer clinical outcome
and is retained in metastatic lesions.
The FR vaccine include a pool of 5 peptides that are immunogenic epitopes and safely
generate tissue-surveying CD4 T cell immune responses in patients tested in a recently
completed phase I clinical trial.
- Female patient, Age 18 years or older;
- Written informed consent;
- Negative for ER, PR and negative for Her2-neu (0 or 1+ on immunohistochemistry and/or
normal gene copy number by fluorescence in-situ hybridization);
- Completed surgery and radio/chemotherapy in adjuvant or neo-adjuvant setting <180
days prior to consent.
- Completed last cycle of chemotherapy or radiation > 60 days prior to consent
- Unilateral or bilateral primary carcinoma of the breast with tumor Stage II-III
according to AJCC 7th edition, and one of the following:
1. For patient treated in the neoadjuvant setting: Histologically detectable tumor
residuals (excludes ypT0/is ypN0), M0 and no evidence of gross tumor or gross
2. For patients treated in the adjuvant setting: pN2-3 and M0. No evidence of gross
tumor or gross residual adenopathy
- Adequate Blood, renal and hepatic function, as determined within 28 days from
- Clinical evidence of distant metastases per practice guidelines for breast cancer;
- Inflammatory breast cancer or tumor with deep adherence or cutaneous invasion;
- Known hypersensitivity reaction to the GM-CSF adjuvant; Any known contra-indication
to GM-CSF or Cyclophosphamide treatment;
- Pregnant or lactating patients.
- History of auto-immune diseases;
- Other uncontrolled illness or medical condition , such as active infection,
symptomatic heart failure, unstable angina pectoris, myocardial infarction or stroke
within last 6 months, psychiatric illness that may limit compliance with study
requirement or interfere with the understanding and giving of informed consent;
- Prior active secondary malignancy < 5 years prior to consent (except non-melanomatous
skin cancer or carcinoma in situ of the uterine cervix) or currently receiving other
specific treatment for this cancer (including monoclonal antibody or pathway
- Completed treatment with systemic corticosteroid or immune-modulators > 30 days prior
- Planned treatment with other experimental drugs or any other anti-cancer therapy;
- Immunocompromised patients including patients with known HIV infection;
- Currently receiving thyroid replacement therapy.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Female