Vaccination of Triple Negative Breast Cancer Patients

The purpose of this study is to evaluate an investigational agent, P10s-PADRE, a peptide
mimotope-based vaccine, in combination with standard neoadjuvant chemotherapy in patients
with clinical stage I, II or III estrogen-receptor (ER) negative, progesterone receptor (PR)
negative and HER2-negative (= triple negative - TN) breast cancer. P10s-PADRE will be
administered with MONTANIDE™ ISA 51 VG as adjuvant. Human breast cancers that express Tumor
Associated Carbohydrate Antigens (TACAs) can be immunogenic, and enhancing the anti-TACA
antibodies and immune effector function already present may augment the cytotoxic effects of
standard therapies.

A randomized two-arm, open-label, multi-center phase II trial is designed with the goal being
to evaluate the efficacy of combining vaccination of the P10s-PADRE formulation with
neoadjuvant chemotherapy. Patients will be randomly assigned in a 2:1 ratio to standard
chemotherapy plus P10s-PADRE or to standard chemotherapy alone. Efficacy will be based on the
rate of pathologic Complete Response (pCR) observed among TN breast-cancer patients treated
with the combination as compared with the group of patients who receive standard chemotherapy
alone.

Inclusion Criteria:

- Females of all races with biopsy-proven clinical stage II, or III TN breast cancer who
will undergo standard neoadjuvant treatment

- Age 18 years and older

- ECOG Performance Status 0 or 1.

- White blood cell (WBC) count ≥ 3,000/mm3 within 3 weeks prior to registration.

- Platelet count ≥ 100,000/mm3 within 3 weeks prior to registration.

- Serum glutamic-oxaloacetic transaminase (SGOT) ≤ 2 x institutional upper limit (IUL)
of normal obtained within 3 weeks prior to registration or Aspartate aminotransferase
test (AST) ≤ 2 x institutional upper limit (IUL) of normal obtained within 3 weeks
prior to registration.

- Serum glutamic pyruvic transaminase (SGPT) ≤ 2 x institutional upper limit (IUL) of
normal obtained within 3 weeks prior to registration or Alanine Aminotransferase (ALT)
≤ 2 x institutional upper limit (IUL) of normal obtained within 3 weeks prior to
registration.

- Bilirubin ≤ 2 x institutional upper limit (IUL) of normal obtained within 3 weeks
prior to registration.

- Serum creatinine ≤ 1.8 mg/dl obtained within 3 weeks prior to registration.

- Must sign an informed consent document approved by the UAMS Institutional Review Board
(IRB).

Exclusion Criteria:

- Active infection requiring treatment with antibiotics.

- Existing diagnosis or history of organic brain syndrome that might preclude
participation in the full protocol.

- Existing diagnosis or history of significant impairment of basal cognitive function
that might preclude participation in the full protocol.

- Other current malignancies. Subjects with prior history at any time of any in situ
cancer, including lobular carcinoma of the breast in situ, cervical cancer in situ,
atypical melanocytic hyperplasia or Clark I melanoma in situ or basal or squamous skin
cancer are eligible, provided they are disease-free at the time of registration.
Subjects with other malignancies are eligible if they have been continuously disease
free for ≥ 5 years prior to the time of registration.

- Existing diagnosis or history of autoimmune disorders or conditions of
immunosuppression. This includes, but is not limited to being treated with
corticosteroids, including oral steroids (i.e. prednisone, dexamethasone [except when
used as an antiemetic in standard therapy]), continuous use of topical steroid creams
or ointments or any steroid-containing inhalers. Subjects who discontinue the use of
these classes of medication for at least 6 weeks prior to registration are eligible
if, in the judgment of the treating physician, the subject is not likely to require
these classes of drugs during the treatment period. Replacement doses of steroids for
subjects with adrenal insufficiency are allowed.

- Pregnancy or breast feeding (due to the unknown effects of peptide/mimotope vaccines
on a fetus or infant). Women of childbearing potential must have a negative urine
pregnancy test within 72 hours prior to starting week 1 and must be counseled to use
an accepted and effective method of contraception (including abstinence) while on
treatment and for a period of 18 months after completing or discontinuing treatment.
Accepted methods of contraception include oral contraceptives, barrier methods, IUDs,
and abstinence.

- Any other significant medical or psychiatric conditions which, in the opinion of the
enrolling investigator, may interfere with consent or compliance of the treatment
regimen.