Vaccine Therapy in Combination With Rintatolimod and/or Sargramostim in Treating Patients With Stage II-IV HER2-Positive Breast Cancer

OBJECTIVES:

I. To choose the most promising (maximum biologic dose [MBD]) of five different doses (4, 20,
79, 495 and 2000 mcg) of Ampligen (rintatolimod) administered intradermally (i.d.) as an
adjuvant with HER2 vaccination, with respect to toxicity and incidence and magnitude of
immune response.

II. To determine, using MBD of Ampligen (defined in first primary aim), whether Ampligen when
given with GM-CSF as a combined adjuvant strategy with HER2 vaccination increases both the
incidence and magnitude of HER2 Th1 immunity as compared to the standard GM-CSF adjuvant
strategy.

OUTLINE: This will be a phase I-II randomized two-stage HER2 vaccine study in breast cancer
patients.

STUDY STAGE I: There are five groups of patients randomized to 1 of 5 arms with each arm
receiving the synthetic HER-2/neu peptide vaccine admixed with rintatolimod (different doses)
given i.d.

STUDY STAGE II: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive the synthetic HER-2/neu peptide vaccine admixed with rintatolimod
given i.d.

ARM II: 24 patients will receive the HER-2/neu peptide vaccine admixed with GM-CSF and the
other 24 patients will receive the HER-2/neu peptide vaccine admixed with GM-CSF in addition
to rintatolimod (dose set by Stage I group that had the most active response) given i.d.

In both study stages, treatment repeats every month for up to 3 months in the absence of
disease progression or unacceptable toxicity.

After completion of last vaccine, patients are followed up at 1 and 12 months.

Inclusion Criteria:

- Patients with stage II, or III HER2+ breast cancer who have completed definitive
standard treatment and are in complete remission - or -

- Patients with stage IV HER2+ breast cancer treated to:

- No evidence of disease, or

- Stable bone only disease after definitive therapy

- Patients must have demonstrated HER2 positive disease, by one of the following
methods:

- Immunohistochemical (IHC) staining of 1+, 2+ or 3+ for the HER2 protein, or

- Amplification of the HER2 gene on fluorescence in situ hybridization (FISH)

- Patients must be at least 14 days post cytotoxic chemotherapy prior to enrollment

- Patients must be at least 14 days post systemic steroids prior to enrollment

- Patients on bisphosphonates or continued hormone therapy are eligible

- Men and women of reproductive ability must agree to contraceptive use during the
entire study period

- Patients must have Zubrod Performance Status Score of =< 2

- Patients must have recovered from major infections and/or surgical procedures, and in
the opinion of the investigator, not have any significant active concurrent medical
illnesses precluding protocol treatment

- White blood cell count (WBC) >= 3000/mm^3

- Hemoglobin (Hgb) >= 10 mg/dl

- Serum creatinine =< 2.0 mg/dl or creatinine clearance > 60 ml/min

- Total bilirubin =< 1.5 mg/dl

- Serum glutamic oxaloacetic transaminase (SGOT) =< 2.5 times the upper limit of normal

- Patients on trastuzumab monotherapy must have adequate cardiac function as
demonstrated by normal ejection fractions (EF) on multi gated acquisition scan (MUGA)
scan or echocardiogram performed within the last 3 months of eligibility sign off

Exclusion Criteria:

- Restrictive cardiomyopathy

- Unstable angina within 6 months prior to enrollment

- New York Heart Association functional class III-IV heart failure

- Symptomatic pericardial effusion

- Patients with any contraindication to receiving rhuGM-CSF based products

- Patients with any clinically significant autoimmune disease requiring active treatment

- Patients receiving any concurrent immunomodulators within 30 days of eligibility
sign-off

- Patients who are pregnant or breast-feeding

- Patients who are simultaneously enrolled in any other treatment study

- Patients who have received a previous HER2 breast cancer vaccine