Vaccine Therapy With or Without Polysaccharide-K in Treating Patients With Stage IV HER2 Positive Breast Cancer Receiving HER2-Targeted Monoclonal Antibody Therapy

PRIMARY OBJECTIVES:

I. To evaluate the safety of polysaccharide-K (PSK) when given with HER2-directed
immunotherapy.

SECONDARY OBJECTIVES:

I. To evaluate the effect of PSK on natural killer (NK) cell functional activity when given
with HER2-directed immunotherapy.

TERTIARY OBJECTIVES:

I. To investigate the effect of PSK when given with HER2-directed immunotherapy on: serum
levels of pro-inflammatory cytokine and/or chemokines; intermolecular epitope spreading;
serum transforming growth factor (TGF)-beta levels; progression free survival (PFS) and
overall survival (OS).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive HER2 ICD peptide-based vaccine intradermally (ID) once monthly for 3
months, trastuzumab (or trastuzumab and pertuzumab) per standard of care, and placebo orally
(PO) twice daily (BID) for 4 months.

ARM II: Patients receive HER2 ICD peptide-based vaccine ID and trastuzumab (or trastuzumab
and pertuzumab) as in Arm I and polysaccharide-K PO BID for 4 months.

After completion of study treatment, patients are followed up for 9 months and then twice
annually for 3 years.

Inclusion Criteria:

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

- No evidence of disease (NED), or

- Stable bone only disease after definitive therapy

- HER2 overexpression by immunohistochemistry (IHC) of 2+ or 3+ in the primary tumor or
metastasis; or documented gene amplification by fluorescent in situ hybridization
(FISH) analysis; IHC =< 2+ must have HER2 gene amplification documented by FISH

- Patients must continue HER2-targeted monoclonal antibody therapy dosing per standard
of care through the entire study period (one year)

- HER2-targeted monoclonal antibody therapy is defined as either trastuzumab
monotherapy, or trastuzumab and pertuzumab combination therapy administered per
standard of care

- Patients must be at least 21 days post cytotoxic chemotherapy prior to enrollment

- Patients must be at least 28 days post immunosuppressants prior to enrollment

- Patients must be at least 28 days from use of any mushroom supplements (examples:
turkey tail, reishi, maitake, shiitake) and agree to withhold them for the entire
study period (one year)

- Patients on bisphosphonates and/or endocrine therapy are eligible

- Patients who are having sex that could lead to pregnancy 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 significant active concurrent medical
illnesses precluding study treatment

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

- Hemoglobin (Hgb) >= 10 g/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 must have adequate cardiac function as demonstrated by normal left
ventricular ejection fraction (LVEF) >= the lower limit of normal for the facility on
multi gated acquisition (MUGA) scan or echocardiogram (ECHO) within 3 months of
enrollment

Exclusion Criteria:

- Patients with any of the following cardiac conditions:

- 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 rhu granulocyte macrophage colony
stimulating factor (rhuGM-CSF) based products

- Patients with any clinically significant autoimmune disease requiring active treatment

- Patients receiving any concurrent immunosuppressants

- Patients who are pregnant or breast-feeding

- Patients who are simultaneously enrolled in other treatment studies

- Patients who have received a previous HER2 breast cancer vaccine

- Known hypersensitivity reaction to mushroom products