Vaccine Therapy in Treating Patients With HER2-Negative Stage III-IV Breast Cancer

OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 4 arms.

Arm 1: Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine with recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) as 1 injection intradermally (ID) every 28 days for 3 months. Patients may also receive 2 additional booster STEMVAC vaccines at 3 and 9 months after the third vaccine in the absence of unacceptable toxicity or disease progression.

ARM 2: Patients receive CD105/Yb-1/SOX2/CDH3/M2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 2 injections ID every 28 days for 3 months. Patients may also receive 2 additional booster STEMVAC vaccines at 3 and 9 months after the third vaccine in the absence of unacceptable toxicity or disease progression.

ARM 3: Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 3 injections ID every 28 days for 3 months. Patients may also receive 2 additional booster STEMVAC vaccines at 3 and 9 months after the third vaccine in the absence of unacceptable toxicity or disease progression.

ARM 4: Patients receive CD105/Yb-1/SOX2/CDH3/MDM2-polyepitope plasmid DNA vaccine with rhuGM-CSF as 2 injections ID every 28 days for 3 months. Patients may also receive 1 additional STEMVAC vaccine at 3 months after the third vaccine in the absence of unacceptable toxicity or disease progression.

After completion of study treatment, patients are followed up twice yearly for up to 5 years.

Inclusion criteria

• Patients with stage III-IV HER2 negative breast cancer treated with primary or salvage therapy and now have:

• No evidence of disease (NED), or
• Stable bone only disease
• Patients who have completed standard of care and recovered with mild to no residual toxicity from recent therapy
• Patients must be at least 28 days post cytotoxic chemotherapy, and/or monoclonal antibody therapy (excluding bone-directed therapy), prior to enrollment
• Patients must be at least 28 days post systemic steroids prior to enrollment
• Patients on bisphosphonates, denosumab, and/or endocrine therapy are eligible
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status score of =< 1
• 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
• Estimated life expectancy of more than 6 months
• White blood cells (WBC) >= 3000/mm^3 (within 30 days of first vaccination)
• Lymphocyte count >= 800/mm^3 (within 30 days of first vaccination)
• Platelet count >= 75,000/mm^3 (within 30 days of first vaccination)
• Hemoglobin (Hgb) >= 10 g/dl (within 30 days of first vaccination)
• Serum creatinine <= 1.2 mg/dl or creatinine clearance > 60 ml/min (within 30 days of first vaccination)
• Total bilirubin <= 1.5 mg/dl (within 30 days of first vaccination)
• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) <= 2 times upper limit of normal (ULN) (within 30 days of first vaccination)
• Blood glucose < 1.5 ULN (within 30 days of first vaccination)
• All patients who are having sex that can lead to pregnancy must agree to contraception for the duration of study

Exclusion criteria

• Patients with any of the following cardiac conditions:

• Symptomatic restrictive cardiomyopathy
• Unstable angina within 4 months prior to enrollment
• New York Heart Association functional class III-IV heart failure on active treatment
• Symptomatic pericardial effusion
• Patients at risk for gastrointestinal bleeding (example: peptic ulcer disease, prolonged daily non-steroidal anti-inflammatory use)
• Patients with any seizure disorder
• Patients with any contraindication to receiving rhuGM-CSF based products
• Patients with any clinically significant autoimmune disease uncontrolled with treatment
• Patients who are simultaneously enrolled in any other treatment study
• Patients who are pregnant or breastfeeding