Clinical Trials

Pre-Registration Inclusion Criteria for All Patients (include Safety Lead-In):

• Female age ≥ 18 years.
• Histologically confirmed adenocarcinoma of the breast clinical stage prior to surgery ≥ cT1c OR ≥ N1 based on the 7th edition of TNM staging system from the American Joint Committee on Cancer.
• Any ER or PR but HER2 positive defined as per the most current ASCO/CAP guideline.
• Willingness to provide adequate pretreatment biopsy sample.
  • NOTE: Adequate tissue samples defined as core needle biopsy or incisional biopsy or excisional samples that can provide ≥ 3 core needle biopsies with at least 14G needle with 12 unstained sections of 5 micron thickness. Fine needle aspiration (FNA) sample alone is not sufficient.
  • NOTE: Patients without adequate pretreatment biopsy samples must be agreeable to have an additional research biopsy prior to neoadjuvant therapy.
• ECOG Performance Status (PS) 0, 1, 2).
• Willing to employ adequate contraception from the time of pre-registration through 6 months after the final vaccine cycle.
• Willing to receive a tetanus vaccination if subject has not had one <1 year prior to pre-registration.
• Provide written informed consent.
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
• Willing to provide mandatory tissue and blood samples for correlative research purposes.
• Negative pregnancy test done ≤ 7 days prior to pre-registration, for persons of childbearing potential only.
  • NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

Pre-Registration – Exclusion Criteria for all patients (include Safety Lead-In):

• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown: • Pregnant person • Nursing person unwilling to stop breast feeding • Person of child bearing potential who are unwilling to employ adequate contraception from the time of registration through 6 months after the final vaccine cycle. 3.22 Clinical evidence of active local recurrence or distant metastases. NOTE: All patients must have either a PET/CT or CT chest, abdomen, and pelvis with bone scan to rule out distant metastases ≤ 365 days prior to pre-registration. If any of these is concerning, follow-up imaging or biopsy should be performed if indicated to rule out distant metastases. 3.23 Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens. 3.24 Immunocompromised patients including patients known to be HIV positive or those on chronic steroids. NOTE: Must be off systemic steroids at least 14 days prior to pre-registration. However, topical steroids, inhalants or steroid eye drops are permitted. 3.25 Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. 3.26 Uncontrolled acute or chronic medical conditions including, but not limited to the following: • Active infection requiring antibiotics • Congestive heart failure with New York Heart Association class III or IV (Appendix III); moderate to severe objective evidence of cardiovascular disease • Myocardial infarction or stroke <6 months prior to pre-registration • Significant cardiac arrhythmia or unstable angina 3.27 Receiving any other investigational agent. 3.28 Other active malignancy at time of pre-registration or <3 years prior to preregistration. EXCEPTIONS: Non-melanoma skin cancer or carcinoma-in-situ (e.g. of cervix, prostate). NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment (cytotoxics, monoclonal antibodies, small molecule inhibitors) for their cancer. 3.29 Known history of active autoimmune disease that has required systemic treatment in the ≤30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to pre-registration. NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. Patients with vitiligo, Graves disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded. 3.29a Any prior hypersensitivity or adverse reaction to GM-CSF. 3.29b History of trastuzumab-related cardiac toxicity requiring interruption or discontinuation of therapy, even if LVEF fully recovered. 3.29c Baseline LVEF <50%.
• Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment. 3.29e History of myocardial infarction ≤ 168 days (6 months) prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life threatening ventricular arrhythmias.

Registration – Inclusion Criteria (Safety Lead-In):

Registration – Exclusion Criteria (Safety Lead In):

Registration – Inclusion Criteria for Patients with No Residual Disease (pCR)- (PHASE II):

Registration – Exclusion Criteria for Patients with no residual disease (pCR)- (PHASE II)

Randomization – Inclusion Criteria for Patients with Residual Disease Post Neoadjuvant Tratuzumab ± Pertuzumab-based Chemotherapy (no PCR)- (PHASE II):