Pre-operative IRX-2 in Early Stage Breast Cancer (ESBC)

This will be a Phase Ib study conducted to determine the safety and tolerability of an IRX-2 regimen in ESBC, to be administered pre-operatively before standard-of-care surgical resection and following standard-of-care diagnostic biopsy. This study will also include triple-negative breast cancer patients who will receive the IRX-2 regimen prior to chemotherapy.

Eligible subjects will have early stage breast cancer of any receptor sub-type, for which standard-of-care surgical resection is planned. To be eligible, a minimum of 1 core of tumor-bearing biopsy material must be available for research analysis.

Cohort B will enroll subjects triple negative breast cancer (defined by ER<10%, PR<10%, and HER2-negative by NCCN guidelines), T1c+ tumors for which neoadjuvant anthracycline-based and non-platinum containing chemotherapy is planned. The IRX-2 regimen will be administered and completed preceding chemotherapy. Cohort B subjects must undergo post-IRX-2 Regimen biopsy (2-3 cores), followed by commencement of chemotherapy preferably within one week after biopsy.

The IRX-2 regimen will be administered in all enrolled subjects. IRX 2 will be administered by subcutaneous injection into the periareolar skin of the affected breast.

Inclusion criteria

• Invasive breast cancer of any receptor subtype diagnosed by core-needle biopsy
• To undergo surgical resection with curative intent by partial mastectomy (lumpectomy) or mastectomy or
• Triple negative breast cancer (defined by ER<10%, PR<10%, and HER2-negative by NCCN guidelines), T1c+ tumors for which neoadjuvant anthracycline-based and non-platinum containing chemotherapy is planned
• Tumor >5 mm in maximum diameter by ultrasound or mammography. (Subjects with smaller tumors may be included at the discretion of the Principal Investigator.)
• Willing and able to provide written informed consent, including consent for use of available tissue and required blood draws for research purposes
• Availability of at least one tumor-bearing core specimen from the breast cancer diagnostic biopsy
• Karnofsky Performance status (KPS) 70% or greater.
• Female or male ≥18 years of age on day of signing informed consent.
• Adequate organ function as defined by protocol specified lab results

Exclusion criteria

• Prior neoadjuvant systemic therapy is planned
• Prior surgery, radiotherapy or chemotherapy for this cancer (other than core-needle biopsy)
• Received an investigational agent within 4 weeks of the first dose of treatment.
• Diagnosis of immunodeficiency or has received more than replacement doses of corticosteroids any other immunosuppressive therapy within 4 weeks of the first dose of treatment
• Hypersensitivity to IRX 2, cyclophosphamide, indomethacin, aspirin or ciprofloxacin.
• Chronic anticoagulation, not including aspirin, but including heparins, warfarin, oral anticoagulants or other platelet function inhibitors, that cannot, in the documented opinion of the investigator, safely be interrupted from at least 2 days prior to the initiation of the study regimen until after surgical resection of the tumor.
• Another malignancy that required active treatment within 6 months of the first dose of treatment
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, such that trial participation is not in the best interest of the subject, including but not limited to uncontrolled hypertension or clinically significant cardiovascular disease, myocardial infarction within the previous 3 months, active infection or pneumonitis or other pulmonary disease requiring systemic therapy, clinically significant gastritis or peptic ulcer disease (that would preclude the use of indomethacin), stroke of other symptoms of cerebral vascular insufficient within the last 3 months, autoimmune disease that has required systemic treatment within the past 2 years (other than hormone replacement doses), or uncontrolled psychiatric or substance abuse disorders.
• Pregnancy or lactation.
• Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).