Evaluation of an Anti-cancer Immunotherapy Combined With Standard Neoadjuvant Treatment in Patients With WT1-positive Primary Invasive Breast Cancer (INDUCT)

This is an interventional treatment trial for Neoplasms, Breast focused on measuring WT1, neoadjuvant, tumor antigen, immunotherapy, breast cancer, adult Read More

Inclusion Criteria:

• The patient is ≥ 18 years of age at the time the informed consent to screening has been obtained.
• The patient has proven T1 with lymph node involvement or T2-T4c, any N, M0 primary invasive breast cancer, histologically confirmed by core needle biopsy.

Isolated supraclavicular lymph node involvement is allowed.

• The patient's tumor shows WT1 antigen expression.

• The patient has one of the following histologically confirmed breast cancer subtypes:

  • Estrogen receptor and/or progesterone positive tumor.
  • Human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer.
  • HER2-negative breast cancer.
• Eastern Cooperative Oncology Group (performance status of 0 or 1 at the time of study treatment allocation.
• Baseline left ventricular ejection fraction of ≥ 50% as measured within six weeks prior to study treatment allocation by echocardiography or multi-gated acquisition(MUGA)scan.

• The patient shows normal organ function according to the following parameters(as measured within six weeks prior to treatment allocation)::

  • Hemoglobin: Within normal range according to institutional standards.
  • Absolute leukocyte count: Within normal range according to institutional standards.
  • Absolute lymphocyte count: Within normal range according to institutional standards.
  • Platelet count: Within normal range according to institutional standards
  • Alanine aminotransferase: ≤ 2.5 x Upper Limit of Normal (ULN)
  • Aspartate aminotransferase: ≤ 2.5 x ULN
  • Total bilirubin: ≤ 1.5 x ULN. In the case of known Gilbert's syndrome ≤ 2 x ULN
  • Serum creatinine: 1.5 x ULN
  • Calculated creatinine clearance: > 50 mL/min

• A female patient of childbearing potential may be enrolled in the study, if the patient:

  • has practiced adequate contraception for 30 days prior to study product administration, and
  • has a negative pregnancy test within one week prior to treatment allocation and
  • has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the study product administration series.In view of the investigator, the patient can and will comply with the requirements of the protocol.
• Written informed consent has been obtained from the patient prior to performance of any study specific procedure.

Exclusion Criteria:

• The patient has inflammatory breast cancer, which is defined as clinically significant erythema of the breast and/or documented dermal lymphatic invasion.
• Diagnosis established by incisional biopsy.
• Prior and concomitant neoadjuvant anti-breast-cancer treatments such as chemotherapy, immunotherapy / biological response modifiers, endocrine therapy, and radiotherapy, unless authorized specifically by the protocol.
• The patient is known to be human immunodeficiency virus -positive.
• The patient has symptomatic autoimmune disease such as, but not limited to multiple sclerosis, lupus, and inflammatory bowel disease. Patients with vitiligo are not excluded.
• The patient is known to have difficult-to-control hypertension, coronary artery disease, arrhythmia requiring treatment, clinically significant valvular disease, cardiomegaly on chest X-ray, ventricular hypertrophy on electrocardiogram or previous myocardial infarction or congestive heart failure.
• The patient has a history of allergic reactions likely to be exacerbated by any component of the investigational product used in the study.
• The patient has other concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
• The patient has (or has had) previous or concomitant malignancies at other sites, except effectively treated malignancy that is considered by the investigator highly likely to have been cured.
• The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the study procedures.
• The patient has received any investigational or non-registered product within 30 days preceding the first dose of study products or planned use during the study period.
• The patient requires concomitant treatment with any immunosuppressive agents or with systemic corticosteroids prescribed for chronic treatment.
• The patient has a significant disorder of coagulation or receives treatment with warfarin derivatives or heparin. Patients receiving individual doses of low molecular weight heparin outside of 24 hours prior to WT1-A10 + AS15 ASCI/placebo administration are eligible. Patients receiving prophylactic antiplatelet medications e.g. low-dose aspirin, and without a clinically-apparent bleeding tendency are eligible.