Safety and Efficacy of Durvalumab Combined to Neoadjuvant Chemotherapy in Localized Luminal B HER2(-) and Triple Negative Breast Cancer.

Exclusion Criteria

• •Involvement in the planning and/or conduct of the study
• •Previous enrolment in the present study
• •Participation in another clinical study with an investigational product during the last 4 weeks
• •Patient has locally recurrent or metastatic invasive BC
• •History of another primary malignancy except for:
• •1. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug
• •2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• •3. Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ or BC in situ.
• •Patient has received any systemic therapy (e.g. chemotherapy, targeted therapy, immunotherapy) or radiotherapy for current breast cancer disease
• •Whatever the indication, receipt of a last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤ 21 days prior to the first dose of study drug
• •Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
• •Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \>Grade 1
• •Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
• •Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from electrocardiograms (ECGs) using Fridericia's Correction
• •Known or suspected congestive heart failure (\>NYHA I) and / or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, uncontrolled or poorly controlled arterial hypertension (i.e. BP \>140 / 90 mm Hg under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease.
• •Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• •Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
• •History of primary immunodeficiency
• •History of allogeneic organ transplant
• •History of hypersensitivity to durvalumab or any excipient
• •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses, any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
• •Subjects with uncontrolled seizures.
• •Known history of active tuberculosis
• •Anticipation that a live attenuated vaccine will be required during the period from 30 days prior to the first planned durvalumab administration (e.i. week 18 and week 14 after study entry for the phase Ib and phase II respectively) to 5 months of durvalumab discontinuation. Influenza vaccination (inactivated forms only but not live attenuated forms) should be given during influenza season only (approximately October to March).
• •Female subjects who are pregnant, breast-feeding or female patients of reproductive potential who are not employing an effective method of birth control
• •Men with female partners of childbearing potential or pregnant female partners who are not employing an effective method of birth control
• •Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results