Short-term Pre-OPerative Durvalumab (MEDI 4736) in Early Small Triple Negative Breast Cancer Patients (POP-Durva)

Exclusion Criteria

• •Patients with triple negative breast cancer and TILs \<5%
• •Any systemic therapy (e.g, chemotherapy, targeted therapy, immune-therapy) or radiotherapy for current breast cancer disease before study entry
• •Known hypersensibility to durvalumab or any of its components
• •Patients with prior allogeneic stem cell or solid organ transplantation
• •Administration of a live, attenuated vaccine within 4 weeks prior to enrolment or anticipation that such a live, attenuated vaccine will be required during the study or within 5 months after the last dose of durvalumab
• •Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment
• •Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate and thalidomide) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:
• •1. Patients who received acute, low-dose systemic immunosuppressant medication, or systemic corticosteroids at physiologic doses not to exceed \<\<10 mg/day\>\> of prednisone or its equivalent, or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids as premedication for hypersensitivity reaction (e.g., CT scan premedication)) are eligible for the study
• •2. Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study
• •3. Patients who received intranasal, inhaled, topical or local steroid injections (e.g., intra articular injection)
• •Active or history of autoimmune disease or immune deficiency, with the exception of history of treated autoimmune-related hypothyroidism and Type 1 diabetes mellitus on insulin regimen
• •History of idiopathic pulmonary fibrosis, organizing pneumonia or interstitial lung disease
• •History of HIV infection
• •Patients with active hepatitis infection (defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive to hepatitis B core antigen \[anti-HBc\] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
• •Active tuberculosis
• •Current treatment with anti-viral therapy for HBV
• •Participation in another clinical study with an investigational product during the last 28 days and while on study treatment
• •Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including antiCTLA-4, antiPD-1, and antiPD-L1 therapeutic antibodies
• •Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol
• •Serious uncontrolled concomitant disease that would put the patient at high risk of treatment-related complications
• •Patient has clinically significant, uncontrolled heart disease and/or recent cardiac events including any of the following:
• •History of angina pectoris, coronary artery bypass graft (CABG), symptomatic pericarditis, or myocardial infarction within 12 months prior to the start of study treatment
• •1. History of documented congestive heart failure (New York Heart Association functional classification III-IV)
• •2. Documented cardiomyopathy
• •3. Patient has a Left Ventricular Ejection Fraction (LVEF) \< 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
• •4. History of any cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block), supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months
• •5. Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mmHg and/or Diastolic Blood Pressure (DBP) ≥ 100 mmHg, with or without antihypertensive medication. Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening.
• •6. Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
• •Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued or replaced by safe alternative medication Bradycardia (heart rate \< 50 at rest), by ECG or pulse.
• •Female patients who are pregnant or breastfeeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes
• •Patients unwilling to or unable (as assessed by the investigator) to comply with the protocol
• •Patients under guardianship or deprived of her liberty by a judicial or administrative decision or incapable of giving its consent.