Study to Compare a Mono Atezolizumab Window Followed by a Atezolizumab - CTX Therapy With Atezolizumab - CTX Therapy

Exclusion Criteria

• •Previous history of malign diseases, non-melanoma skin cancer and carcinoma of the cervix are allowed if treated with curative intent
• •Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of Paclitaxel, Carboplatin, Epirubicin, Cyclophosphamide or Atezolizumab
• •Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol
• •Concurrent treatment with other drugs that are contraindicating the use of the study drugs
• •Existing pregnancy
• •Breastfeeding
• •Sequential breast cancer
• •Concurrent treatment with other experimental drugs and participation in another clinical trial or clinical research project (except registry study) within 30 days prior to study entry
• •Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study including but not confined to:
• •* Uncompensated chronic heart failure or systolic dysfunction (LVEF \< 55%, congestive heart failure (CHF) New York Heart Association (NYHA) classes II-IV),
• •* unstable arrhythmias requiring treatment i.e., atrial tachycardia with a heart rate ≥ 100/bpm at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher grade AV-block,
• •* Angina pectoris within the last 6 months requiring anti-anginal medication,
• •* Clinically significant valvular heart disease,
• •* Evidence of myocardial infarction on electrocardiogram (ECG),
• •* Poorly controlled hypertension (e.g., systolic \> 180 mmHg or diastolic \> 100 mmHg).
• •Inadequate organ function including but not confined to:
• •* hepatic impairment as defined by bilirubin \> 1.5 x ULN
• •* pulmonary disease (severe dyspnea at rest requiring oxygen therapy)
• •Abnormal blood values:
• •* Platelet count below 100,000/mm3
• •* AST/ALT \> 1.5 x ULN
• •* Hypokalaemia \> CTCAE grade 1
• •* Neutropenia \> CTCAE grade 1
• •* Anaemia \> CTCAE grade 1
• •Administration of a live, attenuated vaccine within 4 weeks before cycle 1 day 1 or anticipation that such a vaccine will be required during the study
• •Treatment with systemic immunosuppressive medications (including but not limited to interferons, IL-2) within 28 days or 5 half-lives of the drug, whichever is longer, prior to randomization.
• •Treatment with systemic immunosuppressive medications (including but not limited to Prednisone, Cyclophosphamide, Azathioprine, Methotrexate, Thalidomide, and anti-tumor necrosis \[anti-TNF\] factor agents) within 14 days prior to screening or anticipation of need for systemic immunosuppressive medications during the study
• •Patients with prior allogeneic stem cell or solid organ transplantation
• •Active or history of autoimmune disease or immune deficiency, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis with the following exceptions:
• •* Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study.
• •* Patients with controlled Type 1 diabetes mellitus on a stable dose of insulin regimen may be eligible for this study.
• •* Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are permitted provided all of following conditions are met: Rash must cover \< 10% of body surface area; Disease is well controlled at baseline and requires only low-potency topical corticosteroids; No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, Methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral Corticosteroids within the previous 12 months.
• •History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
• •History of HIV infection, hepatitis B or hepatitis C infection.
• •Patients with significant cardiovascular disease
• •Patients with inadequate hematological and end-organ function
• •Patients receiving therapeutic anti-coagulants
• •Stage N3, as soon as 21 patients with stage N3 are randomized