Neoadjuvant Ontruzant (SB3) in Patients With HER2-positive Early Breast Cancer: An Open-Label (NeoON)

Inclusion Criteria:

1. Written informed consent prior to beginning of trial specific procedures.
2. Subject must be female and aged ≥ 18 years on day of signing informed consent.
3. ECOG 0-1.
4. Histologically confirmed, early HER2 positive breast cancer determined by core biopsyof breast tumor lesion.
5. Measurable tumor lesion with a size of ≥ 1 cm assessed by sonography or magneticresonance imaging (MRI) within ≤ 28 days prior to entry. In case of inflammatorydisease, the extent of inflammation will be measured.
6. Indication for chemotherapy.
7. Multicentric and/or multifocal disease as well as synchronous bilateral breast canceris eligible as long as one measurable lesion meets all inclusion criteria. Theinvestigator has to determine which lesion will be used for tumor evaluation beforeinitiation of treatment.
8. Complete staging within 8 weeks prior to entry with no evidence of distant disease,including bilateral mammography, breast ultrasound, chest-X-ray (or chest CT-scan),liver ultrasound (or liver CT-scan or liver MRI) and bone scan.
9. Subjects must provide a core biopsy from tumor lesion before first chemotherapy, after 3 cycles of chemotherapy and after last neoadjuvant study treatment for biomarkeranalyses.
10. Adequate organ function defined as: Absolute neutrophile count ≥1500/µL, Platelets ≥100 000/µL, Hemoglobin ≥10.0 g/dL or ≥6.2 mmol/L, Creatinine ≤1.5 × ULN OR measuredor calculated creatinine clearance ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN (GFR can also be used in place of creatinine or CrCl), Totalbilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubinlevels >1.5 × ULN, AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participantswith liver metastases), International normalized ratio (INR) OR prothrombin time (PT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTTis within therapeutic range of intended use of anticoagulants, LVEF > 50 %
11. Female subjects of childbearing potential must have a negative urine pregnancy testwithin 72 h prior to study entry and be willing to use an adequate method ofcontraception for course of the study through 7 months after the last dose of trialtreatment.

Exclusion Criteria:

1. Concurrent participation in a study with an investigational agent/device or within 14days of study entry.
2. Prior chemotherapy, radiation therapy or small molecule therapy for any reason.
3. Previous malignant disease being disease-free for less than 3 years (except in situcarcinoma of the cervix and basal cell carcinoma of the skin).
4. Pregnancy or lactation.
5. Prior neoadjuvant therapy.
6. Active infection requiring systemic therapy.
7. History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
8. Active autoimmune disease or other diseases that requires systemic treatment withcorticosteroids or immunosuppressive drugs (physiologic corticosteroid replacementtherapy for adrenal or pituitary insufficiency is allowed).
9. History of primary or acquired immunodeficiency (including allogenic organtransplant).
10. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,ulcerative colitis).
11. Known history of following infections: Human immunodeficiency virus (HIV), History ofacute or chronic Hepatitis B or Hepatitis C, has received a live-virus vaccinationwithin 30 days of planned treatment start. Seasonal flu vaccines that do not containlive virus are permitted.
12. Known congestive heart failure > NYHA I and/or coronary heart disease, anginapectoris, previous history of myocardial infarction, uncontrolled or poorly controlledarterial hypertension (e.g. blood pressure >160/90 mmHg under treatment with two ormore antihypertensive drugs), rhythm disorders with clinically significant valvularheart disease.
13. Pre-existing motor or sensory neuropathy of a severity grade ≥2 by National CancerInstitute Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
14. Any other condition in opinion of the investigator that would interfere with appliedsystemic treatment or other trial procedures.