Efficacy and Safety Study of EG12014 Compared With Herceptin in Subjects With HER2 Positive Early Breast Cancer

A Phase III, Randomized, Multicenter, Double-blind Study to Compare Efficacy and Safety of EG12014 With Herceptin as Neoadjuvant Treatment in Combination With Anthracycline/Paclitaxel Systemic Therapy in HER2-Positive Early Breast Cancer

The purpose of this research study is to compare the efficacy and safety of EG12014 with Herceptin as neoadjuvant treatment for 12 weeks, followed by surgery and subsequent EG12014 or Herceptin adjuvant treatment for up to 12 months.

1. Provide signed and dated written informed consent before entering the study. The informed consent will cover both parts of the study (neoadjuvant part and adjuvant part).

2. Female, ≥18 and ≤65 years of age.

3. Histologically-confirmed invasive carcinoma of the breast (American Joint Committee on Cancer [AJCC, vs. 8.0] Stage II, IIIa).

4. Operable breast cancer, planned surgical resection of breast tumor (mastectomy or lumpectomy) and sentinel or axillary lymph nodes.

5. Unilateral, measurable tumor of the breast >2 cm in diameter.

6. HER2 positive tumor, defined as 3+ score by IHC or fluorescence positive by FISH, as confirmed by central laboratory.

7. Known estrogen receptor (ER) and progesterone receptor (PrR) status at study entry.

8. Adequate bone marrow function, defined as granulocyte count of ≥1.500/µL, and platelet count of ≥100.000/µL.

9. Adequate hepatic and renal function, defined as:

   bilirubin within normal range

   alanine aminotransferase (ALT) ≤2 x upper limit of normal (ULN)

   aspartate aminotransferase (AST) ≤2 x ULN

   gamma glutamyl transferase (GGT) ≤3 x ULN

   serum creatinine <1.5 ULN

10. International normalized ratio ≤1.5×ULN (2 to 3×ULN if on anticoagulants) or prothrombin time ≤1.5×ULN; activated partial thromboplastin time ≤1.5×ULN.

11. Hemoglobin concentrations ≥10 g/dL.

12. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.

13. LVEF ≥55%, measured by multiple-gated acquisition (MUGA) scan or echocardiography.

14. Negative pregnancy test at entry, women of childbearing potential have to use contraceptives during the course of the study.

Females with childbearing potential must provide a negative serum pregnancy test at Screening and must be using adequate birth control. Adequate birth control is defined as agreement to consistently practice an effective and accepted method of contraception throughout the duration of the study and for 7 months after study drug treatment. These methods include hormonal contraceptives, intrauterine device, or double barrier contraception (i.e., condom + diaphragm) or a male partner with documented vasectomy.

Non-childbearing potential is defined as post-menopausal for at least 1 year or surgical sterilization or hysterectomy at least 3 months before study start.

Exclusion Criteria:

1. Bilateral breast cancer.
2. Pregnancy or lactation or considering becoming pregnant.
3. Metastases, other than sentinel/axillary lymph nodes.
4. Previous treatment (chemotherapy, biologic therapy, radiation, or surgery) for invasive malignant disease or other concomitant malignancy, other than basal cell carcinoma of the skin. Previous treatment for carcinoma in situ of the cervix is allowed.
5. Previous treatment with Herceptin.
6. Angina pectoris or arrhythmia requiring medication; poorly controlled hypertension; history of myocardial infarction or cardiac failure, New York Heart Association (NYHA) class II or higher; clinically significant cardiac valvular disease; hemodynamic effective pericardial effusion; other cardiomyopathies; LVEF of <55%.
7. Any investigational treatment less than 30 days prior to study entry, or within a time interval less than at least 5 half-lives of the investigational medicinal product, whichever is longer.
8. Positive diagnostic test for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
9. History of hypersensitivity to drugs with similar chemical structures to trastuzumab.
10. History of, or known current problems with, drug or alcohol abuse.
11. Other serious illness, medical disorder or condition that, in the opinion of the Investigator, would make the patient unsuitable for participation in the study.