A Study to Compare the Effect of SB3 and Herceptin® in Women With HER2 Positive Breast Cancer

A Phase III Randomised, Double-Blind, Parallel Group, Multicentre Study to Compare the Efficacy, Safety, Pharmacokinetics and Immunogenicity Between SB3 (Proposed Trastuzumab Biosimilar) and Herceptin® in Women With Newly Diagnosed HER2 Positive Early or Locally Advanced Breast Cancer in Neoadjuvant Setting

A Phase III Randomised, Double-Blind, Parallel Group, Multicentre Study to Compare the Efficacy, Safety, Pharmacokinetics and Immunogenicity between SB3 (proposed trastuzumab biosimilar) and Herceptin® in Women with Newly Diagnosed HER2 Positive Early or Locally Advanced Breast Cancer in Neoadjuvant Setting

Inclusion Criteria:

• Female aged 18-65 years

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

• Non-metastatic, unilateral newly diagnosed primary breast cancer of clinical stage II to III including inflammatory breast cancer with:

  1. tumour size ≥ 2 cm
  2. histologically confirmed primary invasive carcinoma of the breast
  3. HER2-positivity confirmed by a central laboratory or an accredited local laboratory and defined as immunohistochemistry (IHC) 3+ or fluorescence in situ hybridisation (FISH)+

• Known hormone receptor (oestrogen receptor and progesterone receptor) status

• Baseline left ventricular ejection fraction (LVEF) ≥ 55% measured by echocardiography or multiple gated acquisition (MUGA) scan

• Subjects must be able to provide informed consent, which must be obtained prior to any study related procedures

Exclusion Criteria:

• Metastatic (stage IV) or bilateral or multifocal/multicentric breast cancer

• History of any prior invasive breast carcinoma, except for subjects with a past history of ductal carcinoma in situ (DCIS) and/or lobular carcinoma in situ (LCIS) treated with surgery only

• Past or current history of malignant neoplasms within 5 years prior to Randomisation, except for curatively treated carcinoma in situ of uterine cervix, basal cell carcinoma of the skin or squamous cell carcinoma of the skin (malignant neoplasms occurring more than 5 years prior to Randomisation are permitted if curatively treated with surgery only)

• Previous history of radiation therapy, immunotherapy, chemotherapy or biotherapy (including prior HER2 directed therapy) Major surgery within 4 weeks prior to Randomisation and minor surgery within 2 weeks prior to Randomisation (major surgery is defined as surgery which requires general anaesthesia)

• Serious cardiac illness that would preclude the use of trastuzumab such as:

  1. history of documented congestive heart failure (CHF) (New York Heart Association, NYHA, class II or greater heart disease)
  2. LVEF < 55% by echocardiography or MUGA scan
  3. angina pectoris requiring anti-anginal medication
  4. evidence of transmural infarction on electrocardiogram (ECG)
  5. uncontrolled hypertension (systolic > 180 mmHg and/or diastolic > 100 mmHg)
  6. clinically significant valvular heart disease
  7. high risk uncontrolled arrhythmias

• Serious pulmonary illness enough to cause dyspnoea at rest or requiring supplementary oxygen therapy

• Known history of hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) infection

• Other concurrent serious illnesses that may interfere with planned therapy including severe cardiovascular, pulmonary, metabolic or infectious conditions

• Known hypersensitivity to the investigational product (IPs), non-IPs or any of the ingredients or excipients of the IPs or non-IPs

• Known hypersensitivity to murine proteins

• Known history of dihydropyrimidine dehydrogenase (DPD) deficiency

• Pre-existing peripheral sensory or motor neuropathy ≥ grade 2, defined by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.0

• Pregnant or lactating women. A pregnancy test result is required for all women of childbearing potential including women who had menopause onset within 2 years prior to Randomisation. Women of childbearing potential must agree to use contraceptive methods (see section 7.4.2) during the study and 6 months after the last dose of IP

• Concurrent hormonal therapy including birth control pills, ovarian hormone replacement for menopause, selective oestrogen receptor modulator (SERM) either for osteoporosis or breast cancer prevention

• Subjects unwilling to follow the study requirements