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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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HER2 Positive Early or Locally Advanced Breast Cancer

Intervention / Treatment
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* Drug: Herceptin (trastuzuamb)
* Drug: SB3 (proposed trastuzumab biosimilar)


Participation Criteria
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Eligibility Criteria
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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: tumour size ≥ 2 cm histologically confirmed primary invasive carcinoma of the breast 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: history of documented congestive heart failure (CHF) (New York Heart Association, NYHA, class II or greater heart disease) LVEF < 55% by echocardiography or MUGA scan angina pectoris requiring anti-anginal medication evidence of transmural infarction on electrocardiogram (ECG) uncontrolled hypertension (systolic > 180 mmHg and/or diastolic > 100 mmHg) clinically significant valvular heart disease 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Herceptin (trastuzumab)<br>Intravenous administration | Drug: Herceptin (trastuzuamb)<br>* Intravenous administration<br>* Other names: Herceptin;|
| Experimental: SB3 (proposed trastuzumab biosimilar)<br>Intravenous administration | Drug: SB3 (proposed trastuzumab biosimilar)<br>* Intravenous administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Pathologic Complete Response (pCR) Rate of the Primary Breast Tumour |  | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Pathological Complete Response (tpCR) Rate |  | Week 24 | 
| Overall Clinical Response Rate (ORR) |  | Week 24 | 
| Event-free Survival (EFS) |  | 1 month after last dose of investigational product | 
| Overall Survival (OS) |  | 1 month after the last administration of investigational product | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HER2 Positive Breast Cancer, Trastuzumab, Biosimilar