HER2 Positive Early or Locally Advanced Breast Cancer
Conditions
Keywords
HER2 Positive Breast Cancer, Trastuzumab, Biosimilar
Brief summary
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
Interventions
DRUGHerceptin (trastuzuamb)
Intravenous administration
Intravenous administration
Sponsors
Samsung Bioepis Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Pathologic Complete Response (pCR) Rate of the Primary Breast Tumour | Week 24 |
Secondary
| Measure | 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 |
Countries
Czechia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Herceptin (Trastuzumab) Intravenous administration
Herceptin (trastuzuamb): Intravenous administration | 438 |
| SB3 (Proposed Trastuzumab Biosimilar) Intravenous administration
SB3 (proposed trastuzumab biosimilar): Intravenous administration | 437 |
| Total | 875 |
Baseline characteristics
| Characteristic | Herceptin (Trastuzumab) | SB3 (Proposed Trastuzumab Biosimilar) | Total |
|---|---|---|---|
| Age, Continuous | 49.6 years STANDARD_DEVIATION 9.38 | 49.5 years STANDARD_DEVIATION 9.51 | 49.6 years STANDARD_DEVIATION 9.44 |
| Sex: Female, Male Female | 438 Participants | 437 Participants | 875 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 438 | 1 / 437 |
| other Total, other adverse events | 420 / 438 | 426 / 437 |
| serious Total, serious adverse events | 58 / 438 | 56 / 437 |
Outcome results
Primary
The Pathologic Complete Response (pCR) Rate of the Primary Breast Tumour
Time frame: Week 24
Population: Per-protocol set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Herceptin (Trastuzumab) | The Pathologic Complete Response (pCR) Rate of the Primary Breast Tumour | 42.0 percentage of responders |
| SB3 (Proposed Trastuzumab Biosimilar) | The Pathologic Complete Response (pCR) Rate of the Primary Breast Tumour | 51.7 percentage of responders |
Secondary
Event-free Survival (EFS)
Time frame: 1 month after last dose of investigational product
Population: Per-protocol set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Herceptin (Trastuzumab) | Event-free Survival (EFS) | 92.7 percentage of subjects without event |
| SB3 (Proposed Trastuzumab Biosimilar) | Event-free Survival (EFS) | 93.8 percentage of subjects without event |
Secondary
Overall Clinical Response Rate (ORR)
Time frame: Week 24
Population: Per-protocol set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Herceptin (Trastuzumab) | Overall Clinical Response Rate (ORR) | 91.2 percentage of responders |
| SB3 (Proposed Trastuzumab Biosimilar) | Overall Clinical Response Rate (ORR) | 96.3 percentage of responders |
Secondary
Overall Survival (OS)
Time frame: 1 month after the last administration of investigational product
Population: Per-protocol set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Herceptin (Trastuzumab) | Overall Survival (OS) | 99.5 percentage of subjects alive |
| SB3 (Proposed Trastuzumab Biosimilar) | Overall Survival (OS) | 100.0 percentage of subjects alive |
Secondary
Total Pathological Complete Response (tpCR) Rate
Time frame: Week 24
Population: Per-protocol set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Herceptin (Trastuzumab) | Total Pathological Complete Response (tpCR) Rate | 35.8 percentage of responders |
| SB3 (Proposed Trastuzumab Biosimilar) | Total Pathological Complete Response (tpCR) Rate | 45.8 percentage of responders |