Clinical trial NCT06038539: Efficacy and Safety of the Proposed Biosimilar Pertuzumab (PERT-IJS) Versus EU-Perjeta® Along With Trastuzumab and Chemotherapy (Carboplatin and Docetaxel) as Neoadjuvant Treatment in Chemotherapy naïve Patients With Early Stage or Locally Advanced HR Negative and HER2 Positive Breast Cancer
Official title: A Multicenter, Double-blind, Randomized, Parallel-group, Phase 3 Study to Compare the Efficacy and Safety of the Proposed Biosimilar PERT-IJS and EU-Perjeta® Along With Trastuzumab and Chemotherapy (Carboplatin and Docetaxel) as Neoadjuvant Treatment in Patients With Hormone Receptor Negative (HR-ve) Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Early Stage or Locally Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: HR Negative HER2 Positive Early Breast Cancer or Locally Advanced Breast Cancer Patients
Keywords: Locally advanced breast cancer patient
HR negative HER2-positive Early breast cancer
PERT-IJS
Pertuzumab
Trastuzumab
Neoadjuvant treatment
Lead sponsor: Biocon Limited
Sponsor class: INDUSTRY
First posted: 2023-09-15
Enrollment: 382
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment
Primary purpose: TREATMENT

Brief summary: To compare the efficacy and safety of PERT-IJS (Proposed biosimilar Pertuzumab) plus trastuzumab and chemotherapy (carboplatin and docetaxel) versus EU-Perjeta plus trastuzumab and chemotherapy (carboplatin and docetaxel) in neoadjuvant treatment of patients with HR-ve and HER-2 positive early stage or locally advanced breast cancer.

Detailed description: This study is designed to compare the efficacy and safety of proposed biosimilar PERT-IJS plus trastuzumab, carboplatin and docetaxel versus EU-Perjeta plus trastuzumab, carboplatin and docetaxel in neoadjuvant treatment of HR-ve HER2-positive Early Breast Cancer (EBC) (invasive breast cancer without distant metastasis) or locally advanced breast cancer patients.

Eligibility criteria: Inclusion Criteria:

1. Patient willing and able to sign informed consent and to follow the protocol requirements
2. Female patients aged ≥ 18 years at the time of Screening
3. Patient with Eastern Cooperative Oncology Group (ECOG) Performance Status \< 2
4. Patients with breast cancer that meets the following criteria:

   1. A known case of histologically confirmed invasive breast carcinoma with a primary tumor size of \> 2 cm by standard local assessment technique
   2. stage at presentation: early stage (T2-3, N0-1, M0) or locally advanced (T2-3, N2 or N3, M0; T4a-c, any N, M0) or inflammatory (T4d, any N, M0)
5. Patients with HER2 overexpression by Immunohistochemistry (IHC) (defined as IHC 3+, or IHC 2+ with Fluorescence In Situ Hybridization (FISH) confirmation) as per the American Society of Clinical Oncology/College of American Pathologist (ASCO-CAP) guidelines prior to Screening and confirmed centrally before randomization
6. Patients with known HR-ve status (ER-negative and PR-negative) as per local laboratory prior to Screening and confirmed centrally before randomization
7. Patient willing to undergo mastectomy or breast-conserving surgery after neoadjuvant therapy
8. Patient who completes all necessary baseline laboratory and radiologic investigations prior to randomization as per Schedule of assessment (SoA)
9. Patient with baseline left ventricular ejection fraction (LVEF) ≥ 55% measured by echocardiography (ECHO; preferred) or multiple-gated acquisition (MUGA) scan
10. Patient is eligible to participant if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

Exclusion Criteria:

1. Patients with metastatic or recurrent bilateral breast cancer, or bilateral breast cancer
2. Patients with a history of concurrent or previously treated non-breast malignancies. A patient with previous invasive non-breast cancer is eligible provided she has been disease free for more than 5 years
3. Patients who have received any previous systemic therapy (including chemotherapy, immunotherapy, HER2-targeted agents, and antitumor vaccines) for treatment or prevention of breast cancer, or radiation therapy for treatment of cancer
4. Concurrent anti-cancer treatment in another investigational study, including hormone therapy or immunotherapy
5. Major surgical procedure that is unrelated to breast cancer within 4 weeks prior to randomization or from which the patient has not fully recovered
6. Serious cardiac illness or medical condition including but not limited to the following as per Investigator's discretion:

   1. Patients with ≥ Class II stage of heart failure as per New York Heart Association Classification
   2. High risk uncontrolled arrhythmia, such as atrial tachycardia with a heart rate \> 100 bpm at rest, significant ventricular arrhythmia (e.g., ventricular tachycardia) required treatment, or higher-grade atrioventricular (AV) block (i.e., Mobitz II second-degree AV block or third-degree AV block)
   3. History of myocardial infarction or unstable angina pectoris within 1 year of randomization or angina pectoris requiring anti-anginal medication
   4. Evidence of transmural infarction on ECG
   5. Clinically significant valvular heart disease
   6. Poorly controlled hypertension (systolic blood pressure \> 180 mmHg and/or diastolic blood pressure \> 100 mmHg) in patients on anti-hypertensive medications
7. Other concurrent serious diseases that may interfere with study primary endpoint and other study assessments, including, but not limited to, severe pulmonary conditions/illness, active liver disease (for example, active viral hepatitis infection \[i.e., hepatitis B or hepatitis C\]), autoimmune disorders, history of or known patient of sclerosing cholangitis, or infection with Human immune deficiency virus (HIV)
8. Patients with a history of any contraindication to the study treatment regimens
9. Any of the following abnormal laboratory test results prior to randomization:

   1. Total bilirubin \> upper limit of normal (ULN) or, for cases of known Gilbert's syndrome, total bilirubin \> 2 × ULN
   2. Aspartate aminotransferase and/or alanine aminotransferase \> 1.5 × ULN, if considered clinically significant by Investigator
   3. Alkaline phosphatase \>2.5 × ULN, if considered clinically significant by Investigator
   4. Serum creatinine \> 1.5 × ULN
   5. Creatinine clearance \< 60 mL/min
   6. Total white blood cells count \< 2500 cells/μL
   7. Absolute neutrophil count \< 2000 cells/μL
   8. Platelet count \< 100,000 cells/μL
10. Participation in any clinical study with an investigational drug, biologic, or device within 1 month prior or within five half-lives (of the drug/ biologic) prior to the enrolment (whichever is longer)
11. Have taken any live vaccines 30 days prior to the 1st dose of study treatment
12. Any known hypersensitivity to any of the study medications, any of the ingredients or excipients of these medications, or benzyl alcohol
13. Patients unwilling to follow the study requirements.
14. Presence of an uncontrolled, unstable, clinically significant medical condition that, in the opinion of the Investigator, may interfere with the interpretation of efficacy and safety parameters or has a medical condition for which the treatment should take precedence over study participation or will interfere with study participation

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Primary outcomes:
measure: Efficacy endpoint - Total pathologic complete response between Treatment arm A and Treatment Arm B
timeFrame: Week 18
Secondary outcomes:
measure: Efficacy endpoint-Total pathologic complete response between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
timeFrame: Week 18
measure: Efficacy endpoint: Pathologic complete response between Treatment Arm A and Treatment Arm B
timeFrame: Week 18
measure: Efficacy endpoint- Breast pathologic complete response between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
timeFrame: Week 18
measure: Efficacy endpoint-Objective response rate between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
timeFrame: Week 18
measure: Efficacy endpoint-Event free survival rate between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
timeFrame: Week 18
measure: Efficacy endpoint- Overall survival rate between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
timeFrame: Week 18
measure: Efficacy endpoint-EFS rate of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
timeFrame: 1 Year
measure: Efficacy endpoint - Overall Survival rate of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
timeFrame: 1 Year
measure: Efficacy endpoint - Overall Response Rate of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
timeFrame: 1 Year
measure: Efficacy Endpoint: EFS rate after the single switch from EU-Perjeta to PERT-IJS+trastuzumab compared with those continuing on Treatment B
timeFrame: 1 year
measure: Efficacy Endpoint: Disease free survival rate after the single switch from from EU-Perjeta to PERT-IJS+trastuzumab compared with those continuing on EU-Perjeta+trastuzumab
timeFrame: 1 year
measure: Efficacy Endpoint: Overall survival rate after the single switch from from EU-Perjeta to PERT-IJS+trastuzumab compared with those continuing on EU-Perjeta+trastuzumab
timeFrame: 1 year
measure: Pharmacokinetic (PK) endpoint-The trough serum concentration
timeFrame: 1 Year
measure: Safety Endpoint: treatment-emergent adverse events and serious adverse events
timeFrame: week 18
measure: Safety Endpoint: left ventricular ejection fraction
timeFrame: week 18
measure: Safety Endpoint: Vital signs
timeFrame: week 18
measure: Safety Endpoint-ECG PR Interval
timeFrame: week 18
measure: Safety Endpoint-ECG QRS Interval
timeFrame: week 18
measure: Safety Endpoint-ECG QT Interval
timeFrame: week 18
measure: Safety Endpoint- ECG corrected QT interval (QTc) Interval
timeFrame: week 18
measure: Safety Endpoint-clinical laboratory assessments
timeFrame: week 18
measure: Safety Endpoint-pregnancy test
timeFrame: week 18
measure: Safety Endpoint-physical examination
timeFrame: week 18
measure: Immunogenicity Endpoint
timeFrame: week 18
measure: Safety Endpoint: treatment-emergent adverse events and serious adverse events of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta
timeFrame: 1 year
measure: Safety Endpoint: left ventricular ejection fraction of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
timeFrame: 1 year
measure: Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS -throughout compared to patients randomized to EU-Perjeta throughout- Vital signs
timeFrame: 1 year
measure: Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout- ECG PR Interval
timeFrame: 1 year
measure: Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-ECG QRS Interval
timeFrame: 1 year
measure: Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-ECG QT Interval
timeFrame: 1 year
measure: Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout- ECG QTc Interval
timeFrame: 1 year
measure: Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-Clinical laboratory assessments
timeFrame: 1 year
measure: Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout- Pregnancy test
timeFrame: 1 year
measure: Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-Physical examination
timeFrame: 1 year
measure: Immunogenicity Endpoint of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
timeFrame: 1 year
measure: Safety Endpoint: Incidence of TEAEs and SAEs after the single switch from EU-Perjeta to PERT-IJS+trastuzumab versus those continuing on EU-Perjeta+trastuzumab throughout
timeFrame: 1 Year
measure: Safety End Point :left ventricular ejection fraction incidences after the single switch from EU-Perjeta to PERT-IJS+trastuzumab versus those continuing on EU-Perjeta+trastuzumab
timeFrame: 1 year
measure: Immunogenicity End Point: after the single switch from EU-Perjeta to PERT-IJS+trastuzumab versus those continuing on EU-Perjeta+trastuzumab
timeFrame: 1 Year
Other outcomes:
Locations:
Study officials:
References: