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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

Primary Purpose

HR Negative HER2 Positive Early Breast Cancer or Locally Advanced Breast Cancer Patients

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
PERT-IJS plus trastuzumab, carboplatin and docetaxel
Perjeta plus trastuzumab, carboplatin and docetaxel
Sponsored by
Biocon Biologics UK Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HR Negative HER2 Positive Early Breast Cancer or Locally Advanced Breast Cancer Patients focused on measuring Locally advanced breast cancer patient, HR negative HER2-positive Early breast cancer, PERT-IJS, Pertuzumab, Trastuzumab, Neoadjuvant treatment

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Patient willing and able to sign informed consent and to follow the protocol requirements Female patients aged ≥ 18 years at the time of Screening Patient with Eastern Cooperative Oncology Group (ECOG) Performance Status < 2 Patients with breast cancer that meets the following criteria: A known case of histologically confirmed invasive breast carcinoma with a primary tumor size of > 2 cm by standard local assessment technique 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) 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 Patients with known HR-ve status (ER-negative and PR-negative) as per local laboratory prior to Screening and confirmed centrally before randomization Patient willing to undergo mastectomy or breast-conserving surgery after neoadjuvant therapy Patient who completes all necessary baseline laboratory and radiologic investigations prior to randomization as per Schedule of assessment (SoA) Patient with baseline left ventricular ejection fraction (LVEF) ≥ 55% measured by echocardiography (ECHO; preferred) or multiple-gated acquisition (MUGA) scan Patient is eligible to participant if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Exclusion Criteria: Patients with metastatic or recurrent bilateral breast cancer, or bilateral breast cancer 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 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 Concurrent anti-cancer treatment in another investigational study, including hormone therapy or immunotherapy Major surgical procedure that is unrelated to breast cancer within 4 weeks prior to randomization or from which the patient has not fully recovered Serious cardiac illness or medical condition including but not limited to the following as per Investigator's discretion: Patients with ≥ Class II stage of heart failure as per New York Heart Association Classification 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) History of myocardial infarction or unstable angina pectoris within 1 year of randomization or angina pectoris requiring anti-anginal medication Evidence of transmural infarction on ECG Clinically significant valvular heart disease Poorly controlled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg) in patients on anti-hypertensive medications 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) Patients with a history of any contraindication to the study treatment regimens Any of the following abnormal laboratory test results prior to randomization: Total bilirubin > upper limit of normal (ULN) or, for cases of known Gilbert's syndrome, total bilirubin > 2 × ULN Aspartate aminotransferase and/or alanine aminotransferase > 1.5 × ULN, if considered clinically significant by Investigator Alkaline phosphatase >2.5 × ULN, if considered clinically significant by Investigator Serum creatinine > 1.5 × ULN Creatinine clearance < 60 mL/min Total white blood cells count < 2500 cells/μL Absolute neutrophil count < 2000 cells/μL Platelet count < 100,000 cells/μL 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) Have taken any live vaccines 30 days prior to the 1st dose of study treatment Any known hypersensitivity to any of the study medications, any of the ingredients or excipients of these medications, or benzyl alcohol Patients unwilling to follow the study requirements. 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 -

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Treatment Arm A: PERT-IJS plus trastuzumab, carboplatin and docetaxel

    Treatment Arm B: EU-Perjeta plus trastuzumab, carboplatin and docetaxel

    Arm Description

    Part 1 (Cycle 1 to 6): Initial loading dose of PERT-IJS is 840 mg administered as an approximately 60-minute IV infusion followed every 3 weeks by a maintenance dose of 420 mg administered as an IV infusion over a period of approximately 30 to 60 minutes. Trastuzumab: Initial dose of trastuzumab is 8 mg/kg administered as approximately 90-minute IV infusion followed every 3 weeks by 6 mg/kg IV infusion over 30 to 90 minutes Carboplatin: Area Under the Curve (AUC) 6 for Cycles 1 to 6 Docetaxel: 75 mg/m2 by IV infusion every 3 weeks for Cycles 1 to 6 Part 2 (Cycle 7 - till end of 1 year from Cycle 1 day 1): Initial loading dose of PERT-IJS is 840 mg administered as approximately 60-minute IV infusion followed every 3 weeks by a maintenance dose of 420 mg administered as an IV infusion over a period of approximately 30 to 60 minutes. Trastuzumab: As mentioned in part 1

    Part 1 (Cycle 1 to 6): Initial loading dose of EU- Perjeta is 840 mg administered as approximately 60-minute IV infusion followed every 3 weeks by a maintenance dose of 420 mg administered as an IV infusion over a period of approximately 30 to 60 minutes. Trastuzumab: Initial dose of trastuzumab is 8 mg/kg administered as approximately 90-minute IV infusion followed every 3 weeks by 6 mg/kg IV infusion over 30 to 90 minutes Carboplatin: Area under the curve 6 for Cycles 1 to 6 Docetaxel: 75 mg/m2 by IV infusion every 3 weeks for Cycles 1 to 6 Part 2 (Cycle 7 onwards till end of 01 year from Cycle 1 day 1): The patients will be re-randomized (1:1) to receive EU- Perjeta + trastuzumab or PERT-IJS + trastuzumab. Initial loading dose of PERT-IJS is 840 mg administered as approximately 60-minute IV infusion followed every 3 weeks by a maintenance dose of 420 mg administered as an IV infusion over a period of approximately 30 to 60 minutes. Trastuzumab: As mentioned in part 1

    Outcomes

    Primary Outcome Measures

    Efficacy endpoint - Total pathologic complete response between Treatment arm A and Treatment Arm B
    Total pathologic complete response (tpCR; ypT0/Tis,ypN0) in breast and axillary nodes after neoadjuvant treatment by Independent Review Committee (IRC)

    Secondary Outcome Measures

    Efficacy endpoint-Total pathologic complete response between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
    Total pathologic complete response (tpCR; ypT0/Tis, ypN0) in breast and axillary nodes after neoadjuvant treatment by local histopathologist
    Efficacy endpoint: Pathologic complete response between Treatment Arm A and Treatment Arm B
    Pathologic complete response (pCR; ypT0/ypN0) after neoadjuvant treatment by IRC and local histopathologist
    Efficacy endpoint- Breast pathologic complete response between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
    Breast pathologic complete response (bpCR; ypT0/Tis) after neoadjuvant treatment by IRC and local histopathologist
    Efficacy endpoint-Objective response rate between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
    Objective response rate (ORR) after neoadjuvant treatment in accordance with Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
    Efficacy endpoint-Event free survival rate between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
    Event free survival (EFS) rate
    Efficacy endpoint- Overall survival rate between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
    Overall survival (OS) rate
    Efficacy endpoint-EFS rate of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
    EFS rate
    Efficacy endpoint - Overall Survival rate of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
    Overall survival rate
    Efficacy endpoint - Overall Response Rate of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
    Overall Response Rate
    Efficacy Endpoint: EFS rate after the single switch from EU-Perjeta to PERT-IJS+trastuzumab compared with those continuing on Treatment B
    EFS rate after switching of treatment from EU-Perjeta to PERT-IJS + trastuzumab
    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
    Disease free survival (DFS) rate after switching of treatment from EU-Perjeta to PERT-IJS + trastuzumab versus those continuing on EU-Perjeta + trastuzumab
    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
    OS rate after switching of treatment from EU-Perjeta to PERT-IJS + trastuzumab versus those continuing on EU-Perjeta + trastuzumab
    Pharmacokinetic (PK) endpoint-The trough serum concentration
    The trough serum concentration (Ctrough)
    Safety Endpoint: treatment-emergent adverse events and serious adverse events
    Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
    Safety Endpoint: left ventricular ejection fraction
    Incidence of patients with a decline in left ventricular ejection fraction (LVEF) of ≥ 10% from baseline to < 50%
    Safety Endpoint: Vital signs
    Number of subjects with clinically significant changes in Vital signs
    Safety Endpoint-ECG PR Interval
    Number of subjects with clinically significant changes in ECG PR Interval
    Safety Endpoint-ECG QRS Interval
    Number of subjects with clinically significant changes in ECG QRS Interval
    Safety Endpoint-ECG QT Interval
    Number of subjects with clinically significant changes in ECG QT Interval
    Safety Endpoint- ECG corrected QT interval (QTc) Interval
    Number of subjects with clinically significant changes in ECG QTc Interval
    Safety Endpoint-clinical laboratory assessments
    Number of subjects with clinically significant changes in Clinical laboratory assessments
    Safety Endpoint-pregnancy test
    Number of subjects with Pregnancy outcome
    Safety Endpoint-physical examination
    Number of subjects with clinically significant changes in Physical examination
    Immunogenicity Endpoint
    Immunogenicity (anti-drug antibodies (ADA) and neutralizing antibodies (nAb) titers)
    Safety Endpoint: treatment-emergent adverse events and serious adverse events of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta
    Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
    Safety Endpoint: left ventricular ejection fraction of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
    Incidence of patients with a decline in left ventricular ejection fraction (LVEF) of ≥ 10% from baseline to < 50%
    Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS -throughout compared to patients randomized to EU-Perjeta throughout- Vital signs
    Number of subjects with clinically significant changes in Vital signs
    Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout- ECG PR Interval
    Number of subjects with clinically significant changes in ECG PR Interval
    Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-ECG QRS Interval
    Number of subjects with clinically significant changes in ECG QRS Interval
    Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-ECG QT Interval
    Number of subjects with clinically significant changes in ECG QT Interval
    Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout- ECG QTc Interval
    Number of subjects with clinically significant changes in ECG QTc Interval
    Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-Clinical laboratory assessments
    Number of subjects with clinically significant changes in Clinical laboratory assessments
    Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout- Pregnancy test
    Number of subjects with Pregnancy outcome
    Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-Physical examination
    Number of subjects with clinically significant changes in Physical examination
    Immunogenicity Endpoint of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
    Immunogenicity (anti-drug antibodies (ADA) and neutralizing antibodies (nAb) titers)
    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
    Incidence of TEAEs and SAEs after switching of treatment from EU-Perjeta to PERT-IJS + trastuzumab versus those continuing on EU-Perjeta + trastuzumab
    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
    Incidence of patients with a decline in left ventricular ejection fraction (LVEF) of ≥ 10% from baseline to < 50%
    Immunogenicity End Point: after the single switch from EU-Perjeta to PERT-IJS+trastuzumab versus those continuing on EU-Perjeta+trastuzumab
    Immunogenicity (ADA titer and nAb titer) after switching of treatment from EU-Perjeta to PERT-IJS plus trastuzumab versus those continuing on EU-Perjeta + trastuzumab

    Full Information

    First Posted
    August 23, 2023
    Last Updated
    September 22, 2023
    Sponsor
    Biocon Biologics UK Ltd
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06038539
    Brief Title
    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

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    December 15, 2023 (Anticipated)
    Primary Completion Date
    February 15, 2026 (Anticipated)
    Study Completion Date
    October 15, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Biocon Biologics UK Ltd

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    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

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Model Description
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    382 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Treatment Arm A: PERT-IJS plus trastuzumab, carboplatin and docetaxel
    Arm Type
    Experimental
    Arm Description
    Part 1 (Cycle 1 to 6): Initial loading dose of PERT-IJS is 840 mg administered as an approximately 60-minute IV infusion followed every 3 weeks by a maintenance dose of 420 mg administered as an IV infusion over a period of approximately 30 to 60 minutes. Trastuzumab: Initial dose of trastuzumab is 8 mg/kg administered as approximately 90-minute IV infusion followed every 3 weeks by 6 mg/kg IV infusion over 30 to 90 minutes Carboplatin: Area Under the Curve (AUC) 6 for Cycles 1 to 6 Docetaxel: 75 mg/m2 by IV infusion every 3 weeks for Cycles 1 to 6 Part 2 (Cycle 7 - till end of 1 year from Cycle 1 day 1): Initial loading dose of PERT-IJS is 840 mg administered as approximately 60-minute IV infusion followed every 3 weeks by a maintenance dose of 420 mg administered as an IV infusion over a period of approximately 30 to 60 minutes. Trastuzumab: As mentioned in part 1
    Arm Title
    Treatment Arm B: EU-Perjeta plus trastuzumab, carboplatin and docetaxel
    Arm Type
    Active Comparator
    Arm Description
    Part 1 (Cycle 1 to 6): Initial loading dose of EU- Perjeta is 840 mg administered as approximately 60-minute IV infusion followed every 3 weeks by a maintenance dose of 420 mg administered as an IV infusion over a period of approximately 30 to 60 minutes. Trastuzumab: Initial dose of trastuzumab is 8 mg/kg administered as approximately 90-minute IV infusion followed every 3 weeks by 6 mg/kg IV infusion over 30 to 90 minutes Carboplatin: Area under the curve 6 for Cycles 1 to 6 Docetaxel: 75 mg/m2 by IV infusion every 3 weeks for Cycles 1 to 6 Part 2 (Cycle 7 onwards till end of 01 year from Cycle 1 day 1): The patients will be re-randomized (1:1) to receive EU- Perjeta + trastuzumab or PERT-IJS + trastuzumab. Initial loading dose of PERT-IJS is 840 mg administered as approximately 60-minute IV infusion followed every 3 weeks by a maintenance dose of 420 mg administered as an IV infusion over a period of approximately 30 to 60 minutes. Trastuzumab: As mentioned in part 1
    Intervention Type
    Biological
    Intervention Name(s)
    PERT-IJS plus trastuzumab, carboplatin and docetaxel
    Intervention Description
    PERT-IJS is a monoclonal antibody, which has been developed by Biocon Biologics (earlier in collaboration with Viatris) as a proposed biosimilar to European Union (EU)-approved and United States (US) licensed Perjeta.
    Intervention Type
    Biological
    Intervention Name(s)
    Perjeta plus trastuzumab, carboplatin and docetaxel
    Intervention Description
    EU Perjeta (Pertuzumab) , an antineoplastic agent, is a recombinant humanized monoclonal antibody that specifically targets sub-domain 2 of the extracellular domain of Human Epidermal Growth Factor Receptor 2 (HER2), blocking heterodimerization of HER2 with other members of the receptor family, including epidermal growth factor, Human Epidermal Growth Factor Receptor 3 (HER3) and Human Epidermal Growth Factor Receptor 4 (HER4).
    Primary Outcome Measure Information:
    Title
    Efficacy endpoint - Total pathologic complete response between Treatment arm A and Treatment Arm B
    Description
    Total pathologic complete response (tpCR; ypT0/Tis,ypN0) in breast and axillary nodes after neoadjuvant treatment by Independent Review Committee (IRC)
    Time Frame
    Week 18
    Secondary Outcome Measure Information:
    Title
    Efficacy endpoint-Total pathologic complete response between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
    Description
    Total pathologic complete response (tpCR; ypT0/Tis, ypN0) in breast and axillary nodes after neoadjuvant treatment by local histopathologist
    Time Frame
    Week 18
    Title
    Efficacy endpoint: Pathologic complete response between Treatment Arm A and Treatment Arm B
    Description
    Pathologic complete response (pCR; ypT0/ypN0) after neoadjuvant treatment by IRC and local histopathologist
    Time Frame
    Week 18
    Title
    Efficacy endpoint- Breast pathologic complete response between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
    Description
    Breast pathologic complete response (bpCR; ypT0/Tis) after neoadjuvant treatment by IRC and local histopathologist
    Time Frame
    Week 18
    Title
    Efficacy endpoint-Objective response rate between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
    Description
    Objective response rate (ORR) after neoadjuvant treatment in accordance with Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
    Time Frame
    Week 18
    Title
    Efficacy endpoint-Event free survival rate between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
    Description
    Event free survival (EFS) rate
    Time Frame
    Week 18
    Title
    Efficacy endpoint- Overall survival rate between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
    Description
    Overall survival (OS) rate
    Time Frame
    Week 18
    Title
    Efficacy endpoint-EFS rate of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
    Description
    EFS rate
    Time Frame
    1 Year
    Title
    Efficacy endpoint - Overall Survival rate of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
    Description
    Overall survival rate
    Time Frame
    1 Year
    Title
    Efficacy endpoint - Overall Response Rate of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
    Description
    Overall Response Rate
    Time Frame
    1 Year
    Title
    Efficacy Endpoint: EFS rate after the single switch from EU-Perjeta to PERT-IJS+trastuzumab compared with those continuing on Treatment B
    Description
    EFS rate after switching of treatment from EU-Perjeta to PERT-IJS + trastuzumab
    Time Frame
    1 year
    Title
    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
    Description
    Disease free survival (DFS) rate after switching of treatment from EU-Perjeta to PERT-IJS + trastuzumab versus those continuing on EU-Perjeta + trastuzumab
    Time Frame
    1 year
    Title
    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
    Description
    OS rate after switching of treatment from EU-Perjeta to PERT-IJS + trastuzumab versus those continuing on EU-Perjeta + trastuzumab
    Time Frame
    1 year
    Title
    Pharmacokinetic (PK) endpoint-The trough serum concentration
    Description
    The trough serum concentration (Ctrough)
    Time Frame
    1 Year
    Title
    Safety Endpoint: treatment-emergent adverse events and serious adverse events
    Description
    Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
    Time Frame
    week 18
    Title
    Safety Endpoint: left ventricular ejection fraction
    Description
    Incidence of patients with a decline in left ventricular ejection fraction (LVEF) of ≥ 10% from baseline to < 50%
    Time Frame
    week 18
    Title
    Safety Endpoint: Vital signs
    Description
    Number of subjects with clinically significant changes in Vital signs
    Time Frame
    week 18
    Title
    Safety Endpoint-ECG PR Interval
    Description
    Number of subjects with clinically significant changes in ECG PR Interval
    Time Frame
    week 18
    Title
    Safety Endpoint-ECG QRS Interval
    Description
    Number of subjects with clinically significant changes in ECG QRS Interval
    Time Frame
    week 18
    Title
    Safety Endpoint-ECG QT Interval
    Description
    Number of subjects with clinically significant changes in ECG QT Interval
    Time Frame
    week 18
    Title
    Safety Endpoint- ECG corrected QT interval (QTc) Interval
    Description
    Number of subjects with clinically significant changes in ECG QTc Interval
    Time Frame
    week 18
    Title
    Safety Endpoint-clinical laboratory assessments
    Description
    Number of subjects with clinically significant changes in Clinical laboratory assessments
    Time Frame
    week 18
    Title
    Safety Endpoint-pregnancy test
    Description
    Number of subjects with Pregnancy outcome
    Time Frame
    week 18
    Title
    Safety Endpoint-physical examination
    Description
    Number of subjects with clinically significant changes in Physical examination
    Time Frame
    week 18
    Title
    Immunogenicity Endpoint
    Description
    Immunogenicity (anti-drug antibodies (ADA) and neutralizing antibodies (nAb) titers)
    Time Frame
    week 18
    Title
    Safety Endpoint: treatment-emergent adverse events and serious adverse events of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta
    Description
    Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
    Time Frame
    1 year
    Title
    Safety Endpoint: left ventricular ejection fraction of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
    Description
    Incidence of patients with a decline in left ventricular ejection fraction (LVEF) of ≥ 10% from baseline to < 50%
    Time Frame
    1 year
    Title
    Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS -throughout compared to patients randomized to EU-Perjeta throughout- Vital signs
    Description
    Number of subjects with clinically significant changes in Vital signs
    Time Frame
    1 year
    Title
    Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout- ECG PR Interval
    Description
    Number of subjects with clinically significant changes in ECG PR Interval
    Time Frame
    1 year
    Title
    Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-ECG QRS Interval
    Description
    Number of subjects with clinically significant changes in ECG QRS Interval
    Time Frame
    1 year
    Title
    Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-ECG QT Interval
    Description
    Number of subjects with clinically significant changes in ECG QT Interval
    Time Frame
    1 year
    Title
    Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout- ECG QTc Interval
    Description
    Number of subjects with clinically significant changes in ECG QTc Interval
    Time Frame
    1 year
    Title
    Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-Clinical laboratory assessments
    Description
    Number of subjects with clinically significant changes in Clinical laboratory assessments
    Time Frame
    1 year
    Title
    Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout- Pregnancy test
    Description
    Number of subjects with Pregnancy outcome
    Time Frame
    1 year
    Title
    Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-Physical examination
    Description
    Number of subjects with clinically significant changes in Physical examination
    Time Frame
    1 year
    Title
    Immunogenicity Endpoint of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
    Description
    Immunogenicity (anti-drug antibodies (ADA) and neutralizing antibodies (nAb) titers)
    Time Frame
    1 year
    Title
    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
    Description
    Incidence of TEAEs and SAEs after switching of treatment from EU-Perjeta to PERT-IJS + trastuzumab versus those continuing on EU-Perjeta + trastuzumab
    Time Frame
    1 Year
    Title
    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
    Description
    Incidence of patients with a decline in left ventricular ejection fraction (LVEF) of ≥ 10% from baseline to < 50%
    Time Frame
    1 year
    Title
    Immunogenicity End Point: after the single switch from EU-Perjeta to PERT-IJS+trastuzumab versus those continuing on EU-Perjeta+trastuzumab
    Description
    Immunogenicity (ADA titer and nAb titer) after switching of treatment from EU-Perjeta to PERT-IJS plus trastuzumab versus those continuing on EU-Perjeta + trastuzumab
    Time Frame
    1 Year

    10. Eligibility

    Sex
    Female
    Gender Based
    Yes
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    99 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patient willing and able to sign informed consent and to follow the protocol requirements Female patients aged ≥ 18 years at the time of Screening Patient with Eastern Cooperative Oncology Group (ECOG) Performance Status < 2 Patients with breast cancer that meets the following criteria: A known case of histologically confirmed invasive breast carcinoma with a primary tumor size of > 2 cm by standard local assessment technique 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) 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 Patients with known HR-ve status (ER-negative and PR-negative) as per local laboratory prior to Screening and confirmed centrally before randomization Patient willing to undergo mastectomy or breast-conserving surgery after neoadjuvant therapy Patient who completes all necessary baseline laboratory and radiologic investigations prior to randomization as per Schedule of assessment (SoA) Patient with baseline left ventricular ejection fraction (LVEF) ≥ 55% measured by echocardiography (ECHO; preferred) or multiple-gated acquisition (MUGA) scan Patient is eligible to participant if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Exclusion Criteria: Patients with metastatic or recurrent bilateral breast cancer, or bilateral breast cancer 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 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 Concurrent anti-cancer treatment in another investigational study, including hormone therapy or immunotherapy Major surgical procedure that is unrelated to breast cancer within 4 weeks prior to randomization or from which the patient has not fully recovered Serious cardiac illness or medical condition including but not limited to the following as per Investigator's discretion: Patients with ≥ Class II stage of heart failure as per New York Heart Association Classification 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) History of myocardial infarction or unstable angina pectoris within 1 year of randomization or angina pectoris requiring anti-anginal medication Evidence of transmural infarction on ECG Clinically significant valvular heart disease Poorly controlled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg) in patients on anti-hypertensive medications 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) Patients with a history of any contraindication to the study treatment regimens Any of the following abnormal laboratory test results prior to randomization: Total bilirubin > upper limit of normal (ULN) or, for cases of known Gilbert's syndrome, total bilirubin > 2 × ULN Aspartate aminotransferase and/or alanine aminotransferase > 1.5 × ULN, if considered clinically significant by Investigator Alkaline phosphatase >2.5 × ULN, if considered clinically significant by Investigator Serum creatinine > 1.5 × ULN Creatinine clearance < 60 mL/min Total white blood cells count < 2500 cells/μL Absolute neutrophil count < 2000 cells/μL Platelet count < 100,000 cells/μL 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) Have taken any live vaccines 30 days prior to the 1st dose of study treatment Any known hypersensitivity to any of the study medications, any of the ingredients or excipients of these medications, or benzyl alcohol Patients unwilling to follow the study requirements. 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 -
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Anoop Chullikana, MBBS, MD
    Phone
    91 80 2808
    Ext
    5306
    Email
    anoop.chullikana@biocon.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Jayanti Panda, MBA,PM
    Phone
    91 80 2808
    Ext
    5304
    Email
    jayanti.panda@biocon.com

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    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

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