xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06038539</url>
    </required_header>
    <id_info>
      <org_study_id>BIO-PERTUZ-301</org_study_id>
      <nct_id>NCT06038539</nct_id>
    </id_info>
    <brief_title>Efficacy and Safety of the Proposed Biosimilar 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</brief_title>
    <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</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Biocon Biologics UK Ltd</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Biocon Limited</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        To compare the efficacy and safety of PERT-IJS plus trastuzumab and chemotherapy (carboplatin&#xD;
        and docetaxel) versus EU-Perjeta plus trastuzumab and chemotherapy (carboplatin and&#xD;
        docetaxel) in neoadjuvant treatment of patients with HR-ve and HER-2 positive early stage or&#xD;
        locally advanced breast cancer.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study is designed to compare the efficacy and safety of proposed biosimilar PERT-IJS&#xD;
        plus trastuzumab, carboplatin and docetaxel versus EU-Perjeta plus trastuzumab, carboplatin&#xD;
        and docetaxel in neoadjuvant treatment of HR-ve HER2-positive EBC (invasive breast cancer&#xD;
        without distant metastasis) or locally advanced breast cancer patients.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">December 15, 2023</start_date>
    <completion_date type="Anticipated">October 15, 2026</completion_date>
    <primary_completion_date type="Anticipated">February 15, 2026</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>Parallel Assignment</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Efficacy endpoint - Total pathologic complete response between Treatment arm A and Treatment Arm B</measure>
      <time_frame>Week 18</time_frame>
      <description>Total pathologic complete responsea (tpCR; ypT0/Tis,ypN0) in breast and axillary nodes after neoadjuvant treatmentb by Independent Review Committee (IRC)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Efficacy endpoint-Total pathologic complete response between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen</measure>
      <time_frame>Week 18</time_frame>
      <description>Total pathologic complete response (tpCR; ypT0/Tis, ypN0) in breast and axillary nodes after neoadjuvant treatment by local histopathologist</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy endpoint: Pathologic complete response between Treatment Arm A and Treatment Arm B</measure>
      <time_frame>Week 18</time_frame>
      <description>Pathologic complete response (pCR; ypT0/ypN0) after neoadjuvant treatment by IRC and local histopathologist</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy endpoint- Breast pathologic complete response between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen</measure>
      <time_frame>Week 18</time_frame>
      <description>Breast pathologic complete responsed (bpCR; ypT0/Tis) after neoadjuvant treatment by IRC and local histopathologist</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy endpoint-Objective response rate between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen</measure>
      <time_frame>Week 18</time_frame>
      <description>Objective response rate (ORR) after neoadjuvant treatment in accordance with Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy endpoint-Event free survival rate between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen</measure>
      <time_frame>Week 18</time_frame>
      <description>Event free survival (EFS) rate</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy endpoint- Overall survival rate between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen</measure>
      <time_frame>Week 18</time_frame>
      <description>Overall survival (OS) rate</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy endpoint-EFS rate of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout</measure>
      <time_frame>1 Year</time_frame>
      <description>EFS rate</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy endpoint - Overall Survival rate of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout</measure>
      <time_frame>1 Year</time_frame>
      <description>Overall survival rate</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy endpoint - Overall Response Rate of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout</measure>
      <time_frame>1 Year</time_frame>
      <description>Overall Response Rate</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Efficacy Endpoint: EFS rate after the single switch from EU-Perjeta to PERT-IJS+trastuzumab compared with those continuing on Treatment B</measure>
      <time_frame>1 year</time_frame>
      <description>EFS rate after switching of treatment from EU-Perjeta to PERT-IJS + trastuzumab</description>
    </secondary_outcome>
    <secondary_outcome>
      <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</measure>
      <time_frame>1 year</time_frame>
      <description>Disease free survival (DFS) rate after switching of treatment from EU-Perjeta to PERT-IJS + trastuzumab versus those continuing on EU-Perjeta + trastuzumab</description>
    </secondary_outcome>
    <secondary_outcome>
      <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</measure>
      <time_frame>1 year</time_frame>
      <description>OS rate after switching of treatment from EU-Perjeta to PERT-IJS + trastuzumab versus those continuing on EU-Perjeta + trastuzumab</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK endpoint-The trough serum concentration</measure>
      <time_frame>1 Year</time_frame>
      <description>The trough serum concentration (Ctrough)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety Endpoint: treatment-emergent adverse events and serious adverse events</measure>
      <time_frame>week 18</time_frame>
      <description>Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety Endpoint: left ventricular ejection fraction</measure>
      <time_frame>week 18</time_frame>
      <description>Incidence of patients with a decline in left ventricular ejection fraction (LVEF) of ≥ 10% from baseline to &lt; 50%</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety Endpoint: Vital signs</measure>
      <time_frame>week 18</time_frame>
      <description>Number of subjects with clinically significant changes in Vital signs</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety Endpoint-ECG PR Interval</measure>
      <time_frame>week 18</time_frame>
      <description>Number of subjects with clinically significant changes in ECG PR Interval</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety Endpoint-ECG QRS Interval</measure>
      <time_frame>week 18</time_frame>
      <description>Number of subjects with clinically significant changes in ECG QRS Interval</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety Endpoint-ECG QT Interval</measure>
      <time_frame>week 18</time_frame>
      <description>Number of subjects with clinically significant changes in ECG QT Interval</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety Endpoint- ECG QTc Interval</measure>
      <time_frame>week 18</time_frame>
      <description>Number of subjects with clinically significant changes in ECG QTc Interval</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety Endpoint-clinical laboratory assessments</measure>
      <time_frame>week 18</time_frame>
      <description>Number of subjects with clinically significant changes in Clinical laboratory assessments</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety Endpoint-pregnancy test</measure>
      <time_frame>week 18</time_frame>
      <description>Number of subjects with Pregnancy outcome</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety Endpoint-physical examination</measure>
      <time_frame>week 18</time_frame>
      <description>Number of subjects with clinically significant changes in Physical examination</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Immunogenicity Endpoint</measure>
      <time_frame>week 18</time_frame>
      <description>Immunogenicity (anti-drug antibodies [ADA] and neutralizing antibodies [nAb] titers)</description>
    </secondary_outcome>
    <secondary_outcome>
      <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</measure>
      <time_frame>1 year</time_frame>
      <description>Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety Endpoint: left ventricular ejection fraction of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout</measure>
      <time_frame>1 year</time_frame>
      <description>Incidence of patients with a decline in left ventricular ejection fraction (LVEF) of ≥ 10% from baseline to &lt; 50%</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS -throughout compared to patients randomized to EU-Perjeta throughout- Vital signs</measure>
      <time_frame>1 year</time_frame>
      <description>Number of subjects with clinically significant changes in Vital signs</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout- ECG PR Interval</measure>
      <time_frame>1 year</time_frame>
      <description>Number of subjects with clinically significant changes in ECG PR Interval</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-ECG QRS Interval</measure>
      <time_frame>1 year</time_frame>
      <description>Number of subjects with clinically significant changes in ECG QRS Interval</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-ECG QT Interval</measure>
      <time_frame>1 year</time_frame>
      <description>Number of subjects with clinically significant changes in ECG QT Interval</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout- ECG QTc Interval</measure>
      <time_frame>1 year</time_frame>
      <description>Number of subjects with clinically significant changes in ECG QTc Interval</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-Clinical laboratory assessments</measure>
      <time_frame>1 year</time_frame>
      <description>Number of subjects with clinically significant changes in Clinical laboratory assessments</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout- Pregnancy test</measure>
      <time_frame>1 year</time_frame>
      <description>Number of subjects with Pregnancy outcome</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-Physical examination</measure>
      <time_frame>1 year</time_frame>
      <description>Number of subjects with clinically significant changes in Physical examination</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Immunogenicity Endpoint of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout</measure>
      <time_frame>1 year</time_frame>
      <description>Immunogenicity (anti-drug antibodies [ADA] and neutralizing antibodies [nAb] titers)</description>
    </secondary_outcome>
    <secondary_outcome>
      <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</measure>
      <time_frame>1 Year</time_frame>
      <description>Incidence of TEAEs and SAEs after switching of treatment from EU-Perjeta to PERT-IJS + trastuzumab versus those continuing on EU-Perjeta + trastuzumab</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Saftey 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</measure>
      <time_frame>1 year</time_frame>
      <description>Incidence of patients with a decline in left ventricular ejection fraction (LVEF) of ≥ 10% from baseline to &lt; 50%</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Immunogenicity End Point: after the single switch from EU-Perjeta to PERT-IJS+trastuzumab versus those continuing on EU-Perjeta+trastuzumab</measure>
      <time_frame>1 Year</time_frame>
      <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</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">382</enrollment>
    <condition>HR Negative HER2 Positive Early Breast Cancer or Locally Advanced Breast Cancer Patients</condition>
    <arm_group>
      <arm_group_label>Treatment Arm A: PERT-IJS plus trastuzumab, carboplatin and docetaxel</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Part 1 (Cycle 1 to 6):&#xD;
  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.&#xD;
  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: AUC 6 for Cycles 1 to 6 Docetaxel: 75 mg/m2 by IV infusion every 3 weeks for Cycles 1 to 6&#xD;
  Part 2 (Cycle 7 - till end of 1 year from Cycle 1 day 1):&#xD;
  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.&#xD;
  Trastuzumab: As mentioned in part 1</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Treatment Arm B: EU-Perjeta plus trastuzumab, carboplatin and docetaxel</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Part 1 (Cycle 1 to 6):&#xD;
  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.&#xD;
  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&#xD;
  Part 2 (Cycle 7 onwards till end of 01 year from Cycle 1 day 1):&#xD;
  The patients will be re-randomized (1:1) to receive EU- Perjeta + trastuzumab or PERT-IJS + trastuzumab.&#xD;
  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.&#xD;
  Trastuzumab: As mentioned in part 1</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>PERT-IJS plus trastuzumab, carboplatin and docetaxel</intervention_name>
      <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.</description>
      <arm_group_label>Treatment Arm A: PERT-IJS plus trastuzumab, carboplatin and docetaxel</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Perjeta plus trastuzumab, carboplatin and docetaxel</intervention_name>
      <description>EU Perjeta (Pertuzumab) , an antineoplastic agent, is a recombinant humanized monoclonal antibody that specifically targets sub-domain 2 of the extracellular domain of HER2, blocking heterodimerization of HER2 with other members of the receptor family, including epidermal growth factor, HER3 and HER4.</description>
      <arm_group_label>Treatment Arm B: EU-Perjeta plus trastuzumab, carboplatin and docetaxel</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Patient willing and able to sign informed consent and to follow the protocol&#xD;
               requirements&#xD;
  &#xD;
            2. Female patients aged ≥ 18 years at the time of Screening&#xD;
  &#xD;
            3. Patient with Eastern Cooperative Oncology Group (ECOG) Performance Status &lt; 2&#xD;
  &#xD;
            4. Patients with breast cancer that meets the following criteria:&#xD;
  &#xD;
                 1. A known case of histologically confirmed invasive breast carcinoma with a primary&#xD;
                    tumor size of &gt; 2 cm by standard local assessment technique&#xD;
  &#xD;
                 2. stage at presentation: early stage (T2-3, N0-1, M0) or locally advanced (T2-3, N2&#xD;
                    or N3, M0; T4a-c, any N, M0) or inflammatory (T4d, any N, M0)&#xD;
  &#xD;
            5. Patients with HER2 overexpression by IHC (defined as IHC3+, or IHC2+ with FISH&#xD;
               confirmation) as per the American Society of Clinical Oncology/College of American&#xD;
               Pathologist (ASCO-CAP) guidelines prior to Screening and confirmed centrally before&#xD;
               randomization&#xD;
  &#xD;
            6. Patients with known HR-ve status (ER-negative and PR-negative) as per local laboratory&#xD;
               prior to Screening and confirmed centrally before randomization&#xD;
  &#xD;
            7. Patient willing to undergo mastectomy or breast-conserving surgery after neoadjuvant&#xD;
               therapy&#xD;
  &#xD;
            8. Patient who completes all necessary baseline laboratory and radiologic investigations&#xD;
               prior to randomization as per SoA&#xD;
  &#xD;
            9. Patient with baseline left ventricular ejection fraction (LVEF) ≥ 55% measured by&#xD;
               echocardiography (ECHO; preferred) or multiple-gated acquisition (MUGA) scan&#xD;
  &#xD;
           10. Patient is eligible to participant if she is not pregnant, not breastfeeding, and at&#xD;
               least one of the following conditions applies:&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Patients with metastatic or recurrent bilateral breast cancer, or bilateral breast&#xD;
               cancer&#xD;
  &#xD;
            2. Patients with a history of concurrent or previously treated non-breast malignancies. A&#xD;
               patient with previous invasive non-breast cancer is eligible provided she has been&#xD;
               disease free for more than 5 years&#xD;
  &#xD;
            3. Patients who have received any previous systemic therapy (including chemotherapy,&#xD;
               immunotherapy, HER2-targeted agents, and antitumor vaccines) for treatment or&#xD;
               prevention of breast cancer, or radiation therapy for treatment of cancer&#xD;
  &#xD;
            4. Concurrent anti-cancer treatment in another investigational study, including hormone&#xD;
               therapy or immunotherapy&#xD;
  &#xD;
            5. Major surgical procedure that is unrelated to breast cancer within 4 weeks prior to&#xD;
               randomization or from which the patient has not fully recovered&#xD;
  &#xD;
            6. Serious cardiac illness or medical condition including but not limited to the&#xD;
               following as per Investigator's discretion:&#xD;
  &#xD;
                 1. Patients with ≥ Class II stage of heart failure as per New York Heart Association&#xD;
                    Classification&#xD;
  &#xD;
                 2. High risk uncontrolled arrhythmia, such as atrial tachycardia with a heart rate &gt;&#xD;
                    100 bpm at rest, significant ventricular arrhythmia (e.g., ventricular&#xD;
                    tachycardiatachycardia) required treatment, or higher-grade atrioventricular (AV)&#xD;
                    block (i.e., Mobitz II second-degree AV block or third-degree AV block)&#xD;
  &#xD;
                 3. History of myocardial infarction or unstable angina pectoris within 1 year of&#xD;
                    randomization or angina pectoris requiring anti-anginal medication&#xD;
  &#xD;
                 4. Evidence of transmural infarction on ECG&#xD;
  &#xD;
                 5. Clinically significant valvular heart disease&#xD;
  &#xD;
                 6. Poorly controlled hypertension (systolic blood pressure &gt; 180 mmHg and/or&#xD;
                    diastolic blood pressure &gt; 100 mmHg) in patients on anti-hypertensive medications&#xD;
  &#xD;
            7. Other concurrent serious diseases that may interfere with study primary endpoint and&#xD;
               other study assessments, including, but not limited to, severe pulmonary&#xD;
               conditions/illness, active liver disease (for example, active viral hepatitis&#xD;
               infection [i.e., hepatitis B or hepatitis C]), autoimmune disorders, history of or&#xD;
               known patient of sclerosing cholangitis, or infection with Human immune deficiency&#xD;
               virus (HIV)&#xD;
  &#xD;
            8. Patients with a history of any contraindication to the study treatment regimens&#xD;
  &#xD;
            9. Any of the following abnormal laboratory test results prior to randomization:&#xD;
  &#xD;
                 1. Total bilirubin &gt; upper limit of normal (ULN) or, for cases of known Gilbert's&#xD;
                    syndrome, total bilirubin &gt; 2 × ULN&#xD;
  &#xD;
                 2. Aspartate aminotransferase and/or alanine aminotransferase &gt; 1.5 × ULN, if&#xD;
                    considered clinically significant by Investigator&#xD;
  &#xD;
                 3. Alkaline phosphatase &gt;2.5 × ULN, if considered clinically significant by&#xD;
                    Investigator&#xD;
  &#xD;
                 4. Serum creatinine &gt; 1.5 × ULN&#xD;
  &#xD;
                 5. Creatinine clearance &lt; 60 mL/min&#xD;
  &#xD;
                 6. Total white blood cells count &lt; 2500 cells/μL&#xD;
  &#xD;
                 7. Absolute neutrophil count &lt; 2000 cells/μL&#xD;
  &#xD;
                 8. Platelet count &lt; 100,000 cells/μL&#xD;
  &#xD;
           10. Participation in any clinical study with an investigational drug, biologic, or device&#xD;
               within 1 month prior or within five half-lives (of the drug/ biologic) prior to the&#xD;
               enrolment (whichever is longer)&#xD;
  &#xD;
           11. Have taken any live vaccines 30 days prior to the 1st dose of study treatment&#xD;
  &#xD;
           12. Any known hypersensitivity to any of the study medications, any of the ingredients or&#xD;
               excipients of these medications, or benzyl alcohol&#xD;
  &#xD;
           13. Patients unwilling to follow the study requirements.&#xD;
  &#xD;
           14. Presence of an uncontrolled, unstable, clinically significant medical condition that,&#xD;
               in the opinion of the Investigator, may interfere with the interpretation of efficacy&#xD;
               and safety parameters or has a medical condition for which the treatment should take&#xD;
               precedence over study participation or will interfere with study participation&#xD;
  &#xD;
               -&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <gender_based>Yes</gender_based>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>99 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Anoop Chullikana, MBBS, MD</last_name>
      <phone>91 80 2808</phone>
      <phone_ext>5306</phone_ext>
      <email>anoop.chullikana@biocon.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Jayanti Panda, MBA,PM</last_name>
      <phone>91 80 2808</phone>
      <phone_ext>5304</phone_ext>
      <email>jayanti.panda@biocon.com</email>
    </overall_contact_backup>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 23, 2023</study_first_submitted>
    <study_first_submitted_qc>September 12, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 15, 2023</study_first_posted>
    <last_update_submitted>September 12, 2023</last_update_submitted>
    <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Locally advanced breast cancer patient</keyword>
    <keyword>HR negative HER2-positive Early breast cancer</keyword>
    <keyword>PERT-IJS</keyword>
    <keyword>Pertuzumab</keyword>
    <keyword>Trastuzumab</keyword>
    <keyword>Neoadjuvant treatment</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Breast Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carboplatin</mesh_term>
      <mesh_term>Docetaxel</mesh_term>
      <mesh_term>Trastuzumab</mesh_term>
      <mesh_term>Pertuzumab</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06038539
  org study id: BIO-PERTUZ-301
  nct id: NCT06038539
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  To compare the efficacy and safety of PERT-IJS 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.
  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 EBC (invasive breast cancer
        without distant metastasis) or locally advanced breast cancer patients.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Parallel Assignment
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  measure: Efficacy endpoint - Total pathologic complete response between Treatment arm A and Treatment Arm B
  time frame: Week 18
  description: Total pathologic complete responsea (tpCR; ypT0/Tis,ypN0) in breast and axillary nodes after neoadjuvant treatmentb by Independent Review Committee (IRC)
  measure: Efficacy endpoint-Total pathologic complete response between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
  time frame: Week 18
  description: Total pathologic complete response (tpCR; ypT0/Tis, ypN0) in breast and axillary nodes after neoadjuvant treatment by local histopathologist
  measure: Efficacy endpoint: Pathologic complete response between Treatment Arm A and Treatment Arm B
  time frame: Week 18
  description: Pathologic complete response (pCR; ypT0/ypN0) after neoadjuvant treatment by IRC and local histopathologist
  measure: Efficacy endpoint- Breast pathologic complete response between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
  time frame: Week 18
  description: Breast pathologic complete responsed (bpCR; ypT0/Tis) after neoadjuvant treatment by IRC and local histopathologist
  measure: Efficacy endpoint-Objective response rate between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
  time frame: Week 18
  description: Objective response rate (ORR) after neoadjuvant treatment in accordance with Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
  measure: Efficacy endpoint-Event free survival rate between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
  time frame: Week 18
  description: Event free survival (EFS) rate
  measure: Efficacy endpoint- Overall survival rate between Treatment Arm A and Treatment Arm B as neoadjuvant treatment regimen
  time frame: Week 18
  description: Overall survival (OS) rate
  measure: Efficacy endpoint-EFS rate of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
  time frame: 1 Year
  description: EFS rate
  measure: Efficacy endpoint - Overall Survival rate of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
  time frame: 1 Year
  description: Overall survival rate
  measure: Efficacy endpoint - Overall Response Rate of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
  time frame: 1 Year
  description: Overall Response Rate
  measure: Efficacy Endpoint: EFS rate after the single switch from EU-Perjeta to PERT-IJS+trastuzumab compared with those continuing on Treatment B
  time frame: 1 year
  description: EFS rate after switching of treatment from EU-Perjeta to PERT-IJS + trastuzumab
  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
  time frame: 1 year
  description: Disease free survival (DFS) rate after switching of treatment from EU-Perjeta to PERT-IJS + trastuzumab versus those continuing on EU-Perjeta + trastuzumab
  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
  time frame: 1 year
  description: OS rate after switching of treatment from EU-Perjeta to PERT-IJS + trastuzumab versus those continuing on EU-Perjeta + trastuzumab
  measure: PK endpoint-The trough serum concentration
  time frame: 1 Year
  description: The trough serum concentration (Ctrough)
  measure: Safety Endpoint: treatment-emergent adverse events and serious adverse events
  time frame: week 18
  description: Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
  measure: Safety Endpoint: left ventricular ejection fraction
  time frame: week 18
  description: Incidence of patients with a decline in left ventricular ejection fraction (LVEF) of ≥ 10% from baseline to < 50%
  measure: Safety Endpoint: Vital signs
  time frame: week 18
  description: Number of subjects with clinically significant changes in Vital signs
  measure: Safety Endpoint-ECG PR Interval
  time frame: week 18
  description: Number of subjects with clinically significant changes in ECG PR Interval
  measure: Safety Endpoint-ECG QRS Interval
  time frame: week 18
  description: Number of subjects with clinically significant changes in ECG QRS Interval
  measure: Safety Endpoint-ECG QT Interval
  time frame: week 18
  description: Number of subjects with clinically significant changes in ECG QT Interval
  measure: Safety Endpoint- ECG QTc Interval
  time frame: week 18
  description: Number of subjects with clinically significant changes in ECG QTc Interval
  measure: Safety Endpoint-clinical laboratory assessments
  time frame: week 18
  description: Number of subjects with clinically significant changes in Clinical laboratory assessments
  measure: Safety Endpoint-pregnancy test
  time frame: week 18
  description: Number of subjects with Pregnancy outcome
  measure: Safety Endpoint-physical examination
  time frame: week 18
  description: Number of subjects with clinically significant changes in Physical examination
  measure: Immunogenicity Endpoint
  time frame: week 18
  description: Immunogenicity (anti-drug antibodies [ADA] and neutralizing antibodies [nAb] titers)
  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
  time frame: 1 year
  description: Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
  measure: Safety Endpoint: left ventricular ejection fraction of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
  time frame: 1 year
  description: Incidence of patients with a decline in left ventricular ejection fraction (LVEF) of ≥ 10% from baseline to < 50%
  measure: Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS -throughout compared to patients randomized to EU-Perjeta throughout- Vital signs
  time frame: 1 year
  description: Number of subjects with clinically significant changes in Vital signs
  measure: Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout- ECG PR Interval
  time frame: 1 year
  description: Number of subjects with clinically significant changes in ECG PR Interval
  measure: Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-ECG QRS Interval
  time frame: 1 year
  description: Number of subjects with clinically significant changes in ECG QRS Interval
  measure: Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-ECG QT Interval
  time frame: 1 year
  description: Number of subjects with clinically significant changes in ECG QT Interval
  measure: Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout- ECG QTc Interval
  time frame: 1 year
  description: Number of subjects with clinically significant changes in ECG QTc Interval
  measure: Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-Clinical laboratory assessments
  time frame: 1 year
  description: Number of subjects with clinically significant changes in Clinical laboratory assessments
  measure: Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout- Pregnancy test
  time frame: 1 year
  description: Number of subjects with Pregnancy outcome
  measure: Safety Endpoint: Routine safety parameters of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout-Physical examination
  time frame: 1 year
  description: Number of subjects with clinically significant changes in Physical examination
  measure: Immunogenicity Endpoint of patients randomized to PERT-IJS throughout compared to patients randomized to EU-Perjeta throughout
  time frame: 1 year
  description: Immunogenicity (anti-drug antibodies [ADA] and neutralizing antibodies [nAb] titers)
  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
  time frame: 1 Year
  description: Incidence of TEAEs and SAEs after switching of treatment from EU-Perjeta to PERT-IJS + trastuzumab versus those continuing on EU-Perjeta + trastuzumab
  measure: Saftey 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
  time frame: 1 year
  description: Incidence of patients with a decline in left ventricular ejection fraction (LVEF) of ≥ 10% from baseline to < 50%
  measure: Immunogenicity End Point: after the single switch from EU-Perjeta to PERT-IJS+trastuzumab versus those continuing on EU-Perjeta+trastuzumab
  time frame: 1 Year
  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
  arm group label: Treatment Arm A: PERT-IJS plus trastuzumab, carboplatin and docetaxel
  arm group type: Experimental
  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: 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 group label: Treatment Arm B: EU-Perjeta plus trastuzumab, carboplatin and docetaxel
  arm group type: Active Comparator
  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: PERT-IJS plus trastuzumab, carboplatin and docetaxel
  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.
  arm group label: Treatment Arm A: PERT-IJS plus trastuzumab, carboplatin and docetaxel
  intervention type: Biological
  intervention name: Perjeta plus trastuzumab, carboplatin and docetaxel
  description: EU Perjeta (Pertuzumab) , an antineoplastic agent, is a recombinant humanized monoclonal antibody that specifically targets sub-domain 2 of the extracellular domain of HER2, blocking heterodimerization of HER2 with other members of the receptor family, including epidermal growth factor, HER3 and HER4.
  arm group label: Treatment Arm B: EU-Perjeta plus trastuzumab, carboplatin and docetaxel
  criteria: 
  gender: Female
  gender based: Yes
  minimum age: 18 Years
  maximum age: 99 Years
  healthy volunteers: No
  last name: Anoop Chullikana, MBBS, MD
  phone: 91 80 2808
  phone ext: 5306
  email: anoop.chullikana@biocon.com
  last name: Jayanti Panda, MBA,PM
  phone: 91 80 2808
  phone ext: 5304
  email: jayanti.panda@biocon.com
  responsible party type: Sponsor
  mesh term: Breast Neoplasms
  mesh term: Carboplatin
  mesh term: Docetaxel
  mesh term: Trastuzumab
  mesh term: Pertuzumab
  sharing ipd: No