<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/NCT04494425</url>
  </required_header>
  <id_info>
    <org_study_id>D9670C00001</org_study_id>
    <secondary_id>2019-004493-26</secondary_id>
    <nct_id>NCT04494425</nct_id>
  </id_info>
  <brief_title>Study of Trastuzumab Deruxtecan (T-DXd) vs Investigator's Choice Chemotherapy in HER2-low, Hormone Receptor Positive, Metastatic Breast Cancer</brief_title>
  <acronym>DB-06</acronym>
  <official_title>A Phase 3, Randomized, Multi-center, Open-label Study of Trastuzumab Deruxtecan (T-DXd) Versus Investigator's Choice Chemotherapy in HER2-Low, Hormone Receptor Positive Breast Cancer Patients Whose Disease Has Progressed on Endocrine Therapy in the Metastatic Setting (DESTINY-Breast06)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Daiichi Sankyo Company, Limited 3-5-1 Nihonbashihoncho, Chuo-ku, Tokyo</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>AstraZeneca</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>
      This study will evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan&#xD;
      compared with investigator's choice chemotherapy in human epidermal growth factor receptor&#xD;
      (HER)2-low, hormone receptor (HR) positive breast cancer patients whose disease has&#xD;
      progressed on endocrine therapy in the metastatic setting.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Eligible patients will be those patients who have had disease progression on at least 2&#xD;
      previous lines of endocrine therapies given for the treatment of metastatic disease or&#xD;
      disease progression within 6 months of starting first line treatment for metastatic disease&#xD;
      with an endocrine therapy combined with a CDK4/6 inhibitor. All patients must have&#xD;
      historically confirmed HR positive (either estrogen receptor and/or progesterone receptor&#xD;
      positive), HER2-low (defined as IHC2+/ISH- and IHC 1+) or HER2 IHC &gt;0 &lt;1+ expression, as&#xD;
      determined by central laboratory testing results, advanced or metastatic breast cancer.&#xD;
&#xD;
      The study aims to evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan&#xD;
      compared with investigator's choice chemotherapy. This study aims to see if trastuzumab&#xD;
      deruxtecan allows patients to live longer without the cancer getting worse, or simply to live&#xD;
      longer, compared to patients receiving standard of care chemotherapy. This study is also&#xD;
      looking to see how the treatment and the cancer affects patients' quality of life.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 24, 2020</start_date>
  <completion_date type="Anticipated">July 20, 2026</completion_date>
  <primary_completion_date type="Anticipated">December 29, 2023</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>The study consists of 2 independent open label treatment arms: trastuzumab deruxtecan and Investigator's choice chemotherapy (paclitaxel, nab-paclitaxel or capecitabine).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>This study is an open-label study that will be conducted &quot;Sponsor-blind&quot;. To maintain the integrity of the study, Sponsor personnel directly involved in study conduct will not undertake or have access to efficacy data aggregated by treatment group prior to final data readout for the primary endpoint.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Progression Free Survival (PFS) - in HR+, HER2-low populaton</measure>
    <time_frame>Until progression or death, assessed up to approximately 60 months</time_frame>
    <description>Defined as time from date of randomization until the date of objective radiological disease progression by blinded independent central review (BICR) assessment according to RECIST 1.1 or death.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) - in HR+, HER2-low population</measure>
    <time_frame>Until death, assessed up to approximately 60 months</time_frame>
    <description>Defined as the time from randomization to death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS) - in intent to treat (ITT) population (HER2-Low and HER2 IHC &gt;0&lt;1+)</measure>
    <time_frame>Until progression or death, assessed up to approximately 60 months</time_frame>
    <description>PFS by BICR according to RECIST 1.1 in ITT population</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival - in intent to treat (ITT) population (HER2-Low and HER2 IHC &gt;0&lt;1+)</measure>
    <time_frame>Until death, assessed up to approximately 60 months</time_frame>
    <description>OS in the ITT population</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) in HR+, HER-2 low populaton</measure>
    <time_frame>Until progression, assessed up to approximately 60 months</time_frame>
    <description>ORR defined as the percentage of patients with at least one visit response of complete or partial response (CR or PR) by BICR and Investigator assessment according to RECIST 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DoR) - in HR+, HER-2 low populaton</measure>
    <time_frame>Until progression, assessed up to approximately 60 months</time_frame>
    <description>DoR defined as the time from the date of first documented response (CR/PR) until the first progression or death in the absence of disease progression by BICR and Investigator assessment according to RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival by Investigator assessment - in the HR+, HER2-low population</measure>
    <time_frame>Until progression or death, assessed up to approximately 60 months</time_frame>
    <description>PFS using investigator assessments according to RECIST 1.1 in the HER2-low population</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) in the ITT population</measure>
    <time_frame>Until progression, assessed up to approximately 60 months</time_frame>
    <description>ORR by BICR and by Investigator assessment according to RECIST 1.1 in the ITT population</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DoR) - in the ITT population</measure>
    <time_frame>Until progression, assessed up to approximately 60 months</time_frame>
    <description>DoR by BICR and by Investigator assessment according to RECIST 1.1 in the ITT population</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS2 by Investigator assessment, time to first subsequent therapy (TFST) and time to second subsequent treatment or death (TSST) - in HR+, HER2-low and the ITT population</measure>
    <time_frame>Assessed up to approximately 60 months</time_frame>
    <description>PFS2 defined as time from randomisation to second progression or death. TFST defined as a time elapsed from randomization to first subsequent therapy or death. TSST defined as a time elapsed from randomization to second subsequent therapy or death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of drugs; number of adverse events (AEs)</measure>
    <time_frame>Up to follow-up period, approximately 60 months</time_frame>
    <description>Number of AEs according to NCI-CTCAE Version 5.0 per each treatment arm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentration of trastuzumab deruxtecan</measure>
    <time_frame>Up to Cycle 8, approximately Week 24; each cycle is 21 days</time_frame>
    <description>Determination of trastuzumab deruxtecan concentration in serum at different time points after trastuzumab deruxtecan administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity of trastuzumab deruxtecan</measure>
    <time_frame>Up to follow-up period, approximately 60 months</time_frame>
    <description>Percentage of patients who develop ADA for trastuzumab deruxtecan</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life - EORTC-QLQ-C30</measure>
    <time_frame>Assessed up to approximately 60 months</time_frame>
    <description>Change from baseline in the physical functioning subscale of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scores. Scale scores range from 0-100. For functioning and global health status/ QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to deterioration in EORTC-QLQ-C30 scores</measure>
    <time_frame>Assessed up to approximately 60 months</time_frame>
    <description>Time to deterioration from baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scores. Scale scores range from 0-100. For functioning and global health status/QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life - EORTC QLQ-BR45</measure>
    <time_frame>Assessed up to approximately 60 months</time_frame>
    <description>Change from baseline in the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC QLQ-BR45) score. Scale scores range from 0-100. For functioning and global health status/QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">866</enrollment>
  <condition>Advanced or Metastatic Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Trastuzumab deruxtecan</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Trastuzumab deruxtecan (T-DXd; DS-8201a) arm</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Investigator's choice standard of care chemotherapy (capecitabine, paclitaxel, nab-paclitaxel) arm</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trastuzumab deruxtecan</intervention_name>
    <description>Trastuzumab deruxtecan by intravenous infusion</description>
    <arm_group_label>Trastuzumab deruxtecan</arm_group_label>
    <other_name>DS-8201a; T-DXd</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>Investigator's choice standard of care single agent chemotherapy; capecitabine tablets will be given orally.</description>
    <arm_group_label>Standard of Care</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>Investigator's choice standard of care single agent chemotherapy; paclitaxel by intravenous infusion.</description>
    <arm_group_label>Standard of Care</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nab-Paclitaxel</intervention_name>
    <description>Investigator's choice standard of care single agent chemotherapy; nab-paclitaxel by intravenous infusion</description>
    <arm_group_label>Standard of Care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Patients must be ≥18 years of age&#xD;
&#xD;
          -  Pathologically documented breast cancer that:&#xD;
&#xD;
               1. is advanced or metastatic&#xD;
&#xD;
               2. has a history of HER2-low or negative expression by local test, defined as IHC&#xD;
                  2+/ISH- or IHC 1+ (ISH- or untested) or HER2 IHC 0 (ISH- or untested)&#xD;
&#xD;
               3. has HER2-low or HER2 IHC &gt;0 &lt;1+ expression as determined by the central&#xD;
                  laboratory result established on a tissue sample taken in the metastatic setting&#xD;
&#xD;
               4. was never previously HER2-positive&#xD;
&#xD;
               5. is documented HR+ disease in the metastatic setting.&#xD;
&#xD;
          -  No prior chemotherapy for advanced or metastatic breast cancer.&#xD;
&#xD;
          -  Has adequate tumor samples for assessment of HER2 status&#xD;
&#xD;
          -  Must have either:&#xD;
&#xD;
               1. disease progression within 6 months of starting first line metastatic treatment&#xD;
                  with an endocrine therapy combined with a CDK4/6 inhibitor or&#xD;
&#xD;
               2. disease progression on at least 2 previous lines of endocrine therapy with or&#xD;
                  without a targeted therapy in the metastatic setting. Of note with regards to the&#xD;
                  ≥2 lines of previous ET requirement: disease recurrence while on the first 24&#xD;
                  months of starting adjuvant ET, will be considered a line of therapy; these&#xD;
                  patients will only require 1 line of ET in the metastatic setting.&#xD;
&#xD;
          -  Has protocol-defined adequate organ and bone marrow function&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Ineligible for all options in the investigator's choice chemotherapy arm&#xD;
&#xD;
          -  Lung-specific intercurrent clinically significant illnesses&#xD;
&#xD;
          -  Uncontrolled or significant cardiovascular disease or infection&#xD;
&#xD;
          -  Prior documented interstitial lung disease (ILD)/ pneumonitis that required steroids,&#xD;
             current ILD/ pneumonitis, or suspected ILD/ pneumonitis that cannot be ruled out by&#xD;
             imaging at screening.&#xD;
&#xD;
          -  Patients with spinal cord compression or clinically active central nervous system&#xD;
             metastases&#xD;
&#xD;
          -  Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless&#xD;
             of treatment arm assignment&#xD;
&#xD;
          -  Concurrent enrolment in another clinical study, unless it is an observational&#xD;
             (non-interventional) clinical study during the follow up period of a prior&#xD;
             interventional study (prescreening for this study while a patient is on treatment in&#xD;
             another clinical study is acceptable)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>105 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85259</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Springdale</city>
        <state>Arkansas</state>
        <zip>72762</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lakewood</city>
        <state>Colorado</state>
        <zip>80228</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Summit</city>
        <state>New Jersey</state>
        <zip>07901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Westbury</city>
        <state>New York</state>
        <zip>11590</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78731</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77090</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792-5666</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Caba</city>
        <zip>1414</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Caba</city>
        <zip>C1012AAR</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Caba</city>
        <zip>C1019ABS</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ciudad Autonoma De Buenos Aire</city>
        <zip>C1125ABD</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ciudad de Buenos Aires</city>
        <zip>1280</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cordoba</city>
        <zip>5000</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>La Plata</city>
        <zip>1900</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Mar del Plata</city>
        <zip>7600</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Rosario</city>
        <zip>S2000DEJ</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Rosario</city>
        <zip>S2002KDS</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Adelaide</city>
        <zip>5000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Birtinya</city>
        <zip>4575</zip>
        <country>Australia</country>
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    <facility>
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      <address>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
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    <facility>
      <name>Research Site</name>
      <address>
        <city>Bukit Merah</city>
        <zip>169610</zip>
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    <facility>
      <name>Research Site</name>
      <address>
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        <zip>119074</zip>
        <country>Singapore</country>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Singapore</city>
        <zip>258499</zip>
        <country>Singapore</country>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Singapore</city>
        <zip>308433</zip>
        <country>Singapore</country>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Singapore</city>
        <zip>329563</zip>
        <country>Singapore</country>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08907</zip>
        <country>Spain</country>
      </address>
    </facility>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cordoba</city>
        <zip>14004</zip>
        <country>Spain</country>
      </address>
    </facility>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>El Palmar</city>
        <zip>30120</zip>
        <country>Spain</country>
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    <facility>
      <name>Research Site</name>
      <address>
        <city>La Coruña</city>
        <zip>15006</zip>
        <country>Spain</country>
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    </facility>
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      <name>Research Site</name>
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        <zip>28005</zip>
        <country>Spain</country>
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        <zip>46026</zip>
        <country>Spain</country>
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    </facility>
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  <location>
    <facility>
      <name>Research Site</name>
      <address>
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        <zip>413 45</zip>
        <country>Sweden</country>
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  <location>
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        <zip>118 83</zip>
        <country>Sweden</country>
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      <name>Research Site</name>
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        <zip>751 85</zip>
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      <name>Research Site</name>
      <address>
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  </location>
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    <facility>
      <name>Research Site</name>
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      <name>Research Site</name>
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    <facility>
      <name>Research Site</name>
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        <country>Taiwan</country>
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    <facility>
      <name>Research Site</name>
      <address>
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        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
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    <facility>
      <name>Research Site</name>
      <address>
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        <zip>CF14 2TL</zip>
        <country>United Kingdom</country>
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    <facility>
      <name>Research Site</name>
      <address>
        <city>Edinburgh</city>
        <zip>EH4 2XR</zip>
        <country>United Kingdom</country>
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    </facility>
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    <facility>
      <name>Research Site</name>
      <address>
        <city>Guildford</city>
        <country>United Kingdom</country>
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    </facility>
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    <facility>
      <name>Research Site</name>
      <address>
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        <zip>SE1 9RT</zip>
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    <facility>
      <name>Research Site</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Northwood</city>
        <zip>HA6 2RN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Australia</country>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Brazil</country>
    <country>Canada</country>
    <country>China</country>
    <country>Denmark</country>
    <country>France</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>India</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Mexico</country>
    <country>Netherlands</country>
    <country>Poland</country>
    <country>Portugal</country>
    <country>Russian Federation</country>
    <country>Saudi Arabia</country>
    <country>Singapore</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>Taiwan</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://BreastCancerStudyLocator.com</url>
    <description>AZ Breast Cancer Study Navigators</description>
  </link>
  <link>
    <url>http://CTRinfo@dsi.com</url>
    <description>Daiichi Sankyo Contact for Clinical Trial Information Phone: 908-992-6400</description>
  </link>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>July 20, 2020</study_first_submitted>
  <study_first_submitted_qc>July 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2020</study_first_posted>
  <last_update_submitted>August 1, 2023</last_update_submitted>
  <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 2, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Breast Cancer</keyword>
  <keyword>HR positive</keyword>
  <keyword>HER2-Low</keyword>
  <keyword>HER2-Negative</keyword>
  <keyword>Trastuzumab Deruxtecan (T-DXd; DS-8201a)</keyword>
  <keyword>Anti-HER2-Antibody Drug Conjugate (ADC)</keyword>
  <keyword>DESTINY-Breast06</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>Paclitaxel</mesh_term>
    <mesh_term>Albumin-Bound Paclitaxel</mesh_term>
    <mesh_term>Capecitabine</mesh_term>
    <mesh_term>Trastuzumab</mesh_term>
    <mesh_term>Trastuzumab deruxtecan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_time_frame>
    <ipd_access_criteria>When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_access_criteria>
    <ipd_url>https://astrazenecagroup-dt.pharmacm.com/DT/Home</ipd_url>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT04494425
org study id: D9670C00001
secondary id: 2019-004493-26
nct id: NCT04494425
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study will evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan
      compared with investigator's choice chemotherapy in human epidermal growth factor receptor
      (HER)2-low, hormone receptor (HR) positive breast cancer patients whose disease has
      progressed on endocrine therapy in the metastatic setting.
Eligible patients will be those patients who have had disease progression on at least 2
      previous lines of endocrine therapies given for the treatment of metastatic disease or
      disease progression within 6 months of starting first line treatment for metastatic disease
      with an endocrine therapy combined with a CDK4/6 inhibitor. All patients must have
      historically confirmed HR positive (either estrogen receptor and/or progesterone receptor
      positive), HER2-low (defined as IHC2+/ISH- and IHC 1+) or HER2 IHC >0 <1+ expression, as
      determined by central laboratory testing results, advanced or metastatic breast cancer.

      The study aims to evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan
      compared with investigator's choice chemotherapy. This study aims to see if trastuzumab
      deruxtecan allows patients to live longer without the cancer getting worse, or simply to live
      longer, compared to patients receiving standard of care chemotherapy. This study is also
      looking to see how the treatment and the cancer affects patients' quality of life.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The study consists of 2 independent open label treatment arms: trastuzumab deruxtecan and Investigator's choice chemotherapy (paclitaxel, nab-paclitaxel or capecitabine).
primary purpose: Treatment
masking: None (Open Label)
masking description: This study is an open-label study that will be conducted "Sponsor-blind". To maintain the integrity of the study, Sponsor personnel directly involved in study conduct will not undertake or have access to efficacy data aggregated by treatment group prior to final data readout for the primary endpoint.
measure: Progression Free Survival (PFS) - in HR+, HER2-low populaton
time frame: Until progression or death, assessed up to approximately 60 months
description: Defined as time from date of randomization until the date of objective radiological disease progression by blinded independent central review (BICR) assessment according to RECIST 1.1 or death.
measure: Overall Survival (OS) - in HR+, HER2-low population
time frame: Until death, assessed up to approximately 60 months
description: Defined as the time from randomization to death due to any cause
measure: Progression Free Survival (PFS) - in intent to treat (ITT) population (HER2-Low and HER2 IHC >0<1+)
time frame: Until progression or death, assessed up to approximately 60 months
description: PFS by BICR according to RECIST 1.1 in ITT population
measure: Overall Survival - in intent to treat (ITT) population (HER2-Low and HER2 IHC >0<1+)
time frame: Until death, assessed up to approximately 60 months
description: OS in the ITT population
measure: Objective Response Rate (ORR) in HR+, HER-2 low populaton
time frame: Until progression, assessed up to approximately 60 months
description: ORR defined as the percentage of patients with at least one visit response of complete or partial response (CR or PR) by BICR and Investigator assessment according to RECIST 1.1.
measure: Duration of response (DoR) - in HR+, HER-2 low populaton
time frame: Until progression, assessed up to approximately 60 months
description: DoR defined as the time from the date of first documented response (CR/PR) until the first progression or death in the absence of disease progression by BICR and Investigator assessment according to RECIST 1.1
measure: Progression Free Survival by Investigator assessment - in the HR+, HER2-low population
time frame: Until progression or death, assessed up to approximately 60 months
description: PFS using investigator assessments according to RECIST 1.1 in the HER2-low population
measure: Objective Response Rate (ORR) in the ITT population
time frame: Until progression, assessed up to approximately 60 months
description: ORR by BICR and by Investigator assessment according to RECIST 1.1 in the ITT population
measure: Duration of response (DoR) - in the ITT population
time frame: Until progression, assessed up to approximately 60 months
description: DoR by BICR and by Investigator assessment according to RECIST 1.1 in the ITT population
measure: PFS2 by Investigator assessment, time to first subsequent therapy (TFST) and time to second subsequent treatment or death (TSST) - in HR+, HER2-low and the ITT population
time frame: Assessed up to approximately 60 months
description: PFS2 defined as time from randomisation to second progression or death. TFST defined as a time elapsed from randomization to first subsequent therapy or death. TSST defined as a time elapsed from randomization to second subsequent therapy or death.
measure: Safety and tolerability of drugs; number of adverse events (AEs)
time frame: Up to follow-up period, approximately 60 months
description: Number of AEs according to NCI-CTCAE Version 5.0 per each treatment arm
measure: Serum concentration of trastuzumab deruxtecan
time frame: Up to Cycle 8, approximately Week 24; each cycle is 21 days
description: Determination of trastuzumab deruxtecan concentration in serum at different time points after trastuzumab deruxtecan administration
measure: Immunogenicity of trastuzumab deruxtecan
time frame: Up to follow-up period, approximately 60 months
description: Percentage of patients who develop ADA for trastuzumab deruxtecan
measure: Health-related quality of life - EORTC-QLQ-C30
time frame: Assessed up to approximately 60 months
description: Change from baseline in the physical functioning subscale of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scores. Scale scores range from 0-100. For functioning and global health status/ QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.
measure: Time to deterioration in EORTC-QLQ-C30 scores
time frame: Assessed up to approximately 60 months
description: Time to deterioration from baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scores. Scale scores range from 0-100. For functioning and global health status/QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.
measure: Health-related quality of life - EORTC QLQ-BR45
time frame: Assessed up to approximately 60 months
description: Change from baseline in the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC QLQ-BR45) score. Scale scores range from 0-100. For functioning and global health status/QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.
arm group label: Trastuzumab deruxtecan
arm group type: Experimental
description: Trastuzumab deruxtecan (T-DXd; DS-8201a) arm
arm group label: Standard of Care
arm group type: Active Comparator
description: Investigator's choice standard of care chemotherapy (capecitabine, paclitaxel, nab-paclitaxel) arm
intervention type: Drug
intervention name: Trastuzumab deruxtecan
description: Trastuzumab deruxtecan by intravenous infusion
arm group label: Trastuzumab deruxtecan
other name: DS-8201a; T-DXd
intervention type: Drug
intervention name: Capecitabine
description: Investigator's choice standard of care single agent chemotherapy; capecitabine tablets will be given orally.
arm group label: Standard of Care
intervention type: Drug
intervention name: Paclitaxel
description: Investigator's choice standard of care single agent chemotherapy; paclitaxel by intravenous infusion.
arm group label: Standard of Care
intervention type: Drug
intervention name: Nab-Paclitaxel
description: Investigator's choice standard of care single agent chemotherapy; nab-paclitaxel by intravenous infusion
arm group label: Standard of Care
criteria: 
gender: All
minimum age: 18 Years
maximum age: 105 Years
healthy volunteers: No
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country: Argentina
country: Australia
country: Austria
country: Belgium
country: Brazil
country: Canada
country: China
country: Denmark
country: France
country: Germany
country: Hungary
country: India
country: Israel
country: Italy
country: Japan
country: Korea, Republic of
country: Mexico
country: Netherlands
country: Poland
country: Portugal
country: Russian Federation
country: Saudi Arabia
country: Singapore
country: Spain
country: Sweden
country: Taiwan
country: United Kingdom
country: United States
url: http://BreastCancerStudyLocator.com
description: AZ Breast Cancer Study Navigators
url: http://CTRinfo@dsi.com
description: Daiichi Sankyo Contact for Clinical Trial Information Phone: 908-992-6400
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Paclitaxel
mesh term: Albumin-Bound Paclitaxel
mesh term: Capecitabine
mesh term: Trastuzumab
mesh term: Trastuzumab deruxtecan
sharing ipd: Yes
ipd description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd access criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd url: https://astrazenecagroup-dt.pharmacm.com/DT/Home