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/NCT06018337</url>
    </required_header>
    <id_info>
      <org_study_id>DB-1303-O-3002</org_study_id>
      <nct_id>NCT06018337</nct_id>
    </id_info>
    <brief_title>A Study of DB-1303 vs Investigator's Choice Chemotherapy in Metastatic Breast Cancer</brief_title>
    <official_title>A Phase 3, Randomized, Multi-center, Open-Label Study of DB-1303 Versus Investigator's Choice Chemotherapy in Human Epidermal Growth Factor Receptor 2 (HER2)-Low, Hormone Receptor Positive (HR+) Metastatic Breast Cancer Patients Whose Disease Has Progressed on Endocrine Therapy (ET) (DYNASTY-Breast02)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>DualityBio Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>DualityBio Inc.</source>
    <oversight_info>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this clinical trial is to assess the efficacy of DB-1303 compared with&#xD;
        investigator's choice chemotherapy in terms of progression-free survival (PFS) by blinded&#xD;
        independent central review (BICR) in the HR+, HER2-low (IHC 2+/ISH- and IHC 1+）population.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The study is an open-label, multi-center, randomized study in HR+, HER2-low breast cancer&#xD;
        subjects whose disease has progressed on at least 2 lines of prior ET or within 6 months of&#xD;
        first line ET + CDK4/6 inhibitor in the metastatic setting. The primary purpose of the study&#xD;
        is to determine the efficacy and safety of DB-1303 compared with investigator's choice single&#xD;
        agent chemotherapy in the target population. Approximately 466 subjects with HER2 IHC 2+/ISH-&#xD;
        and IHC 1+ (HER2-low] expression will be randomized 1:1 across approximately 180 centers&#xD;
        globally to receive either DB-1303 or investigator's choice single agent chemotherapy&#xD;
        (capecitabine, paclitaxel or nab-paclitaxel) until RECIST 1.1 defined disease progression&#xD;
        (PD), unless there is unacceptable toxicity, withdrawal of consent, or another criterion for&#xD;
        discontinuation is met.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 2023</start_date>
    <completion_date type="Anticipated">June 2027</completion_date>
    <primary_completion_date type="Anticipated">August 2025</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>To assess the efficacy of DB-1303 compared with chemotherapy in terms of progression-free survival (PFS)</measure>
      <time_frame>From the date of randomization until objective (RECIST 1.1 defined) disease progression</time_frame>
      <description>Tumor evaluation scans will be performed at screening (as baseline) with follow ups every 6 weeks (Q6W ± 1 week)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>To assess the efficacy of DB-1303 compared with chemotherapy in terms of overall survival (OS) in the HR+, HER2-low populationchemotherapy in terms of overall survival (OS)</measure>
      <time_frame>From the date of randomization until objective (RECIST 1.1 defined) disease progression</time_frame>
      <description>Tumor evaluation scans will be performed at screening (as baseline) with follow ups every 6 weeks (Q6W ± 1 week)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To further assess the efficacy of DB-1303 in terms of PFS by Investigator assessment, objective response rate (ORR), duration of response (DoR), disease control rate (DCR), and time to response (TTR) by BICR and Investigator assessment</measure>
      <time_frame>From the date of randomization until objective (RECIST 1.1 defined) disease progression</time_frame>
      <description>Tumor evaluation scans will be performed at screening (as baseline) with follow ups every 6 weeks (Q6W ± 1 week)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the safety and tolerability profile of DB-1303 compared with investigator's choice chemotherapy.</measure>
      <time_frame>From the date of randomization until objective (RECIST 1.1 defined) disease progression</time_frame>
      <description>Tumor evaluation scans will be performed at screening (as baseline) with follow ups every 6 weeks (Q6W ± 1 week)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the pharmacokinetics (PK) of DB-1303 (DB-1303 antibody-drug conjugate [ADC] and free payload P1003).</measure>
      <time_frame>From the date of randomization until objective (RECIST 1.1 defined) disease progression</time_frame>
      <description>Tumor evaluation scans will be performed at screening (as baseline) with follow ups every 6 weeks (Q6W ± 1 week)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess symptoms, functioning and health-related quality of life (HRQoL) in subjects treated with DB-1303 compared with investigator's choice single agent chemotherapy</measure>
      <time_frame>From the date of randomization until objective (RECIST 1.1 defined) disease progression</time_frame>
      <description>Tumor evaluation scans will be performed at screening (as baseline) with follow ups every 6 weeks (Q6W ± 1 week)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To assess the impact of treatment and disease state on health utility using the EQ-5D-5L</measure>
      <time_frame>From the date of randomization until objective (RECIST 1.1 defined) disease progression</time_frame>
      <description>Tumor evaluation scans will be performed at screening (as baseline) with follow ups every 6 weeks (Q6W ± 1 week)</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">466</enrollment>
    <condition>Metastatic Breast Cancer</condition>
    <arm_group>
      <arm_group_label>DB-1303</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Enrolled Subjects will be randomized to receive a 8 mg/kg IV dose of DB-1303 on Day 1 of each cycle Q3W</description>
    </arm_group>
    <arm_group>
      <arm_group_label>investigator's choice single agent chemotherapy</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Enrolled Subjects will be randomized to receive investigator's choice single agent chemotherapy (capecitabine:1000 or 1250 mg/m2, Oral, Twice daily orally for 2 weeks followed by a 1-week rest period in 3-week cycles; paclitaxel：80 mg/m2， IV, Every week (QW) in 3-week cycles; or nab-paclitaxel: 100 mg/m2, IV, Every week (QW) for 3 weeks followed by a one-week rest period in 4-week cycles) until RECIST 1.1 defined disease progression (PD), unless there is unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation is met.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>DB-1303</intervention_name>
      <description>IV</description>
      <arm_group_label>DB-1303</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Capecitabine</intervention_name>
      <description>Oral</description>
      <arm_group_label>investigator's choice single agent chemotherapy</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Paclitaxel</intervention_name>
      <description>IV</description>
      <arm_group_label>investigator's choice single agent chemotherapy</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Nab-paclitaxel</intervention_name>
      <description>IV</description>
      <arm_group_label>investigator's choice single agent chemotherapy</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Male or female adults (defined as ≥ 18 years of age or acceptable age according to&#xD;
               local regulations at the time of voluntarily signing of informed consent).&#xD;
  &#xD;
            2. Pathologically documented breast cancer that:&#xD;
  &#xD;
          1) Is advanced or metastatic 2) Has HER2-low expression (IHC 1+ or IHC 2+/ISH-) as&#xD;
          determined by the central laboratory result.&#xD;
  &#xD;
          3) Was never previously reported as HER2-positive (IHC 3+ or ISH+) as per ASCO/CAP&#xD;
          guidelines.&#xD;
  &#xD;
          4) Is documented as HR+ (either ER and/or PgR positive [ER or PgR ≥1%]) per ASCO/CAP&#xD;
          guidelines (Allison et al 2020).&#xD;
  &#xD;
          3. Must have an adequate tumor tissue sample available for assessment of HER2 by central&#xD;
          laboratory, preferably in formalin fixation and paraffin embedding (FFPE) blocks based on a&#xD;
          mandatory FFPE tumor sample obtained at the time of metastatic disease or later;&#xD;
  &#xD;
          4. ECOG performance status of 0 or 1.&#xD;
  &#xD;
          5. Must have had either:&#xD;
  &#xD;
            1. Disease progression on endocrine therapy + CDK4/6 inhibitor within 6 months of&#xD;
               starting first line treatment for metastatic disease and considered appropriate for&#xD;
               chemotherapy as the next treatment by the investigator, OR&#xD;
  &#xD;
            2. Disease progression on at least 2 previous lines of ET with or without a targeted&#xD;
               therapy (such as CDK4/6, mTOR or PI3-K inhibitors) administered for the treatment of&#xD;
               metastatic disease.&#xD;
  &#xD;
          6. No prior chemotherapy for advanced or metastatic breast cancer. Subjects who have&#xD;
          received chemotherapy in the neo-adjuvant or adjuvant setting are eligible, as long as they&#xD;
          have had a disease-free interval (defined as completion of systemic chemotherapy to&#xD;
          diagnosis of advanced or metastatic disease) of &gt;12 months.&#xD;
  &#xD;
          7. Life expectancy ≥12 weeks at screening.&#xD;
  &#xD;
          8. Subjects must have at least one measurable lesion as defined per RECIST v1.1 or have&#xD;
          non-measurable, bone-only disease that can be assessed by CT or MRI or X-Ray. Lytic or&#xD;
          mixed lytic bone lesions that can be assessed by CT or MRI or X-Ray in the absence of&#xD;
          measurable disease as defined above is acceptable; subjects with sclerotic/osteoblastic&#xD;
          bone lesions only in the absence of measurable disease are not eligible.&#xD;
  &#xD;
          9. Female subjects of childbearing potential who are sexually active with a non-sterilized&#xD;
          male partner must use at least one highly effective method of contraception from the time&#xD;
          of screening and must agree to continue using such precautions for 7 months after the last&#xD;
          dose of study treatment.&#xD;
  &#xD;
          10. Non-sterilized male subjects who are sexually active with a female partner of&#xD;
          childbearing potential must use a condom with spermicide from screening and throughout the&#xD;
          duration of the study treatment and the washout period&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Ineligible for all options in the investigator's choice chemotherapy arm.&#xD;
  &#xD;
            2. Uncontrolled intercurrent illness, including but not limited to, ongoing or active&#xD;
               infection, uncontrolled or significant cardiovascular disease, serious chronic&#xD;
               gastrointestinal conditions associated with diarrhea, or psychiatric illness/social&#xD;
               situations that would limit compliance with study requirement, substantially increase&#xD;
               risk of incurring AEs or compromise the ability of the subject to give written&#xD;
               informed consent.&#xD;
  &#xD;
            3. Clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring&#xD;
               drainage, peritoneal shunt or cell-free concentrated ascites reinfusion therapy within&#xD;
               2 weeks prior to the randomization.&#xD;
  &#xD;
            4. Uncontrolled or significant cardiovascular disease&#xD;
  &#xD;
            5. Has as a history of (non-infectious) ILD/pneumonitis that required steroids, has&#xD;
               current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by&#xD;
               imaging at screening.&#xD;
  &#xD;
            6. Subjects with prior use of immunosuppressive medication within 14 days prior to first&#xD;
               study dose, except for intranasal and inhaled corticosteroids or systemic&#xD;
               corticosteroids at doses less than 10 mg/day of prednisone or equivalent.&#xD;
  &#xD;
            7. Has unresolved toxicities from previous anticancer therapy, defined as toxicities&#xD;
               (other than alopecia) not yet resolved to Grade ≤ 1 or baseline.&#xD;
  &#xD;
            8. Previous treatment with anti-HER2 therapy.&#xD;
  &#xD;
            9. Prior treatment with antibody-drug conjugate that comprised an exatecan derivative&#xD;
               that is a topoisomerase I inhibitor.&#xD;
  &#xD;
           10. Prior randomization or treatment in a previous DB-1303 study regardless of treatment&#xD;
               assignment.20. Has substance abuse or any other medical conditions such as&#xD;
               psychological conditions, that may, in the opinion of the Investigator, interfere with&#xD;
               the subject's participation in the clinical study or evaluation of the clinical study&#xD;
               results.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Raymond Zhao</last_name>
      <role>Study Director</role>
      <affiliation>DualityBio Inc.</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Helen Liu</last_name>
      <phone>86-21-26018730</phone>
      <email>helen.liu@dualitybiologics.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Michael Sun</last_name>
      <email>michael.sun@dualitybiologics.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Texas Oncology - Baylor Charles A. Sammons Cancer Center</name>
        <address>
          <city>Dallas</city>
          <state>Texas</state>
          <zip>75246</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Joyce O Shaughnessy</last_name>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 25, 2023</study_first_submitted>
    <study_first_submitted_qc>August 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 30, 2023</study_first_posted>
    <last_update_submitted>August 25, 2023</last_update_submitted>
    <last_update_submitted_qc>August 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 30, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>HER2-low</keyword>
    <keyword>IHC 2+</keyword>
    <keyword>BC</keyword>
    <keyword>Breast Cancer</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>
    </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/NCT06018337
  org study id: DB-1303-O-3002
  nct id: NCT06018337
  lead sponsor: 
  is fda regulated drug: Yes
  is fda regulated device: No
  The goal of this clinical trial is to assess the efficacy of DB-1303 compared with
        investigator's choice chemotherapy in terms of progression-free survival (PFS) by blinded
        independent central review (BICR) in the HR+, HER2-low (IHC 2+/ISH- and IHC 1+）population.
  The study is an open-label, multi-center, randomized study in HR+, HER2-low breast cancer
        subjects whose disease has progressed on at least 2 lines of prior ET or within 6 months of
        first line ET + CDK4/6 inhibitor in the metastatic setting. The primary purpose of the study
        is to determine the efficacy and safety of DB-1303 compared with investigator's choice single
        agent chemotherapy in the target population. Approximately 466 subjects with HER2 IHC 2+/ISH-
        and IHC 1+ (HER2-low] expression will be randomized 1:1 across approximately 180 centers
        globally to receive either DB-1303 or investigator's choice single agent chemotherapy
        (capecitabine, paclitaxel or nab-paclitaxel) until RECIST 1.1 defined disease progression
        (PD), unless there is unacceptable toxicity, withdrawal of consent, or another criterion for
        discontinuation is met.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: To assess the efficacy of DB-1303 compared with chemotherapy in terms of progression-free survival (PFS)
  time frame: From the date of randomization until objective (RECIST 1.1 defined) disease progression
  description: Tumor evaluation scans will be performed at screening (as baseline) with follow ups every 6 weeks (Q6W ± 1 week)
  measure: To assess the efficacy of DB-1303 compared with chemotherapy in terms of overall survival (OS) in the HR+, HER2-low populationchemotherapy in terms of overall survival (OS)
  time frame: From the date of randomization until objective (RECIST 1.1 defined) disease progression
  description: Tumor evaluation scans will be performed at screening (as baseline) with follow ups every 6 weeks (Q6W ± 1 week)
  measure: To further assess the efficacy of DB-1303 in terms of PFS by Investigator assessment, objective response rate (ORR), duration of response (DoR), disease control rate (DCR), and time to response (TTR) by BICR and Investigator assessment
  time frame: From the date of randomization until objective (RECIST 1.1 defined) disease progression
  description: Tumor evaluation scans will be performed at screening (as baseline) with follow ups every 6 weeks (Q6W ± 1 week)
  measure: To assess the safety and tolerability profile of DB-1303 compared with investigator's choice chemotherapy.
  time frame: From the date of randomization until objective (RECIST 1.1 defined) disease progression
  description: Tumor evaluation scans will be performed at screening (as baseline) with follow ups every 6 weeks (Q6W ± 1 week)
  measure: To assess the pharmacokinetics (PK) of DB-1303 (DB-1303 antibody-drug conjugate [ADC] and free payload P1003).
  time frame: From the date of randomization until objective (RECIST 1.1 defined) disease progression
  description: Tumor evaluation scans will be performed at screening (as baseline) with follow ups every 6 weeks (Q6W ± 1 week)
  measure: To assess symptoms, functioning and health-related quality of life (HRQoL) in subjects treated with DB-1303 compared with investigator's choice single agent chemotherapy
  time frame: From the date of randomization until objective (RECIST 1.1 defined) disease progression
  description: Tumor evaluation scans will be performed at screening (as baseline) with follow ups every 6 weeks (Q6W ± 1 week)
  measure: To assess the impact of treatment and disease state on health utility using the EQ-5D-5L
  time frame: From the date of randomization until objective (RECIST 1.1 defined) disease progression
  description: Tumor evaluation scans will be performed at screening (as baseline) with follow ups every 6 weeks (Q6W ± 1 week)
  arm group label: DB-1303
  arm group type: Experimental
  description: Enrolled Subjects will be randomized to receive a 8 mg/kg IV dose of DB-1303 on Day 1 of each cycle Q3W
  arm group label: investigator's choice single agent chemotherapy
  arm group type: Active Comparator
  description: Enrolled Subjects will be randomized to receive investigator's choice single agent chemotherapy (capecitabine:1000 or 1250 mg/m2, Oral, Twice daily orally for 2 weeks followed by a 1-week rest period in 3-week cycles; paclitaxel：80 mg/m2， IV, Every week (QW) in 3-week cycles; or nab-paclitaxel: 100 mg/m2, IV, Every week (QW) for 3 weeks followed by a one-week rest period in 4-week cycles) until RECIST 1.1 defined disease progression (PD), unless there is unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation is met.
  intervention type: Drug
  intervention name: DB-1303
  description: IV
  arm group label: DB-1303
  intervention type: Drug
  intervention name: Capecitabine
  description: Oral
  arm group label: investigator's choice single agent chemotherapy
  intervention type: Drug
  intervention name: Paclitaxel
  description: IV
  arm group label: investigator's choice single agent chemotherapy
  intervention type: Drug
  intervention name: Nab-paclitaxel
  description: IV
  arm group label: investigator's choice single agent chemotherapy
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Raymond Zhao
  role: Study Director
  affiliation: DualityBio Inc.
  last name: Helen Liu
  phone: 86-21-26018730
  email: helen.liu@dualitybiologics.com
  last name: Michael Sun
  email: michael.sun@dualitybiologics.com
  facility: 
  contact: 
  country: United States
  responsible party type: Sponsor
  mesh term: Breast Neoplasms
  mesh term: Paclitaxel
  mesh term: Albumin-Bound Paclitaxel
  mesh term: Capecitabine
  sharing ipd: No