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Study of Trastuzumab Deruxtecan (T-DXd) vs Investigator's Choice Chemotherapy in HER2-low, Hormone Receptor Positive, Metastatic Breast Cancer (DB-06)

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ClinicalTrials.gov Identifier: NCT04494425
Recruitment Status : Recruiting
First Posted : July 31, 2020
Last Update Posted : September 16, 2021
Sponsor:
Collaborator:
Daiichi Sankyo Company, Limited 3-5-1 Nihonbashihoncho, Chuo-ku, Tokyo
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE July 20, 2020
First Posted Date  ICMJE July 31, 2020
Last Update Posted Date September 16, 2021
Actual Study Start Date  ICMJE July 24, 2020
Estimated Primary Completion Date December 16, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 28, 2020)
Progression Free Survival (PFS) - in HR+, HER2-low populaton [ Time Frame: Until progression or death, assessed up to approximately 60 months ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 19, 2020)
  • Overall Survival (OS) - in HR+, HER2-low population [ Time Frame: Until death, assessed up to approximately 60 months ]
    Defined as the time from randomization to death due to any cause
  • 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 ]
    PFS by BICR according to RECIST 1.1 in ITT population
  • 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 ]
    OS in the ITT population
  • Objective Response Rate (ORR) in HR+, HER-2 low populaton [ Time Frame: Until progression, assessed up to approximately 60 months ]
    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.
  • Duration of response (DoR) - in HR+, HER-2 low populaton [ Time Frame: Until progression, assessed up to approximately 60 months ]
    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
  • Progression Free Survival by Investigator assessment - in the HR+, HER2-low population [ Time Frame: Until progression or death, assessed up to approximately 60 months ]
    PFS using investigator assessments according to RECIST 1.1 in the HER2-low population
  • Objective Response Rate (ORR) in the ITT population [ Time Frame: Until progression, assessed up to approximately 60 months ]
    ORR by BICR and by Investigator assessment according to RECIST 1.1 in the ITT population
  • Duration of response (DoR) - in the ITT population [ Time Frame: Until progression, assessed up to approximately 60 months ]
    DoR by BICR and by Investigator assessment according to RECIST 1.1 in the ITT population
  • 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 ]
    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.
  • Safety and tolerability of drugs; number of adverse events (AEs) [ Time Frame: Up to follow-up period, approximately 60 months ]
    Number of AEs according to NCI-CTCAE Version 5.0 per each treatment arm
  • Serum concentration of trastuzumab deruxtecan [ Time Frame: Up to Cycle 8, approximately Week 24; each cycle is 21 days ]
    Determination of trastuzumab deruxtecan concentration in serum at different time points after trastuzumab deruxtecan administration
  • Immunogenicity of trastuzumab deruxtecan [ Time Frame: Up to follow-up period, approximately 60 months ]
    Percentage of patients who develop ADA for trastuzumab deruxtecan
  • Health-related quality of life - EORTC-QLQ-C30 [ Time Frame: Assessed up to approximately 60 months ]
    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.
  • Time to deterioration in EORTC-QLQ-C30 scores [ Time Frame: Assessed up to approximately 60 months ]
    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.
  • Health-related quality of life - EORTC QLQ-BR45 [ Time Frame: Assessed up to approximately 60 months ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 28, 2020)
  • Overall Survival (OS) - in HR+, HER2-low population [ Time Frame: Until death, assessed up to approximately 60 months ]
    Defined as the time from randomization to death due to any cause
  • 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 ]
    PFS by BICR according to RECIST 1.1 in ITT population
  • 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 ]
    OS in the ITT population
  • Objective Response Rate (ORR) in HR+, HER-2 low populaton [ Time Frame: Until progression, assessed up to approximately 60 months ]
    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.
  • Duration of response (DoR) - in HR+, HER-2 low populaton [ Time Frame: Until progression, assessed up to approximately 60 months ]
    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
  • Progression Free Survival by Investigator assessment - in the HR+, HER2-low population [ Time Frame: Until progression or death, assessed up to approximately 60 months ]
    PFS using investigator assessments according to RECIST 1.1 in the HER2-low population
  • Objective Response Rate (ORR) in the ITT population [ Time Frame: Until progression, assessed up to approximately 60 months ]
    ORR by BICR and by Investigator assessment according to RECIST 1.1 in the ITT population
  • Duration of response (DoR) - in the ITT population [ Time Frame: Until progression, assessed up to approximately 60 months ]
    DoR by BICR and by Investigator assessment according to RECIST 1.1 in the ITT population
  • 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 ]
    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.
  • Safety and tolerability of drugs; number of adverse events (AEs) [ Time Frame: Up to follow-up period, approximately 60 months ]
    Number of AEs according to NCI-CTCAE Version 5.0 per each treatment arm
  • Serum concentration of trastuzumab deruxtecan [ Time Frame: Up to Cycle 8, approximately Week 24; each cycle is 21 days ]
    Determination of trastuzumab deruxtecan concentration in serum at different time points after trastuzumab deruxtecan administration
  • Health-related quality of life - EORTC-QLQ-C30 [ Time Frame: Assessed up to approximately 60 months ]
    Change from baseline in the physical functioning subscale of the EORTC-QLQ-C30
  • Immunogenicity of trastuzumab deruxtecan [ Time Frame: Up to follow-up period, approximately 60 months ]
    Percentage of patients who develop ADA for trastuzumab deruxtecan
  • Time to deterioration in EORTC-QLQ-C30 scores [ Time Frame: Assessed up to approximately 60 months ]
    Time to deterioration from baseline in EORTC-QLQ-C30 scores
  • Health-related quality of life - EORTC-QLQ-C45 [ Time Frame: Assessed up to approximately 60 months ]
    Change from baseline in the physical functioning subscale of the EORTC-QLQ-C45
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Trastuzumab Deruxtecan (T-DXd) vs Investigator's Choice Chemotherapy in HER2-low, Hormone Receptor Positive, Metastatic Breast Cancer
Official Title  ICMJE 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)
Brief Summary 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.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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).
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.
Primary Purpose: Treatment
Condition  ICMJE Advanced or Metastatic Breast Cancer
Intervention  ICMJE
  • Drug: Trastuzumab deruxtecan
    Trastuzumab deruxtecan by intravenous infusion
    Other Name: DS-8201a; T-DXd
  • Drug: Capecitabine
    Investigator's choice standard of care single agent chemotherapy; capecitabine tablets will be given orally.
  • Drug: Paclitaxel
    Investigator's choice standard of care single agent chemotherapy; paclitaxel by intravenous infusion.
  • Drug: Nab-Paclitaxel
    Investigator's choice standard of care single agent chemotherapy; nab-paclitaxel by intravenous infusion
Study Arms  ICMJE
  • Experimental: Trastuzumab deruxtecan
    Trastuzumab deruxtecan (T-DXd; DS-8201a) arm
    Intervention: Drug: Trastuzumab deruxtecan
  • Active Comparator: Standard of Care
    Investigator's choice standard of care chemotherapy (capecitabine, paclitaxel, nab-paclitaxel) arm
    Interventions:
    • Drug: Capecitabine
    • Drug: Paclitaxel
    • Drug: Nab-Paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 28, 2020)
850
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 18, 2025
Estimated Primary Completion Date December 16, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Patients must be ≥18 years of age
  • Pathologically documented breast cancer that:

    1. is advanced or metastatic
    2. has a history of HER2-low or negative expression defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) or HER2 IHC 0 (ISH- or untested)
    3. has HER2-low or HER2 IHC >0 <1+ expression
    4. was never previously HER2-positive
    5. is documented HR+ disease in the metastatic setting.
    6. No prior chemotherapy for advanced or metastatic breast cancer.
    7. Has adequate tumor samples for assessment of HER2 status
    8. Must have either:

      1. disease progression within 6 months of starting first line metastatic treatment with an endocrine therapy combined with a CDK4/6 inhibitor or
      2. disease progression on at least 2 previous lines of endocrine therapy with or without a targeted therapy in the metastatic setting. Of note with regards to the ≥2 lines of previous ET requirement: disease recurrence while on the first 24 months of starting adjuvant ET, will be considered a line of therapy; these patients will only require 1 line of ET in the metastatic setting.
    9. Has protocol-defined adequate organ and bone marrow function

Key Exclusion Criteria:

  • Ineligible for all options in the investigator's choice chemotherapy arm
  • Lung-specific intercurrent clinically significant illnesses
  • Uncontrolled or significant cardiovascular disease or infection
  • Active or prior documented interstitial lung disease (ILD)/pneumonitis or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
  • Patients with spinal cord compression or clinically active central nervous system metastases
  • Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless of treatment arm assignment
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 105 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   Canada,   China,   Denmark,   France,   Germany,   Hungary,   India,   Israel,   Italy,   Japan,   Korea, Republic of,   Mexico,   Netherlands,   Poland,   Russian Federation,   Saudi Arabia,   Singapore,   Spain,   Sweden,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04494425
Other Study ID Numbers  ICMJE D9670C00001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan 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.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
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.
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.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Daiichi Sankyo Company, Limited 3-5-1 Nihonbashihoncho, Chuo-ku, Tokyo
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP