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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04494425
Recruitment Status : Recruiting
First Posted : July 31, 2020
Last Update Posted : March 15, 2023
Sponsor:
Collaborator:
Daiichi Sankyo Company, Limited 3-5-1 Nihonbashihoncho, Chuo-ku, Tokyo
Information provided by (Responsible Party):
AstraZeneca

Study Description
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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.

Condition or disease Intervention/treatment Phase
Advanced or Metastatic Breast Cancer Drug: Trastuzumab deruxtecan Drug: Capecitabine Drug: Paclitaxel Drug: Nab-Paclitaxel Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 850 participants
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
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)
Actual Study Start Date : July 24, 2020
Estimated Primary Completion Date : July 31, 2023
Estimated Study Completion Date : June 19, 2026

Resource links provided by the National Library of Medicine

Drug Information available for: Trastuzumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Trastuzumab deruxtecan
Trastuzumab deruxtecan (T-DXd; DS-8201a) arm
 Drug: Trastuzumab deruxtecan
Trastuzumab deruxtecan by intravenous infusion
Other Name: DS-8201a; T-DXd
Active Comparator: Standard of Care
Investigator's choice standard of care chemotherapy (capecitabine, paclitaxel, nab-paclitaxel) arm
 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


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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

  12. Immunogenicity of trastuzumab deruxtecan [ Time Frame: Up to follow-up period, approximately 60 months ]
    Percentage of patients who develop ADA for trastuzumab deruxtecan

  13. 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.

  14. 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.

  15. 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.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 105 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 by local test, 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 as determined by the central laboratory result established on a tissue sample taken in the metastatic setting
    4. was never previously HER2-positive
    5. is documented HR+ disease in the metastatic setting.
  • No prior chemotherapy for advanced or metastatic breast cancer.
  • Has adequate tumor samples for assessment of HER2 status

  • 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.
  • 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
  • Prior documented interstitial lung disease (ILD)/ pneumonitis that required steroids, current 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
  • Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study during the follow up period of a prior interventional study (prescreening for this study while a patient is on treatment in another clinical study is acceptable)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04494425


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: AZ Breast Cancer Study Navigators +1-877-400-4656 AstraZeneca@CareboxHealth.com

Locations
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Sponsors and Collaborators
AstraZeneca
Daiichi Sankyo Company, Limited 3-5-1 Nihonbashihoncho, Chuo-ku, Tokyo
More Information
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Additional Information:

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04494425    
Other Study ID Numbers: D9670C00001
First Posted: July 31, 2020    Key Record Dates
Last Update Posted: March 15, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
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
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Breast Cancer
HR positive
HER2-Low
HER2-Negative
 Trastuzumab Deruxtecan (T-DXd; DS-8201a)
Anti-HER2-Antibody Drug Conjugate (ADC)
DESTINY-Breast06
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Capecitabine
Trastuzumab
Trastuzumab deruxtecan
Antineoplastic Agents, Phytogenic
 Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antineoplastic Agents, Immunological
Immunoconjugates
Immunologic Factors
Physiological Effects of Drugs