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DS-8201a Versus T-DM1 for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane [DESTINY-Breast03]

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ClinicalTrials.gov Identifier: NCT03529110
Recruitment Status : Active, not recruiting
First Posted : May 18, 2018
Results First Posted : April 29, 2022
Last Update Posted : April 18, 2024
Sponsor:
Collaborators:
Daiichi Sankyo Co., Ltd.
AstraZeneca
Information provided by (Responsible Party):
Daiichi Sankyo

Study Description
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Brief Summary:
This study is designed to compare the anti-tumor activity as well as the safety and efficacy of DS-8201a versus T-DM1 in HER2-positive, unresectable and/or metastatic breast cancer subjects previously treated with trastuzumab and taxane.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Trastuzumab deruxtecan (T-DXd) Drug: Ado-trastuzumab emtansine (T-DM1) Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 524 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Study of DS-8201a (Trastuzumab Deruxtecan), an Anti-HER2 Antibody Drug Conjugate (ADC), Versus Ado Trastuzumab Emtansine (T-DM1) for HER2-Positive, Unresectable and/or Metastatic Breast Cancer Subjects Previously Treated With Trastuzumab and Taxane
Actual Study Start Date : August 9, 2018
Actual Primary Completion Date : May 21, 2021
Estimated Study Completion Date : June 1, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Trastuzumab deruxtecan (T-DXd)
Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DXd as a sterile intravenous (IV) solution at a dose of 5.4 mg/kg every 3 weeks (Q3W).
 Drug: Trastuzumab deruxtecan (T-DXd)
T-DXd is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered intravenously.
Other Name: DS-8201a
Active Comparator: Ado-trastuzumab emtansine (T-DM1)
Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DM1 in accordance with the approved label.
 Drug: Ado-trastuzumab emtansine (T-DM1)
The treatment will be in accordance with the approved label.
Other Name: T-DM1


Outcome Measures
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Primary Outcome Measures :
  1. Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane [ Time Frame: Up to 33 months (data cut-off) ]
    Progression-free survival (PFS) by BICR was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.


Secondary Outcome Measures :
  1. Overall Survival (OS) in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane [ Time Frame: Up to 33 months (data cut-off) ]
    Overall survival (OS) was defined as the time from the date of first dose of study drug to the date of death due to any cause.

  2. Percentage of Participants With Objective Response Rate (ORR) Based on BICR and Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane [ Time Frame: Up to 33 months (data cut-off) ]
    The Objective Response Rate (ORR) was defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by BICR and investigator assessment based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR is reported.

  3. Duration of Response (DoR) Based on BICR and Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane [ Time Frame: Up to 33 months (data cut-off) ]
    Duration of Response (DoR) was defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DoR in participants with confirmed CR/PR based on BICR and investigator assessment is reported.

  4. Progression-Free Survival (PFS) Based on Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane [ Time Frame: Up to 33 months (data cut-off) ]
    Progression-free survival (PFS) by investigator assessment was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Is the age of majority in their country

  • Has pathologically documented breast cancer that:

    1. is unresectable or metastatic
    2. has confirmed HER2-positive expression as determined according to American Society of Clinical Oncology - College of American Pathologists guidelines evaluated at a central laboratory
    3. was previously treated with trastuzumab and taxane in the advanced/metastatic setting or progressed within 6 months after neoadjuvant or adjuvant treatment involving a regimen including trastuzumab and taxane
  • Has documented radiologic progression (during or after most recent treatment or within 6 months after completing adjuvant therapy)
  • Is HER2 positive as confirmed by central laboratory assessment of most recent tumor tissue sample available. If archived tissue is not available, agrees to provide a fresh biopsy.
  • If of reproductive/childbearing potential, agrees to use a highly effective form of contraception or avoid intercourse during and upon completion of the study for 7 months after the last dose of DS-8201a (females); 4.5 months after last dose of DS-8201a (males) or 7 months after the last dose of T-DM1
  • Has adequate renal and hepatic function

Exclusion Criteria:

  • Has previously been treated with an anti-HER2 antibody drug conjugate (ADC) in the metastatic setting. Prior treatment in the adjuvant/neo-adjuvant setting would be allowed if progression of disease did not occur within 12 months of end of adjuvant therapy
  • Has uncontrolled or significant cardiovascular disease
  • Has a history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening

  • Has spinal cord compression or clinically active central nervous system (CNS) metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.

    1. Participants with clinically inactive brain metastases may be included in the study.
    2. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment.
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): NCT03529110


Locations
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Sponsors and Collaborators
Daiichi Sankyo
Daiichi Sankyo Co., Ltd.
AstraZeneca
Investigators
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Study Director: Global Team Leader Daiichi Sankyo
  Study Documents (Full-Text)

Documents provided by Daiichi Sankyo:
Study Protocol and Statistical Analysis Plan  [PDF] September 25, 2020

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Daiichi Sankyo
ClinicalTrials.gov Identifier: NCT03529110    
Other Study ID Numbers: DS8201-A-U302
2018-000222-61 ( EudraCT Number )
183976 ( Registry Identifier: JAPIC CTI )
DESTINY-B03 ( Other Identifier: Daiichi Sankyo and AstraZeneca )
CTR20190378 ( Registry Identifier: CDE )
First Posted: May 18, 2018    Key Record Dates
Results First Posted: April 29, 2022
Last Update Posted: April 18, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://vivli.org/ourmember/daiichi-sankyo/

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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 Daiichi Sankyo:
Breast Cancer
Metastatic breast cancer
DS-8201a
DESTINY - Breast 03
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Ado-Trastuzumab Emtansine
Maytansine
Trastuzumab deruxtecan
Antineoplastic Agents, Immunological
 Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunotoxins
Immunoconjugates
Immunologic Factors
Physiological Effects of Drugs