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Trastuzumab Deruxtecan (DS-8201a) Versus Investigator's Choice for HER2-low Breast Cancer That Has Spread or Cannot be Surgically Removed [DESTINY-Breast04]

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03734029
Recruitment Status : Active, not recruiting
First Posted : November 7, 2018
Last Update Posted : December 15, 2022
Sponsor:
Collaborators:
Daiichi Sankyo Co., Ltd.
AstraZeneca
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Study Description
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Brief Summary:

This study will compare DS-8201a to physician choice standard treatment.

Participants must have HER2-low breast cancer that has been treated before.

Participants' cancer:

  • Cannot be removed by an operation
  • Has spread to other parts of the body

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Trastuzumab deruxtecan (DS-8201a) Drug: Capecitabine Drug: Eribulin Drug: Gemcitabine Drug: Paclitaxel Drug: Nab-paclitaxel Phase 3

Detailed Description:

This is a randomized, 2-arm, Phase 3, open-label, multicenter study to compare the safety and efficacy of trastuzumab deruxtecan versus the physician's choice (2:1) in HER2-low, unresectable and/or metastatic breast cancer participants.

The Sponsor proposes to define a new HER2-low population in this trial including tumors with IHC 1+ and IHC 2+/ISH- HER2 expression.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 557 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Parallel model, randomized at a 2:1 ratio
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Open-label, Active Controlled Trial of DS-8201a, an Anti-HER2-antibody Drug Conjugate (ADC), Versus Treatment of Physician's Choice for HER2-low, Unresectable and/or Metastatic Breast Cancer Subjects
Actual Study Start Date : December 27, 2018
Actual Primary Completion Date : January 11, 2022
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Trastuzumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Trastuzumab deruxtecan
HER2-low, unresectable, and/or metastatic breast cancer participants previously treated with chemotherapy randomized to DS8201a
 Drug: Trastuzumab deruxtecan (DS-8201a)
DS-8201a is a lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered intravenously
Other Name: DS-8201a
Active Comparator: Physician's Choice

HER2-low, unresectable, and/or metastatic breast cancer participants previously treated with chemotherapy randomized to Physician's choice from the following options:

  • Capecitabine
  • Eribulin
  • Gemcitabine
  • Paclitaxel
  • Nab-paclitaxel
 Drug: Capecitabine
Administered according to label, as one option for Physician's Choice (determined before randomization)

Drug: Eribulin
Administered according to label, as one option for Physician's Choice (determined before randomization)

Drug: Gemcitabine
Administered according to label, as one option for Physician's Choice (determined before randomization)

Drug: Paclitaxel
Administered according to label, as one option for Physician's Choice (determined before randomization)

Drug: Nab-paclitaxel
Administered according to label, as one option for Physician's Choice (determined before randomization)


Outcome Measures
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Primary Outcome Measures :
  1. Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) [ Time Frame: within approximately 3 years ]
    Time from the date of randomization to the earliest date of the first objective documentation of radiographic disease progression via blinded independent central review (BICR) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1 or death due to any cause.


Secondary Outcome Measures :
  1. PFS based on Investigator Assessment [ Time Frame: within approximately 3 years ]
    Time from the date of randomization to the first objective documentation of radiographic disease progression via investigator assessment according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1 or death due to any cause.

  2. Overall Survival (OS) [ Time Frame: within approximately 3 years ]
    Time from the date of randomization to the date of death for any cause. If there is no death reported for a participant before the data cutoff for OS analysis, OS will be censored at the last contact date at which the participant is known to be alive.

  3. Objective Response Rate (ORR) [ Time Frame: within approximately 3 years ]
    Percentage of participants who achieved a best overall response of complete response (CR) or partial response (PR), confirmed by a second assessment.

  4. Duration of Response (DoR), Based on Blinded Independent Central Review (BICR) and Investigator Assessment [ Time Frame: within approximately 3 years ]
    DoR is defined as the time from the first documented objective response (CR or PR) to the first documented disease progression or death


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 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 low-HER2 expression defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested)
    3. Is HR-positive or HR-negative
    4. Has progressed on, and would no longer benefit from, endocrine therapy
    5. Has been treated with 1 to 2 prior lines of chemotherapy/adjuvant in the metastatic setting
    6. Was never previously HER2-positive (ICH 3+ or ISH+) on prior pathology testing (per American Society of Clinical Oncology-College of American Pathologists [ASCO-CAP] guidelines)
  • Has documented radiologic progression (during or after most recent treatment)

  • Has adequate archival tumor samples available or is wiling to provide fresh biopsies prior to randomization for:

    1. assessment of HER2 status
    2. assessment of post-treatment status
  • Has at least 1 protocol-defined measurable lesion
  • Has protocol-defined adequate cardiac, bone marrow, renal, hepatic and blood clotting functions
  • Male and female participants of reproductive/childbearing potential, agrees to follow instructions for method(s) of contraception and agrees to avoid preserving ova or sperm for at least 4.5 months after treatment (or longer, per locally approved labels)

Exclusion Criteria:

  • Is ineligible for all options in the physician's choice arm
  • Has breast cancer ever assessed with high-HER2 expression
  • Has previously been treated with any anti-HER2 therapy, including an antibody drug conjugate
  • Has uncontrolled or significant cardiovascular disease
  • Has spinal cord compression or clinically active central nervous system metastases
  • Has history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
  • Has any medical history or condition that per protocol or in the opinion of the investigator is inappropriate for the study
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): NCT03734029


Locations
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Sponsors and Collaborators
Daiichi Sankyo, Inc.
Daiichi Sankyo Co., Ltd.
AstraZeneca
Investigators
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Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
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, Inc.
ClinicalTrials.gov Identifier: NCT03734029    
Other Study ID Numbers: DS8201-A-U303
2018-003069-33 ( EudraCT Number )
184223 ( Registry Identifier: JAPIC CTI )
DESTINY-B04 ( Other Identifier: Daiichi Sankyo and AstraZeneca )
First Posted: November 7, 2018    Key Record Dates
Last Update Posted: December 15, 2022
Last Verified: December 2022
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, Inc.:
Anti-HER2-Antibody Drug Conjugate (ADC)
Unresectable or Metastatic
Human epidermal growth factor receptor 2 (HER2)-low
DESTINY - Breast 04
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Camptothecin
Albumin-Bound Paclitaxel
Gemcitabine
Capecitabine
Trastuzumab
Trastuzumab deruxtecan
Immunoconjugates
Antineoplastic Agents, Phytogenic
 Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antineoplastic Agents, Immunological
Immunologic Factors
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors