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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]

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ClinicalTrials.gov Identifier: NCT03734029
Recruitment Status : Recruiting
First Posted : November 7, 2018
Last Update Posted : June 23, 2020
Sponsor:
Collaborators:
Daiichi Sankyo Co., Ltd.
AstraZeneca UK Limited
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Tracking Information
First Submitted Date  ICMJE November 6, 2018
First Posted Date  ICMJE November 7, 2018
Last Update Posted Date June 23, 2020
Actual Study Start Date  ICMJE December 27, 2018
Estimated Primary Completion Date January 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 19, 2019)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 6, 2018)
Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) [ Time Frame: at approximately 3 years ]
PFS based on BICR is defined as the time from the date of randomization to the earliest date of the first objective documentation of radiographic disease progression, assessed via BICR according to the modified response evaluation criteria in solid tumors (mRECIST) version 1.1, or death due to any cause. First dose at Cycle 1 Day 1 should occur within 7 days after the date the subject is randomized.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 19, 2019)
  • 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.
  • 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.
  • 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.
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: November 6, 2018)
  • PFS based on Investigator Assessment [ Time Frame: at approximately 3 years ]
    PFS based on Investigator Assessment is defined as the time from the date of randomization to the earliest date of the first clinical observation of disease progression or death due to any cause, assessed by BICR review using mRECIST version 1.1.
  • Overall Survival (OS) [ Time Frame: at approximately 3 years ]
    OS is defined as the time from the date of randomization to the date of death for any cause, assessed by BICR review using mRECIST version 1.1.
  • Confirmed Objective Response Rate (ORR) [ Time Frame: at approximately 3 years ]
    Confirmed ORR is defined as the sum of complete response (CR) rate and partial response (PR) rate, based on BICR and Investigator Assessment, and confirmed by a second assessment by BICR review using mRECIST version 1.1.
  • Duration of Response (DoR), based on BICR and Investigator assessment [ Time Frame: at approximately 3 years ]
    DoR is defined as the time from the date of the first documentation of objective response (CR or PR) to the date of the first documentation of disease progression, based on BICR and Investigator assessment, or death. Duration of response will be measured for responding subjects (PR or CR) only, and be assessed by BICR review using mRECIST version 1.1.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trastuzumab Deruxtecan (DS-8201a) Versus Investigator's Choice for HER2-low Breast Cancer That Has Spread or Cannot be Surgically Removed [DESTINY-Breast04]
Official Title  ICMJE 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
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
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Parallel model, randomized at a 2:1 ratio
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • 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
  • 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)
Study Arms  ICMJE
  • Experimental: Trastuzumab deruxtecan
    HER2-low, unresectable, and/or metastatic breast cancer participants previously treated with chemotherapy randomized to DS8201a
    Intervention: Drug: Trastuzumab deruxtecan (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
    Interventions:
    • Drug: Capecitabine
    • Drug: Eribulin
    • Drug: Gemcitabine
    • 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: November 6, 2018)
540
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 1, 2023
Estimated Primary Completion Date January 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: (Asia Sites Only) Daiichi Sankyo Contact for Clinical Trial Information +81-3-6225-1111 (M-F 9-5 JST) dsclinicaltrial@daiichisankyo.co.jp
Contact: (US sites) Contact for Clinical Trial Information 908-992-6400 CTRinfo@dsi.com
Listed Location Countries  ICMJE Austria,   Belgium,   Canada,   China,   France,   Germany,   Greece,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   Portugal,   Spain,   Sweden,   Switzerland,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03734029
Other Study ID Numbers  ICMJE DS8201-A-U303
2018-003069-33 ( EudraCT Number )
184223 ( Registry Identifier: JAPIC CTI )
DESTINY-B04 ( Other Identifier: Daiichi Sankyo and AstraZeneca )
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: 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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: 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/
Responsible Party Daiichi Sankyo, Inc.
Study Sponsor  ICMJE Daiichi Sankyo, Inc.
Collaborators  ICMJE
  • Daiichi Sankyo Co., Ltd.
  • AstraZeneca UK Limited
Investigators  ICMJE
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
PRS Account Daiichi Sankyo, Inc.
Verification Date June 2020

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