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]

• 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: Daiichi Sankyo
• Collaborators: Daiichi Sankyo Co., Ltd.; AstraZeneca
• Information provided by (Responsible Party): Daiichi Sankyo

Tracking Information

• First Submitted Date: April 13, 2018
• First Posted Date: May 18, 2018
• Results First Submitted Date: March 7, 2022
• Results First Posted Date: April 29, 2022
• Last Update Posted Date: April 18, 2024
• Actual Study Start Date: August 9, 2018
• Actual Primary Completion Date: May 21, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 7, 2022)

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.

Original Primary Outcome Measures (submitted: May 7, 2018)

Progression-free survival (PFS) based on blinded independent central review (BICR) [ Time Frame: Within 45 months ]

Time from the date of randomization to the earliest date of the first objective documentation of radiographic disease progression via BICR according to RECIST version 1.1 or death due to any cause

Current Secondary Outcome Measures (submitted: March 7, 2022)

• 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.
• 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.
• 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.
• 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.

Original Secondary Outcome Measures (submitted: May 7, 2018)

• Overall survival (OS) [ Time Frame: At 45 months ]
  Time from the date of randomization to the date of death for any cause. If there is no death reported for a subject before the data cutoff for OS analysis, OS will be censored at the last contact date at which the subject is known to be alive
• Objective response rate (ORR) based on BICR and investigator's assessment [ Time Frame: Within 45 months ]
  Percentage of participants with complete response (CR) and partial response (PR) based on BICR and based on investigator assessment
• Duration of response (DoR) based on BICR and investigator's assessment [ Time Frame: Within 45 months ]
  Length of time response continued based on BICR and investigator's assessment
• Clinical benefit rate (CBR) [ Time Frame: Within 45 months ]
  Percentage of participants receiving clinical benefit from the treatment based on BICR and investigator's assessment
• Progression-free survival (PFS) based on investigator's assessment [ Time Frame: Within 45 months ]
  PFS based on investigator's assessment is time from the date of randomization to the earliest date of the first objective documentation of radiographic disease progression via investigator-assessed disease progression according to RECIST version 1.1 or death due to any cause

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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]
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

• 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
• Drug: Ado-trastuzumab emtansine (T-DM1)
  The treatment will be in accordance with the approved label.
  Other Name: T-DM1

Study Arms

• 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).
  Intervention: Drug: Trastuzumab deruxtecan (T-DXd)
• 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.
  Intervention: Drug: Ado-trastuzumab emtansine (T-DM1)

Publications *

• Rugo HS, Bianchini G, Cortes J, Henning JW, Untch M. Optimizing treatment management of trastuzumab deruxtecan in clinical practice of breast cancer. ESMO Open. 2022 Aug;7(4):100553. doi: 10.1016/j.esmoop.2022.100553. Epub 2022 Aug 11.
• Cortes J, Kim SB, Chung WP, Im SA, Park YH, Hegg R, Kim MH, Tseng LM, Petry V, Chung CF, Iwata H, Hamilton E, Curigliano G, Xu B, Huang CS, Kim JH, Chiu JWY, Pedrini JL, Lee C, Liu Y, Cathcart J, Bako E, Verma S, Hurvitz SA; DESTINY-Breast03 Trial Investigators. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022 Mar 24;386(12):1143-1154. doi: 10.1056/NEJMoa2115022.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 7, 2022): 524
• Original Estimated Enrollment (submitted: May 7, 2018): 500
• Estimated Study Completion Date: June 1, 2025
• Actual Primary Completion Date: May 21, 2021 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Brazil, Canada, China, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: 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 )
• 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

• 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/

• Current Responsible Party: Daiichi Sankyo
• Original Responsible Party: Same as current
• Current Study Sponsor: Daiichi Sankyo
• Original Study Sponsor: Same as current

Collaborators

• Daiichi Sankyo Co., Ltd.
• AstraZeneca

Investigators

• Study Director: Global Team Leader; Daiichi Sankyo

• PRS Account: Daiichi Sankyo
• Verification Date: April 2024