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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03523585




Registration number
NCT03523585
Ethics application status
Date submitted
13/04/2018
Date registered
14/05/2018
Date last updated
5/11/2024

Titles & IDs
Public title
DS-8201a in Pre-treated HER2 Breast Cancer That Cannot be Surgically Removed or Has Spread [DESTINY-Breast02]
Scientific title
A Phase 3, Multicenter, Randomized, Open-label, Active-controlled Study of Trastuzumab Deruxtecan (DS-8201a), an Anti-HER2-antibody Drug Conjugate, Versus Treatment of Investigator's Choice for HER2-positive, Unresectable and/or Metastatic Breast Cancer Subjects Previously Treated With T-DM1
Secondary ID [1] 0 0
2018-000221-31
Secondary ID [2] 0 0
DS8201-A-U301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Trastuzumab deruxtecan
Treatment: Drugs - Capecitabine
Treatment: Drugs - Lapatinib
Treatment: Drugs - Trastuzumab

Experimental: Trastuzumab deruxtecan (DS-8201a) - HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), randomized to treatment with DS-8201a

Active comparator: Trastuzumab+capecitabine - HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), randomized to investigator's choice treatment with Trastuzumab/capecitabine

Active comparator: Lapatinib+capecitabine - HER2 positive, unresectable and/or metastatic breast cancer participants previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine (T-DM1), randomized to investigator's choice treatment with Lapatinib/capecitabine


Treatment: Drugs: Trastuzumab deruxtecan
DS-8201a is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered as intravenous (IV) dose

Treatment: Drugs: Capecitabine
Investigator's choice Standard of Care when combined with trastuzumab or lapatinib

Treatment: Drugs: Lapatinib
Investigator's choice Standard of Care when combined with capecitabine

Treatment: Drugs: Trastuzumab
Investigator's choice Standard of Care when combined with capecitabine
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants With HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated With Trastuzumab Emtansine
Timepoint [1] 0 0
Baseline up to 46 months postdose
Secondary outcome [1] 0 0
Overall Survival (OS) in Participants With HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated With Trastuzumab Emtansine
Timepoint [1] 0 0
Baseline up to 46 months postdose
Secondary outcome [2] 0 0
Percentage of Participants With Objective Response Rate (ORR) in Participants With HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated With Trastuzumab Emtansine
Timepoint [2] 0 0
Baseline up to 46 months postdose
Secondary outcome [3] 0 0
Duration of Response (DoR) Based on BICR in Participants With HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated With Trastuzumab Emtansine
Timepoint [3] 0 0
Baseline up to 46 months postdose
Secondary outcome [4] 0 0
Progression-Free Survival (PFS) Based on Investigator Assessment in Participants With HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated With Trastuzumab Emtansine
Timepoint [4] 0 0
Up to 46 months

Eligibility
Key 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 ado-trastuzumab emtansine (T-DM1)
* 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.
* Male and female participants of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least:

1. 7 months after the last dose of DS-8201a (females); 4.5 months after last dose of DS-8201a (males)
2. 6 months after the last dose of lapatinib/capecitabine for female participants (3 months for male participants)
3. 7 months after the last dose of trastuzumab/capecitabine
* Has adequate hematopoietic, renal and hepatic functions
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Has previously participated in an antibody drug conjugate study sponsored by Daiichi Sankyo. 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 had prior treatment with capecitabine
* Has uncontrolled or significant cardiovascular disease
* Has a 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 active central nervous system (CNS) metastases

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/07/2025
Actual
Sample size
Target
Accrual to date
Final
608
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
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St Vincent's Hospital Sydney - Darlinghurst
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Liverpool Hospital - Liverpool
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Macquarie University Hospital - Sydney
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The Tweed Hospital - Tweed Heads
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Princess Alexandra Hospital - Woolloongabba
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Ashford Cancer Centre Research - Kurralta Park
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Box Hill Hospital - Box Hill
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Frankston Hospital - Frankston
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Peninsula and South Eastern Haematology & Oncology Group - Frankston
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Austin Health - Heidelberg
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Peter MacCallum Cancer Centre - Melbourne
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Sunshine Hospital - Saint Albans
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South West Oncology - Warrnambool
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Ballarat Oncology & Haematology Service - Wendouree
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St John of God Subiaco Hospital - Subiaco
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Calvary North Adelaide Hospital - Bruce
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2010 - Darlinghurst
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2170 - Liverpool
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2109 - Sydney
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2485 - Tweed Heads
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4102 - Woolloongabba
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5037 - Kurralta Park
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3128 - Box Hill
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3199 - Frankston
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3084 - Heidelberg
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3000 - Melbourne
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3021 - Saint Albans
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3280 - Warrnambool
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3355 - Wendouree
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6008 - Subiaco
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2614 - Bruce
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Madrid
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Salamanca
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Sevilla
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Valencia
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Zaragoza
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Turkey
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Adana
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Ankara
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Antalya
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Bursa
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Istanbul
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Izmir
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Konya
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Samsun
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Tekirdag
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United Kingdom
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Cornwall
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Devon
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Grampian Region
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Greater London
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Lothian Region
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United Kingdom
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Nottinghamshire

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Daiichi Sankyo
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Daiichi Sankyo Co., Ltd.
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
AstraZeneca
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study will compare DS 8201a to standard treatment.

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

Their cancer:

* cannot be removed by an operation
* has spread to other parts of the body
Trial website
https://clinicaltrials.gov/study/NCT03523585
Trial related presentations / publications
Andre F, Hee Park Y, Kim SB, Takano T, Im SA, Borges G, Lima JP, Aksoy S, Gavila Gregori J, De Laurentiis M, Bianchini G, Roylance R, Miyoshi Y, Armstrong A, Sinha R, Ruiz Borrego M, Lim E, Ettl J, Yerushalmi R, Zagouri F, Duhoux FP, Fehm T, Gambhire D, Cathcart J, Wu C, Chu C, Egorov A, Krop I. Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2023 May 27;401(10390):1773-1785. doi: 10.1016/S0140-6736(23)00725-0. Epub 2023 Apr 20. Erratum In: Lancet. 2023 Dec 9;402(10418):2196. doi: 10.1016/S0140-6736(23)02709-5. Lancet. 2024 Mar 9;403(10430):912. doi: 10.1016/S0140-6736(24)00420-3.
Fehm T, Cottone F, Dunton K, Andre F, Krop I, Park YH, De Laurentiis M, Miyoshi Y, Armstrong A, Borrego MR, Yerushalmi R, Duhoux FP, Takano T, Lu W, Egorov A, Kim SB. Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): patient-reported outcomes from a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2024 May;25(5):614-625. doi: 10.1016/S1470-2045(24)00128-1.
Public notes

Contacts
Principal investigator
Name 0 0
Global Team Leader
Address 0 0
Daiichi Sankyo
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03523585