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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03529110




Registration number
NCT03529110
Ethics application status
Date submitted
13/04/2018
Date registered
18/05/2018
Date last updated
20/08/2019

Titles & IDs
Public 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]
Scientific 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
Secondary ID [1] 0 0
2018-000222-61
Secondary ID [2] 0 0
DS8201-A-U302
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 (DS-8201a)
Treatment: Drugs - Ado-trastuzumab emtansine (T-DM1)

Experimental: Trastuzumab deruxtecan (DS-8201a) - HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane randomized to treatment with DS-8201a

Active Comparator: Ado-trastuzumab emtansine (T-DM1) - HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane randomized to treatment with T-DM1


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

Treatment: Drugs: Ado-trastuzumab emtansine (T-DM1)
The treatment will be in accordance with the approved label

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) - Time from the date of randomization to the earliest date of the first objective documentation of radiographic disease progression via BICR according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1 or death due to any cause
Timepoint [1] 0 0
Within 45 months
Secondary outcome [1] 0 0
Overall survival (OS) - 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.
Timepoint [1] 0 0
At 45 months
Secondary outcome [2] 0 0
Objective response rate (ORR) based on BICR and investigator's assessment - Percentage of participants who achieved a best overall response of complete response (CR) or partial response (PR), based on BICR and based on investigator assessment
Timepoint [2] 0 0
Within 45 months
Secondary outcome [3] 0 0
Duration of response (DoR) based on BICR and investigator's assessment - Length of time response continued, based on BICR and investigator's assessment
Timepoint [3] 0 0
Within 45 months
Secondary outcome [4] 0 0
Clinical benefit rate (CBR) - Percentage of participants receiving clinical benefit (CR, PR or more than 6 months stable disease) from the treatment, based on BICR and investigator's assessment
Timepoint [4] 0 0
Within 45 months
Secondary outcome [5] 0 0
Progression-free survival (PFS) based on investigator's assessment - Time from the date of randomization to the first objective documentation of radiographic disease progression via investigator assessment, according to mRECIST version 1.1 or death due to any cause
Timepoint [5] 0 0
Within 45 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 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 at
least 4.5 months after the last dose of DS-8201a or 7 months after the last dose of
T-DM1

- Has adequate renal and hepatic function
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Has previously been treated with an anti-HER2 antibody drug conjugate (ADC)

- 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.

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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC,WA
Recruitment hospital [1] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [2] 0 0
Peninsula and South Eastern Haematology & Oncology Group - Frankston
Recruitment hospital [3] 0 0
Peter MacCallum Cancer - Melbourne
Recruitment hospital [4] 0 0
St John of God Subiaco Hospital - Subiaco
Recruitment postcode(s) [1] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 0 0
3199 - Frankston
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment postcode(s) [4] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Kentucky
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
Nebraska
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Utah
Country [15] 0 0
United States of America
State/province [15] 0 0
Washington
Country [16] 0 0
Belgium
State/province [16] 0 0
Bruxelles
Country [17] 0 0
Belgium
State/province [17] 0 0
Edegem
Country [18] 0 0
Belgium
State/province [18] 0 0
Gent
Country [19] 0 0
Belgium
State/province [19] 0 0
Leuven
Country [20] 0 0
Belgium
State/province [20] 0 0
Namur
Country [21] 0 0
Brazil
State/province [21] 0 0
Bahia
Country [22] 0 0
Brazil
State/province [22] 0 0
Santa Catarina
Country [23] 0 0
Brazil
State/province [23] 0 0
Sao Paulo
Country [24] 0 0
Brazil
State/province [24] 0 0
Rio De Janeiro
Country [25] 0 0
Brazil
State/province [25] 0 0
São Paulo
Country [26] 0 0
Canada
State/province [26] 0 0
Alberta
Country [27] 0 0
Canada
State/province [27] 0 0
Ontario
Country [28] 0 0
France
State/province [28] 0 0
Bas Rhin
Country [29] 0 0
France
State/province [29] 0 0
Bouches-du-Rhone
Country [30] 0 0
France
State/province [30] 0 0
Calvados
Country [31] 0 0
France
State/province [31] 0 0
Cotes d'Armor
Country [32] 0 0
France
State/province [32] 0 0
Doubs
Country [33] 0 0
France
State/province [33] 0 0
Herault
Country [34] 0 0
France
State/province [34] 0 0
Ille Et Vilaine
Country [35] 0 0
France
State/province [35] 0 0
Loire Atlantique
Country [36] 0 0
France
State/province [36] 0 0
Rhone
Country [37] 0 0
France
State/province [37] 0 0
Sarthe
Country [38] 0 0
France
State/province [38] 0 0
Vaculuse
Country [39] 0 0
France
State/province [39] 0 0
Val De Marne
Country [40] 0 0
France
State/province [40] 0 0
Paris
Country [41] 0 0
Hong Kong
State/province [41] 0 0
Hong Kong
Country [42] 0 0
Hong Kong
State/province [42] 0 0
Shatin
Country [43] 0 0
Italy
State/province [43] 0 0
Milano
Country [44] 0 0
Italy
State/province [44] 0 0
Pordenone
Country [45] 0 0
Italy
State/province [45] 0 0
Bergamo
Country [46] 0 0
Italy
State/province [46] 0 0
Genova
Country [47] 0 0
Italy
State/province [47] 0 0
Lecco
Country [48] 0 0
Italy
State/province [48] 0 0
Messina
Country [49] 0 0
Italy
State/province [49] 0 0
Napoli
Country [50] 0 0
Japan
State/province [50] 0 0
Aichi
Country [51] 0 0
Japan
State/province [51] 0 0
Ehime
Country [52] 0 0
Japan
State/province [52] 0 0
Fukuoka
Country [53] 0 0
Japan
State/province [53] 0 0
Hiroshima
Country [54] 0 0
Japan
State/province [54] 0 0
Hokkaido
Country [55] 0 0
Japan
State/province [55] 0 0
Kanagawa
Country [56] 0 0
Japan
State/province [56] 0 0
Kumamoto
Country [57] 0 0
Japan
State/province [57] 0 0
Niigata
Country [58] 0 0
Japan
State/province [58] 0 0
Okayama
Country [59] 0 0
Japan
State/province [59] 0 0
Osaka
Country [60] 0 0
Japan
State/province [60] 0 0
Saitama
Country [61] 0 0
Japan
State/province [61] 0 0
Shizuoka
Country [62] 0 0
Japan
State/province [62] 0 0
Tokyo
Country [63] 0 0
Korea, Republic of
State/province [63] 0 0
Gyeonggi-do
Country [64] 0 0
Korea, Republic of
State/province [64] 0 0
Seoul
Country [65] 0 0
Spain
State/province [65] 0 0
Barcelona
Country [66] 0 0
Spain
State/province [66] 0 0
Sevill
Country [67] 0 0
Spain
State/province [67] 0 0
Tenerife
Country [68] 0 0
Spain
State/province [68] 0 0
Badajoz
Country [69] 0 0
Spain
State/province [69] 0 0
Madrid
Country [70] 0 0
Spain
State/province [70] 0 0
Málaga
Country [71] 0 0
Spain
State/province [71] 0 0
Sevilla
Country [72] 0 0
Taiwan
State/province [72] 0 0
Taichung
Country [73] 0 0
Taiwan
State/province [73] 0 0
Tainan
Country [74] 0 0
Taiwan
State/province [74] 0 0
Taipei
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Devon
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Grampian Region
Country [77] 0 0
United Kingdom
State/province [77] 0 0
Greater London
Country [78] 0 0
United Kingdom
State/province [78] 0 0
Greater Manchester
Country [79] 0 0
United Kingdom
State/province [79] 0 0
Lothian Region
Country [80] 0 0
United Kingdom
State/province [80] 0 0
Nottinghamshire

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Daiichi Sankyo, Inc.
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 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.
Trial website
https://clinicaltrials.gov/show/NCT03529110
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Global Team Leader
Address 0 0
Daiichi Sankyo, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
(For Sites in Asia Only) Daiichi Sankyo Contact for Clinical Trial Information
Address 0 0
Country 0 0
Phone 0 0
+81-3-6225-1111(M-F 9-5 JST)
Fax 0 0
Email 0 0
dsclinicaltrial@daiichisankyo.co.jp
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03529110