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]

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03529110
• Other study ID #: DS8201-A-U302
• Secondary ID: 2018-000222-6118
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 9, 2018
• Est. completion date: June 1, 2025

Study information

• Verified date: April 2024
• Source: Daiichi Sankyo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 524
• Est. completion date: June 1, 2025
• Est. primary completion date: May 21, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

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

Locations

Country	Name	City	State
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Peninsula and South Eastern Haematology & Oncology Group	Frankston	Victoria
Australia	Peter MacCallum Cancer	Melbourne	Victoria
Australia	St John of God Subiaco Hospital	Subiaco	Western Australia
Australia	The Tweed Hospital	Tweed Heads	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Belgium	Institut Jules-Bordet	Bruxelles
Belgium	Universitair Ziekenhuis Brussel	Bruxelles
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	AZ Sint-Lucas - Campus Sint-Lucas	Gent
Belgium	Universitaire Ziekenhuizen Leuven	Leuven
Belgium	CHU UCL Namur site de Sainte Elisabeth	Namur
Brazil	Catarina Pesquisa Clinica	Itajaí	Santa Catarina
Brazil	Hospital Nossa Senhora da Conceição	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto Americas	Rio De Janeiro
Brazil	NOB - Nucleo de Oncologia da Bahia	Salvador	Bahia
Brazil	CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia	Santo André	Sao Paulo
Brazil	A. C. Camargo Cancer Center	São Paulo
Brazil	Clínica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária Ltda.	São Paulo	Sao Paulo
Brazil	ICESP - Instituto do Cancer do Estado de São Paulo Octavio Frias de Oliveira	São Paulo	Sao Paulo
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	St. Mary's Hospital	Montréal	Quebec
Canada	Toronto Sunnybrook Hospital	Toronto	Ontario
China	Beijing Hospital	Beijing	Beijing
China	Cancer Hospital Chinese Academy of Medical Sciences	Beijing	Beijing
China	The First Hospital of Jilin University	Chang chun	Jilin
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	Sun Yat-sen Memorial Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	Sun Yat-sen University, Cancer Center	Guangzhou	Guangdong
China	Sir Run Run Shaw Hospital Xiasha Branch, Zhejiang University, School of Medicine	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Liaoning Cancer Hospital & Institute	Shenyang	Liaoning
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin
France	ICO - Site Paul Papin	Angers Cedex 2	Maine Et Loire
France	Institut Sainte Catherine	Avignon Cedex 9	Vaculuse
France	CHRU Jean Minjoz	Besançon	Doubs
France	Institut Bergonié	Bordeaux cedex	Gironde
France	Centre François Baclesse	Caen Cedex 05	Calvados
France	Centre Georges François Leclerc	Dijon cedex	Côte-d'Or
France	Clinique Victor Hugo - Centre Jean Bernard	Le Mans	Cedex 02, Sarthe
France	Centre Leon Berard	Lyon Cedex 08	Rhone
France	Hôpital Nord - CHU Marseille	Marseille Cedex 20	Bouches-du-Rhone
France	ICM Val d'Aurelle	Montpellier	Herault
France	Hôpital Saint-Louis	Paris
France	Hopital Tenon	Paris
France	Institut Curie - site de Paris	Paris
France	Centre Hospitalier Lyon Sud	Pierre Benite Cedex	Rhone
France	CARIO - Centre Armoricain de Radiothérapie, Imagerie médicale et Oncologie	Plérin	Cotes d'Armor
France	CRLCC Eugene Marquis	Rennes cedex	Ille Et Vilaine
France	Centre René Huguenin	Saint-Cloud	Hauts De Seine
France	ICO - Site René Gauducheau	Saint-Herblain	Loire Atlantique
France	Hôpital d'Instruction des Armees Begin	Saint-Mandé	Val De Marne
France	Centre Paul Strauss	Strasbourg Cedex	Bas Rhin
France	Centre de cancerologie les Dentellieres	Valenciennes	Nord
France	Institut Gustave Roussy	Villejuif cedex	Val De Marne
Germany	Marienhospital Bottrop gGmbH	Bottrop	Rheinland Pfalz
Germany	Universitaetsklinikum Duesseldorf AoeR	Düsseldorf	Nordrhein Westfalen
Germany	Universitaetsklinikum Erlangen	Erlangen	Bayern
Germany	Universitaetsklinikum Schleswig-Holstein - Campus Luebeck	Luebeck	Schleswig Holstein
Germany	Klinikum rechts der Isar der TU Muenchen	Muenchen	Bayern
Germany	Rotkreuzklinikum Muenchen gGmbH	Muenchen	Bayern
Germany	Haematologisch-Onkologische Schwerpunktpraxis	Troisdorf	Nordrhein Westfalen
Hong Kong	The Chinese	Hong Kong
Hong Kong	The University of Hong Kong	Shatin
Italy	IRCCS Centro di Riferimento Oncologico	Aviano	Pordenone
Italy	Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)	Bergamo
Italy	Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi	Bologna
Italy	Azienda Ospedaliera Universitaria Arcispedale Sant'Anna	Cona	Ferrara
Italy	Istituto Nazionale per la Ricerca sul Cancro di Genova	Genova
Italy	Azienda Ospealiera della Provincia di Lecco	Lecco
Italy	Azienda Ospedaliera Ospedali Riuniti Papardo-Piemonte	Messina
Italy	IEO Istituto Europeo di Oncologia	Milano
Italy	Ospedale San Raffaele	Milano
Italy	A.O.U. Policlinico di Modena	Modena
Italy	Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo), U.O Oncologia Medica	Monza	Milano
Italy	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli
Italy	Azienda Ospedaliero Universitaria di Parma	Parma
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	Istituto Clinico Humanitas	Rozzano	Milano
Italy	Azienda Ospedaliera Città della Salute e della Scienza di Torino	Torino
Japan	Aichi Cancer Center Hospital	Aichi
Japan	NHO Shikoku Cancer Center	Ehime
Japan	NHO Kyushu Cancer Center	Fukuoka
Japan	Hiroshima City Hiroshima Citizens Hospital	Hiroshima
Japan	NHO Hokkaido Cancer Center	Hokkaido
Japan	Kanagawa Cancer Center	Kanagawa
Japan	Kumamoto University Hospital	Kumamoto
Japan	Niigata Cancer Center	Niigata
Japan	Okayama University Hospital	Okayama
Japan	NHO Osaka National Hospital	Osaka
Japan	Osaka International Cancer Institute	Osaka
Japan	Saitama Cancer Center	Saitama
Japan	Center Hospital of the National Center for Global Health and Medicine	Shinjuku-Ku	Tokyo-To
Japan	Shizuoka Cancer Center	Shizuoka
Japan	National Cancer Center Hospital	Tokyo
Japan	Showa University Hospital	Tokyo
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University	Seoul
Spain	Complejo Hospitalario Universitario A Coruña	A Coruña	La Coruña
Spain	Hospital Infanta Cristina	Badajoz
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	IOB-Institute of Oncology	Barcelona
Spain	ICO l'Hospitalet - Hospital Duran i Reynals	L'Hospitalet De Llobregat	Barcelona
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Clinico San Carlos	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	MD Anderson Cancer Centre	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria	Málaga
Spain	Hospital Universitario de Canarias	San Cristobal de la Laguna	Tenerife
Spain	Complejo Hospitalario Universitario de Santiago	Santiago De Compostela	La Coruña
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitario Virgen Macarena	Sevilla	Sevill
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Koo Foundation, Sun Yat-Sen Cancer Center	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Grampian Region
United Kingdom	Western General Hospital	Edinburgh	Lothian Region
United Kingdom	Royal Devon and Exeter Hospital (Wonford)	Exeter	Devon
United Kingdom	Royal Surrey County Hospital	Guildford	Surrey
United Kingdom	Guy's Hospital	London	Greater London
United Kingdom	Queen Mary University of London	London	Greater London
United Kingdom	Sarah Cannon Research Institute UK	London	Greater London
United Kingdom	University College London Hospitals	London	Greater London
United Kingdom	The Christie Hospital	Manchester	Greater Manchester
United Kingdom	Nottingham University Hospitals City Campus	Nottingham	Nottinghamshire
United States	Piedmont Cancer Institute, PC	Atlanta	Georgia
United States	MultiCare Health System Institute for Research and Innovation	Auburn	Washington
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Seidman Cancer Center	Cleveland	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	North Shore Hematology Oncology Associates, PC	East Setauket	New York
United States	Florida Cancer Specialists-Broadway	Fort Myers	Florida
United States	Houston Methodist Hospital / Houston Methodist Cancer Center	Houston	Texas
United States	MD Anderson Cancer Center	Houston	Texas
United States	Millennium Oncology	Houston	Texas
United States	Dayton Physicians, LLC	Kettering	Ohio
United States	UCLA Hematology Oncology	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Loyola University Health System	Maywood	Illinois
United States	Tennessee Oncology- St Thomas Location	Nashville	Tennessee
United States	Vanderbilt Breast Center at One Hundred Oaks	Nashville	Tennessee
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Magee-Womens Hospital of UPMC	Pittsburgh	Pennsylvania
United States	University of Rochester	Rochester	New York
United States	Florida Cancer Specialists NORTH	Saint Petersburg	Florida
United States	Sharp Memorial Hospital	San Diego	California
United States	University of California San Francisco	San Francisco	California
United States	The University of Texas Health Science Center at Tyler	Tyler	Texas
United States	Washington Cancer Institute	Washington	District of Columbia
United States	Innovative Clinical Research Institute	Whittier	California
United States	Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Daiichi Sankyo	AstraZeneca, Daiichi Sankyo Co., Ltd.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  China,  France,  Germany,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Up to 33 months (data cut-off)
Secondary	Overall Survival (OS) in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane	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.	Up to 33 months (data cut-off)
Secondary	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	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.	Up to 33 months (data cut-off)
Secondary	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	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.	Up to 33 months (data cut-off)
Secondary	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	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.	Up to 33 months (data cut-off)