Clinical trial NCT03529110: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Keywords: Breast Cancer
Metastatic breast cancer
DS-8201a
DESTINY - Breast 03
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo Co., Ltd.
name: AstraZeneca
First posted: 2018-05-18
Enrollment: 524
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: 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
timeFrame: Up to 33 months (data cut-off)
Secondary outcomes:
measure: Overall Survival (OS) in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane
timeFrame: Up to 33 months (data cut-off)
measure: 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
timeFrame: Up to 33 months (data cut-off)
measure: 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
timeFrame: Up to 33 months (data cut-off)
measure: 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
timeFrame: Up to 33 months (data cut-off)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Hematology Oncology
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research Institute
state: California
city: Washington
country: United States
facility: Washington Cancer Institute
state: District of Columbia
city: Fort Myers
country: United States
facility: Florida Cancer Specialists-Broadway
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists NORTH
state: Florida
city: Atlanta
country: United States
facility: Piedmont Cancer Institute, PC
state: Georgia
city: Maywood
country: United States
facility: Loyola University Health System
state: Illinois
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: East Setauket
country: United States
facility: North Shore Hematology Oncology Associates, PC
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Seidman Cancer Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Kettering
country: United States
facility: Dayton Physicians, LLC
state: Ohio
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital of UPMC
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology- St Thomas Location
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Breast Center at One Hundred Oaks
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital / Houston Methodist Cancer Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: Millennium Oncology
state: Texas
city: Tyler
country: United States
facility: The University of Texas Health Science Center at Tyler
state: Texas
city: Auburn
country: United States
facility: MultiCare Health System Institute for Research and Innovation
state: Washington
city: Tweed Heads
country: Australia
facility: The Tweed Hospital
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Frankston
country: Australia
facility: Peninsula and South Eastern Haematology & Oncology Group
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer
state: Victoria
city: Subiaco
country: Australia
facility: St John of God Subiaco Hospital
state: Western Australia
city: Bruxelles
country: Belgium
facility: Institut Jules-Bordet
city: Bruxelles
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Gent
country: Belgium
facility: AZ Sint-Lucas - Campus Sint-Lucas
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
city: Namur
country: Belgium
facility: CHU UCL Namur site de Sainte Elisabeth
city: Salvador
country: Brazil
facility: NOB - Nucleo de Oncologia da Bahia
state: Bahia
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceição
state: Rio Grande Do Sul
city: Itajaí
country: Brazil
facility: Catarina Pesquisa Clinica
state: Santa Catarina
city: Santo André
country: Brazil
facility: CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
state: Sao Paulo
city: São Paulo
country: Brazil
facility: ICESP - Instituto do Cancer do Estado de São Paulo Octavio Frias de Oliveira
state: Sao Paulo
city: São Paulo
country: Brazil
facility: Clínica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária Ltda.
state: Sao Paulo
city: Rio De Janeiro
country: Brazil
facility: Instituto Americas
city: São Paulo
country: Brazil
facility: A. C. Camargo Cancer Center
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Toronto
country: Canada
facility: Toronto Sunnybrook Hospital
state: Ontario
city: Montréal
country: Canada
facility: St. Mary's Hospital
state: Quebec
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat-sen University, Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
state: Guangdong
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Chang chun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: Liaoning Cancer Hospital & Institute
state: Liaoning
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital Xiasha Branch, Zhejiang University, School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Strasbourg Cedex
country: France
facility: Centre Paul Strauss
state: Bas Rhin
city: Marseille Cedex 20
country: France
facility: Hôpital Nord - CHU Marseille
state: Bouches-du-Rhone
city: Caen Cedex 05
country: France
facility: Centre François Baclesse
state: Calvados
city: Le Mans
country: France
facility: Clinique Victor Hugo - Centre Jean Bernard
state: Cedex 02, Sarthe
city: Plérin
country: France
facility: CARIO - Centre Armoricain de Radiothérapie, Imagerie médicale et Oncologie
state: Cotes d'Armor
city: Dijon cedex
country: France
facility: Centre Georges François Leclerc
state: Côte-d'Or
city: Besançon
country: France
facility: CHRU Jean Minjoz
state: Doubs
city: Bordeaux cedex
country: France
facility: Institut Bergonié
state: Gironde
city: Saint-Cloud
country: France
facility: Centre René Huguenin
state: Hauts De Seine
city: Montpellier
country: France
facility: ICM Val d'Aurelle
state: Herault
city: Rennes cedex
country: France
facility: CRLCC Eugene Marquis
state: Ille Et Vilaine
city: Saint-Herblain
country: France
facility: ICO - Site René Gauducheau
state: Loire Atlantique
city: Angers Cedex 2
country: France
facility: ICO - Site Paul Papin
state: Maine Et Loire
city: Valenciennes
country: France
facility: Centre de cancerologie les Dentellieres
state: Nord
city: Lyon Cedex 08
country: France
facility: Centre Leon Berard
state: Rhone
city: Pierre Benite Cedex
country: France
facility: Centre Hospitalier Lyon Sud
state: Rhone
city: Avignon Cedex 9
country: France
facility: Institut Sainte Catherine
state: Vaculuse
city: Saint-Mandé
country: France
facility: Hôpital d'Instruction des Armees Begin
state: Val De Marne
city: Villejuif cedex
country: France
facility: Institut Gustave Roussy
state: Val De Marne
city: Paris
country: France
facility: Institut Curie - site de Paris
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Paris
country: France
facility: Hopital Tenon
city: Erlangen
country: Germany
facility: Universitaetsklinikum Erlangen
state: Bayern
city: Muenchen
country: Germany
facility: Rotkreuzklinikum Muenchen gGmbH
state: Bayern
city: Muenchen
country: Germany
facility: Klinikum rechts der Isar der TU Muenchen
state: Bayern
city: Düsseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf AoeR
state: Nordrhein Westfalen
city: Troisdorf
country: Germany
facility: Haematologisch-Onkologische Schwerpunktpraxis
state: Nordrhein Westfalen
city: Bottrop
country: Germany
facility: Marienhospital Bottrop gGmbH
state: Rheinland Pfalz
city: Luebeck
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein - Campus Luebeck
state: Schleswig Holstein
city: Hong Kong
country: Hong Kong
facility: The Chinese
city: Shatin
country: Hong Kong
facility: The University of Hong Kong
city: Cona
country: Italy
facility: Azienda Ospedaliera Universitaria Arcispedale Sant'Anna
state: Ferrara
city: Monza
country: Italy
facility: Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo), U.O Oncologia Medica
state: Milano
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milano
city: Aviano
country: Italy
facility: IRCCS Centro di Riferimento Oncologico
state: Pordenone
city: Bergamo
country: Italy
facility: Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi
city: Genova
country: Italy
facility: Istituto Nazionale per la Ricerca sul Cancro di Genova
city: Lecco
country: Italy
facility: Azienda Ospealiera della Provincia di Lecco
city: Messina
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti Papardo-Piemonte
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Milano
country: Italy
facility: IEO Istituto Europeo di Oncologia
city: Modena
country: Italy
facility: A.O.U. Policlinico di Modena
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale
city: Parma
country: Italy
facility: Azienda Ospedaliero Universitaria di Parma
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Torino
country: Italy
facility: Azienda Ospedaliera Città della Salute e della Scienza di Torino
city: Shinjuku-Ku
country: Japan
facility: Center Hospital of the National Center for Global Health and Medicine
state: Tokyo-To
city: Aichi
country: Japan
facility: Aichi Cancer Center Hospital
city: Ehime
country: Japan
facility: NHO Shikoku Cancer Center
city: Fukuoka
country: Japan
facility: NHO Kyushu Cancer Center
city: Hiroshima
country: Japan
facility: Hiroshima City Hiroshima Citizens Hospital
city: Hokkaido
country: Japan
facility: NHO Hokkaido Cancer Center
city: Kanagawa
country: Japan
facility: Kanagawa Cancer Center
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Niigata
country: Japan
facility: Niigata Cancer Center
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: NHO Osaka National Hospital
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Saitama
country: Japan
facility: Saitama Cancer Center
city: Shizuoka
country: Japan
facility: Shizuoka Cancer Center
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Tokyo
country: Japan
facility: Showa University Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: L'Hospitalet De Llobregat
country: Spain
facility: ICO l'Hospitalet - Hospital Duran i Reynals
state: Barcelona
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
state: La Coruña
city: Santiago De Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago
state: La Coruña
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
state: Madrid
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
state: Sevill
city: San Cristobal de la Laguna
country: Spain
facility: Hospital Universitario de Canarias
state: Tenerife
city: Badajoz
country: Spain
facility: Hospital Infanta Cristina
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: IOB-Institute of Oncology
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: MD Anderson Cancer Centre
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Málaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Koo Foundation, Sun Yat-Sen Cancer Center
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital (Wonford)
state: Devon
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Grampian Region
city: London
country: United Kingdom
facility: Queen Mary University of London
state: Greater London
city: London
country: United Kingdom
facility: University College London Hospitals
state: Greater London
city: London
country: United Kingdom
facility: Guy's Hospital
state: Greater London
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
state: Greater London
city: Manchester
country: United Kingdom
facility: The Christie Hospital
state: Greater Manchester
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
state: Lothian Region
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals City Campus
state: Nottinghamshire
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
state: Surrey
Study officials:
affiliation: Daiichi Sankyo
name: Global Team Leader
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.