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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]

Phase 3
Active, not recruiting
Conditions
Breast Cancer
Interventions
Registration Number
NCT03529110
Lead Sponsor
Daiichi Sankyo
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 available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
524
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Trastuzumab deruxtecan (T-DXd)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).
Ado-trastuzumab emtansine (T-DM1)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.
Primary Outcome Measures
NameTimeMethod
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 TaxaneUp 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.

Secondary Outcome Measures
NameTimeMethod
Overall Survival (OS) in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and TaxaneUp 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.

Progression-Free Survival (PFS) Based on Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and TaxaneUp 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.

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 TaxaneUp 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 TaxaneUp 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.

Trial Locations

Locations (164)

Florida Cancer Specialists-Broadway

🇺🇸

Fort Myers, Florida, United States

Piedmont Cancer Institute, PC

🇺🇸

Atlanta, Georgia, United States

The Ohio State University

🇺🇸

Columbus, Ohio, United States

NOB - Nucleo de Oncologia da Bahia

🇧🇷

Salvador, Bahia, Brazil

Toronto Sunnybrook Hospital

🇨🇦

Toronto, Ontario, Canada

Sharp Memorial Hospital

🇺🇸

San Diego, California, United States

Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

University of Cincinnati Medical Center

🇺🇸

Cincinnati, Ohio, United States

MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

Millennium Oncology

🇺🇸

Houston, Texas, United States

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

🇨🇳

Guangzhou, Guangdong, China

Tianjin Medical University Cancer Institute & Hospital

🇨🇳

Tianjin, Tianjin, China

Zhejiang Cancer Hospital

🇨🇳

Hangzhou, Zhejiang, China

University of Rochester

🇺🇸

Rochester, New York, United States

National Cheng Kung University Hospital

🇨🇳

Tainan, Taiwan

Azienda Ospedaliera Ospedali Riuniti Papardo-Piemonte

🇮🇹

Messina, Italy

ICO - Site Paul Papin

🇫🇷

Angers Cedex 2, Maine Et Loire, France

Centre Leon Berard

🇫🇷

Lyon Cedex 08, Rhone, France

Institut Curie - site de Paris

🇫🇷

Paris, France

Hôpital Saint-Louis

🇫🇷

Paris, France

Institut Gustave Roussy

🇫🇷

Villejuif cedex, Val De Marne, France

Centre Hospitalier Lyon Sud

🇫🇷

Pierre Benite Cedex, Rhone, France

Shizuoka Cancer Center

🇯🇵

Shizuoka, Japan

Queen Mary University of London

🇬🇧

London, Greater London, United Kingdom

St. Mary's Hospital

🇨🇦

Montréal, Quebec, Canada

CHRU Jean Minjoz

🇫🇷

Besançon, Doubs, France

University of California San Francisco

🇺🇸

San Francisco, California, United States

University of Nebraska Medical Center

🇺🇸

Omaha, Nebraska, United States

Vanderbilt Breast Center at One Hundred Oaks

🇺🇸

Nashville, Tennessee, United States

Loyola University Health System

🇺🇸

Maywood, Illinois, United States

Box Hill Hospital

🇦🇺

Box Hill, Victoria, Australia

UCLA Hematology Oncology

🇺🇸

Los Angeles, California, United States

Washington Cancer Institute

🇺🇸

Washington, District of Columbia, United States

Florida Cancer Specialists NORTH

🇺🇸

Saint Petersburg, Florida, United States

Dayton Physicians, LLC

🇺🇸

Kettering, Ohio, United States

Seidman Cancer Center

🇺🇸

Cleveland, Ohio, United States

UT Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

Houston Methodist Hospital / Houston Methodist Cancer Center

🇺🇸

Houston, Texas, United States

MultiCare Health System Institute for Research and Innovation

🇺🇸

Auburn, Washington, United States

Princess Alexandra Hospital

🇦🇺

Woolloongabba, Queensland, Australia

The Tweed Hospital

🇦🇺

Tweed Heads, New South Wales, Australia

Universitair Ziekenhuis Antwerpen

🇧🇪

Edegem, Belgium

St John of God Subiaco Hospital

🇦🇺

Subiaco, Western Australia, Australia

Institut Jules-Bordet

🇧🇪

Bruxelles, Belgium

Peter MacCallum Cancer

🇦🇺

Melbourne, Victoria, Australia

Universitair Ziekenhuis Brussel

🇧🇪

Bruxelles, Belgium

Peninsula and South Eastern Haematology & Oncology Group

🇦🇺

Frankston, Victoria, Australia

AZ Sint-Lucas - Campus Sint-Lucas

🇧🇪

Gent, Belgium

Universitaire Ziekenhuizen Leuven

🇧🇪

Leuven, Belgium

CHU UCL Namur site de Sainte Elisabeth

🇧🇪

Namur, Belgium

CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia

🇧🇷

Santo André, Sao Paulo, Brazil

ICESP - Instituto do Cancer do Estado de São Paulo Octavio Frias de Oliveira

🇧🇷

São Paulo, Sao Paulo, Brazil

Instituto Americas

🇧🇷

Rio De Janeiro, Brazil

Clínica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária Ltda.

🇧🇷

São Paulo, Sao Paulo, Brazil

Beijing Hospital

🇨🇳

Beijing, Beijing, China

Liaoning Cancer Hospital & Institute

🇨🇳

Shenyang, Liaoning, China

Cancer Hospital Chinese Academy of Medical Sciences

🇨🇳

Beijing, Beijing, China

The First Hospital of Jilin University

🇨🇳

Chang chun, Jilin, China

Sun Yat-sen University, Cancer Center

🇨🇳

Guangzhou, Guangdong, China

Fudan University Shanghai Cancer Center

🇨🇳

Shanghai, Shanghai, China

West China Hospital, Sichuan University

🇨🇳

Chengdu, Sichuan, China

Sir Run Run Shaw Hospital Xiasha Branch, Zhejiang University, School of Medicine

🇨🇳

Hangzhou, Zhejiang, China

Centre Paul Strauss

🇫🇷

Strasbourg Cedex, Bas Rhin, France

Hôpital Nord - CHU Marseille

🇫🇷

Marseille Cedex 20, Bouches-du-Rhone, France

Centre Georges François Leclerc

🇫🇷

Dijon cedex, Côte-d'Or, France

ICM Val d'Aurelle

🇫🇷

Montpellier, Herault, France

CRLCC Eugene Marquis

🇫🇷

Rennes cedex, Ille Et Vilaine, France

Centre de cancerologie les Dentellieres

🇫🇷

Valenciennes, Nord, France

Institut Sainte Catherine

🇫🇷

Avignon Cedex 9, Vaculuse, France

Hopital Tenon

🇫🇷

Paris, France

Hôpital d'Instruction des Armees Begin

🇫🇷

Saint-Mandé, Val De Marne, France

Universitaetsklinikum Erlangen

🇩🇪

Erlangen, Bayern, Germany

Rotkreuzklinikum Muenchen gGmbH

🇩🇪

Muenchen, Bayern, Germany

Universitaetsklinikum Duesseldorf AoeR

🇩🇪

Düsseldorf, Nordrhein Westfalen, Germany

The Chinese

🇭🇰

Hong Kong, Hong Kong

Haematologisch-Onkologische Schwerpunktpraxis

🇩🇪

Troisdorf, Nordrhein Westfalen, Germany

Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo), U.O Oncologia Medica

🇮🇹

Monza, Milano, Italy

Istituto Nazionale per la Ricerca sul Cancro di Genova

🇮🇹

Genova, Italy

A.O.U. Policlinico di Modena

🇮🇹

Modena, Italy

Istituto Nazionale Tumori Fondazione G. Pascale

🇮🇹

Napoli, Italy

Azienda Ospedaliera Città della Salute e della Scienza di Torino

🇮🇹

Torino, Italy

NHO Kyushu Cancer Center

🇯🇵

Fukuoka, Japan

Azienda Ospedaliero Universitaria di Parma

🇮🇹

Parma, Italy

Aichi Cancer Center Hospital

🇯🇵

Aichi, Japan

Fondazione IRCCS Policlinico San Matteo

🇮🇹

Pavia, Italy

NHO Shikoku Cancer Center

🇯🇵

Ehime, Japan

NHO Hokkaido Cancer Center

🇯🇵

Hokkaido, Japan

Hiroshima City Hiroshima Citizens Hospital

🇯🇵

Hiroshima, Japan

Kanagawa Cancer Center

🇯🇵

Kanagawa, Japan

Niigata Cancer Center

🇯🇵

Niigata, Japan

Showa University Hospital

🇯🇵

Tokyo, Japan

NHO Osaka National Hospital

🇯🇵

Osaka, Japan

ICO l'Hospitalet - Hospital Duran i Reynals

🇪🇸

L'Hospitalet De Llobregat, Barcelona, Spain

Asan Medical Center

🇰🇷

Seoul, Korea, Republic of

Hospital Infanta Cristina

🇪🇸

Badajoz, Spain

Hospital Universitario de Canarias

🇪🇸

San Cristobal de la Laguna, Tenerife, Spain

Hospital General Universitario Gregorio Maranon

🇪🇸

Madrid, Spain

MD Anderson Cancer Centre

🇪🇸

Madrid, Spain

Hospital Universitario Virgen del Rocio

🇪🇸

Sevilla, Spain

Sarah Cannon Research Institute UK

🇬🇧

London, Greater London, United Kingdom

Innovative Clinical Research Institute

🇺🇸

Whittier, California, United States

North Shore Hematology Oncology Associates, PC

🇺🇸

East Setauket, New York, United States

Tennessee Oncology- St Thomas Location

🇺🇸

Nashville, Tennessee, United States

The University of Texas Health Science Center at Tyler

🇺🇸

Tyler, Texas, United States

Hospital Nossa Senhora da Conceição

🇧🇷

Porto Alegre, Rio Grande Do Sul, Brazil

Tom Baker Cancer Centre

🇨🇦

Calgary, Alberta, Canada

A. C. Camargo Cancer Center

🇧🇷

São Paulo, Brazil

Harbin Medical University Cancer Hospital

🇨🇳

Harbin, Heilongjiang, China

CARIO - Centre Armoricain de Radiothérapie, Imagerie médicale et Oncologie

🇫🇷

Plérin, Cotes d'Armor, France

Centre René Huguenin

🇫🇷

Saint-Cloud, Hauts De Seine, France

Clinique Victor Hugo - Centre Jean Bernard

🇫🇷

Le Mans, Cedex 02, Sarthe, France

ICO - Site René Gauducheau

🇫🇷

Saint-Herblain, Loire Atlantique, France

Ospedale San Raffaele

🇮🇹

Milano, Italy

Klinikum rechts der Isar der TU Muenchen

🇩🇪

Muenchen, Bayern, Germany

Universitaetsklinikum Schleswig-Holstein - Campus Luebeck

🇩🇪

Luebeck, Schleswig Holstein, Germany

Marienhospital Bottrop gGmbH

🇩🇪

Bottrop, Rheinland Pfalz, Germany

Istituto Clinico Humanitas

🇮🇹

Rozzano, Milano, Italy

Azienda Ospedaliera Universitaria Arcispedale Sant'Anna

🇮🇹

Cona, Ferrara, Italy

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)

🇮🇹

Bergamo, Italy

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi

🇮🇹

Bologna, Italy

Azienda Ospealiera della Provincia di Lecco

🇮🇹

Lecco, Italy

IEO Istituto Europeo di Oncologia

🇮🇹

Milano, Italy

Center Hospital of the National Center for Global Health and Medicine

🇯🇵

Shinjuku-Ku, Tokyo-To, Japan

Kumamoto University Hospital

🇯🇵

Kumamoto, Japan

Okayama University Hospital

🇯🇵

Okayama, Japan

Osaka International Cancer Institute

🇯🇵

Osaka, Japan

National Cancer Center Hospital

🇯🇵

Tokyo, Japan

Saitama Cancer Center

🇯🇵

Saitama, Japan

The Cancer Institute Hospital of JFCR

🇯🇵

Tokyo, Japan

Seoul National University Bundang Hospital

🇰🇷

Seongnam-si, Gyeonggi-do, Korea, Republic of

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

Severance Hospital, Yonsei University

🇰🇷

Seoul, Korea, Republic of

Samsung Medical Center

🇰🇷

Seoul, Korea, Republic of

Complejo Hospitalario Universitario A Coruña

🇪🇸

A Coruña, La Coruña, Spain

Complejo Hospitalario Universitario de Santiago

🇪🇸

Santiago De Compostela, La Coruña, Spain

Hospital Universitario Virgen Macarena

🇪🇸

Sevilla, Sevill, Spain

Hospital Universitario Puerta de Hierro Majadahonda

🇪🇸

Majadahonda, Madrid, Spain

IOB-Institute of Oncology

🇪🇸

Barcelona, Spain

Hospital Universitari Vall d'Hebron

🇪🇸

Barcelona, Spain

Hospital Clinic de Barcelona

🇪🇸

Barcelona, Spain

Hospital Universitario Ramon y Cajal

🇪🇸

Madrid, Spain

Hospital Universitario Clinico San Carlos

🇪🇸

Madrid, Spain

Hospital Universitario 12 de Octubre

🇪🇸

Madrid, Spain

Hospital Clinico Universitario Virgen de la Victoria

🇪🇸

Málaga, Spain

China Medical University Hospital

🇨🇳

Taichung, Taiwan

Taipei Veterans General Hospital

🇨🇳

Taipei, Taiwan

Koo Foundation, Sun Yat-Sen Cancer Center

🇨🇳

Taipei, Taiwan

Aberdeen Royal Infirmary

🇬🇧

Aberdeen, Grampian Region, 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 Kingdom

Western General Hospital

🇬🇧

Edinburgh, Lothian Region, United Kingdom

Royal Surrey County Hospital

🇬🇧

Guildford, Surrey, United Kingdom

Magee-Womens Hospital of UPMC

🇺🇸

Pittsburgh, Pennsylvania, United States

Norton Cancer Institute

🇺🇸

Louisville, Kentucky, United States

Wake Forest University Baptist Medical Center

🇺🇸

Winston-Salem, North Carolina, United States

Centre François Baclesse

🇫🇷

Caen Cedex 05, Calvados, France

Institut Bergonié

🇫🇷

Bordeaux cedex, Gironde, France

IRCCS Centro di Riferimento Oncologico

🇮🇹

Aviano, Pordenone, Italy

Royal Devon and Exeter Hospital (Wonford)

🇬🇧

Exeter, Devon, United Kingdom

Catarina Pesquisa Clinica

🇧🇷

Itajaí, Santa Catarina, Brazil

National Taiwan University Hospital

🇨🇳

Taipei, Taiwan

Guy's Hospital

🇬🇧

London, Greater London, United Kingdom

The University of Hong Kong

🇭🇰

Shatin, Hong Kong

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