DS-8201a in Pre-treated HER2 Breast Cancer That Cannot be Surgically Removed or Has Spread [DESTINY-Breast02]

Breast Cancer Clinical Trial

Official 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03523585
• Other study ID #: DS8201-A-U301
• Secondary ID: 2018-000221-3118
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 1, 2018
• Est. completion date: May 1, 2025

Study information

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

Clinical Trial 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

Description:

The study is designed to compare DS 8201a versus standard of care (investigator's choice) in subjects with unresectable and/or metastatic breast cancer previously treated with T-DM1.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 608
• Est. completion date: May 1, 2025
• Est. primary completion date: June 30, 2022
• 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 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

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• 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
• Capecitabine
Investigator's choice Standard of Care when combined with trastuzumab or lapatinib
• Lapatinib
Investigator's choice Standard of Care when combined with capecitabine
• Trastuzumab
Investigator's choice Standard of Care when combined with capecitabine

Locations

Country	Name	City	State
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Calvary North Adelaide Hospital	Bruce
Australia	St Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	Frankston Hospital	Frankston	Victoria
Australia	Peninsula and South Eastern Haematology & Oncology Group	Frankston	Victoria
Australia	Austin Health	Heidelberg	Victoria
Australia	Ashford Cancer Centre Research	Kurralta Park	South Australia
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Sunshine Hospital	Saint Albans	Victoria
Australia	St John of God Subiaco Hospital	Subiaco	Western Australia
Australia	Macquarie University Hospital	Sydney	New South Wales
Australia	The Tweed Hospital	Tweed Heads	New South Wales
Australia	South West Oncology	Warrnambool	Victoria
Australia	Ballarat Oncology & Haematology Service	Wendouree	Victoria
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	Universitair Ziekenhuis Brussel	Bruxelles
Belgium	AZ Maria Middelares	Gent
Belgium	Az Groeninge	Kortrijk
Belgium	UZ Leuven	Leuven
Belgium	CHU UCL Namur site de Sainte Elisabeth	Namur
Brazil	Pronutrir	Fortaleza	Ceará
Brazil	Clínica de Neoplasias Litoral Ltda.	Itajaí	Santa Catarina
Brazil	Oncobio Servicos de Saude	Nova Lima	Minas Gerais
Brazil	CliniOnco - Tratamento Integrado do Câncer	Porto Alegre	Rio Grande Do Sul
Brazil	Escosteguy Barrios, Carlos Henrique	Porto Alegre	Rio Grande Do Sul
Brazil	HGB - Hospital Giovanni Battista - Mãe de Deus Center	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital Nossa Senhora da Conceição	Porto Alegre	Rio Grande Do Sul
Brazil	COI - Clínicas Oncológicas Integradas	Rio De Janeiro
Brazil	AMO - Assistência Multidisciplinar em Oncologia	Salvador	Bahia
Brazil	NOB - Núcleo 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	IBCC - Instituto Brasileiro de Controle do Câncer	São Paulo	Sao Paulo
Brazil	Sociedade Beneficiente de Senhoras Hospital Sírio Libanês	São Paulo
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Fakultni nemocnice Olomouc	Olomouc
Czechia	Fakultni nemocnice v Motole	Prague 5
Czechia	Nemocnice Na Bulovce	Praha
France	Hôpital Privé d'Antony	Antony	Hauts De Seine
France	Institut Sainte Catherine	Avignon Cedex 9	Vaculuse
France	Centre Hospitalier de la côte Basque	Bayonne Cedex	Pyrenees Atlantiques
France	CHU Besançon - Hôpital Jean Minjoz	Besançon	Doubs
France	CHU Brest - Hôpital Morvan	Brest Cedex	Finistere
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 Oscar Lambret	Lille cedex	Nord
France	Hôpital Nord - CHU Marseille	Marseille cedex 20	Bouches-du-Rhône
France	Clinique Clementville	Montpellier	Herault
France	Institut Régional du Cancer de Montpellier	Montpellier	Herault
France	Institut Régional du Cancer de Montpellier	Montpellier
France	Hopital Tenon	Paris
France	Institut Curie - site de Paris	Paris
France	Institut Curie - site de Paris	Paris Cedex 05	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 Henri Becquerel	Rouen	Seine Maritime
France	Centre René Huguenin	Saint-Cloud	Hauts De Seine
France	Centre de cancerologie les Dentellieres	Valenciennes	Nord
France	Institut Gustave Roussy	Villejuif cedex	Val De Marne
Germany	Helios-Kliniken Berlin-Buch	Berlin
Germany	Marienhospital Bottrop gGmbH	Bottrop	Rheinland Pfalz
Germany	Universitaetsklinikum Duesseldorf AoeR	Düsseldorf
Germany	Universitaetsklinikum Erlangen	Erlangen
Germany	Kliniken Koeln	Koeln
Germany	Universitaetsklinikum Leipzig AoeR	Leipzig
Germany	Universitaetsklinikum Schleswig-Holstein - Campus Luebeck	Luebeck	Schleswig Holstein
Germany	Klinikum rechts der Isar der TU Muenchen	Muenchen	Bayern
Germany	Universitaetsklinikum Muenster	Müenster
Germany	Klinikum der Universitaet Muenchen - Campus Grosshardern	Munich
Germany	Haematologisch-Onkologische Schwerpunktpraxis	Troisdorf
Greece	251 General Air Force Hospital	Athens
Greece	General Hospital of Athens "Alexandra"	Athens
Greece	General Oncology Hospital of Kifissia " Agioi Anargyroi"	Athens
Greece	University General Hospital of Heraklion	Heraklion
Greece	Euromedica General Clinic Thessaloniki	Thessaloníki
Israel	Rambam Health Care Center	Haifa
Israel	Hadassah University Hospital - Ein Kerem	Jerusalem
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Sapir Medical Center, Meir Hospital	Kfar Saba
Israel	Rabin Medical Center-Beilinson Campus	Petah tikva
Israel	Chaim Sheba Medical Center	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
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
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	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
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)	Monza	Milano
Italy	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli
Italy	Ospedale Sacro Cuore Don Calabria	Negrar	Verona
Italy	IOV - Istituto Oncologico Veneto IRCCS	Padova
Italy	Azienda Ospedaliero Universitaria di Parma	Parma
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Azienda Ospedaliera Città della Salute e della Scienza di Torino	Torino
Japan	National Cancer Center Hospital	Chuo Ku	Tokyo-To
Japan	NHO Shikoku Cancer Center	Ehime
Japan	NHO Kyushu Cancer Center	Fukuoka
Japan	Fukushima Medical University Hospital	Fukushima-shi	Fukushima-Ken
Japan	Hiroshima City Hiroshima Citizens Hospital	Hiroshima
Japan	NHO Hokkaido Cancer Center	Hokkaido
Japan	Hyogo College of Medicine Hospital	Hyogo
Japan	Kanagawa Cancer Center	Kanagawa
Japan	St. Marianna University School of Medicine Hospital	Kanagawa
Japan	Kyoto University Hospital	Kyoto
Japan	Tohoku University Hospital	Miyagi
Japan	Aichi Cancer Center Hospital	Nagoya
Japan	Niigata Cancer Center Hospital	Niigata
Japan	Okayama University Hospital	Okayama
Japan	NHO Osaka National Hospital	Osaka
Japan	Osaka International Cancer Institute	Osaka
Japan	Kindai University Hospital	Osakasayama-shi	Osaka-Fu
Japan	Kindai University Hospital	Osakasayama-shi	Osaka-Fu
Japan	Saitama Cancer Center	Saitama
Japan	Shizuoka Cancer Center	Shizuoka
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Japan	Tokyo Medical University Hospital	Tokyo
Japan	Toranomon Hospital	Tokyo
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si	Chungcheongbuk-do
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Inha University Hospital	Incheon	Gyeonggi-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Korea, Republic of	Ajou University Hospital	Suwon	Gyeonggi-do
Korea, Republic of	The Catholic University of Korea, St. Vincent's Hospital	Suwon-si	Gyeonggi-do
Spain	Complejo Hospitalario Universitario A Coruña	A Coruña	La Coruña
Spain	Hospital Infanta Cristina	Badajoz
Spain	ICO Badalona - Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Quironsalud Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital de Especialidades de Jerez de la Frontera	Jerez De La Frontera	Cádiz
Spain	ICO l'Hospitalet - Hospital Duran i Reynals	L'Hospitalet De Llobregat	Barcelona
Spain	Hospital Universitari Arnau de Vilanova	Lleida
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario Clinico San Carlos	Madrid
Spain	MD Anderson Cancer Centre	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria	Málaga
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario de Canarias	San Cristobal de la Laguna	Tenerife
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Instituto Valenciano de Oncologia IVO	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza
Turkey	Acibadem Adana Hospital	Adana
Turkey	Adana Numune Training and Research Hospital	Adana
Turkey	Ankara Yildirim Beyazit Uni. Med. Fac.Ankara City Hospital	Ankara
Turkey	Akdeniz University Medical Faculty	Antalya
Turkey	Uludag University Medical Faculty	Bursa
Turkey	Bakirkoy Dr. Sadi Konuk Teaching and Research Hospital	Istanbul
Turkey	Istanbul Medeniyet Uni Goztepe Training & Research Hospital	Istanbul
Turkey	Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty	Istanbul
Turkey	Kartal Lutfi Kirdar Research and Training Hospital	Istanbul
Turkey	Medical Park Goztepe Hospital	Istanbul
Turkey	Medipol University Medical Faculty	Istanbul
Turkey	Izmir Medicalpark Hospital	Izmir
Turkey	Konya Necmettin Erbakan University Meram Faculty of Medicine	Konya
Turkey	Sakarya Traning and Research Hospital	Sakarya
Turkey	Medical Park Samsun Hastanesi	Samsun
Turkey	Namik Kemal University	Tekirdag
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	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	Nottingham University Hospitals City Campus	Nottingham	Nottinghamshire
United Kingdom	Derriford Hospital	Plymouth	Devon
United Kingdom	Royal Cornwall Hospital	Truro	Cornwall
United States	Piedmont Cancer Institute, PC	Atlanta	Georgia
United States	University of Maryland	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Ironwood Cancer Research Centers	Chandler	Arizona
United States	Tennessee Oncology, PLLC Chattanooga	Chattanooga	Tennessee
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Main Campus	Cleveland	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	North Shore Hematology Oncology Associates, PC	East Setauket	New York
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Florida Cancer Specialists-Broadway	Fort Myers	Florida
United States	The West Clinic	Germantown	Tennessee
United States	Kapiolani Medical Center for Women and Children/Univ of HI	Honolulu	Hawaii
United States	MD Anderson Cancer Center	Houston	Texas
United States	The Methodist Hospital Research Institute	Houston	Texas
United States	Cornell-Beshore Cancer Institute	Joplin	Missouri
United States	Health Midwest Ventures Group, Inc d/b/a HCA MidAmerica Division, LLC	Kansas City	Missouri
United States	Saint Luke's Cancer Institute	Kansas City	Missouri
United States	Dayton Physicians, LLC	Kettering	Ohio
United States	UCLA Hematology Oncology - Main Site	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Loyola University Health System	Maywood	Illinois
United States	Pacific Cancer Care	Monterey	California
United States	Community Hospital	Munster	Indiana
United States	SCRI - Tennessee Oncology	Nashville	Tennessee
United States	Smilow Cancer Hospital at Yale New Haven	New Haven	Connecticut
United States	Memorial Sloan-Kettering Cancer Center (MSKCC) - New York	New York	New York
United States	Community Cancer Trials of Utah	Ogden	Utah
United States	Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	UPMC Cancer Center	Pittsburgh	Pennsylvania
United States	Washington University	Saint Louis	Missouri
United States	Sharp Memorial Hospital	San Diego	California
United States	Maine Center for Cancer Medicine	Scarborough	Maine
United States	MultiCare Health System Institute for Research and Innovation	Tacoma	Washington
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

Sponsors (3)

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

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Czechia,  France,  Germany,  Greece,  Israel,  Italy,  Japan,  Korea, Republic of,  Spain,  Turkey,  United Kingdom, 

References & Publications (1)

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, C — View Citation

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 Participants Previously Treated With Trastuzumab Emtansine	Progression-free survival (PFS) by BICR was defined as the time from the date of randomization 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.	Baseline up to 46 months postdose
Secondary	Overall Survival (OS) in Participants With HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated With Trastuzumab Emtansine	Overall survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. If there is no death reported for a subject before the data cutoff for OS analysis, OS will be censored at the last contact date at which the subject is known to be alive.	Baseline up to 46 months postdose
Secondary	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	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 based on BICR and Investigator Assessment is reported.	Baseline up to 46 months postdose
Secondary	Duration of Response (DoR) Based on BICR in Participants With HER2-positive, Unresectable and/or Metastatic Breast Cancer Participants Previously Treated With Trastuzumab Emtansine	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.	Baseline up to 46 months postdose
Secondary	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	Progression-free survival (PFS) by investigator assessment was defined as the time from the date of randomization 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.	Up to 46 months