Trastuzumab Deruxtecan (DS-8201a) Versus Investigator's Choice for HER2-low Breast Cancer That Has Spread or Cannot be Surgically Removed [DESTINY-Breast04]

• ClinicalTrials.gov Identifier: NCT03734029
• Recruitment Status: Active, not recruiting
• First Posted: November 7, 2018
• Results First Posted: June 15, 2023
• Last Update Posted: April 11, 2024
• Sponsor: Daiichi Sankyo
• Collaborators: Daiichi Sankyo Co., Ltd.; AstraZeneca
• Information provided by (Responsible Party): Daiichi Sankyo

Study Description

Brief Summary:

This study will compare DS-8201a to physician choice standard treatment.

Participants must have HER2-low breast cancer that has been treated before.

Participants' cancer:

• Cannot be removed by an operation
• Has spread to other parts of the body

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: Trastuzumab deruxtecan (DS-8201a); Drug: Capecitabine; Drug: Eribulin; Drug: Gemcitabine; Drug: Paclitaxel; Drug: Nab-paclitaxel	Phase 3

Detailed Description:

This is a randomized, 2-arm, Phase 3, open-label, multicenter study to compare the safety and efficacy of trastuzumab deruxtecan versus the physician's choice (2:1) in HER2-low, unresectable and/or metastatic breast cancer participants.

The Sponsor proposes to define a new HER2-low population in this trial including tumors with IHC 1+ and IHC 2+/ISH- HER2 expression.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 557 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Parallel model, randomized at a 2:1 ratio
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Randomized, Open-label, Active Controlled Trial of DS-8201a, an Anti-HER2-antibody Drug Conjugate (ADC), Versus Treatment of Physician's Choice for HER2-low, Unresectable and/or Metastatic Breast Cancer Subjects
• Actual Study Start Date: December 27, 2018
• Actual Primary Completion Date: January 11, 2022
• Estimated Study Completion Date: October 1, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Trastuzumab deruxtecan; HER2-low, unresectable, and/or metastatic breast cancer participants previously treated with chemotherapy randomized to DS8201a	Drug: Trastuzumab deruxtecan (DS-8201a); DS-8201a is a lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered intravenously; Other Name: DS-8201a
Active Comparator: Physician's Choice; HER2-low, unresectable, and/or metastatic breast cancer participants previously treated with chemotherapy randomized to Physician's choice from the following options: Capecitabine; Eribulin; Gemcitabine; Paclitaxel; Nab-paclitaxel	Drug: Capecitabine; Administered according to label, as one option for Physician's Choice (determined before randomization); Drug: Eribulin; Administered according to label, as one option for Physician's Choice (determined before randomization); Drug: Gemcitabine; Administered according to label, as one option for Physician's Choice (determined before randomization); Drug: Paclitaxel; Administered according to label, as one option for Physician's Choice (determined before randomization); Drug: Nab-paclitaxel; Administered according to label, as one option for Physician's Choice (determined before randomization)

Outcome Measures

Primary Outcome Measures :

1. Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer [ Time Frame: From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years ]
   Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on blinded independent central review (BICR) in the hormone receptor-positive cohort according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.

Secondary Outcome Measures :

1. Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants With HER2-low Breast Cancer (All Patients) Regardless of Hormone Receptor Status [ Time Frame: From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years ]
   Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on blinded independent central review (BICR) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.
2. Progression-free Survival Based on Investigator Assessment in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer [ Time Frame: From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years ]
   Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on investigator assessment in the hormone receptor-positive cohort according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.
3. Progression-free Survival Based on Investigator Assessment in Participants With HER2-low Breast Cancer (All Patients) [ Time Frame: From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years ]
   Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on investigator assessment according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.
4. Overall Survival (OS) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer [ Time Frame: From the date of randomization up to the date of death due to any cause, up to approximately 3 years ]
   Overall survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. If there was no death reported for a participant before the data cutoff for OS analysis, OS was censored at the last contact date at which the participant was known to be alive.
5. Number of Overall Survival Events (Deaths) [ Time Frame: From the date of randomization up to the date of death due to any cause, up to approximately 3 years ]
6. Overall Survival (OS) in All Patients [ Time Frame: From the date of randomization up to the date of death due to any cause, up to approximately 3 years ]
   Overall survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. If there was no death reported for a participant before the data cutoff for OS analysis, OS was censored at the last contact date at which the participant was known to be alive.
7. Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer [ Time Frame: From screening and every 6 weeks up to withdrawal of subject consent, progressive disease (PD), or unacceptable toxicity, up to approximately 3 years ]
   Best overall response rate and confirmed objective response rate (ORR) were assessed by blinded independent central review (BICR) and investigator assessment. Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Confirmed ORR was defined as the number of participants with complete and partial responses and confirmed by a second assessment.
8. Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) [ Time Frame: From screening and every 6 weeks up to withdrawal of subject consent, progressive disease (PD), or unacceptable toxicity, up to approximately 3 years ]
   Best overall response rate and confirmed objective response rate (ORR) were assessed by blinded independent central review (BICR) and investigator assessment. Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Confirmed ORR was defined as the number of participants with complete and partial responses and confirmed by a second assessment.
9. Duration of Response in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer [ Time Frame: From the date of the first documented objective response (CR or PR) to the first documented disease progression or death, whichever occurs first, up to approximately 3 years ]
   Duration of Response (DoR) is defined as the date of the first documented objective response (complete response [CR] or partial response [PR]) to the first documented disease progression or death, whichever occurs first. DoR was based on blinded independent central review (BICR) and investigator assessment. Median was from Kaplan-Meier estimate. Confidence interval for median was computed using the Brookmeyer-Crowley method.
10. Duration of Response in Participants With HER2-low Breast Cancer (All Patients) [ Time Frame: From the date of the first documented objective response (CR or PR) to the first documented disease progression or death, whichever occurs first, up to approximately 3 years ]
    Duration of Response (DoR) is defined as the date of the first documented objective response (complete response [CR] or partial response [PR]) to the first documented disease progression or death, whichever occurs first. DoR was based on blinded independent central review (BICR) and investigator assessment. Median was from Kaplan-Meier estimate. Confidence interval for median was computed using the Brookmeyer-Crowley method.

Other Outcome Measures:

1. All-Cause Mortality [ Time Frame: From the date of randomization up to the date of death due to any cause, up to approximately 3 years ]
   All-cause mortality is defined as all anticipated and unanticipated deaths due to any cause, with the number and frequency of such events by arm or comparison group of the clinical study.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Is the age of majority in their country

• Has pathologically documented breast cancer that:

  1. Is unresectable or metastatic
  2. Has low-HER2 expression defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested)
  3. Is HR-positive or HR-negative
  4. Has progressed on, and would no longer benefit from, endocrine therapy
  5. Has been treated with 1 to 2 prior lines of chemotherapy/adjuvant in the recurrent or metastatic setting
  6. Was never previously HER2-positive (ICH 3+ or ISH+) on prior pathology testing (per American Society of Clinical Oncology-College of American Pathologists [ASCO-CAP] guidelines)
• Has documented radiologic progression (during or after most recent treatment)

• Has adequate archival tumor samples available or is wiling to provide fresh biopsies prior to randomization for:

  1. assessment of HER2 status
  2. assessment of post-treatment status
• Has at least 1 measurable lesion per Response Evaluation Criteria In Solid Tumors 1.1
• Has protocol-defined adequate cardiac, bone marrow, renal, hepatic and blood clotting functions
• Male and female participants of reproductive/childbearing potential, agrees to follow instructions for method(s) of contraception and agrees to avoid preserving ova or sperm for at least 4.5 months after treatment (or longer, per locally approved labels)

Exclusion Criteria:

• Is ineligible for all options in the physician's choice arm
• Has breast cancer ever assessed with high-HER2 expression
• Has previously been treated with any anti-HER2 therapy, including an antibody drug conjugate
• Has uncontrolled or significant cardiovascular disease
• Has spinal cord compression or clinically active central nervous system metastases
• Has 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 any medical history or condition that per protocol or in the opinion of the investigator is inappropriate for the study

Contacts and Locations

Locations

United States, Arizona

Ironwood Cancer & Research Centers - Chandler II

Chandler, Arizona, United States, 85224

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States, 85234-2165

Cancer Treatment Centers of America at Western Regional Medical Center

Goodyear, Arizona, United States, 85338

United States, California

UCLA School of Medicine

Los Angeles, California, United States, 90095-1690

Stanford Cancer Institute

Palo Alto, California, United States, 94305

Cancer Care Associates Medical Group, Inc. TORI

Redondo Beach, California, United States, 90277

University of California at San Francisco (PARENT)

San Francisco, California, United States, 94158

United States, Connecticut

Eastern Connecticut Hematology/Oncology Assoc.

Norwich, Connecticut, United States, 06360

United States, Delaware

Christiana Care Health Services, Inc.

Newark, Delaware, United States, 19713

United States, Florida

Sylvester Comprehensive Cancer Center - Deerfield Beach

Boca Raton, Florida, United States, 33426

Florida Cancer Specialists (South Region)

Fort Myers, Florida, United States, 33916

Memorial Healthcare System MRH Cancer Center

Hollywood, Florida, United States, 33021

Orlando Health, Inc.

Orlando, Florida, United States, 32806

Moffitt Cancer Center -Tampa

Tampa, Florida, United States, 33139

United States, Georgia

Cancer Treatment Centers of America-Georgia

Newnan, Georgia, United States, 30263

United States, Illinois

University of Chicago Medical Center

Chicago, Illinois, United States, 60637

Cancer Treatment Centers of America

Zion, Illinois, United States, 60099

United States, Kansas

Cancer Center of Kansas

Wichita, Kansas, United States, 67214

United States, Louisiana

Touro Infirmary

New Orleans, Louisiana, United States, 70115

United States, Massachusetts

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Michigan

Henry Ford Hospital

Detroit, Michigan, United States, 48202

United States, Missouri

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, United States, 64111

United States, New Jersey

Saint Barnabas Medical Center

Livingston, New Jersey, United States, 07039

United States, New York

New York University Medical Center

New York, New York, United States, 10016

Memorial Sloan Kettering Hospital

New York, New York, United States, 10065-6007

Weill Cornell Medicine Breast Center

New York, New York, United States, 10065

United States, Ohio

The Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44195

United States, Oregon

Oregon Health & Science University

Portland, Oregon, United States, 97239

United States, Pennsylvania

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States, 15212

University of Pittsburgh Medical Center Health System

Pittsburgh, Pennsylvania, United States, 15219

United States, South Carolina

St Francis Hospital

Greenville, South Carolina, United States, 29601

United States, Tennessee

Brig Center for Cancer Care and Survivorship

Knoxville, Tennessee, United States, 37909

Baptist Cancer Center

Memphis, Tennessee, United States, 38120

Tennessee Oncology - Skyline Satellite

Nashville, Tennessee, United States, 37201

United States, Texas

BloomTrials Clinical Research, LLC

Dallas, Texas, United States, 75234

The Methodist Hospital Research Institute

Houston, Texas, United States, 77030

University of Texas M. D. Anderson Cancer Center - Investigational Cancer Therapeutics

Houston, Texas, United States, 77030

United States, Virginia

Virginia Cancer Specialists

Fairfax, Virginia, United States, 22031

Austria

Medizinische Universität Innsbruck

Innsbruck, Austria, 6020

Kepler Universitätsklinikum

Linz, Austria, 4020

LKH - Universitätsklinikum der PMU Salzburg

Salzburg, Austria, 5020

AKH - Medizinische Universität Wien (4305)

Vienna, Austria, 1090

Klinikum Wels-Grieskirchen GmbH

Wels, Austria, 4600

Belgium

Institut Jules Bordet

Bruxelles, Belgium, 1000

Universitair Ziekenhuis Brussel

Bruxelles, Belgium, 1090

Cliniques Universitaires Saint-Luc

Bruxelles, Belgium, 1200

UZ Leuven

Leuven, Belgium, 3000

Grand Hôpital de Charleroi

Loverval, Belgium, 6280

CHU UCL Namur

Namur, Belgium, 5000

Centre Hospitalier Wallonie picarde - Site IMC

Tournai, Belgium, 7500

Canada, Alberta

Tom Baker Cancer Center

Calgary, Alberta, Canada, T2N4N2

Canada, Ontario

Toronto Sunnybrook Hospital

Toronto, Ontario, Canada, M4N 3M5

Canada, Quebec

McGill University - Dept. Oncology Clinical Research Program

Montréal, Quebec, Canada, H2W 1S6

China, Anhui

Anhui Provincial Hospital

Hefei, Anhui, China, 230001

China, Beijing

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing, China, 100021

Chinese PLA General Hospital

Beijing, Beijing, China, 100853

China, Fujian

Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA

Fuzhou, Fujian, China, 350025

China, Guangdong

Sun Yat-sen Memorial hospital, Sun Yat-sen University

Guangzhou, Guangdong, China, 510120

China, Heilongjiang

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China, 150081

China, Hubei

Hubei Cancer Hospital

Wuhan, Hubei, China, 430079

China, Jiangsu

The Affiliated Drum Tower Hospital of Nanjing University

Nanjing, Jiangsu, China, 210008

China, Jilin

The First Hospital of Jilin University

Chang chun, Jilin, China, 130000

Jilin Cancer Hospital

Chang chun, Jilin, China, 130012

China, Liaoning

Liaoning Cancer Hospital & Institute

Shenyang, Liaoning, China, 110042

China, Ningxia

General Hospital of Ningxia Medical University

Yinchuan, Ningxia, China, 750004

China, Shandong

Linyi Cancer Hospital

Linyi, Shandong, China, 276001

China, Shanghai

Shanghai General Hospital

Shanghai, Shanghai, China, 200080

Fudan University Shanghai Cancer Center

Shanghai, Shanghai, China, 20032

China, Sichuan

West China Hospital, Sichuan University

Chengdu, Sichuan, China, 610041

China, Zhejiang

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

Hangzhou, Zhejiang, China, 310016

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China, 310022

France

Institut Paoli Calmettes

Marseille cedex 9, Bouches-du-Rhône, France, 13009

Centre François Baclesse

Caen, Calvados, France, 14076

CARIO - Centre Armoricain de Radiothérapie, Imagerie médicale et Oncologie

Plérin, Cotes d'Armor, France, 22190

CHU Brest - Hôpital Morvan

Brest Cedex, Finistere, France, 29609

Institut Bergonié

Bordeaux cedex, Gironde, France, 33076

Clinique Clementville

Montpellier, Herault, France, 34070

Institut Régional du Cancer de Montpellier

Montpellier, Herault, France, 34298

CRLCC Eugene Marquis

Rennes-cedex, Ille Et Vilaine, France, 35042

ICO - Site René Gauducheau

Saint-Herblain, Loire Atlantique, France, 44805

Centre Hospitalier Emile Roux

Le Puy-en-Velay, Loiret, France, 43012

ICO - Site Paul Papin

Angers Cedex 2, Maine Et Loire, France, 49055

Centre Hospitalier Valenciennes

Valenciennes, Nord, France, 59322

Hôpital Saint-Louis - Paris

Paris Cedex 10, Paris, France, 75475

Clinique Victor Hugo - Centre Jean Bernard

Le Mans Cedex 02, Sarthe, France, 72015

Institut Sainte Catherine

Avignon Cedex 9, Vaculuse, France, 84918

Hôpital d'Instruction des Armees Begin*

Saint Mande, Val De Marne, France, 94160

Institut Gustave Roussy

Villejuif cedex, Val De Marne, France, 94805

Institut Curie - site de Paris

Paris, France, 75005

Hopital Tenon

Paris, France, 75020

Germany

Universitaetsklinikum Heidelberg

Heidelberg, Baden Wuerttemberg, Germany, 69120

Klinikum der Universitaet Muenchen - Campus Grosshardern

Munich, Bayern, Germany, 81377

Greece

General Hospital of Athens "Alexandra"

Athens, Greece, 11528

General Oncology Hospital of Kifissia " Agioi Anargyroi"

Athens, Greece, 14564

Athens Medical Center

Athens, Greece, 15125

University General Hospital of Heraklion

Heraklion, Greece, 71110

University General Hospital of Larissa

Larissa, Greece, 41110

Bioclinic Thessaloniki

Thessaloníki, Greece, 54622

Euromedica General Clinic Thessaloniki

Thessaloníki, Greece, 54645

General Hospital Papageorgiou

Thessaloníki, Greece, 56429

Interbalkan Hospital of Thessaloniki

Thessaloníki, Greece, 57001

Hungary

Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet

Budapest, Hungary, 1097

Orszagos Onkologiai Intezet

Budapest, Hungary, 1122

Debreceni Egyetem

Debrecen, Hungary, 4032

Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza

Gyula, Hungary, 5700

SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz

Nyiregyhaza, Hungary, 4400

Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet

Szolnok, Hungary, 5004

Israel

Rambam Health Care Center

Haifa, Israel, 3109601

Shaare Zedek Medical Center

Jerusalem, Israel, 9103102

Hadassah University Hospital - Ein Kerem

Jerusalem, Israel, 9112001

Rabin Medical Center-Beilinson Campus

Petah tikva, Israel, 49100

Chaim Sheba Medical Center

Ramat Gan, Israel, 52363

Kaplan Medical Center

Rechovot, Israel, 7610001

Ziv Medical Center

Safed, Israel, 13100

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel, 6423906

Italy

Azienda Ospedaliera Card. G. Panico

Tricase, Lecce, Italy, 73039

Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo)

Monza, Milano, Italy, 20900

Istituto Clinico Humanitas

Rozzano, Milano, Italy, 20089

Ospedale Sacro Cuore Don Calabria

Negrar, Verona, Italy, 37024

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi

Bologna, Italy, 40138

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)

Brescia, Italy, 25100

Azienda Ospedaliera Univ. Policlinico Gaspare Rodolico

Catania, Italy, 95125

Azienda Ospedaliero Universitaria Mater Domini-Campus Universitario

Catanzaro, Italy, 88100

IEO Istituto Europeo di Oncologia

Milano, Italy, 20141

Istituto Nazionale Tumori Fondazione G. Pascale

Napoli, Italy, 80131

Ospedale degli Infermi

Rimini, Italy, 47923

Azienda Ospedaliera Universitaria Policlinico Tor Vergata

Roma, Italy, 00133

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, Italy, 00168

Japan

Aichi Cancer Center Hospital

Nagoya, Aichi-Ken, Japan, 464-8681

National Cancer Center Hospital East

Kashiwa-shi, Chiba-Ken, Japan, 277-8577

NHO Shikoku Cancer Center

Matsuyama-shi, Ehime-Ken, Japan, 791-0280

NHO Kyushu Cancer Center

Fukuoka-shi, Fukuoka-Ken, Japan, 811-1395

Fukushima Medical University Hospital

Fukushima, Fukushima-Ken, Japan, 960-1295

Hiroshima City Hiroshima Citizens Hospital

Hiroshima-shi, Hiroshima-Ken, Japan, 730-8518

NHO Hokkaido Cancer Center

Sapporo-shi, Hokkaido, Japan, 003-0804

Hyogo College of Medicine Hospital

Nishinomiya-shi, Hyogo-Ken, Japan, 663-8501

Hakuaikai Sagara Hospital

Kagoshima, Kagoshima-Ken, Japan, 892-0833

Tokai University Hospital

Isehara, Kanagawa-Ken, Japan, 259-1193

Kanagawa Cancer Center

Yokohama, Kanagawa, Japan, 241-8515

NHO Osaka National Hospital

Osaka-shi, Osaka-Fu, Japan, 540-0006

Kindai University Hospital

Onohigashi, Osakasayama-shi, Japan, 589-8511

Saitama Cancer Center

Kitaadachi-gun, Saitama-Ken, Japan, 362-0806

Shizuoka Cancer Center

Sunto-gun, Shizuoka-Ken, Japan, 411-8777

Cancer Institute Hospital of JFCR

Koto-Ku, Tokyo-To, Japan, 135-8550

Toranomon Hospital

Minato-Ku, Tokyo-To, Japan, 105-8470

Showa University Hospital

Shinagawa-Ku, Tokyo-To, Japan, 142-8666

Korea, Republic of

Chungbuk National University Hospital

Cheongju-si, Chungcheongbuk-do, Korea, Republic of, 361-711

National Cancer Center

Goyang-si, Gyeonggi-do, Korea, Republic of, 10408

Inha University Hospital

Incheon, Gyeonggi-do, Korea, Republic of, 22332

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620

Ajou University Hospital

Suwon, Gyeonggi-do, Korea, Republic of, 16499

Kyungpook National University Chilgok Hospital

Daegu, Korea, Republic of, 41404

Seoul National University Hospital

Seoul, Korea, Republic of, 03080

Asan Medical Center

Seoul, Korea, Republic of, 05505

Samsung Medical Center

Seoul, Korea, Republic of, 06351

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, Korea, Republic of, 06591

Severance Hospital, Yonsei University Health System

Seoul, Korea, Republic of, 120-752

Portugal

Hospital de Braga

Braga, Portugal, 4710-243

Centro Hospitalar do Alto do Ave, EPE

Guimarães, Portugal, 4835-044

Fundação Champalimaud

Lisboa, Portugal, 1400-038

Centro Hospitalar de Lisboa Norte, E.P.E. - Hospital de Santa Maria

Lisboa, Portugal, 1649-035

Unidade Local de Saúde de Matosinhos, EPE (Hospital Pedro Hispano)

Matosinhos, Portugal, 4464-509

Centro Hospitalar do Porto, E.P.E. - Hospital de Santo António

Porto, Portugal, 4099-001

Instituto Português de Oncologia do Porto Francisco Gentil, EPE

Porto, Portugal, 4200-072

Centro Hospitalar de Entre o Douro e Vouga, E.P.E - Hospital de São Sebastião

Santa Maria Da Feira, Portugal, 4520-211

Centro Hospitalar Vila Nova de Gaia/Espinho, E.P.E

Vila Nova De Gaia, Portugal, 4434-502

Centro Hospitalar de Trás-os-Montes e Alto Douro, EPE

Vila Real, Portugal, 5000-508

Russian Federation

FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"

Moscow, Russian Federation, 115478

SBIH of Moscow City "Moscow City Oncology Hospital №62" of Moscow Healthcare Departement

Moscow, Russian Federation, 143423

SBIH of Yaroslavl Region "Regional Clinical Oncological Hospital"

Yaroslavl, Russian Federation, 150054

Spain

ICO l'Hospitalet - Hospital Duran i Reynals

L'Hospitalet De Llobregat, Barcelona, Spain, 08908

Hospital Universitario Donostia

San Sebastián, Guipuzcoa, Spain, 20014

Complejo Hospitalario Universitario A Coruña

A Coruña, La Coruña, Spain, 15006

Hospital Universitario de Canarias

San Cristobal de la Laguna, Tenerife, Spain, 38320

Hospital de Basurto

Bilbao, Vizcaya, Spain, 48013

Hospital del Mar

Barcelona, Spain, 08003

Hospital Quironsalud Barcelona

Barcelona, Spain, 08023

Hospital Universitari Vall d'Hebron

Barcelona, Spain, 08035

Hospital Clinic de Barcelona

Barcelona, Spain, 08036

MD Anderson Cancer Centre

Madrid, Spain, 28033

Hospital Ruber Internacional

Madrid, Spain, 28034

Hospital Universitario Ramon y Cajal

Madrid, Spain, 28034

Hospital Universitario Clinico San Carlos

Madrid, Spain, 28040

Hospital Clinico Universitario Virgen de la Victoria

Málaga, Spain, 29010

Hospital Universitario Virgen Macarena

Sevilla, Spain, 41009

Hospital Universitario Virgen del Rocio

Sevilla, Spain, 41013

Instituto Valenciano de Oncologia IVO

Valencia, Spain, 46009

Hospital General Universitario de Valencia

Valencia, Spain, 46014

Sweden

Karolinska universitetssjukhuset - Solna

Solna, Sweden, 17176

Länssjukhuset Sundsvall-Härnösand

Sundsvall, Sweden, 85186

Akademiska Sjukhuset

Uppsala, Sweden, 75185

Switzerland

Hirslanden Medical Center

Aarau, Switzerland, 5000

Universitaetsspital Basel

Basel, Switzerland, 4031

Kantonsspital Graubuenden

Chur, Switzerland, 7000

Centre Hospitalier Universitaire Vaudois

Lausanne, Switzerland, 1011

Kantonsspital St. Gallen

Saint Gallen, Switzerland, 9007

Kantonsspital Winterthur

Winterthur, Switzerland, 8401

Universitaetsspital Zuerich

Zürich, Switzerland, 8091

Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung, Taiwan, 807

National Cheng Kung University Hospital

Tainan, Taiwan, 704

National Taiwan University Hospital

Taipei, Taiwan, 100

United Kingdom

Royal Cornwall Hospital

Truro, Cornwall, United Kingdom, TR1 3LJ

Queen Mary University of London

London, Greater London, United Kingdom, EC1M 6BQ

University College London Hospitals

London, Greater London, United Kingdom, NW1 2PG

Royal Free Hospital

London, Greater London, United Kingdom, NW3 2QG

Western General Hospital

Edinburgh, Lothian Region, United Kingdom, EH4 2XU

Nottingham University Hospitals City Campus

Nottingham, Nottinghamshire, United Kingdom, NG5 1PB

Royal Surrey County Hospital

Guildford, Surrey, United Kingdom, GU2 7XX

Sponsors and Collaborators

Daiichi Sankyo

Daiichi Sankyo Co., Ltd.

AstraZeneca

Investigators

• Study Director: Global Clinical Leader; Daiichi Sankyo

  Study Documents (Full-Text)

Documents provided by Daiichi Sankyo:

Study Protocol and Statistical Analysis Plan  [PDF] October 12, 2020

More Information

Publications of Results:

Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga JY, Im SA, Moore HCF, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim SB, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20. doi: 10.1056/NEJMoa2203690. Epub 2022 Jun 5.

• Responsible Party: Daiichi Sankyo
• ClinicalTrials.gov Identifier: NCT03734029
• Other Study ID Numbers: DS8201-A-U303; 2018-003069-33 ( EudraCT Number ); 184223 ( Registry Identifier: JAPIC CTI ); DESTINY-B04 ( Other Identifier: Daiichi Sankyo and AstraZeneca )
• First Posted: November 7, 2018
• Results First Posted: June 15, 2023
• Last Update Posted: April 11, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• URL: https://vivli.org/ourmember/daiichi-sankyo/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Daiichi Sankyo:

Anti-HER2-Antibody Drug Conjugate (ADC); Unresectable or Metastatic; Human epidermal growth factor receptor 2 (HER2)-low; DESTINY - Breast 04

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Paclitaxel; Camptothecin; Albumin-Bound Paclitaxel; Gemcitabine; Capecitabine; Trastuzumab; Trastuzumab deruxtecan; Immunoconjugates; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents, Immunological; Immunologic Factors; Physiological Effects of Drugs; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors