Breast CancerPhase 3NCT03734029
Trastuzumab Deruxtecan (DS-8201a) Versus Investigator's Choice for HER2-low Breast Cancer That Has Spread or Cannot be Surgically Removed [DESTINY-Breast04]
A Phase 3 study testing Trastuzumab deruxtecan (DS-8201a), Capecitabine and Eribulin in people with Breast Cancer, run by Daiichi Sankyo at 208 sites in 20 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Trastuzumab deruxtecan (DS-8201a), Capecitabine and Eribulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 557 participants
- Where
- 208 sitesin 20 countries
- Study dates
- 27 Dec 2018to 19 May 2026
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Is the age of majority in their country
- Has pathologically documented breast cancer that:
- Is unresectable or metastatic
- Has low-HER2 expression defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested)
- Is HR-positive or HR-negative
- Has progressed on, and would no longer benefit from, endocrine therapy
Show all 15Show fewer
- Has been treated with 1 to 2 prior lines of chemotherapy/adjuvant in the recurrent or metastatic setting
- 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:
- assessment of HER2 status
- 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)
Who cannot join
- 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
Trial locations and contacts
208 sites in 20 countries.
208 sites in 20 countries
United States38 sites
Sylvester Comprehensive Cancer Center - Deerfield Beach
Boca Raton, Florida, 33426
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Ironwood Cancer & Research Centers - Chandler II
Chandler, Arizona, 85224
University of Chicago Medical Center
Chicago, Illinois, 60637
The Cleveland Clinic Foundation
Cleveland, Ohio, 44195
BloomTrials Clinical Research, LLC
Dallas, Texas, 75234
Henry Ford Hospital
Detroit, Michigan, 48202
Virginia Cancer Specialists
Fairfax, Virginia, 22031
Florida Cancer Specialists (South Region)
Fort Myers, Florida, 33916
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234
Cancer Treatment Centers of America at Western Regional Medical Center
Goodyear, Arizona, 85338
St Francis Hospital
Greenville, South Carolina, 29601
Memorial Healthcare System MRH Cancer Center
Hollywood, Florida, 33021
The Methodist Hospital Research Institute
Houston, Texas, 77030
University of Texas M. D. Anderson Cancer Center - Investigational Cancer Therapeutics
Houston, Texas, 77030
Saint Luke's Hospital of Kansas City
Kansas City, Missouri, 64111
Brig Center for Cancer Care and Survivorship
Knoxville, Tennessee, 37909
Saint Barnabas Medical Center
Livingston, New Jersey, 07039
UCLA School of Medicine
Los Angeles, California, 90095
Baptist Cancer Center
Memphis, Tennessee, 38120
Tennessee Oncology - Skyline Satellite
Nashville, Tennessee, 37201
Touro Infirmary
New Orleans, Louisiana, 70115
New York University Medical Center
New York, New York, 10016
Memorial Sloan Kettering Hospital
New York, New York, 10065
Weill Cornell Medicine Breast Center
New York, New York, 10065
Christiana Care Health Services, Inc.
Newark, Delaware, 19713
Cancer Treatment Centers of America-Georgia
Newnan, Georgia, 30263
Eastern Connecticut Hematology/Oncology Assoc.
Norwich, Connecticut, 06360
Orlando Health, Inc.
Orlando, Florida, 32806
Stanford Cancer Institute
Palo Alto, California, 94305
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
University of Pittsburgh Medical Center Health System
Pittsburgh, Pennsylvania, 15219
Oregon Health & Science University
Portland, Oregon, 97239
Cancer Care Associates Medical Group, Inc. TORI
Redondo Beach, California, 90277
University of California at San Francisco (PARENT)
San Francisco, California, 94158
Moffitt Cancer Center -Tampa
Tampa, Florida, 33139
Cancer Center of Kansas
Wichita, Kansas, 67214
Cancer Treatment Centers of America
Zion, Illinois, 60099
France19 sites
ICO - Site Paul Papin
Angers, Maine Et Loire, 49055
Institut Sainte Catherine
Avignon, Vaculuse, 84918
Institut Bergonié
Bordeaux, Gironde, 33076
CHU Brest - Hôpital Morvan
Brest, Finistere, 29609
Centre François Baclesse
Caen, Calvados, 14076
Clinique Victor Hugo - Centre Jean Bernard
Le Mans, Sarthe, 72015
Centre Hospitalier Emile Roux
Le Puy-en-Velay, Loiret, 43012
Institut Paoli Calmettes
Marseille, Bouches-du-Rhône, 13009
Clinique Clementville
Montpellier, Herault, 34070
Institut Régional du Cancer de Montpellier
Montpellier, Herault, 34298
Hôpital Saint-Louis - Paris
Paris, Paris, 75475
Institut Curie - site de Paris
Paris, 75005
Hopital Tenon
Paris, 75020
CARIO - Centre Armoricain de Radiothérapie, Imagerie médicale et Oncologie
Plérin, Cotes d'Armor, 22190
CRLCC Eugene Marquis
Rennes, Ille Et Vilaine, 35042
ICO - Site René Gauducheau
Saint-Herblain, Loire Atlantique, 44805
Hôpital d'Instruction des Armees Begin*
Saint-Mandé, Val De Marne, 94160
Centre Hospitalier Valenciennes
Valenciennes, Nord, 59322
Institut Gustave Roussy
Villejuif, Val De Marne, 94805
China18 sites
Cancer Hospital Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, 100021
Chinese PLA General Hospital
Beijing, Beijing Municipality, 100853
The First Hospital of Jilin University
Changchun, Jilin, 130000
Jilin Cancer Hospital
Changchun, Jilin, 130012
West China Hospital, Sichuan University
Chengdu, Sichuan, 610041
Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA
Fuzhou, Fujian, 350025
Sun Yat-sen Memorial hospital, Sun Yat-sen University
Guangzhou, Guangdong, 510120
Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
Hangzhou, Zhejiang, 310016
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310022
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, 150081
Anhui Provincial Hospital
Hefei, Anhui, 230001
Linyi Cancer Hospital
Linyi, Shandong, 276001
The Affiliated Drum Tower Hospital of Nanjing University
Nanjing, Jiangsu, 210008
Shanghai General Hospital
Shanghai, Shanghai Municipality, 200080
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 20032
Liaoning Cancer Hospital & Institute
Shenyang, Liaoning, 110042
Hubei Cancer Hospital
Wuhan, Hubei, 430079
General Hospital of Ningxia Medical University
Yinchuan, Ningxia Hui, 750004
Japan18 sites
NHO Kyushu Cancer Center
Fukuoka, Fukuoka, 811-1395
Fukushima Medical University Hospital
Fukushima, Fukushima, 960-1295
Hiroshima City Hiroshima Citizens Hospital
Hiroshima, Hiroshima, 730-8518
Tokai University Hospital
Isehara, Kanagawa, 259-1193
Hakuaikai Sagara Hospital
Kagoshima, Kagoshima-ken, 892-0833
National Cancer Center Hospital East
Kashiwa-shi, Chiba, 277-8577
Saitama Cancer Center
Kitaadachi-gun, Saitama, 362-0806
Cancer Institute Hospital of JFCR
Kōtoku, Tokyo-To, 135-8550
NHO Shikoku Cancer Center
Matsuyama, Ehime, 791-0280
Toranomon Hospital
Minatoku, Tokyo-To, 105-8470
Aichi Cancer Center Hospital
Nagoya, Aichi-ken, 464-8681
Hyogo College of Medicine Hospital
Nishinomiya-shi, Hyōgo, 663-8501
Kindai University Hospital
Onohigashi, Osakasayama-shi, 589-8511
NHO Osaka National Hospital
Osaka, Osaka, 540-0006
NHO Hokkaido Cancer Center
Sapporo, Hokkaido, 003-0804
Showa University Hospital
Shinagawa-Ku, Tokyo-To, 142-8666
Shizuoka Cancer Center
Sunto-gun, Shizuoka, 411-8777
Kanagawa Cancer Center
Yokohama, Kanagawa, 241-8515
Spain18 sites
Complejo Hospitalario Universitario A Coruña
A Coruña, La Coruña, 15006
Hospital del Mar
Barcelona, 08003
Hospital Quironsalud Barcelona
Barcelona, 08023
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Clinic de Barcelona
Barcelona, 08036
Hospital de Basurto
Bilbao, Vizcaya, 48013
ICO l'Hospitalet - Hospital Duran i Reynals
L'Hospitalet de Llobregat, Barcelona, 08908
MD Anderson Cancer Centre
Madrid, 28033
Hospital Ruber Internacional
Madrid, 28034
Hospital Universitario Ramon y Cajal
Madrid, 28034
Hospital Universitario Clinico San Carlos
Madrid, 28040
Hospital Clinico Universitario Virgen de la Victoria
Málaga, 29010
Hospital Universitario de Canarias
San Cristóbal de La Laguna, Tenerife, 38320
Hospital Universitario Donostia
San Sebastián, Guipuzcoa, 20014
Hospital Universitario Virgen Macarena
Seville, 41009
Hospital Universitario Virgen del Rocio
Seville, 41013
Instituto Valenciano de Oncologia IVO
Valencia, 46009
Hospital General Universitario de Valencia
Valencia, 46014
Italy13 sites
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi
Bologna, 40138
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
Brescia, 25100
Azienda Ospedaliera Univ. Policlinico Gaspare Rodolico
Catania, 95125
Azienda Ospedaliero Universitaria Mater Domini-Campus Universitario
Catanzaro, 88100
IEO Istituto Europeo di Oncologia
Milan, 20141
Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo)
Monza, Milano, 20900
Istituto Nazionale Tumori Fondazione G. Pascale
Naples, 80131
Ospedale Sacro Cuore Don Calabria
Negrar, Verona, 37024
Ospedale degli Infermi
Rimini, 47923
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
Roma, 00133
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Roma, 00168
Istituto Clinico Humanitas
Rozzano, Milano, 20089
Azienda Ospedaliera Card. G. Panico
Tricase, Lecce, 73039
South Korea11 sites
Chungbuk National University Hospital
Cheongju-si, North Chungcheong, 361-711
Kyungpook National University Chilgok Hospital
Daegu, 41404
National Cancer Center
Goyang-si, Gyeonggi-do, 10408
Inha University Hospital
Incheon, Gyeonggi-do, 22332
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620
Seoul National University Hospital
Seoul, 03080
Asan Medical Center
Seoul, 05505
Samsung Medical Center
Seoul, 06351
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, 06591
Severance Hospital, Yonsei University Health System
Seoul, 120-752
Ajou University Hospital
Suwon, Gyeonggi-do, 16499
Portugal10 sites
Hospital de Braga
Braga, 4710-243
Centro Hospitalar do Alto do Ave, EPE
Guimarães, 4835-044
Fundação Champalimaud
Lisbon, 1400-038
Centro Hospitalar de Lisboa Norte, E.P.E. - Hospital de Santa Maria
Lisbon, 1649-035
Unidade Local de Saúde de Matosinhos, EPE (Hospital Pedro Hispano)
Matosinhos Municipality, 4464-509
Centro Hospitalar do Porto, E.P.E. - Hospital de Santo António
Porto, 4099-001
Instituto Português de Oncologia do Porto Francisco Gentil, EPE
Porto, 4200-072
Centro Hospitalar de Entre o Douro e Vouga, E.P.E - Hospital de São Sebastião
Santa Maria da Feira, 4520-211
Centro Hospitalar Vila Nova de Gaia/Espinho, E.P.E
Vila Nova de Gaia, 4434-502
Centro Hospitalar de Trás-os-Montes e Alto Douro, EPE
Vila Real, 5000-508
Greece9 sites
General Hospital of Athens "Alexandra"
Athens, 11528
General Oncology Hospital of Kifissia " Agioi Anargyroi"
Athens, 14564
Athens Medical Center
Athens, 15125
University General Hospital of Heraklion
Heraklion, 71110
University General Hospital of Larissa
Larissa, 41110
Bioclinic Thessaloniki
Thessaloniki, 54622
Euromedica General Clinic Thessaloniki
Thessaloniki, 54645
General Hospital Papageorgiou
Thessaloniki, 56429
Interbalkan Hospital of Thessaloniki
Thessaloniki, 57001
Israel8 sites
Rambam Health Care Center
Haifa, 3109601
Shaare Zedek Medical Center
Jerusalem, 9103102
Hadassah University Hospital - Ein Kerem
Jerusalem, 9112001
Rabin Medical Center-Beilinson Campus
Petah Tikva, 49100
Chaim Sheba Medical Center
Ramat Gan, 52363
Kaplan Medical Center
Rehovot, 7610001
Ziv Medical Center
Safed, 13100
Tel Aviv Sourasky Medical Center
Tel Aviv, 6423906
Belgium7 sites
Institut Jules Bordet
Brussels, 1000
Universitair Ziekenhuis Brussel
Brussels, 1090
Cliniques Universitaires Saint-Luc
Brussels, 1200
UZ Leuven
Leuven, 3000
Grand Hôpital de Charleroi
Loverval, 6280
CHU UCL Namur
Namur, 5000
Centre Hospitalier Wallonie picarde - Site IMC
Tournai, 7500
Switzerland7 sites
Hirslanden Medical Center
Aarau, 5000
Universitaetsspital Basel
Basel, 4031
Kantonsspital Graubuenden
Chur, 7000
Centre Hospitalier Universitaire Vaudois
Lausanne, 1011
Kantonsspital St. Gallen
Sankt Gallen, 9007
Kantonsspital Winterthur
Winterthur, 8401
Universitaetsspital Zuerich
Zurich, 8091
United Kingdom7 sites
Western General Hospital
Edinburgh, Lothian Region, EH4 2XU
Royal Surrey County Hospital
Guildford, Surrey, GU2 7XX
Queen Mary University of London
London, Greater London, EC1M 6BQ
University College London Hospitals
London, Greater London, NW1 2PG
Royal Free Hospital
London, Greater London, NW3 2QG
Nottingham University Hospitals City Campus
Nottingham, Nottinghamshire, NG5 1PB
Royal Cornwall Hospital
Truro, Cornwall, TR1 3LJ
Hungary6 sites
Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet
Budapest, 1097
Orszagos Onkologiai Intezet
Budapest, 1122
Debreceni Egyetem
Debrecen, 4032
Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza
Gyula, 5700
SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz
Nyíregyháza, 4400
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet
Szolnok, 5004
Austria5 sites
Medizinische Universität Innsbruck
Innsbruck, 6020
Kepler Universitätsklinikum
Linz, 4020
LKH - Universitätsklinikum der PMU Salzburg
Salzburg, 5020
AKH - Medizinische Universität Wien (4305)
Vienna, 1090
Klinikum Wels-Grieskirchen GmbH
Wels, 4600
Canada3 sites
Tom Baker Cancer Center
Calgary, Alberta, T2N4N2
McGill University - Dept. Oncology Clinical Research Program
Montreal, Quebec, H2W 1S6
Toronto Sunnybrook Hospital
Toronto, Ontario, M4N 3M5
Russia3 sites
FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
Moscow, 115478
SBIH of Moscow City "Moscow City Oncology Hospital №62" of Moscow Healthcare Departement
Moscow, 143423
SBIH of Yaroslavl Region "Regional Clinical Oncological Hospital"
Yaroslavl, 150054
Sweden3 sites
Karolinska universitetssjukhuset - Solna
Solna, 17176
Länssjukhuset Sundsvall-Härnösand
Sundsvall, 85186
Akademiska Sjukhuset
Uppsala, 75185
Taiwan3 sites
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, 807
National Cheng Kung University Hospital
Tainan, 704
National Taiwan University Hospital
Taipei, 100
Germany2 sites
Universitaetsklinikum Heidelberg
Heidelberg, Baden-Wurttemberg, 69120
Klinikum der Universitaet Muenchen - Campus Grosshardern
Munich, Bavaria, 81377
About this study
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
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
Read the 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.
- Conditions
- Breast Cancer
- Being tested
- Trastuzumab deruxtecan (DS-8201a), Capecitabine, Eribulin, Gemcitabine, Paclitaxel
- Keywords
- Anti-HER2-Antibody Drug Conjugate (ADC), Unresectable or Metastatic, Human epidermal growth factor receptor 2 (HER2)-low, DESTINY - Breast 04
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trastuzumab deruxtecan (DS-8201a)Drug
Also called DS-8201a
DS-8201a is a lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered intravenously
CapecitabineDrug
Administered according to label, as one option for Physician's Choice (determined before randomization)
EribulinDrug
Administered according to label, as one option for Physician's Choice (determined before randomization)
GemcitabineDrug
Administered according to label, as one option for Physician's Choice (determined before randomization)
PaclitaxelDrug
Administered according to label, as one option for Physician's Choice (determined before randomization)
Nab-paclitaxelDrug
Administered according to label, as one option for Physician's Choice (determined before randomization)
| Study group | Role | What they receive |
|---|---|---|
| Trastuzumab deruxtecan | Experimental | HER2-low, unresectable, and/or metastatic breast cancer participants previously treated with chemotherapy randomized to DS8201a Receives: Drug: Trastuzumab deruxtecan (DS-8201a) |
| Physician's Choice | Active comparator | 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 Receives: Drug: Capecitabine; Drug: Eribulin; Drug: Gemcitabine; Drug: Paclitaxel; Drug: Nab-paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer
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.
Measured: 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
Secondary outcomes (10)
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
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.
Measured: 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 Based on Investigator Assessment in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer
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.
Measured: 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 Based on Investigator Assessment in Participants With HER2-low Breast Cancer (All Patients)
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.
Measured: 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
Overall Survival (OS) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer
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.
Measured: From the date of randomization up to the date of death due to any cause, up to approximately 3 years
Number of Overall Survival Events (Deaths)
Measured: From the date of randomization up to the date of death due to any cause, up to approximately 3 years
Overall Survival (OS) in All Patients
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.
Measured: From the date of randomization up to the date of death due to any cause, up to approximately 3 years
Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer
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.
Measured: 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 and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients)
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.
Measured: From screening and every 6 weeks up to withdrawal of subject consent, progressive disease (PD), or unacceptable toxicity, up to approximately 3 years
Duration of Response in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer
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.
Measured: 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 in Participants With HER2-low Breast Cancer (All Patients)
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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2018
- Study start27 Dec 2018
- Primary completion11 Jan 2022
- Study completion19 May 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Daiichi SankyoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel model, randomized at a 2:1 ratio
- Masking
- None (open label)
- Enrolment
- 557 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Daiichi Sankyo Co., Ltd., AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Global Clinical Leader, Study director, Daiichi Sankyo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03734029
- Sponsor's protocol ID
- DS8201-A-U303
- Other IDs
- 2018-003069-33, 184223, DESTINY-B04, 2018
- Status last verified
- Sep 2026
- First submitted
- 6 Nov 2018
- Last updated
- 28 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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/
Publications
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.
PubMed 35665782Iyengar AR, Downs EP, Mehta S, Rangarajan N, Woo MS, Sredni ST, Donato RD, Simsek S, Wilson DM, Krieser K, Patzke EB, Kyek N, Anderson C, Wagner T, Hipp J, Nassar A, Barman H. HER2-Ultralow: Prevalence, Characteristics, and Treatment Choices Among Advanced Breast Cancer Patients With Tumors Initially Scored as IHC 0. Breast J. 2026;2026(1):e7212120. doi: 10.1155/tbj/7212120.
PubMed 42340017Modi S, Jacot W, Iwata H, Park YH, Vidal Losada M, Li W, Tsurutani J, Ueno NT, Zaman K, Prat A, Papazisis K, Rugo HS, Yamashita T, Harbeck N, Im SA, De Laurentiis M, Pierga JY, Wang X, Gombos A, Tokunaga E, Orbegoso Aguilar C, Yung L, Xiao F, Cheng Y, Cameron D. Trastuzumab deruxtecan in HER2-low metastatic breast cancer: long-term survival analysis of the randomized, phase 3 DESTINY-Breast04 trial. Nat Med. 2025 Dec;31(12):4205-4213. doi: 10.1038/s41591-025-03981-4. Epub 2025 Oct 8.
PubMed 41062831Ueno NT, Cottone F, Dunton K, Jacot W, Yamashita T, Sohn J, Tokunaga E, Prat A, Tsurutani J, Park YH, Rugo HS, Xu B, Cardoso F, Mitri Z, Mahtani R, Aguilar CO, Xiao F, Harbeck N, Cameron DA, Modi S. Patient-reported outcomes from DESTINY-Breast04: trastuzumab deruxtecan versus physician's choice of chemotherapy in patients with HER2-low mBC. Oncologist. 2025 May 8;30(5):oyaf048. doi: 10.1093/oncolo/oyaf048.
PubMed 40349139Yamashita T, Sohn JH, Tokunaga E, Niikura N, Park YH, Lee KS, Chae YS, Xu B, Wang X, Im SA, Li W, Lu YS, Aguilar CO, Nishijima S, Nishiyama Y, Sugihara M, Modi S, Tsurutani J. Trastuzumab deruxtecan versus treatment of physician's choice in previously treated Asian patients with HER2-low unresectable/metastatic breast cancer: subgroup analysis of the DESTINY-Breast04 study. Breast Cancer. 2024 Sep;31(5):858-868. doi: 10.1007/s12282-024-01600-7. Epub 2024 Jun 17.
PubMed 38884900Ma R, Shi Y, Yan R, Yin S, Bu H, Huang J. Efficacy and safety of trastuzumab deruxtecan in treating human epidermal growth factor receptor 2-low/positive advanced breast cancer:A meta-analysis of randomized controlled trials. Crit Rev Oncol Hematol. 2024 Apr;196:104305. doi: 10.1016/j.critrevonc.2024.104305. Epub 2024 Mar 3.
PubMed 38442809Jhaveri K, Eli LD, Wildiers H, Hurvitz SA, Guerrero-Zotano A, Unni N, Brufsky A, Park H, Waisman J, Yang ES, Spanggaard I, Reid S, Burkard ME, Vinayak S, Prat A, Arnedos M, Bidard FC, Loi S, Crown J, Bhave M, Piha-Paul SA, Suga JM, Chia S, Saura C, Garcia-Saenz JA, Gambardella V, de Miguel MJ, Gal-Yam EN, Rapael A, Stemmer SM, Ma C, Hanker AB, Ye D, Goldman JW, Bose R, Peterson L, Bell JSK, Frazier A, DiPrimeo D, Wong A, Arteaga CL, Solit DB. Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial. Ann Oncol. 2023 Oct;34(10):885-898. doi: 10.1016/j.annonc.2023.08.003. Epub 2023 Aug 18.
PubMed 37597578Rugo HS, Crossno CL, Gesthalter YB, Kelley K, Moore HB, Rimawi MF, Westbrook KE, Buys SS. Real-World Perspectives and Practices for Pneumonitis/Interstitial Lung Disease Associated With Trastuzumab Deruxtecan Use in Human Epidermal Growth Factor Receptor 2-Expressing Metastatic Breast Cancer. JCO Oncol Pract. 2023 Aug;19(8):539-546. doi: 10.1200/OP.22.00480. Epub 2023 May 19.
PubMed 37207306Narayan P, Dilawari A, Osgood C, Feng Z, Bloomquist E, Pierce WF, Jafri S, Kalavar S, Kondratovich M, Jha P, Ghosh S, Tang S, Pazdur R, Beaver JA, Amiri-Kordestani L. US Food and Drug Administration Approval Summary: Fam-Trastuzumab Deruxtecan-nxki for Human Epidermal Growth Factor Receptor 2-Low Unresectable or Metastatic Breast Cancer. J Clin Oncol. 2023 Apr 10;41(11):2108-2116. doi: 10.1200/JCO.22.02447. Epub 2023 Feb 13.
PubMed 36780610