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

April 9, 2024 updated by: Daiichi Sankyo

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

Study Overview

Status

Active, not recruiting

Conditions

Breast Cancer

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

557

Phase

Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Austria
- - Innsbruck, Austria, 6020
    - Medizinische Universität Innsbruck
  - Linz, Austria, 4020
    - Kepler Universitätsklinikum
  - Salzburg, Austria, 5020
    - LKH - Universitätsklinikum der PMU Salzburg
  - Vienna, Austria, 1090
    - AKH - Medizinische Universität Wien (4305)
  - Wels, Austria, 4600
    - Klinikum Wels-Grieskirchen GmbH
Belgium
- - Bruxelles, Belgium, 1000
    - Institut Jules Bordet
  - Bruxelles, Belgium, 1200
    - Cliniques Universitaires Saint-Luc
  - Bruxelles, Belgium, 1090
    - Universitair Ziekenhuis Brussel
  - Leuven, Belgium, 3000
    - UZ Leuven
  - Loverval, Belgium, 6280
    - Grand Hôpital de Charleroi
  - Namur, Belgium, 5000
    - CHU UCL Namur
  - Tournai, Belgium, 7500
    - Centre Hospitalier Wallonie picarde - Site IMC
Canada
- Alberta
  - Calgary, Alberta, Canada, T2N4N2
    - Tom Baker Cancer Center
- Ontario
  - Toronto, Ontario, Canada, M4N 3M5
    - Toronto Sunnybrook Hospital
- Quebec
  - Montréal, Quebec, Canada, H2W 1S6
    - McGill University - Dept. Oncology Clinical Research Program
China
- Anhui
  - Hefei, Anhui, China, 230001
    - Anhui Provincial Hospital
- Beijing
  - Beijing, Beijing, China, 100853
    - Chinese PLA General Hospital
  - Beijing, Beijing, China, 100021
    - Cancer Hospital Chinese Academy of Medical Sciences
- Fujian
  - Fuzhou, Fujian, China, 350025
    - Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA
- Guangdong
  - Guangzhou, Guangdong, China, 510120
    - Sun Yat-sen Memorial Hospital, Sun Yat-sen University
- Heilongjiang
  - Harbin, Heilongjiang, China, 150081
    - Harbin Medical University Cancer Hospital
- Hubei
  - Wuhan, Hubei, China, 430079
    - Hubei Cancer Hospital
- Jiangsu
  - Nanjing, Jiangsu, China, 210008
    - The Affiliated Drum Tower Hospital of Nanjing University
- Jilin
  - Chang chun, Jilin, China, 130000
    - The first hospital of Jilin University
  - Chang chun, Jilin, China, 130012
    - Jilin Cancer Hospital
- Liaoning
  - Shenyang, Liaoning, China, 110042
    - Liaoning cancer Hospital & Institute
- Ningxia
  - Yinchuan, Ningxia, China, 750004
    - General Hospital of Ningxia Medical University
- Shandong
  - Linyi, Shandong, China, 276001
    - Linyi Cancer Hospital
- Shanghai
  - Shanghai, Shanghai, China, 200080
    - Shanghai General Hospital
  - Shanghai, Shanghai, China, 20032
    - Fudan University Shanghai Cancer Center
- Sichuan
  - Chengdu, Sichuan, China, 610041
    - West China Hospital, Sichuan University
- Zhejiang
  - Hangzhou, Zhejiang, China, 310022
    - Zhejiang Cancer Hospital
  - Hangzhou, Zhejiang, China, 310016
    - Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
France
- - Paris, France, 75020
    - Hopital Tenon
  - Paris, France, 75005
    - Institut Curie - Site de Paris
- Bouches-du-Rhône
  - Marseille cedex 9, Bouches-du-Rhône, France, 13009
    - Institut Paoli Calmettes
- Calvados
  - Caen, Calvados, France, 14076
    - Centre francois Baclesse
- Cotes d'Armor
  - Plérin, Cotes d'Armor, France, 22190
    - CARIO - Centre Armoricain de Radiothérapie, Imagerie médicale et Oncologie
- Finistere
  - Brest Cedex, Finistere, France, 29609
    - Chu Brest - Hôpital Morvan
- Gironde
  - Bordeaux cedex, Gironde, France, 33076
    - Institut Bergonie
- Herault
  - Montpellier, Herault, France, 34070
    - Clinique Clementville
  - Montpellier, Herault, France, 34298
    - Institut Régional du Cancer de Montpellier
- Ille Et Vilaine
  - Rennes-cedex, Ille Et Vilaine, France, 35042
    - CRLCC Eugene Marquis
- Loire Atlantique
  - Saint-Herblain, Loire Atlantique, France, 44805
    - ICO - Site René Gauducheau
- Loiret
  - Le Puy-en-Velay, Loiret, France, 43012
    - Centre Hospitalier Emile ROUX
- Maine Et Loire
  - Angers Cedex 2, Maine Et Loire, France, 49055
    - ICO - Site Paul Papin
- Nord
  - Valenciennes, Nord, France, 59322
    - Centre Hospitalier Valenciennes
- Paris
  - Paris Cedex 10, Paris, France, 75475
    - Hôpital Saint-Louis - Paris
- Sarthe
  - Le Mans Cedex 02, Sarthe, France, 72015
    - Clinique Victor Hugo - Centre Jean Bernard
- Vaculuse
  - Avignon Cedex 9, Vaculuse, France, 84918
    - Institut Sainte Catherine
- Val De Marne
  - Saint Mande, Val De Marne, France, 94160
    - Hôpital d'Instruction des Armees Begin*
  - Villejuif cedex, Val De Marne, France, 94805
    - Institut Gustave Roussy
Germany
- Baden Wuerttemberg
  - Heidelberg, Baden Wuerttemberg, Germany, 69120
    - Universitaetsklinikum Heidelberg
- Bayern
  - Munich, Bayern, Germany, 81377
    - Klinikum der Universitaet Muenchen - Campus Grosshardern
Greece
- - Athens, Greece, 15125
    - Athens Medical Center
  - Athens, Greece, 11528
    - General Hospital of Athens "ALEXANDRA"
  - Athens, Greece, 14564
    - General Oncology Hospital of Kifissia " Agioi Anargyroi"
  - Heraklion, Greece, 71110
    - University General Hospital of Heraklion
  - Larissa, Greece, 41110
    - University General Hospital of Larissa
  - Thessaloníki, Greece, 54622
    - BioClinic Thessaloniki
  - Thessaloníki, Greece, 54645
    - Euromedica General Clinic Thessaloniki
  - Thessaloníki, Greece, 56429
    - General Hospital Papageorgiou
  - Thessaloníki, Greece, 57001
    - Interbalkan Hospital of Thessaloniki
Hungary
- - Budapest, Hungary, 1122
    - Országos Onkológiai Intézet
  - Budapest, Hungary, 1097
    - Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet
  - Debrecen, Hungary, 4032
    - Debreceni Egyetem
  - Gyula, Hungary, 5700
    - Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza
  - Nyiregyhaza, Hungary, 4400
    - SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz
  - Szolnok, Hungary, 5004
    - Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Rendelointézet
Israel
- - Haifa, Israel, 3109601
    - Rambam Health Care Center
  - Jerusalem, Israel, 9103102
    - Shaare Zedek Medical Center
  - Jerusalem, Israel, 9112001
    - Hadassah University Hospital - Ein Kerem
  - Petah tikva, Israel, 49100
    - Rabin Medical Center-Beilinson Campus
  - Ramat Gan, Israel, 52363
    - Chaim Sheba Medical Center
  - Rechovot, Israel, 7610001
    - Kaplan Medical Center
  - Safed, Israel, 13100
    - Ziv Medical Center
  - Tel Aviv, Israel, 6423906
    - Tel Aviv Sourasky Medical Center
Italy
- - Bologna, Italy, 40138
    - Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi
  - Brescia, Italy, 25100
    - Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
  - Catania, Italy, 95125
    - Azienda Ospedaliera Univ. Policlinico Gaspare Rodolico
  - Catanzaro, Italy, 88100
    - Azienda Ospedaliero Universitaria Mater Domini-Campus Universitario
  - Milano, Italy, 20141
    - IEO Istituto Europeo di Oncologia
  - Napoli, Italy, 80131
    - Istituto Nazionale Tumori Fondazione G. Pascale
  - Rimini, Italy, 47923
    - Ospedale Degli Infermi
  - Roma, Italy, 00168
    - Fondazione Policlinico Universitario Agostino Gemelli Irccs
  - Roma, Italy, 00133
    - Azienda Ospedaliera Universitaria Policlinico Tor Vergata
- Lecce
  - Tricase, Lecce, Italy, 73039
    - Azienda Ospedaliera Card. G. Panico
- Milano
  - Monza, Milano, Italy, 20900
    - Azienda Socio Sanitaria Territoriale Di Monza (Presidio San Gerardo)
  - Rozzano, Milano, Italy, 20089
    - Istituto Clinico Humanitas
- Verona
  - Negrar, Verona, Italy, 37024
    - Ospedale Sacro Cuore Don Calabria
Japan
- Aichi-Ken
  - Nagoya, Aichi-Ken, Japan, 464-8681
    - Aichi Cancer Center Hospital
- Chiba-Ken
  - Kashiwa-shi, Chiba-Ken, Japan, 277-8577
    - National Cancer Center Hospital East
- Ehime-Ken
  - Matsuyama-shi, Ehime-Ken, Japan, 791-0280
    - Nho Shikoku Cancer Center
- Fukuoka-Ken
  - Fukuoka-shi, Fukuoka-Ken, Japan, 811-1395
    - NHO Kyushu Cancer Center
- Fukushima-Ken
  - Fukushima, Fukushima-Ken, Japan, 960-1295
    - Fukushima Medical University Hospital
- Hiroshima-Ken
  - Hiroshima-shi, Hiroshima-Ken, Japan, 730-8518
    - Hiroshima City Hiroshima Citizens Hospital
- Hokkaido
  - Sapporo-shi, Hokkaido, Japan, 003-0804
    - Nho Hokkaido Cancer Center
- Hyogo-Ken
  - Nishinomiya-shi, Hyogo-Ken, Japan, 663-8501
    - Hyogo College of Medicine Hospital
- Kagoshima-Ken
  - Kagoshima, Kagoshima-Ken, Japan, 892-0833
    - Hakuaikai Sagara Hospital
- Kanagawa
  - Yokohama, Kanagawa, Japan, 241-8515
    - Kanagawa Cancer Center
- Kanagawa-Ken
  - Isehara, Kanagawa-Ken, Japan, 259-1193
    - Tokai University Hospital
- Osaka-Fu
  - Osaka-shi, Osaka-Fu, Japan, 540-0006
    - NHO Osaka National Hospital
- Osakasayama-shi
  - Onohigashi, Osakasayama-shi, Japan, 589-8511
    - Kindai University Hospital
- Saitama-Ken
  - Kitaadachi-gun, Saitama-Ken, Japan, 362-0806
    - Saitama Cancer Center
- Shizuoka-Ken
  - Sunto-gun, Shizuoka-Ken, Japan, 411-8777
    - Shizuoka Cancer Center
- Tokyo-To
  - Koto-Ku, Tokyo-To, Japan, 135-8550
    - Cancer Institute Hospital of JFCR
  - Minato-Ku, Tokyo-To, Japan, 105-8470
    - Toranomon Hospital
  - Shinagawa-Ku, Tokyo-To, Japan, 142-8666
    - Showa University Hospital
Korea, Republic of
- - Daegu, Korea, Republic of, 41404
    - Kyungpook National University Chilgok Hospital
  - Seoul, Korea, Republic of, 03080
    - Seoul National University Hospital
  - Seoul, Korea, Republic of, 05505
    - Asan Medical Center
  - Seoul, Korea, Republic of, 06591
    - The Catholic University of Korea, Seoul St. Mary's Hospital
  - Seoul, Korea, Republic of, 06351
    - Samsung Medical Center
  - Seoul, Korea, Republic of, 120-752
    - Severance Hospital, Yonsei University Health System
- Chungcheongbuk-do
  - Cheongju-si, Chungcheongbuk-do, Korea, Republic of, 361-711
    - Chungbuk National University Hospital
- Gyeonggi-do
  - Goyang-si, Gyeonggi-do, Korea, Republic of, 10408
    - National Cancer Center
  - Incheon, Gyeonggi-do, Korea, Republic of, 22332
    - Inha University Hospital
  - Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
    - Seoul National University Bundang Hospital
  - Suwon, Gyeonggi-do, Korea, Republic of, 16499
    - Ajou University Hospital
Portugal
- - Braga, Portugal, 4710-243
    - Hospital de Braga
  - Guimarães, Portugal, 4835-044
    - Centro Hospitalar do Alto do Ave, EPE
  - Lisboa, Portugal, 1649-035
    - Centro Hospitalar de Lisboa Norte, E.P.E. - Hospital de Santa Maria
  - Lisboa, Portugal, 1400-038
    - Fundacao Champalimaud
  - Matosinhos, Portugal, 4464-509
    - Unidade Local de Saúde de Matosinhos, EPE (Hospital Pedro Hispano)
  - Porto, Portugal, 4200-072
    - Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE
  - Porto, Portugal, 4099-001
    - Centro Hospitalar do Porto, E.P.E. - Hospital de Santo António
  - Santa Maria Da Feira, Portugal, 4520-211
    - Centro Hospitalar de Entre o Douro e Vouga, E.P.E - Hospital de São Sebastião
  - Vila Nova De Gaia, Portugal, 4434-502
    - Centro Hospitalar Vila Nova de Gaia/Espinho, E.P.E
  - Vila Real, Portugal, 5000-508
    - Centro Hospitalar de Trás-os-Montes e Alto Douro, EPE
Russian Federation
- - Moscow, Russian Federation, 115478
    - FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
  - Moscow, Russian Federation, 143423
    - SBIH of Moscow City "Moscow City Oncology Hospital №62" of Moscow Healthcare Departement
  - Yaroslavl, Russian Federation, 150054
    - SBIH of Yaroslavl Region "Regional Clinical Oncological Hospital"
Spain
- - Barcelona, Spain, 08003
    - Hospital Del Mar
  - Barcelona, Spain, 08036
    - Hospital Clínic de Barcelona
  - Barcelona, Spain, 08035
    - Hospital Universitari Vall d'Hebrón
  - Barcelona, Spain, 08023
    - Hospital Quirónsalud Barcelona
  - Madrid, Spain, 28034
    - Hospital Universitario Ramon Y Cajal
  - Madrid, Spain, 28040
    - Hospital Universitario Clinico San Carlos
  - Madrid, Spain, 28034
    - Hospital Ruber Internacional
  - Madrid, Spain, 28033
    - MD Anderson Cancer Centre
  - Málaga, Spain, 29010
    - Hospital Clinico Universitario Virgen de la Victoria
  - Sevilla, Spain, 41009
    - Hospital Universitario Virgen Macarena
  - Sevilla, Spain, 41013
    - Hospital Universitario Virgen del Rocio
  - Valencia, Spain, 46014
    - Hospital General Universitario de Valencia
  - Valencia, Spain, 46009
    - Instituto Valenciano de Oncologia IVO
- Barcelona
  - L'Hospitalet De Llobregat, Barcelona, Spain, 08908
    - ICO l'Hospitalet - Hospital Duran i Reynals
- Guipuzcoa
  - San Sebastián, Guipuzcoa, Spain, 20014
    - Hospital Universitario Donostia
- La Coruña
  - A Coruña, La Coruña, Spain, 15006
    - Complejo Hospitalario Universitario A Coruña
- Tenerife
  - San Cristobal de la Laguna, Tenerife, Spain, 38320
    - Hospital Universitario de Canarias
- Vizcaya
  - Bilbao, Vizcaya, Spain, 48013
    - Hospital de Basurto
Sweden
- - Solna, Sweden, 17176
    - Karolinska Universitetssjukhuset - Solna
  - Sundsvall, Sweden, 85186
    - Länssjukhuset Sundsvall-Härnösand
  - Uppsala, Sweden, 75185
    - Akademiska Sjukhuset
Switzerland
- - Aarau, Switzerland, 5000
    - Hirslanden Medical Center
  - Basel, Switzerland, 4031
    - Universitaetsspital Basel
  - Chur, Switzerland, 7000
    - Kantonsspital Graubuenden
  - Lausanne, Switzerland, 1011
    - Centre Hospitalier Universitaire Vaudois
  - Saint Gallen, Switzerland, 9007
    - Kantonsspital St. Gallen
  - Winterthur, Switzerland, 8401
    - Kantonsspital Winterthur
  - Zürich, Switzerland, 8091
    - Universitaetsspital Zuerich
Taiwan
- - Kaohsiung, Taiwan, 807
    - Kaohsiung Medical University Chung-Ho Memorial Hospital
  - Tainan, Taiwan, 704
    - National Cheng Kung University Hospital
  - Taipei, Taiwan, 100
    - National Taiwan University Hospital
United Kingdom
- Cornwall
  - Truro, Cornwall, United Kingdom, TR1 3LJ
    - Royal Cornwall Hospital
- Greater London
  - London, Greater London, United Kingdom, NW3 2QG
    - Royal Free Hospital
  - London, Greater London, United Kingdom, EC1M 6BQ
    - Queen Mary University of London
  - London, Greater London, United Kingdom, NW1 2PG
    - University College London Hospitals
- Lothian Region
  - Edinburgh, Lothian Region, United Kingdom, EH4 2XU
    - Western General Hospital
- Nottinghamshire
  - Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
    - Nottingham University Hospitals City Campus
- Surrey
  - Guildford, Surrey, United Kingdom, GU2 7XX
    - Royal Surrey County Hospital
United States
- Arizona
  - Chandler, Arizona, United States, 85224
    - Ironwood Cancer & Research Centers - Chandler II
  - Gilbert, Arizona, United States, 85234-2165
    - Banner MD Anderson Cancer Center
  - Goodyear, Arizona, United States, 85338
    - Cancer Treatment Centers of America at Western Regional Medical Center
- California
  - Los Angeles, California, United States, 90095-1690
    - UCLA School of Medicine
  - Palo Alto, California, United States, 94305
    - Stanford Cancer Institute
  - Redondo Beach, California, United States, 90277
    - Cancer Care Associates Medical Group, Inc. TORI
  - San Francisco, California, United States, 94158
    - University of California at San Francisco (PARENT)
- Connecticut
  - Norwich, Connecticut, United States, 06360
    - Eastern Connecticut Hematology/Oncology Assoc.
- Delaware
  - Newark, Delaware, United States, 19713
    - Christiana Care Health Services, Inc.
- Florida
  - Boca Raton, Florida, United States, 33426
    - Sylvester Comprehensive Cancer Center - Deerfield Beach
  - Fort Myers, Florida, United States, 33916
    - Florida Cancer Specialists (South Region)
  - Hollywood, Florida, United States, 33021
    - Memorial Healthcare System MRH Cancer Center
  - Orlando, Florida, United States, 32806
    - Orlando Health, Inc.
  - Tampa, Florida, United States, 33139
    - Moffitt Cancer Center -Tampa
- Georgia
  - Newnan, Georgia, United States, 30263
    - Cancer Treatment Centers of America-Georgia
- Illinois
  - Chicago, Illinois, United States, 60637
    - University of Chicago Medical Center
  - Zion, Illinois, United States, 60099
    - Cancer Treatment Centers of America
- Kansas
  - Wichita, Kansas, United States, 67214
    - Cancer Center of Kansas
- Louisiana
  - New Orleans, Louisiana, United States, 70115
    - Touro Infirmary
- Massachusetts
  - Boston, Massachusetts, United States, 02215
    - Dana-Farber Cancer Institute
- Michigan
  - Detroit, Michigan, United States, 48202
    - Henry Ford Hospital
- Missouri
  - Kansas City, Missouri, United States, 64111
    - Saint Luke'S Hospital of Kansas City
- New Jersey
  - Livingston, New Jersey, United States, 07039
    - Saint Barnabas Medical Center
- New York
  - New York, New York, United States, 10016
    - New York University Medical Center
  - New York, New York, United States, 10065-6007
    - Memorial Sloan Kettering Hospital
  - New York, New York, United States, 10065
    - Weill Cornell Medicine Breast Center
- Ohio
  - Cleveland, Ohio, United States, 44195
    - The Cleveland Clinic Foundation
- Oregon
  - Portland, Oregon, United States, 97239
    - Oregon Health & Science University
- Pennsylvania
  - Pittsburgh, Pennsylvania, United States, 15212
    - Allegheny General Hospital
  - Pittsburgh, Pennsylvania, United States, 15219
    - University of Pittsburgh Medical Center Health System
- South Carolina
  - Greenville, South Carolina, United States, 29601
    - St Francis Hospital
- Tennessee
  - Knoxville, Tennessee, United States, 37909
    - Brig Center for Cancer Care and Survivorship
  - Memphis, Tennessee, United States, 38120
    - Baptist Cancer Center
  - Nashville, Tennessee, United States, 37201
    - Tennessee Oncology - Skyline Satellite
- Texas
  - Dallas, Texas, United States, 75234
    - BloomTrials Clinical Research, LLC
  - Houston, Texas, United States, 77030
    - The Methodist Hospital Research Institute
  - Houston, Texas, United States, 77030
    - University of Texas M. D. Anderson Cancer Center - Investigational Cancer Therapeutics
- Virginia
  - Fairfax, Virginia, United States, 22031
    - Virginia Cancer Specialists

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: None (Open Label)

Number of Arms

Arms and Interventions

Participant Group / 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 Names: 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)

Participant Group / 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 Names:

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