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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03734029
• Other study ID #: DS8201-A-U303
• Secondary ID: 2018-003069-3318
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 27, 2018
• Est. completion date: October 1, 2025

Study information

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

Clinical 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 557
• Est. completion date: October 1, 2025
• Est. primary completion date: January 11, 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 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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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
• Capecitabine
Administered according to label, as one option for Physician's Choice (determined before randomization)
• Eribulin
Administered according to label, as one option for Physician's Choice (determined before randomization)
• Gemcitabine
Administered according to label, as one option for Physician's Choice (determined before randomization)
• Paclitaxel
Administered according to label, as one option for Physician's Choice (determined before randomization)
• Nab-paclitaxel
Administered according to label, as one option for Physician's Choice (determined before randomization)

Locations

Country	Name	City	State
Austria	Medizinische Universität Innsbruck	Innsbruck
Austria	Kepler Universitätsklinikum	Linz
Austria	LKH - Universitätsklinikum der PMU Salzburg	Salzburg
Austria	AKH - Medizinische Universität Wien (4305)	Vienna
Austria	Klinikum Wels-Grieskirchen GmbH	Wels
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	Institut Jules Bordet	Bruxelles
Belgium	Universitair Ziekenhuis Brussel	Bruxelles
Belgium	UZ Leuven	Leuven
Belgium	Grand Hôpital de Charleroi	Loverval
Belgium	CHU UCL Namur	Namur
Belgium	Centre Hospitalier Wallonie picarde - Site IMC	Tournai
Canada	Tom Baker Cancer Center	Calgary	Alberta
Canada	McGill University - Dept. Oncology Clinical Research Program	Montréal	Quebec
Canada	Toronto Sunnybrook Hospital	Toronto	Ontario
China	Cancer Hospital Chinese Academy of Medical Sciences	Beijing	Beijing
China	Chinese PLA General Hospital	Beijing	Beijing
China	Jilin Cancer Hospital	Chang chun	Jilin
China	The First Hospital of Jilin University	Chang chun	Jilin
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA	Fuzhou	Fujian
China	Sun Yat-sen Memorial hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Anhui Provincial Hospital	Hefei	Anhui
China	Linyi Cancer Hospital	Linyi	Shandong
China	The Affiliated Drum Tower Hospital of Nanjing University	Nanjing	Jiangsu
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Shanghai General Hospital	Shanghai	Shanghai
China	Liaoning Cancer Hospital & Institute	Shenyang	Liaoning
China	Hubei Cancer Hospital	Wuhan	Hubei
China	General Hospital of Ningxia Medical University	Yinchuan	Ningxia
France	ICO - Site Paul Papin	Angers Cedex 2	Maine Et Loire
France	Institut Sainte Catherine	Avignon Cedex 9	Vaculuse
France	Institut Bergonié	Bordeaux cedex	Gironde
France	CHU Brest - Hôpital Morvan	Brest Cedex	Finistere
France	Centre François Baclesse	Caen	Calvados
France	Clinique Victor Hugo - Centre Jean Bernard	Le Mans Cedex 02	Sarthe
France	Centre Hospitalier Emile Roux	Le Puy-en-Velay	Loiret
France	Institut Paoli Calmettes	Marseille cedex 9	Bouches-du-Rhône
France	Clinique Clementville	Montpellier	Herault
France	Institut Régional du Cancer de Montpellier	Montpellier	Herault
France	Hopital Tenon	Paris
France	Institut Curie - site de Paris	Paris
France	Hôpital Saint-Louis - Paris	Paris Cedex 10	Paris
France	CARIO - Centre Armoricain de Radiothérapie, Imagerie médicale et Oncologie	Plérin	Cotes d'Armor
France	CRLCC Eugene Marquis	Rennes-cedex	Ille Et Vilaine
France	Hôpital d'Instruction des Armees Begin*	Saint Mande	Val De Marne
France	ICO - Site René Gauducheau	Saint-Herblain	Loire Atlantique
France	Centre Hospitalier Valenciennes	Valenciennes	Nord
France	Institut Gustave Roussy	Villejuif cedex	Val De Marne
Germany	Universitaetsklinikum Heidelberg	Heidelberg	Baden Wuerttemberg
Germany	Klinikum der Universitaet Muenchen - Campus Grosshardern	Munich	Bayern
Greece	Athens Medical Center	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	University General Hospital of Larissa	Larissa
Greece	Bioclinic Thessaloniki	Thessaloníki
Greece	Euromedica General Clinic Thessaloniki	Thessaloníki
Greece	General Hospital Papageorgiou	Thessaloníki
Greece	Interbalkan Hospital of Thessaloniki	Thessaloníki
Hungary	Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet	Budapest
Hungary	Orszagos Onkologiai Intezet	Budapest
Hungary	Debreceni Egyetem	Debrecen
Hungary	Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza	Gyula
Hungary	SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz	Nyiregyhaza
Hungary	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet	Szolnok
Israel	Rambam Health Care Center	Haifa
Israel	Hadassah University Hospital - Ein Kerem	Jerusalem
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Rabin Medical Center-Beilinson Campus	Petah tikva
Israel	Chaim Sheba Medical Center	Ramat Gan
Israel	Kaplan Medical Center	Rechovot
Israel	Ziv Medical Center	Safed
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi	Bologna
Italy	Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)	Brescia
Italy	Azienda Ospedaliera Univ. Policlinico Gaspare Rodolico	Catania
Italy	Azienda Ospedaliero Universitaria Mater Domini-Campus Universitario	Catanzaro
Italy	IEO Istituto Europeo di Oncologia	Milano
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	Ospedale degli Infermi	Rimini
Italy	Azienda Ospedaliera Universitaria Policlinico Tor Vergata	Roma
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma
Italy	Istituto Clinico Humanitas	Rozzano	Milano
Italy	Azienda Ospedaliera Card. G. Panico	Tricase	Lecce
Japan	NHO Kyushu Cancer Center	Fukuoka-shi	Fukuoka-Ken
Japan	Fukushima Medical University Hospital	Fukushima	Fukushima-Ken
Japan	Hiroshima City Hiroshima Citizens Hospital	Hiroshima-shi	Hiroshima-Ken
Japan	Tokai University Hospital	Isehara	Kanagawa-Ken
Japan	Hakuaikai Sagara Hospital	Kagoshima	Kagoshima-Ken
Japan	National Cancer Center Hospital East	Kashiwa-shi	Chiba-Ken
Japan	Saitama Cancer Center	Kitaadachi-gun	Saitama-Ken
Japan	Cancer Institute Hospital of JFCR	Koto-Ku	Tokyo-To
Japan	NHO Shikoku Cancer Center	Matsuyama-shi	Ehime-Ken
Japan	Toranomon Hospital	Minato-Ku	Tokyo-To
Japan	Aichi Cancer Center Hospital	Nagoya	Aichi-Ken
Japan	Hyogo College of Medicine Hospital	Nishinomiya-shi	Hyogo-Ken
Japan	Kindai University Hospital	Onohigashi	Osakasayama-shi
Japan	NHO Osaka National Hospital	Osaka-shi	Osaka-Fu
Japan	NHO Hokkaido Cancer Center	Sapporo-shi	Hokkaido
Japan	Showa University Hospital	Shinagawa-Ku	Tokyo-To
Japan	Shizuoka Cancer Center	Sunto-gun	Shizuoka-Ken
Japan	Kanagawa Cancer Center	Yokohama	Kanagawa
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	Gyeonggi-do
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	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Korea, Republic of	Ajou University Hospital	Suwon	Gyeonggi-do
Portugal	Hospital de Braga	Braga
Portugal	Centro Hospitalar do Alto do Ave, EPE	Guimarães
Portugal	Centro Hospitalar de Lisboa Norte, E.P.E. - Hospital de Santa Maria	Lisboa
Portugal	Fundação Champalimaud	Lisboa
Portugal	Unidade Local de Saúde de Matosinhos, EPE (Hospital Pedro Hispano)	Matosinhos
Portugal	Centro Hospitalar do Porto, E.P.E. - Hospital de Santo António	Porto
Portugal	Instituto Português de Oncologia do Porto Francisco Gentil, EPE	Porto
Portugal	Centro Hospitalar de Entre o Douro e Vouga, E.P.E - Hospital de São Sebastião	Santa Maria Da Feira
Portugal	Centro Hospitalar Vila Nova de Gaia/Espinho, E.P.E	Vila Nova De Gaia
Portugal	Centro Hospitalar de Trás-os-Montes e Alto Douro, EPE	Vila Real
Russian Federation	FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"	Moscow
Russian Federation	SBIH of Moscow City "Moscow City Oncology Hospital ?62" of Moscow Healthcare Departement	Moscow
Russian Federation	SBIH of Yaroslavl Region "Regional Clinical Oncological Hospital"	Yaroslavl
Spain	Complejo Hospitalario Universitario A Coruña	A Coruña	La Coruña
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 Basurto	Bilbao	Vizcaya
Spain	ICO l'Hospitalet - Hospital Duran i Reynals	L'Hospitalet De Llobregat	Barcelona
Spain	Hospital Ruber Internacional	Madrid
Spain	Hospital Universitario Clinico San Carlos	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	MD Anderson Cancer Centre	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria	Málaga
Spain	Hospital Universitario de Canarias	San Cristobal de la Laguna	Tenerife
Spain	Hospital Universitario Donostia	San Sebastián	Guipuzcoa
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital General Universitario de Valencia	Valencia
Spain	Instituto Valenciano de Oncologia IVO	Valencia
Sweden	Karolinska universitetssjukhuset - Solna	Solna
Sweden	Länssjukhuset Sundsvall-Härnösand	Sundsvall
Sweden	Akademiska Sjukhuset	Uppsala
Switzerland	Hirslanden Medical Center	Aarau
Switzerland	Universitaetsspital Basel	Basel
Switzerland	Kantonsspital Graubuenden	Chur
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	Kantonsspital St. Gallen	Saint Gallen
Switzerland	Kantonsspital Winterthur	Winterthur
Switzerland	Universitaetsspital Zuerich	Zürich
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
United Kingdom	Western General Hospital	Edinburgh	Lothian Region
United Kingdom	Royal Surrey County Hospital	Guildford	Surrey
United Kingdom	Queen Mary University of London	London	Greater London
United Kingdom	Royal Free Hospital	London	Greater London
United Kingdom	University College London Hospitals	London	Greater London
United Kingdom	Nottingham University Hospitals City Campus	Nottingham	Nottinghamshire
United Kingdom	Royal Cornwall Hospital	Truro	Cornwall
United States	Sylvester Comprehensive Cancer Center - Deerfield Beach	Boca Raton	Florida
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Ironwood Cancer & Research Centers - Chandler II	Chandler	Arizona
United States	University of Chicago Medical Center	Chicago	Illinois
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	BloomTrials Clinical Research, LLC	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Florida Cancer Specialists (South Region)	Fort Myers	Florida
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Cancer Treatment Centers of America at Western Regional Medical Center	Goodyear	Arizona
United States	St Francis Hospital	Greenville	South Carolina
United States	Memorial Healthcare System MRH Cancer Center	Hollywood	Florida
United States	The Methodist Hospital Research Institute	Houston	Texas
United States	University of Texas M. D. Anderson Cancer Center - Investigational Cancer Therapeutics	Houston	Texas
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Brig Center for Cancer Care and Survivorship	Knoxville	Tennessee
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	UCLA School of Medicine	Los Angeles	California
United States	Baptist Cancer Center	Memphis	Tennessee
United States	Tennessee Oncology - Skyline Satellite	Nashville	Tennessee
United States	Touro Infirmary	New Orleans	Louisiana
United States	Memorial Sloan Kettering Hospital	New York	New York
United States	New York University Medical Center	New York	New York
United States	Weill Cornell Medicine Breast Center	New York	New York
United States	Christiana Care Health Services, Inc.	Newark	Delaware
United States	Cancer Treatment Centers of America-Georgia	Newnan	Georgia
United States	Eastern Connecticut Hematology/Oncology Assoc.	Norwich	Connecticut
United States	Orlando Health, Inc.	Orlando	Florida
United States	Stanford Cancer Institute	Palo Alto	California
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Medical Center Health System	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Cancer Care Associates Medical Group, Inc. TORI	Redondo Beach	California
United States	University of California at San Francisco (PARENT)	San Francisco	California
United States	Moffitt Cancer Center -Tampa	Tampa	Florida
United States	Cancer Center of Kansas	Wichita	Kansas
United States	Cancer Treatment Centers of America	Zion	Illinois

Sponsors (3)

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

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  China,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Portugal,  Russian Federation,  Spain,  Sweden,  Switzerland,  Taiwan,  United Kingdom, 

References & Publications (1)

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, Sau — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	All-Cause Mortality	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.	From the date of randomization up to the date of death due to any cause, up to approximately 3 years
Primary	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.	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	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.	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	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.	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	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.	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	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.	From the date of randomization up to the date of death due to any cause, up to approximately 3 years
Secondary	Number of Overall Survival Events (Deaths)		From the date of randomization up to the date of death due to any cause, up to approximately 3 years
Secondary	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.	From the date of randomization up to the date of death due to any cause, up to approximately 3 years
Secondary	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.	From screening and every 6 weeks up to withdrawal of subject consent, progressive disease (PD), or unacceptable toxicity, up to approximately 3 years
Secondary	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.	From screening and every 6 weeks up to withdrawal of subject consent, progressive disease (PD), or unacceptable toxicity, up to approximately 3 years
Secondary	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.	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
Secondary	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.	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