Breast CancerPhase 3NCT05950945
Trastuzumab Deruxtecan (T-DXd) in Patients Who Have Hormone Receptor-negative and Hormone Receptor-positive HER2-low or HER2 IHC 0 Metastatic Breast Cancer
A Phase 3 study testing Trastuzumab Deruxtecan in people with Breast Cancer, run by Daiichi Sankyo at 88 sites in 10 countries.
Trial summary
This study will evaluate the safety and efficacy of trastuzumab deruxtecan (T-DXd) in participants with human epidermal growth factor receptor 2 (HER2)-low or HER2 immunohistochemistry (IHC) 0 (who are both hormone receptor [HR]-negative and HR-positive) unresectable and/or metastatic breast cancer. 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
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 88 sitesin 10 countries
- Study dates
- 30 Dec 2023to 1 Oct 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- Sign and date the main informed consent form
- Must agree to provide a newly obtained or archival baseline biopsy from primary and/or metastatic lesion.
- Pathologically documented Breast Cancer (BC) tumor
- Is unresectable and/or metastatic.
- Is hormone receptor-negative or hormone receptor-positive.
- Must include percentage of positively stained cells to characterize if hormone receptor-positive or -negative.
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- Has confirmed HER2 IHC 1+ or IHC 2+/ISH- (HER2-low) status or HER2 IHC 0 status as determined according to ASCO CAP 2018 guidelines1 based on sample collected during Tissue Screening as described above.
- Was never previously HER2-positive (IHC 3+ or IHC 2+/ISH+) on prior pathology testing (per ASCO CAP guidelines).
- Was never previously treated with anti-HER2 therapy in the metastatic setting.
- Has had at least one and up to two prior lines of therapy in the metastatic setting.
- In participants with hormone receptor-positive HER2-low metastatic BC (Cohort 3):
- Has recurrent disease <2 years from the initiation of adjuvant ET OR
- Has disease progression on CDK4/6 inhibitor-based regimen within 12 months of completion of adjuvant therapy with a CDK4/6 inhibitor OR
- Has disease progression within the first 12 months of CDK4/6 in the first line metastatic setting
- Presence of at least one measurable lesion based on computed tomography or magnetic resonance imaging.
- Participants with brain metastases are allowed in the study. The brain lesion(s) should be small (<2 cm), untreated, asymptomatic, not requiring urgent medical intervention, and are asymptomatic and clinically stable.
- Has an Eastern Cooperative Oncology Group performance status of 0 or 1.
- Has a minimum life expectancy of 12 weeks at Screening.
- Has a left ventricular ejection fraction ≥50% within 28 days before enrollment.
- Has adequate organ and bone marrow function within 28 days before enrollment.
- Has adequate treatment washout period before enrollment.
- Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception.
Who cannot join
- Prior treatment with an antibody drug conjugate (ADC).
- Uncontrolled or significant cardiovascular disease.
- Has a corrected QT interval prolongation.
- Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
- Has spinal cord compression or clinically active central nervous system metastases.
- Has multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, other solid tumors curatively treated, or contralateral BC.
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- Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product.
- Has a history of severe hypersensitivity reactions to other monoclonal antibodies.
- Has an uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals.
- Active primary immunodeficiency, known uncontrolled active human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection.
- Has history of receiving a live, attenuated vaccine (messenger RNA and replication-deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first exposure to study drug.
- Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤1 or baseline.
- Is pregnant or breastfeeding or planning to become pregnant.
- Lung-specific intercurrent clinically significant illnesses.
- Any autoimmune, connective tissue, or inflammatory disorders.
- Prior complete pneumonectomy.
Trial locations and contacts
88 sites in 10 countries. Contact the study team or a site near you to ask about taking part.
(Asia Sites) Daiichi Sankyo Contact for Clinical Trial Information contact
88 sites in 10 countries
Brazil15 sites, 15 recruiting
- Recruiting
Centro de Oncologia - Unidade Brasília - Hospital Sírio Libanês
Brasília, 71635-610
Study Coordinator
- Recruiting
CIONC-Centro Integrado de Oncologia de Curitiba
Curitiba, 80810-050
Study Coordinator
- Recruiting
Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer
Curitiba, 81520-060
Study Coordinator
- Recruiting
CEPON - Centro de Pesquisas Oncológicas de Santa Catarina
Florianópolis, 88034-000
Study Coordinator
- Recruiting
Oncosite - Centro de Pesquisa Clinica e Oncologia
Ijuí, 98700-000
Study Coordinator
- Recruiting
Fundação Doutor Amaral Carvalho
Jaú, 17.210 - 080
Study Coordinator
- Recruiting
Instituto de Cancer de Londrina
Londrina, 86015-520
Study Coordinator
- Recruiting
Hospital das Clínicas FMRP-USP
Riberão Preto, 14015-010
Study Coordinator
- Recruiting
Hospital Nossa Senhora da Conceicao
Rio Grande, 88701-160
Study Coordinator
- Recruiting
Ensino e Terapia de Inovação Clínica AMO-ETICA
Salvador, 41810-570
Study Coordinator
- Recruiting
Catarina Pesquisa Clinica
Santa Catarina, 88301-220
Study Coordinator
- Recruiting
CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
Santo André, 09060-650
Study Coordinator
- Recruiting
Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto
São José do Rio Preto, 15090-000
Study Coordinator
- Recruiting
ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira
São Paulo, 01246-000
Study Coordinator
- Recruiting
Clínica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária Ltda
São Paulo, 01317-001
Study Coordinator
China14 sites, 11 recruiting
- Recruiting
Beijing Hospital
Beijing, 100006
Study Coordinator
- Recruiting
307 Hospital of PLA
Beijing, 100161
Principal Investigator
- Recruiting
Fujian Cancer Hospital
Fujian, 350011
Study Coordinator
- Recruiting
Sun Yat sen University Cancer Center
Guangzhou, 510060
Study Coordinator
- Recruiting
Zhejiang Cancer Hospital
Hangzhou, 310022
Study Coordinator
- Recruiting
Anhui Provincial Cancer Hospital
Hefei, 230031
Study Coordinator
- Recruiting
Shandong Cancer Hospital
Jinan, 250117
Study Coordinator
- Withdrawn
Yunnan Cancer Hospital
Kunming, 650107
- Recruiting
Nanchang People's Hospital
Nanchang, 330006
Study Coordinator
- Recruiting
Jiangxi Cancer Hospital
Nanchang, 330029
Study Coordinator
- Withdrawn
The Affiliated Hospital of Qingdao University
Qingdao, 266000
- Recruiting
Fudan University Shanghai Cancer Center
Shanghai, 200032
Principal Investigator
- Withdrawn
Xijing Hospital (The First Affiliated Hospital of the Air Force Medical University)
Xi'an, 710032
- Recruiting
Henan Cancer Hospital
Zhengzhou, 450008
Study Coordinator
Spain14 sites, 13 recruiting
- Recruiting
Hospital de la Santa Creu i Sant Pau
Barcelona, 08025
Study Coordinator
- Recruiting
ICO l'Hospitalet - Hospital Duran i Reynals
Barcelona, 08908
Study Coordinator
- Withdrawn
Hospital Universitario Donostia
Donostia / San Sebastian, 20014
- Recruiting
Hospital Universitario Virgen de las Nieves
Granada, 18014
Site Coordinator
- Recruiting
Complejo Hospitalario Universitario Insular Materno-Infantil
Las Palmas de Gran Canaria, 35016
Study Coordinator
- Recruiting
Hospital Beata Maria Ana
Madrid, 28007
Study Coordinator
- Recruiting
Hospital Universitario 12 de Octubre
Madrid, 28041
Site Coordinator
- Recruiting
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda, 28222
Study Coordinator
- Recruiting
Hospital General Universitario Morales Meseguer
Murcia, 30008
Study Coordinator
- Recruiting
Clinica Universidad de Navarra
Pamplona, 31008
Study Coordinator
- Recruiting
Complejo Hospitalario Universitario de Santiago
Santiago de Compostela, 15706
Site Coordinator
- Recruiting
Hospital Universitario Virgen Macarena
Seville, 41009
Study Coordinator
- Recruiting
Hospital Clinico Universitario de Valencia
Valencia, 46010
Study Coordinator
- Recruiting
Hospital Arnau de Vilanova de Valencia
Valencia, 46015
Study Coordinator
Italy11 sites, 10 recruiting
- Withdrawn
Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari
Bari, 70124
- Recruiting
Azienda Ospedaliera Universitaria Policlinico Sant Orsola Malpighi IRCCS
Bologna, 40138
Study Coordinator
- Recruiting
Istituto Nazionale per la Ricerca sul Cancro di Genova
Genova, 16132
Study Coordinator
- Recruiting
Ospedale San Raffaele
Milan, 20132
Study Coordinator
- Recruiting
Humanitas Istituto Clinico Catanese
Misterbianco, 95045
Study Coordinator
- Recruiting
Istituto Nazionale Tumori Fondazione G Pascale
Naples, 80131
Study Coordinator
- Recruiting
IOV - Istituto Oncologico Veneto IRCCS
Padova, 35128
Study Coordinator
- Recruiting
Nuovo Ospedale di Prato
Prato, 59100
Study Coordinator
- Recruiting
Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza
Rome, 00161
Study Coordinator
- Recruiting
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Rome, 00168
Principal Investigator
- Recruiting
Ospedale Santa Chiara
Trento, 38123
Study Coordinator
Netherlands8 sites, 8 recruiting
- Recruiting
Amsterdam UMC, Locatie VUMC
Amsterdam, 1081 HV
Study Coordinator
- Recruiting
Amphia Ziekenhuis Molengracht
Breda, 4818 CK
Study Coordinator
- Recruiting
Medisch Centrum Leeuwarden
Leeuwarden, 8934 AD
Study Coordinator
- Recruiting
Alrijne Ziekenhuis Leiden
Leiden, 2334
Principal Investigator
- Recruiting
Maastricht University Medical Center
Maastricht, 6229 HX
Study Coordinator
- Recruiting
Haga Ziekenhuis
The Hague, 2545 AA
Study Coordinator
- Recruiting
Elisabeth TweeSteden Ziekenhuis
Tilburg, 5022 GC
Study Coordinator
- Recruiting
Bernhoven Uden
Uden, 5406
Principal Investigator
Belgium7 sites, 2 recruiting
- Recruiting
Institut Jules Bordet
Anderlecht, 1070
Study Coordinator
- Withdrawn
GZA Ziekenhuizen
Antwerp, 2610
- Withdrawn
Universitair Ziekenhuis Brussel
Brussels, 1090
- Withdrawn
Cliniques Universitaires Saint-Luc
Brussels, 1200
- Withdrawn
UZ Leuven
Leuven, 3000
- Withdrawn
Centre Hospitalier Universitaire de Liege Sart-Tilman
Liège, 4000
- Recruiting
GZA Ziekenhuizen
Wilrijk, 2610
Study Coordinator
United States5 sites, 2 recruiting
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Study Coordinator
- Withdrawn
Beth Israel Lahey Health
Burlington, Massachusetts, 01805
- Terminated
Mount Sinai Medical Center
Miami Beach, Florida, 33140
- Recruiting
Overlook Medical Center
Summit, New Jersey, 07901
Study Coordinator
- Withdrawn
USF College of Medicine
Tampa, Florida, 33602
Ireland5 sites, 4 recruiting
- Recruiting
Cork University Hospital
Cork, T12 EC8P
Study Coordinator
- Recruiting
St Vincent's University Hospital
Dublin, D04 T6F4
Study Coordinator
- Recruiting
St James Hospital
Dublin, D08 NHY1
Principal Investigator
- Recruiting
Beaumont Hospital
Dublin, Dublin 9
Principal Investigator
- Withdrawn
Galway University Hospital
Galway, H91 YR71
Portugal5 sites, 3 recruiting
- Recruiting
Hospital de Braga
Braga, 4710-243
Study Coordinator
- Withdrawn
Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE
Lisbon, 1099-023
- Recruiting
Fundação Champalimaud
Lisbon, 1400-038
Study Coordinator
- Recruiting
Centro Hospitalar de Lisboa Norte E P E Hospital de Santa Maria
Lisbon, 1649-028
Study Coordinator
- Withdrawn
Instituto Português de Oncologia do Porto Francisco Gentil, EPE
Porto, 4200-072
Australia4 sites
- Terminated
GenesisCare St Andrews Hospital
Adelaide, 5000
- Terminated
Monash Medical Centre Moorabbin
East Bentleigh, Victoria, 3165
- Withdrawn
Fiona Stanley Hospital
Murdoch, 6150
- Terminated
Mater Hospital Sydney
North Sydney, New South Wales, 2065
About this study
Official title: A Phase 3b, Multicenter, Global, Interventional, Open-label Study of Trastuzumab Deruxtecan (T-DXd), an Anti-HER2-Antibody Drug Conjugate (ADC), in Subjects Who Have Unresectable and/or Metastatic HER2-low or HER2 Immunohistochemistry (IHC) 0 Breast Cancer (DESTINY-Breast15)
This study will evaluate the safety and efficacy of trastuzumab deruxtecan (T-DXd) in participants with human epidermal growth factor receptor 2 (HER2)-low or HER2 immunohistochemistry (IHC) 0 (who are both hormone receptor [HR]-negative and HR-positive) unresectable and/or metastatic breast cancer.
Read the detailed description
The primary endpoint of interest in this study is time to next treatment (TTNT), a measure that will determine how long T-DXd allows patients to derive clinical benefit from the study drug.
- Conditions
- Breast Cancer
- Being tested
- Trastuzumab Deruxtecan
- Keywords
- Trastuzumab Derextecan, Enhertu®, DS8201-a, Breast Cancer, Anti-HER2-Antibody Drug Conjugate
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trastuzumab DeruxtecanDrug
Also called T-DXd, DS-8201a (trastuzumab derextecan), Enhertu®
Intravenous administration, 5.4 mg/kg on Day 1 of each 21-day cycle until radiographic disease progression as assessed by the investigator, unacceptable toxicity, other discontinuation criteria are met, or 2 years after first dose of study drug
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: HR-negative, HER2-low | Experimental | Participants with HR-negative HER2-low unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd. Receives: Drug: Trastuzumab Deruxtecan |
| Cohort 2: HR-negative, HER2 IHC 0 | Experimental | Participants with HR-negative HER2 IHC 0 unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd. Receives: Drug: Trastuzumab Deruxtecan |
| Cohort 3: HR-positive, HER2-low | Experimental | Participants with HR-positive HER2-low unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd.
Participants must also have recurrent disease <2 years from the initiation of adjuvant ET or have disease progression on CDK4/6 inhibitor-based regimen within 12 months of completion of adjuvant therapy with a CDK4/6 inhibitor or have disease progression within the first 12 months of CDK4/6 in the first line metastatic setting. Receives: Drug: Trastuzumab Deruxtecan |
| Cohort 4: HR-positive, HER2 IHC 0 | Experimental | Participants with HR-positive HER2 IHC 0 unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd. Receives: Drug: Trastuzumab Deruxtecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time From the Start of T-DXd to Initiation of Subsequent Anticancer Treatment (TTNT)
TTNT is defined as the time interval from the date of first dose of T-DXd to the initiation of the next anticancer treatment or death due to any cause.
Measured: Until subsequent therapy or death, assessed up to 24 months
Secondary outcomes (14)
Real-World Progression Free Survival (PFS)
Real-world PFS is defined as time from date of first dose of T-DXd to time of disease progression per investigator assessment based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause.
Measured: Until progression or death, assessed up to 24 months
Time From Start of T-DXd to Discontinuation of T-DXd or Death (TTD)
TTD is defined as the time interval from the date of first dose of T-DXd to the date of discontinuation of T-DXd or death due to any cause.
Measured: Until treatment discontinuation or death, up to 24 months
Objective Response Rate (ORR)
ORR is defined as the proportion of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) according to the investigator and per RECIST version 1.1 criteria.
Measured: Until progression, assessed up to 24 months
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
TEAEs are graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0. A TEAE is defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after initiating the study drug until 47 days after the last dose of the study drug.
Measured: Up to follow up period, up to 24 months
Mean Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC-QLQ)-C30 Score
Change from baseline in the EORTC-QLQ-C30 scale scores range from 0-100. For functioning and global health status/ QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.
Measured: Assessed up to 24 months
Mean Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC-QLQ)-BR45 Score
Change from baseline in the EORTC QLQ-BR45 scale scores range from 0-100. For functioning and global health status/ QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.
Measured: Assessed up to 24 months
Time to First and Definitive Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC-QLQ) Scales
Time to first and definitive deterioration in EORTC-QLQ scales. Scale scores range from 0-100. For functioning and global health status/ QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.
Measured: Assessed up to 24 months
Mean Change from Baseline in EuroQol Questionnaire-5 Dimensions-5 Levels (EQ-5D-5L)
Change from baseline in EQ-5D-5L. The EQ-5D-5L is a health-related QoL questionnaire based on five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension contains five levels: no problems, slight, moderate, severe, and extreme problems. The EQ-5D-5L results can be converted into a single utility value. Utility values range from 0 to 1, with 1 corresponding to perfect health and 0 corresponding to a health status equivalent to death. In addition, participants can provide an overall rating of their current health status using a visual analog scale ranging from 0 (worse) to 100 (better).
Measured: Assessed up to 24 months
Mean Change From Baseline in EuroQol Questionnaire-5 Dimensions-5 Levels (EQ-5D-5L) Index Score
Change from baseline in EQ-5D-5L index score. The EQ-5D-5L index score ranges from less than 0 (worse) to 1 (better), with higher scores representing a better health status.
Measured: Assessed up to 24 months
Mean Change From Baseline in EuroQol Questionnaire-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS)
Change from baseline in EQ-5D-5L VAS. The EQ-5D-5L VAS ranging from 0 (worse) to 100 (better) is used to assess an overall rating of participant's current health status. Higher scores indicate better clinical outcomes.
Measured: Assessed up to 24 months
Time to First and Definitive Deterioration in EuroQol Questionnaire-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS)
Time to first and definitive deterioration in EQ-5D-5L VAS. The EQ-5D-5L VAS ranging from 0 (worse) to 100 (better) is used to assess an overall rating of participant's current health status. Higher scores indicate better clinical outcomes.
Measured: Assessed up to 24 months
Patient's Global Impression of Change (PGI-C) Response
The PGI-C is a single-item questionnaire asking for the participant's overall impression of changes in clinical condition from baseline (prior to study drug initiation), where 1 is "Normal" and 7 is "Severely ill". Lower scores indicate better clinical outcome.
Measured: Assessed up to 24 months
Patient's Global Impression of Severity (PGI-S) Response
The PGI-S is a single-item questionnaire asking for the subject's overall impression of symptoms assessed over the past week, where 1 is "Normal" and 4 is "Severe". Lower scores indicate better clinical outcome.
Measured: Assessed up to 24 months
Patient's Global Impression of Treatment Tolerability (PGI-TT) Response
The PGI-TT is a single-item questionnaire asking for the subject's overall impression of treatment tolerability over the past week, where 1 is "Not at all" and 5 is "Very much". Higher scores indicate a worse outcome.
Measured: Assessed up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2023
- Study start30 Dec 2023
- Primary completion1 Oct 2027 (estimated)
- Study completion1 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Global Clinical Leader, Study director, Daiichi Sankyo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05950945
- Sponsor's protocol ID
- DS8201-0001-CIS-MA
- Other IDs
- 2023-505616-38-00, 2023
- Status last verified
- Jun 2026
- First submitted
- 22 May 2023
- Last updated
- 12 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) on completed studies 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
Yaziji H, Hornick JL, Troxell ML. The Suitability of Repurposed, Legacy HER2 Immunohistochemistry Assays for the Detection of HER2 Low and Ultralow Expression: Current Limitations and Potential Considerations. Appl Immunohistochem Mol Morphol. 2026 Jan 1;34(1):1-4. doi: 10.1097/PAI.0000000000001296. Epub 2025 Dec 4. No abstract available.
PubMed 41342740
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3b, Multicenter, Global, Interventional, Open-label Study of Trastuzumab Deruxtecan (T-DXd), an Anti-HER2-Antibody Drug Conjugate (ADC), in Subjects Who Have Unresectable and/or Metastatic HER2-low or HER2 Immunohistochemistry (IHC) 0 Breast Cancer (DESTINY-Breast15)
- ClinicalTrials.gov ID
- NCT05950945
- Acronym / sponsor ID
- DS8201-0001-CIS-MA
- Conditions
- Breast Cancer
- Keywords
- Trastuzumab Derextecan, Enhertu®, DS8201-a, Breast Cancer, Anti-HER2-Antibody Drug Conjugate
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Daiichi SankyoIndustry (pharma, biotech, devices)
- Collaborators
- AstraZeneca
- Study start
- 30 Dec 2023 (actual)
- Primary completion
- 1 Oct 2027 (estimated)
- Study completion
- 1 Oct 2027 (estimated)
- First posted
- 18 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety and efficacy of trastuzumab deruxtecan (T-DXd) in participants with human epidermal growth factor receptor 2 (HER2)-low or HER2 immunohistochemistry (IHC) 0 (who are both hormone receptor [HR]-negative and HR-positive) unresectable and/or metastatic breast cancer.
Detailed description
The primary endpoint of interest in this study is time to next treatment (TTNT), a measure that will determine how long T-DXd allows patients to derive clinical benefit from the study drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: HR-negative, HER2-low | Experimental | Drug: Trastuzumab DeruxtecanParticipants with HR-negative HER2-low unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd. |
| Cohort 2: HR-negative, HER2 IHC 0 | Experimental | Drug: Trastuzumab DeruxtecanParticipants with HR-negative HER2 IHC 0 unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd. |
| Cohort 3: HR-positive, HER2-low | Experimental | Drug: Trastuzumab DeruxtecanParticipants with HR-positive HER2-low unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd. Participants must also have recurrent disease <2 years from the initiation of adjuvant ET or have disease progression on CDK4/6 inhibitor-based regimen within 12 months of completion of adjuvant therapy with a CDK4/6 inhibitor or have disease progression within the first 12 months of CDK4/6 in the first line metastatic setting. |
| Cohort 4: HR-positive, HER2 IHC 0 | Experimental | Drug: Trastuzumab DeruxtecanParticipants with HR-positive HER2 IHC 0 unresectable and/or metastatic breast cancer who have received at least one and at most two prior lines of therapy in the metastatic setting will receive T-DXd. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Sign and date the main informed consent form
- Must agree to provide a newly obtained or archival baseline biopsy from primary and/or metastatic lesion.
- Pathologically documented Breast Cancer (BC) tumor
- Has had at least one and up to two prior lines of therapy in the metastatic setting.
- Presence of at least one measurable lesion based on computed tomography or magnetic resonance imaging.
Key exclusion criteria (16 listed)
- Prior treatment with an antibody drug conjugate (ADC).
- Uncontrolled or significant cardiovascular disease.
- Has a corrected QT interval prolongation.
- Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
- Has spinal cord compression or clinically active central nervous system metastases.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Trastuzumab DeruxtecanAlso: T-DXd, DS-8201a (trastuzumab derextecan), Enhertu®Intravenous administration, 5.4 mg/kg on Day 1 of each 21-day cycle until radiographic disease progression as assessed by the investigator, unacceptable toxicity, other discontinuation criteria are met, or 2 years after first dose of study drug | Drug | Cohort 1: HR-negative, HER2-low, Cohort 2: HR-negative, HER2 IHC 0, Cohort 3: HR-positive, HER2-low, Cohort 4: HR-positive, HER2 IHC 0 |
Primary outcome
Time From the Start of T-DXd to Initiation of Subsequent Anticancer Treatment (TTNT)
Time frame: Until subsequent therapy or death, assessed up to 24 months
TTNT is defined as the time interval from the date of first dose of T-DXd to the initiation of the next anticancer treatment or death due to any cause.
14 secondary outcomes
Real-World Progression Free Survival (PFS)
Time frame: Until progression or death, assessed up to 24 months
Time From Start of T-DXd to Discontinuation of T-DXd or Death (TTD)
Time frame: Until treatment discontinuation or death, up to 24 months
Objective Response Rate (ORR)
Time frame: Until progression, assessed up to 24 months
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: Up to follow up period, up to 24 months
Mean Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC-QLQ)-C30 Score
Time frame: Assessed up to 24 months
Mean Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC-QLQ)-BR45 Score
Time frame: Assessed up to 24 months
Time to First and Definitive Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC-QLQ) Scales
Time frame: Assessed up to 24 months
Mean Change from Baseline in EuroQol Questionnaire-5 Dimensions-5 Levels (EQ-5D-5L)
Time frame: Assessed up to 24 months
Mean Change From Baseline in EuroQol Questionnaire-5 Dimensions-5 Levels (EQ-5D-5L) Index Score
Time frame: Assessed up to 24 months
Mean Change From Baseline in EuroQol Questionnaire-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS)
Time frame: Assessed up to 24 months
Time to First and Definitive Deterioration in EuroQol Questionnaire-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS)
Time frame: Assessed up to 24 months
Patient's Global Impression of Change (PGI-C) Response
Time frame: Assessed up to 24 months
Patient's Global Impression of Severity (PGI-S) Response
Time frame: Assessed up to 24 months
Patient's Global Impression of Treatment Tolerability (PGI-TT) Response
Time frame: Assessed up to 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2026.
- Derived from this study: PubMed 41342740Yaziji H, Hornick JL, Troxell ML. The Suitability of Repurposed, Legacy HER2 Immunohistochemistry Assays for the Detection of HER2 Low and Ultralow Expression: Current Limitations and Potential Considerations. Appl Immunohistochem Mol Morphol. 2026 Jan 1;34(1):1-4. doi: 10.1097/PAI.0000000000001296. Epub 2025 Dec 4. No abstract available.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) on completed studies 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/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
(Asia Sites) Daiichi Sankyo Contact for Clinical Trial Information contact
Global Clinical Leader study director
Daiichi Sankyo
88 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Trastuzumab Deruxtecan in people with Breast Cancer, run by Daiichi Sankyo at 88 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 88 sites in Brazil, China, Spain, Italy, Netherlands and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact (US Sites) Daiichi Sankyo Contact for Clinical Trial Information (908-992-6400, CTRinfo@dsi.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time From the Start of T-DXd to Initiation of Subsequent Anticancer Treatment (TTNT) (time frame: Until subsequent therapy or death, assessed up to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05950945, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2026.