Trastuzumab Deruxtecan (T-DXd) in Patients Who Have Hormone Receptor-negative and Hormone Receptor-positive HER2-low or HER2 IHC 0 Metastatic Breast Cancer

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified March 2026 by Daiichi Sankyo
Sponsor
Daiichi Sankyo
Information Provided by (Responsible Party)
Daiichi Sankyo
Clinicaltrials.gov Identifier
NCT05950945
Other Study ID Numbers:
DS8201-0001-CIS-MA
First Submitted
May 21, 2023
First Posted
July 17, 2023
Last Update Posted
April 7, 2026
Last Verified
March 2026

ClinicalTrials.gov processed this data on April 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study 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.

Condition or DiseaseIntervention/Treatment
Breast Cancer
Drug: Trastuzumab DeruxtecanDrug: Trastuzumab DeruxtecanDrug: Trastuzumab DeruxtecanDrug: Trastuzumab Deruxtecan

Study Design

Study TypeInterventional
Actual Enrollment250 participants
Design AllocationNon-Randomized
Interventional ModelParallel Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleA 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)
Study Start DateDecember 29, 2023
Actual Primary Completion Date1yr 5mos from now
Actual Study Completion Date1yr 5mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Cohort 1: HR-negative, HER2-low
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.
Drug: Trastuzumab Deruxtecan
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
Cohort 2: HR-negative, HER2 IHC 0
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.
Drug: Trastuzumab Deruxtecan
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
Cohort 3: HR-positive, HER2-low
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.
Drug: Trastuzumab Deruxtecan
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
Cohort 4: HR-positive, HER2 IHC 0
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.
Drug: Trastuzumab Deruxtecan
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

Outcome Measures

Primary Outcome Measures
  1. 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.
Secondary Outcome Measures
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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).
  9. 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.
  10. 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&#039;s current health status. Higher scores indicate better clinical outcomes.
  11. 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&#039;s current health status. Higher scores indicate better clinical outcomes.
  12. Patient's Global Impression of Change (PGI-C) Response
    The PGI-C is a single-item questionnaire asking for the participant&#039;s overall impression of changes in clinical condition from baseline (prior to study drug initiation), where 1 is &quot;Normal&quot; and 7 is &quot;Severely ill&quot;. Lower scores indicate better clinical outcome.
  13. Patient's Global Impression of Severity (PGI-S) Response
    The PGI-S is a single-item questionnaire asking for the subject&#039;s overall impression of symptoms assessed over the past week, where 1 is &quot;Normal&quot; and 4 is &quot;Severe&quot;. Lower scores indicate better clinical outcome.
  14. Patient's Global Impression of Treatment Tolerability (PGI-TT) Response
    The PGI-TT is a single-item questionnaire asking for the subject&#039;s overall impression of treatment tolerability over the past week, where 1 is &quot;Not at all&quot; and 5 is &quot;Very much&quot;. Higher scores indicate a worse outcome.

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
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.
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.
Exclusion Criteria
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.
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.

Contacts and Locations

Sponsors and CollaboratorsDaiichi Sankyo
Locations
Mount Sinai Medical Center | Miami Beach Florida, United States, 33140USF College of Medicine | Tampa Florida, United States, 33602Dana-Farber Cancer Institute | Boston Massachusetts, United States, 02215Beth Israel Lahey Health | Burlington Massachusetts, United States, 01805Overlook Medical Center | Summit New Jersey, United States, 07901Mater Hospital Sydney | North Sydney New South Wales, Australia, 2065Monash Medical Centre Moorabbin | East Bentleigh Victoria, Australia, 3165GenesisCare St Andrews Hospital | Adelaide , Australia, 5000Fiona Stanley Hospital | Murdoch , Australia, 6150Institut Jules Bordet | Anderlecht , Belgium, 1070GZA Ziekenhuizen | Antwerp , Belgium, 2610Universitair Ziekenhuis Brussel | Brussels , Belgium, 1090Cliniques Universitaires Saint-Luc | Brussels , Belgium, 1200UZ Leuven | Leuven , Belgium, 3000Centre Hospitalier Universitaire de Liege Sart-Tilman | Liège , Belgium, 4000GZA Ziekenhuizen | Wilrijk , Belgium, 2610Centro de Oncologia - Unidade Brasília - Hospital Sírio Libanês | Brasília , Brazil, 71635-610CIONC-Centro Integrado de Oncologia de Curitiba | Curitiba , Brazil, 80810-050Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer | Curitiba , Brazil, 81520-060CEPON - Centro de Pesquisas Oncológicas de Santa Catarina | Florianópolis , Brazil, 88034-000Oncosite - Centro de Pesquisa Clinica e Oncologia | Ijuí , Brazil, 98700-000Fundação Doutor Amaral Carvalho | Jaú , Brazil, 17.210 - 080Instituto de Cancer de Londrina | Londrina , Brazil, 86015-520Hospital das Clínicas FMRP-USP | Riberão Preto , Brazil, 14015-010Hospital Nossa Senhora da Conceicao | Rio Grande , Brazil, 88701-160Ensino e Terapia de Inovação Clínica AMO-ETICA | Salvador , Brazil, 41810-570Catarina Pesquisa Clinica | Santa Catarina , Brazil, 88301-220CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia | Santo André , Brazil, 09060-650Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto | São José do Rio Preto , Brazil, 15090-000ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira | São Paulo , Brazil, 01246-000Clínica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária Ltda | São Paulo , Brazil, 01317-001Beijing Hospital | Beijing , China, 100006307 Hospital of PLA | Beijing , China, 100161Fujian Cancer Hospital | Fujian , China, 350011Sun Yat sen University Cancer Center | Guangzhou , China, 510060Zhejiang Cancer Hospital | Hangzhou , China, 310022Anhui Provincial Cancer Hospital | Hefei , China, 230031Shandong Cancer Hospital | Jinan , China, 250117Yunnan Cancer Hospital | Kunming , China, 650107Nanchang People's Hospital | Nanchang , China, 330006Jiangxi Cancer Hospital | Nanchang , China, 330029The Affiliated Hospital of Qingdao University | Qingdao , China, 266000Fudan University Shanghai Cancer Center | Shanghai , China, 200032Henan Cancer Hospital | Zhengzhou , China, 450008Cork University Hospital | Cork , Ireland, T12 EC8PSt Vincent's University Hospital | Dublin , Ireland, D04 T6F4St James Hospital | Dublin , Ireland, D08 NHY1Beaumont Hospital | Dublin , Ireland, Dublin 9Galway University Hospital | Galway , Ireland, H91 YR71Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari | Bari , Italy, 70124Azienda Ospedaliera Universitaria Policlinico Sant Orsola Malpighi IRCCS | Bologna , Italy, 40138Istituto Nazionale per la Ricerca sul Cancro di Genova | Genova , Italy, 16132Ospedale San Raffaele | Milan , Italy, 20132Humanitas Istituto Clinico Catanese | Misterbianco , Italy, 95045Istituto Nazionale Tumori Fondazione G Pascale | Naples , Italy, 80131IOV - Istituto Oncologico Veneto IRCCS | Padova , Italy, 35128Nuovo Ospedale di Prato | Prato , Italy, 59100Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza | Rome , Italy, 00161Fondazione Policlinico Universitario Agostino Gemelli IRCCS | Rome , Italy, 00168Ospedale Santa Chiara | Trento , Italy, 38123Amsterdam UMC, Locatie VUMC | Amsterdam , Netherlands, 1081 HVAmphia Ziekenhuis Molengracht | Breda , Netherlands, 4818 CKMedisch Centrum Leeuwarden | Leeuwarden , Netherlands, 8934 ADAlrijne Ziekenhuis Leiden | Leiden , Netherlands, 2334Maastricht University Medical Center | Maastricht , Netherlands, 6229 HXHaga Ziekenhuis | The Hague , Netherlands, 2545 AAElisabeth TweeSteden Ziekenhuis | Tilburg , Netherlands, 5022 GCBernhoven Uden | Uden , Netherlands, 5406Hospital de Braga | Braga , Portugal, 4710-243Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE | Lisbon , Portugal, 1099-023Fundação Champalimaud | Lisbon , Portugal, 1400-038Centro Hospitalar de Lisboa Norte E P E Hospital de Santa Maria | Lisbon , Portugal, 1649-028Hospital de la Santa Creu i Sant Pau | Barcelona , Spain, 08025ICO l'Hospitalet - Hospital Duran i Reynals | Barcelona , Spain, 08908Hospital Universitario Donostia | Donostia / San Sebastian , Spain, 20014Hospital Universitario Virgen de las Nieves | Granada , Spain, 18014Complejo Hospitalario Universitario Insular Materno-Infantil | Las Palmas de Gran Canaria , Spain, 35016Hospital Beata Maria Ana | Madrid , Spain, 28007Hospital Universitario 12 de Octubre | Madrid , Spain, 28041Hospital Universitario Puerta de Hierro Majadahonda | Majadahonda , Spain, 28222Hospital General Universitario Morales Meseguer | Murcia , Spain, 30008Clinica Universidad de Navarra | Pamplona , Spain, 31008Complejo Hospitalario Universitario de Santiago | Santiago de Compostela , Spain, 15706Hospital Universitario Virgen Macarena | Seville , Spain, 41009Hospital Clinico Universitario de Valencia | Valencia , Spain, 46010Hospital Arnau de Vilanova de Valencia | Valencia , Spain, 46015
Investigators
Study Director: Global Clinical Leader, Daiichi Sankyo