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

NCT ID: NCT05950945

Last Updated: 2025-11-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

250 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-12-30

Study Completion Date

2027-10-01

Brief Summary

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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

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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

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Breast Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Trastuzumab Deruxtecan

Intervention Type DRUG

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.

Group Type EXPERIMENTAL

Trastuzumab Deruxtecan

Intervention Type DRUG

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.

Group Type EXPERIMENTAL

Trastuzumab Deruxtecan

Intervention Type DRUG

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.

Group Type EXPERIMENTAL

Trastuzumab Deruxtecan

Intervention Type DRUG

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

Interventions

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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

Intervention Type DRUG

Other Intervention Names

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T-DXd DS-8201a (trastuzumab derextecan) Enhertu®

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role collaborator

Daiichi Sankyo

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Global Clinical Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

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Mount Sinai Medical Center

Miami Beach, Florida, United States

Site Status TERMINATED

USF College of Medicine

Tampa, Florida, United States

Site Status RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Beth Israel Lahey Health

Burlington, Massachusetts, United States

Site Status RECRUITING

Overlook Medical Center

Summit, New Jersey, United States

Site Status RECRUITING

Mater Hospital Sydney

North Sydney, New South Wales, Australia

Site Status RECRUITING

Monash Medical Centre Moorabbin

East Bentleigh, Victoria, Australia

Site Status RECRUITING

Fiona Stanley Hospital

Murdoch, , Australia

Site Status RECRUITING

Institut Jules Bordet

Anderlecht, , Belgium

Site Status RECRUITING

GZA Ziekenhuizen

Antwerp, , Belgium

Site Status RECRUITING

Universitair Ziekenhuis Brussel

Brussels, , Belgium

Site Status RECRUITING

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Site Status RECRUITING

UZ Leuven

Leuven, , Belgium

Site Status RECRUITING

Centre Hospitalier Universitaire de Liege Sart-Tilman

Liège, , Belgium

Site Status RECRUITING

GZA Ziekenhuizen

Wilrijk, , Belgium

Site Status RECRUITING

Centro de Oncologia - Unidade Brasília - Hospital Sírio Libanês

Brasília, , Brazil

Site Status RECRUITING

CIONC-Centro Integrado de Oncologia de Curitiba

Curitiba, , Brazil

Site Status RECRUITING

Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer

Curitiba, , Brazil

Site Status RECRUITING

CEPON - Centro de Pesquisas Oncológicas de Santa Catarina

Florianópolis, , Brazil

Site Status RECRUITING

Oncosite - Centro de Pesquisa Clinica e Oncologia

Ijuí, , Brazil

Site Status RECRUITING

Fundação Doutor Amaral Carvalho

Jaú, , Brazil

Site Status RECRUITING

Instituto de Cancer de Londrina

Londrina, , Brazil

Site Status RECRUITING

Hospital das Clínicas FMRP-USP

Riberão Preto, , Brazil

Site Status RECRUITING

Hospital Nossa Senhora da Conceicao

Rio Grande, , Brazil

Site Status RECRUITING

Ensino e Terapia de Inovação Clínica AMO-ETICA

Salvador, , Brazil

Site Status RECRUITING

Catarina Pesquisa Clinica

Santa Catarina, , Brazil

Site Status RECRUITING

CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia

Santo André, , Brazil

Site Status RECRUITING

Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto

São José do Rio Preto, , Brazil

Site Status RECRUITING

ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira

São Paulo, , Brazil

Site Status RECRUITING

Clínica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária Ltda

São Paulo, , Brazil

Site Status RECRUITING

Beijing Hospital

Beijing, , China

Site Status RECRUITING

307 Hospital of PLA

Beijing, , China

Site Status RECRUITING

Fujian Cancer Hospital

Fujian, , China

Site Status RECRUITING

Sun Yat sen University Cancer Center

Guangzhou, , China

Site Status RECRUITING

Zhejiang Cancer Hospital

Hangzhou, , China

Site Status RECRUITING

Anhui Provincial Cancer Hospital

Hefei, , China

Site Status RECRUITING

Shandong Cancer Hospital

Jinan, , China

Site Status RECRUITING

Yunnan Cancer Hospital

Kunming, , China

Site Status RECRUITING

Nanchang People's Hospital

Nanchang, , China

Site Status RECRUITING

Jiangxi Cancer Hospital

Nanchang, , China

Site Status RECRUITING

The Affiliated Hospital of Qingdao University

Qingdao, , China

Site Status RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, , China

Site Status RECRUITING

Henan Cancer Hospital

Zhengzhou, , China

Site Status RECRUITING

Cork University Hospital

Cork, , Ireland

Site Status RECRUITING

St Vincent's University Hospital

Dublin, , Ireland

Site Status RECRUITING

St James Hospital

Dublin, , Ireland

Site Status RECRUITING

Beaumont Hospital

Dublin, , Ireland

Site Status RECRUITING

Galway University Hospital

Galway, , Ireland

Site Status RECRUITING

Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari

Bari, , Italy

Site Status RECRUITING

Azienda Ospedaliera Universitaria Policlinico Sant Orsola Malpighi IRCCS

Bologna, , Italy

Site Status RECRUITING

Istituto Nazionale per la Ricerca sul Cancro di Genova

Genova, , Italy

Site Status RECRUITING

Ospedale San Raffaele

Milan, , Italy

Site Status RECRUITING

Humanitas Istituto Clinico Catanese

Misterbianco, , Italy

Site Status RECRUITING

Istituto Nazionale Tumori Fondazione G Pascale

Naples, , Italy

Site Status RECRUITING

IOV - Istituto Oncologico Veneto IRCCS

Padua, , Italy

Site Status RECRUITING

Nuovo Ospedale di Prato

Prato, , Italy

Site Status RECRUITING

Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza

Rome, , Italy

Site Status RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, , Italy

Site Status RECRUITING

Ospedale Santa Chiara

Trento, , Italy

Site Status RECRUITING

Amsterdam UMC, Locatie VUMC

Amsterdam, , Netherlands

Site Status RECRUITING

Amphia Ziekenhuis Molengracht

Breda, , Netherlands

Site Status RECRUITING

Medisch Centrum Leeuwarden

Leeuwarden, , Netherlands

Site Status RECRUITING

Alrijne Ziekenhuis Leiden

Leiden, , Netherlands

Site Status RECRUITING

Maastricht University Medical Center

Maastricht, , Netherlands

Site Status RECRUITING

Haga Ziekenhuis

The Hague, , Netherlands

Site Status RECRUITING

Elisabeth TweeSteden Ziekenhuis

Tilburg, , Netherlands

Site Status RECRUITING

Bernhoven Uden

Uden, , Netherlands

Site Status RECRUITING

Hospital de Braga

Braga, , Portugal

Site Status RECRUITING

Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE

Lisbon, , Portugal

Site Status RECRUITING

Centro Hospitalar de Lisboa Norte E P E Hospital de Santa Maria

Lisbon, , Portugal

Site Status RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Site Status RECRUITING

ICO l'Hospitalet - Hospital Duran i Reynals

Barcelona, , Spain

Site Status RECRUITING

Hospital Universitario Donostia

Donostia / San Sebastian, , Spain

Site Status RECRUITING

Hospital Universitario Virgen de las Nieves

Granada, , Spain

Site Status RECRUITING

Complejo Hospitalario Universitario Insular Materno-Infantil

Las Palmas de Gran Canaria, , Spain

Site Status RECRUITING

Hospital Beata Maria Ana

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, , Spain

Site Status RECRUITING

Hospital General Universitario Morales Meseguer

Murcia, , Spain

Site Status RECRUITING

Clinica Universidad de Navarra

Pamplona, , Spain

Site Status RECRUITING

Complejo Hospitalario Universitario de Santiago

Santiago de Compostela, , Spain

Site Status RECRUITING

Hospital Universitario Virgen Macarena

Seville, , Spain

Site Status RECRUITING

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Site Status RECRUITING

Hospital Arnau de Vilanova de Valencia

Valencia, , Spain

Site Status RECRUITING

Countries

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United States Australia Belgium Brazil China Ireland Italy Netherlands Portugal Spain

Central Contacts

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(US Sites) Daiichi Sankyo Contact for Clinical Trial Information

Role: CONTACT

908-992-6400

(Asia Sites) Daiichi Sankyo Contact for Clinical Trial Information

Role: CONTACT

+81-3-6225-1111 (M-F 9-5 JST)

Facility Contacts

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Other Identifiers

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2023-505616-38-00

Identifier Type: OTHER

Identifier Source: secondary_id

DS8201-0001-CIS-MA

Identifier Type: -

Identifier Source: org_study_id

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