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

NCT05950945 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: DS8201-0001-CIS-MA2023-505616-38-00
• Study Type: interventional
• Target: 250
• Locations: 10 countries
• Sites: 86

Brief 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.

Conditions

Breast Cancer

Keywords

Trastuzumab Derextecan; Enhertu®; DS8201-a; Breast Cancer; Anti-HER2-Antibody Drug Conjugate

Outcome Measures

Primary Outcomes (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.

  Until subsequent therapy or death, assessed up to 24 months

Secondary Outcomes (14)

• Real-World Progression Free Survival (PFS)

  Until progression or death, assessed up to 24 months

• Time From Start of T-DXd to Discontinuation of T-DXd or Death (TTD)

  Until treatment discontinuation or death, up to 24 months

• Objective Response Rate (ORR)

  Until progression, assessed up to 24 months

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  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

  Assessed up to 24 months

Study Arms (4)

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.

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.

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.

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.

Drug: Trastuzumab Deruxtecan

Interventions

Trastuzumab Deruxtecan 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

Also known as: T-DXd, DS-8201a (trastuzumab derextecan), Enhertu®

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: collaborator
• Daiichi Sankyo: lead

Study Sites (86)

Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

TERMINATED

USF College of Medicine

Tampa, Florida, 33602, United States

WITHDRAWN

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Beth Israel Lahey Health

Burlington, Massachusetts, 01805, United States

WITHDRAWN

Overlook Medical Center

Summit, New Jersey, 07901, United States

RECRUITING

Mater Hospital Sydney

North Sydney, New South Wales, 2065, Australia

TERMINATED

Monash Medical Centre Moorabbin

East Bentleigh, Victoria, 3165, Australia

TERMINATED

GenesisCare St Andrews Hospital

Adelaide, 5000, Australia

TERMINATED

Fiona Stanley Hospital

Murdoch, 6150, Australia

WITHDRAWN

Institut Jules Bordet

Anderlecht, 1070, Belgium

RECRUITING

GZA Ziekenhuizen

Antwerp, 2610, Belgium

RECRUITING

Universitair Ziekenhuis Brussel

Brussels, 1090, Belgium

RECRUITING

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

RECRUITING

UZ Leuven

Leuven, 3000, Belgium

WITHDRAWN

Centre Hospitalier Universitaire de Liege Sart-Tilman

Liège, 4000, Belgium

WITHDRAWN

GZA Ziekenhuizen

Wilrijk, 2610, Belgium

RECRUITING

Centro de Oncologia - Unidade Brasília - Hospital Sírio Libanês

Brasília, 71635-610, Brazil

RECRUITING

CIONC-Centro Integrado de Oncologia de Curitiba

Curitiba, 80810-050, Brazil

RECRUITING

Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer

Curitiba, 81520-060, Brazil

RECRUITING

CEPON - Centro de Pesquisas Oncológicas de Santa Catarina

Florianópolis, 88034-000, Brazil

RECRUITING

Oncosite - Centro de Pesquisa Clinica e Oncologia

Ijuí, 98700-000, Brazil

RECRUITING

Fundação Doutor Amaral Carvalho

Jaú, 17.210 - 080, Brazil

RECRUITING

Instituto de Cancer de Londrina

Londrina, 86015-520, Brazil

RECRUITING

Hospital das Clínicas FMRP-USP

Riberão Preto, 14015-010, Brazil

RECRUITING

Hospital Nossa Senhora da Conceicao

Rio Grande, 88701-160, Brazil

RECRUITING

Ensino e Terapia de Inovação Clínica AMO-ETICA

Salvador, 41810-570, Brazil

RECRUITING

Catarina Pesquisa Clinica

Santa Catarina, 88301-220, Brazil

RECRUITING

CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia

Santo André, 09060-650, Brazil

RECRUITING

Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto

São José do Rio Preto, 15090-000, Brazil

RECRUITING

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

São Paulo, 01246-000, Brazil

RECRUITING

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

São Paulo, 01317-001, Brazil

RECRUITING

Beijing Hospital

Beijing, 100006, China

RECRUITING

307 Hospital of PLA

Beijing, 100161, China

RECRUITING

Fujian Cancer Hospital

Fujian, 350011, China

RECRUITING

Sun Yat sen University Cancer Center

Guangzhou, 510060, China

RECRUITING

Zhejiang Cancer Hospital

Hangzhou, 310022, China

RECRUITING

Anhui Provincial Cancer Hospital

Hefei, 230031, China

RECRUITING

Shandong Cancer Hospital

Jinan, 250117, China

RECRUITING

Yunnan Cancer Hospital

Kunming, 650107, China

RECRUITING

Nanchang People's Hospital

Nanchang, 330006, China

RECRUITING

Jiangxi Cancer Hospital

Nanchang, 330029, China

RECRUITING

The Affiliated Hospital of Qingdao University

Qingdao, 266000, China

RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

RECRUITING

Henan Cancer Hospital

Zhengzhou, 450008, China

RECRUITING

Cork University Hospital

Cork, T12 EC8P, Ireland

RECRUITING

St Vincent's University Hospital

Dublin, D04 T6F4, Ireland

RECRUITING

St James Hospital

Dublin, D08 NHY1, Ireland

RECRUITING

Beaumont Hospital

Dublin, Dublin 9, Ireland

RECRUITING

Galway University Hospital

Galway, H91 YR71, Ireland

RECRUITING

Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari

Bari, 70124, Italy

RECRUITING

Azienda Ospedaliera Universitaria Policlinico Sant Orsola Malpighi IRCCS

Bologna, 40138, Italy

RECRUITING

Istituto Nazionale per la Ricerca sul Cancro di Genova

Genova, 16132, Italy

RECRUITING

Ospedale San Raffaele

Milan, 20132, Italy

RECRUITING

Humanitas Istituto Clinico Catanese

Misterbianco, 95045, Italy

RECRUITING

Istituto Nazionale Tumori Fondazione G Pascale

Naples, 80131, Italy

RECRUITING

IOV - Istituto Oncologico Veneto IRCCS

Padova, 35128, Italy

RECRUITING

Nuovo Ospedale di Prato

Prato, 59100, Italy

RECRUITING

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

Rome, 00161, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, 00168, Italy

RECRUITING

Ospedale Santa Chiara

Trento, 38123, Italy

RECRUITING

Amsterdam UMC, Locatie VUMC

Amsterdam, 1081 HV, Netherlands

RECRUITING

Amphia Ziekenhuis Molengracht

Breda, 4818 CK, Netherlands

RECRUITING

Medisch Centrum Leeuwarden

Leeuwarden, 8934 AD, Netherlands

RECRUITING

Alrijne Ziekenhuis Leiden

Leiden, 2334, Netherlands

RECRUITING

Maastricht University Medical Center

Maastricht, 6229 HX, Netherlands

RECRUITING

Haga Ziekenhuis

The Hague, 2545 AA, Netherlands

RECRUITING

Elisabeth TweeSteden Ziekenhuis

Tilburg, 5022 GC, Netherlands

RECRUITING

Bernhoven Uden

Uden, 5406, Netherlands

RECRUITING

Hospital de Braga

Braga, 4710-243, Portugal

RECRUITING

Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE

Lisbon, 1099-023, Portugal

RECRUITING

Fundação Champalimaud

Lisbon, 1400-038, Portugal

RECRUITING

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

Lisbon, 1649-028, Portugal

RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

RECRUITING

ICO l'Hospitalet - Hospital Duran i Reynals

Barcelona, 08908, Spain

RECRUITING

Hospital Universitario Donostia

Donostia / San Sebastian, 20014, Spain

RECRUITING

Hospital Universitario Virgen de las Nieves

Granada, 18014, Spain

RECRUITING

Complejo Hospitalario Universitario Insular Materno-Infantil

Las Palmas de Gran Canaria, 35016, Spain

RECRUITING

Hospital Beata Maria Ana

Madrid, 28007, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, 28222, Spain

RECRUITING

Hospital General Universitario Morales Meseguer

Murcia, 30008, Spain

RECRUITING

Clinica Universidad de Navarra

Pamplona, 31008, Spain

RECRUITING

Complejo Hospitalario Universitario de Santiago

Santiago de Compostela, 15706, Spain

RECRUITING

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

RECRUITING

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

RECRUITING

Hospital Arnau de Vilanova de Valencia

Valencia, 46015, Spain

RECRUITING

Related Publications (1)

• 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.

  PMID: 41342740 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Central Study Contacts

(US Sites) Daiichi Sankyo Contact for Clinical Trial Information

CONTACT

908-992-6400; CTRinfo@dsi.com

(Asia Sites) Daiichi Sankyo Contact for Clinical Trial Information

CONTACT

+81-3-6225-1111 (M-F 9-5 JST); dsclinicaltrial@daiichisankyo.co.jp

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2023
• First Posted: July 18, 2023
• Study Start: December 30, 2023
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

US (5); BR (15); NL (8); BE (7); PT (4); ES (14); IE (5); CN (13); AU (4); IT (11)