Clinical trial NCT05950945: Trastuzumab Deruxtecan (T-DXd) in Patients Who Have Hormone Receptor-negative and Hormone Receptor-positive HER2-low or HER2 IHC 0 Metastatic Breast Cancer
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Keywords: Trastuzumab Derextecan
Enhertu®
DS8201-a
Breast Cancer
Anti-HER2-Antibody Drug Conjugate
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
First posted: 2023-07-18
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time From the Start of T-DXd to Initiation of Subsequent Anticancer Treatment (TTNT)
timeFrame: Until subsequent therapy or death, assessed up to 24 months
Secondary outcomes:
measure: Real-World Progression Free Survival (PFS)
timeFrame: Until progression or death, assessed up to 24 months
measure: Time From Start of T-DXd to Discontinuation of T-DXd or Death (TTD)
timeFrame: Until treatment discontinuation or death, up to 24 months
measure: Objective Response Rate (ORR)
timeFrame: Until progression, assessed up to 24 months
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to follow up period, up to 24 months
measure: Mean Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC-QLQ)-C30 Score
timeFrame: Assessed up to 24 months
measure: Mean Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC-QLQ)-BR45 Score
timeFrame: Assessed up to 24 months
measure: Time to First and Definitive Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC-QLQ) Scales
timeFrame: Assessed up to 24 months
measure: Mean Change from Baseline in EuroQol Questionnaire-5 Dimensions-5 Levels (EQ-5D-5L)
timeFrame: Assessed up to 24 months
measure: Mean Change From Baseline in EuroQol Questionnaire-5 Dimensions-5 Levels (EQ-5D-5L) Index Score
timeFrame: Assessed up to 24 months
measure: Mean Change From Baseline in EuroQol Questionnaire-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS)
timeFrame: Assessed up to 24 months
measure: Time to First and Definitive Deterioration in EuroQol Questionnaire-5 Dimensions-5 Levels (EQ-5D-5L) Visual Analog Scale (VAS)
timeFrame: Assessed up to 24 months
measure: Patient's Global Impression of Change (PGI-C) Response
timeFrame: Assessed up to 24 months
measure: Patient's Global Impression of Severity (PGI-S) Response
timeFrame: Assessed up to 24 months
measure: Patient's Global Impression of Treatment Tolerability (PGI-TT) Response
timeFrame: Assessed up to 24 months
Other outcomes:
Locations:
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Tampa
country: United States
facility: USF College of Medicine
state: Florida
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Burlington
country: United States
facility: Beth Israel Lahey Health
state: Massachusetts
city: Summit
country: United States
facility: Overlook Medical Center
state: New Jersey
city: North Sydney
country: Australia
facility: Mater Hospital Sydney
state: New South Wales
city: East Bentleigh
country: Australia
facility: Monash Medical Centre Moorabbin
state: Victoria
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet
city: Antwerpen
country: Belgium
facility: GZA Ziekenhuizen
city: Bruxelles
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire de Liege Sart-Tilman
city: Wilrijk
country: Belgium
facility: GZA Ziekenhuizen
city: Brasilia
country: Brazil
facility: Centro de Oncologia - Unidade Brasília - Hospital Sírio Libanês
city: Curitiba
country: Brazil
facility: CIONC-Centro Integrado de Oncologia de Curitiba
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer
city: Florianopolis
country: Brazil
facility: CEPON - Centro de Pesquisas Oncológicas de Santa Catarina
city: Ijuí
country: Brazil
facility: Oncosite - Centro de Pesquisa Clinica e Oncologia
city: Jaú
country: Brazil
facility: Fundação Doutor Amaral Carvalho
city: Londrina
country: Brazil
facility: Instituto de Cancer de Londrina
city: Riberão Preto
country: Brazil
facility: Hospital das Clínicas FMRP-USP
city: Rio Grande Do Sul
country: Brazil
facility: Hospital Nossa Senhora da Conceicao
city: Salvador
country: Brazil
facility: Ensino e Terapia de Inovação Clínica AMO-ETICA
city: Santa Catarina
country: Brazil
facility: Catarina Pesquisa Clinica
city: Santo André
country: Brazil
facility: CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
city: Sao Jose do Rio Preto
country: Brazil
facility: Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto
city: São Paulo
country: Brazil
facility: ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira
city: São Paulo
country: Brazil
facility: Clínica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária Ltda
city: Beijing
country: China
facility: Beijing Hospital
city: Beijing
country: China
facility: 307 Hospital of PLA
city: Fujian
country: China
facility: Fujian Cancer Hospital
city: Guangzhou
country: China
facility: Sun Yat sen University Cancer Center
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Hefei
country: China
facility: Anhui Provincial Cancer Hospital
city: Jinan
country: China
facility: Shandong Cancer Hospital
city: Kunming
country: China
facility: Yunnan Cancer Hospital
city: Nanchang
country: China
facility: Nanchang People's Hospital
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: St Vincent's University Hospital
city: Dublin
country: Ireland
facility: St James Hospital
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Galway
country: Ireland
facility: Galway University Hospital
city: Bari
country: Italy
facility: Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Sant Orsola Malpighi IRCCS
city: Genova
country: Italy
facility: Istituto Nazionale per la Ricerca sul Cancro di Genova
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Misterbianco
country: Italy
facility: Humanitas Istituto Clinico Catanese
city: Naples
country: Italy
facility: Istituto Nazionale Tumori Fondazione G Pascale
city: Padova
country: Italy
facility: IOV - Istituto Oncologico Veneto IRCCS
city: Prato
country: Italy
facility: Nuovo Ospedale di Prato
city: Rome
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Trento
country: Italy
facility: Ospedale Santa Chiara
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, Locatie VUMC
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis Molengracht
city: Den Haag
country: Netherlands
facility: Haga Ziekenhuis
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
city: Leiden
country: Netherlands
facility: Alrijne Ziekenhuis Leiden
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Tilburg
country: Netherlands
facility: Elisabeth TweeSteden Ziekenhuis
city: Uden
country: Netherlands
facility: Bernhoven Uden
city: Braga
country: Portugal
facility: Hospital de Braga
city: Lisboa
country: Portugal
facility: Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Norte E P E Hospital de Santa Maria
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: ICO l'Hospitalet - Hospital Duran i Reynals
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Las Palmas de Gran Canaria
country: Spain
facility: Complejo Hospitalario Universitario Insular Materno-Infantil
city: Madrid
country: Spain
facility: Hospital Beata Maria Ana
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
city: Murcia
country: Spain
facility: Hospital General Universitario Morales Meseguer
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: San Sebastian
country: Spain
facility: Hospital Universitario Donostia
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Arnau de Vilanova de Valencia
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: