Clinical trial • Phase III • Oncology
TRASTUZUMAB DERUXTECAN for HER2-positive metastatic breast cancer | Metastatic breast cancer
Phase III trial of TRASTUZUMAB DERUXTECAN for HER2-positive metastatic breast cancer | Metastatic breast cancer.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- HER2-positive metastatic breast cancer | Metastatic breast cancer
- Trial Stage
- Phase III
- Drug Modality
- ADC
Key dates
- Initial CTIS Submission Date
- 26-03-2024
- First CTIS Authorization Date
- 23-05-2024
Trial design
Randomised, open-label, test: ds-8201a (trastuzumab deruxtecan) — intravenous infusion; maximum total dose amount listed 5.4 mg/kg. comparator: ado-trastuzumab emtansine (t-dm1) (kadcyla 100 mg powder for concentrate for solution for infusion) — intravenous infusion; maximum total dose amount listed 3.6 mg/kg.-controlled Phase III trial in Belgium, France, Italy and others.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- Test: DS-8201a (trastuzumab deruxtecan) — intravenous infusion; maximum total dose amount listed 5.4 mg/Kg. Comparator: ado-trastuzumab emtansine (T-DM1) (Kadcyla 100 mg powder for concentrate for solution for infusion) — intravenous infusion; maximum total dose amount listed 3.6 mg/Kg.
- Target Sample Size
- 177
Eligibility
Recruits 177 Vulnerable population selected. Study enrols adults ≥18 years; "Please follow local regulatory requirements if the legal age of consent for study participation is >18 y old." No specific assent procedures for minors are described in the available documents..
- Pregnancy Exclusion
- Female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 7 mo after the last dose of trastuzumab deruxtecan and 7 mo after the last dose of T-DM1. Male subjects must agree to inform all potential female partners that they are participating in a clinical trial of a drug that may cause birth defects. Male subjects must also agree to either avoid intercourse or that they and/or any female partners of reproductive / childbearing potential will use a highly effective form of contraception during and upon completion of the study and for at least 4.5 mo after the last dose of trastuzumab deruxtecan or 4 mo after the last dose of T-DM1.
- Vulnerable Population
- Vulnerable population selected. Study enrols adults ≥18 years; "Please follow local regulatory requirements if the legal age of consent for study participation is >18 y old." No specific assent procedures for minors are described in the available documents.
Inclusion criteria
- {"criterion_text":"- Adults ≥18 years old. (Please follow local regulatory requirements if the legal age of consent for study participation is >18 y old.)\n- Pathologically documented breast cancer that:\n- - is unresectable or metastatic\n- - has confirmed HER2 positive expression as determined according to American Society of Clinical Oncology – College of American Pathologists guidelines evaluated at a central laboratory.\n- - was previously treated with trastuzumab and taxane in the advanced/metastatic setting or progressed within 6 mo after neoadjuvant or adjuvant treatment involving a regimen including trastuzumab and taxane.\n- Documented radiologic progression (during or after most recent treatment or within 6 mo after completing adjuvant therapy).\n- Subjects must be HER2 positive as confirmed by central laboratory assessment of most recent tumor tissue sample available.\n- Female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 7 mo after the last dose of trastuzumab deruxtecan and 7 mo after the last dose of T-DM1. Male subjects must agree to inform all potential female partners that they are participating in a clinical trial of a drug that may cause birth defects. Male subjects must also agree to either avoid intercourse or that they and/or any female partners of reproductive / childbearing potential will use a highly effective form of contraception during and upon completion of the study and for at least 4.5 mo after the last dose of trastuzumab deruxtecan or 4 mo after the last dose of T-DM1.\n- Adequate renal function, defined as:\n- - Creatinine clearance ≥ 30 mL/min, as calculated using the Cockcroft-Gault equation\n- Adequate hepatic function, defined as:\n- - Total bilirubin ≤ 1.5 × upper limit of normal (ULN) if no liver metastases or < 3 × ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline and\n- - Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤5 × ULN."}
Exclusion criteria
- {"criterion_text":"- Prior treatment with an anti-HER2 ADC (such as T-DM1) in the metastatic setting. Prior treatment in the adjuvant/neo-adjuvant setting would be allowed if progression of disease did not occur within 12 mo of end of adjuvant therapy.\n- Uncontrolled or significant cardiovascular disease, including any of the following:\n- - History of myocardial infarction within 6 mo before randomization\n- - History of symptomatic congestive heart failure (New York Heart Association Class II to IV)\n- - Troponin levels consistent with myocardial infarction as defined according to the manufacturer within 28 d prior to randomization\n- - Corrected QT interval prolongation to > 470 ms (females) or > 450 ms (male) based on average of Screening triplicate 12 lead electrocardiogram (ECG)\n- - Left ventricular ejection fraction (LVEF) < 50% within 28 d prior to randomization\n- Has a history of (noninfectious) 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.\n- Spinal cord compression or clinically active central nervous system (CNS) metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.\n- - Subjects with clinically inactive brain metastases may be included in the study.\n- - Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment.\n- Prior participation in a study involving an antibody drug conjugate (ADC) produced by Daiichi Sankyo."}
Endpoints
Primary endpoints
- {"endpoint_text":"- The primary efficacy endpoint is PFS as determined by blinded independent central review (BICR).","definition_or_measurement_approach":"PFS measured as determined by blinded independent central review (BICR)."}
Secondary endpoints
- {"endpoint_text":"- The key secondary efficacy endpoint is OS.","definition_or_measurement_approach":"Overall survival (OS)."}
Other endpoints
- {"endpoint_text":"- To evaluate efficacy of trastuzumab deruxtecan compared to T-DM1 on: Confirmed objective response rate (ORR);\n- To evaluate efficacy of trastuzumab deruxtecan compared to T-DM1 on: Duration of response (DoR);\n- To further determine PK of trastuzumab deruxtecan;\n- To further evaluate safety of trastuzumab deruxtecan compared to TDM1;\n- To evaluate Health Economic and Outcomes Research (HEOR) endpoints for trastuzumab deruxtecan compared to T-DM1.","definition_or_measurement_approach":"ORR and DoR as efficacy measures (confirmed objective response rate; duration of response). PK assessed by pharmacokinetic sampling and analysis. Safety assessed by adverse event reporting and laboratory monitoring. HEOR endpoints assessed per health economic/outcomes measures. (Descriptions are from secondary objectives; detailed measurement methods not provided in the available data.)"}
Recruitment
- Planned Sample Size
- 177
- Recruitment Window Months
- 87
- Consent Approach
- Informed consent provided by adult participants (≥18 years); follow local regulatory requirements if legal age of consent is >18. Informed consent forms and patient information documents available in multiple language versions (documents list includes English, French, Spanish, Italian and regional BE-FR/BE-NL versions). No specific remote consent or assent procedures for minors are described in the available documents.
Geography
- Total Number Of Sites
- 36
- Total Number Of Participants
- 63
Belgium
- Earliest CTIS Part Ii Submission Date
- 02-02-2024
- Latest Decision Or Authorization Date
- 11-03-2025
- Processing Time Days
- 403
- Number Of Sites
- 4
- Number Of Participants
- 5
Sites
- Site Name
- Institut Jules Bordet
- Department Name
- Oncology
- Contact Person Name
- Andrea Gombos
- Contact Person Email
- andrea.gombos@hubruxelles.be
- Site Name
- UZ Leuven
- Department Name
- Oncology
- Contact Person Name
- Hans Wildiers
- Contact Person Email
- hans.wildiers@uzleuven.be
- Site Name
- Antwerp University Hospital
- Department Name
- Oncology
- Contact Person Name
- Selvilay Altintas
- Contact Person Email
- sevilay.altintas@uza.be
- Site Name
- UZ Brussel
- Department Name
- Oncology
- Contact Person Name
- Christel Fontaire
- Contact Person Email
- christel.fontaine@uzbrussel.be
France
- Earliest CTIS Part Ii Submission Date
- 02-02-2024
- Latest Decision Or Authorization Date
- 14-03-2025
- Processing Time Days
- 406
- Number Of Sites
- 11
- Number Of Participants
- 23
Sites
- Site Name
- Institut Curie
- Department Name
- Medical Oncology
- Contact Person Name
- Jean-Yves Pierga
- Contact Person Email
- jean-yves.pierga@curie.fr
- Site Name
- Institut Regional Du Cancer De Montpellier
- Department Name
- Medical Oncology Service
- Contact Person Name
- William Jacot
- Contact Person Email
- William.Jacot@icm.unicancer.fr
- Site Name
- Institut Curie
- Department Name
- Medical Oncology department
- Contact Person Name
- Jean-Yves Pierga
- Contact Person Email
- jean-yves.pierga@curie.fr
- Site Name
- Institut De Cancerologie De L Ouest
- Department Name
- Medical Oncology Service
- Contact Person Name
- Jean-Sebastien Frenel
- Contact Person Email
- jean-sebastien.frenel@ico.unicancer.fr
- Site Name
- Clinique Victor Hugo
- Department Name
- Onco-radiotherapy
- Contact Person Name
- Sophie Roche
- Contact Person Email
- essaisroche@ilcgroupe.fr
- Site Name
- Institut Sainte Catherine
- Department Name
- Oncology
- Contact Person Name
- Julien Grenier
- Contact Person Email
- j.grenier@isc84.org
- Site Name
- Centre Leon Berard
- Department Name
- Medical Oncology department
- Contact Person Name
- Thomas Bachelot
- Contact Person Email
- thomas.bachelot@lyon.unicancer.fr
- Site Name
- Centre Francois Baclesse
- Department Name
- Gynecological pathologies
- Contact Person Name
- Christelle Levy
- Contact Person Email
- c.levy@baclesse.unicancer.fr
- Site Name
- Hopital Tenon
- Department Name
- Medical Oncology department
- Contact Person Name
- Joseph Gligorov
- Contact Person Email
- joseph.gligorov@aphp.fr
- Site Name
- Centre Hospitalier Regional De Marseille
- Department Name
- Multidisciplinary Oncology and Therapeutic Innovations Department
- Contact Person Name
- Marjorie Baciuchka-Palmaro
- Contact Person Email
- marjorie.baciuchka@ap-hm.fr
- Site Name
- Institut Gustave Roussy
- Department Name
- Medical Oncology
- Contact Person Name
- Fabrice André
- Contact Person Email
- fabrice.andre@gustaveroussy.fr
Italy
- Earliest CTIS Part Ii Submission Date
- 02-02-2024
- Latest Decision Or Authorization Date
- 13-03-2025
- Processing Time Days
- 405
- Number Of Sites
- 9
- Number Of Participants
- 19
Sites
- Site Name
- Ospedale San Raffaele S.r.l.
- Department Name
- Oncology
- Contact Person Name
- Giampaolo Bianchini
- Contact Person Email
- bianchini.giampaolo@hsr.it
- Site Name
- Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
- Department Name
- Oncology
- Contact Person Name
- Elena Rota Caremoli
- Contact Person Email
- ecrota@hpg23.it
- Site Name
- Azienda Ospedaliero Universitaria Di Modena
- Department Name
- Oncology
- Contact Person Name
- Federico Piacentini
- Contact Person Email
- federico.piacentini@unimore.it
- Site Name
- Azienda Ospedaliero Universitaria Parma
- Department Name
- Oncology
- Contact Person Name
- Daniela Boggiani
- Contact Person Email
- boggiani@ao.pr.it
- Site Name
- IRCCS Istituto Nazionale Tumori Fondazione Pascale
- Department Name
- Oncology
- Contact Person Name
- Michelino De Laurentiis
- Contact Person Email
- delauren@breastunit.org
- Site Name
- Humanitas Research Hospital
- Department Name
- Oncology and Hematology
- Contact Person Name
- Armando Santoro
- Contact Person Email
- armando.santoro@cancercenter.humanitas.it
- Site Name
- Centro Di Riferimento Oncologico Di Aviano
- Department Name
- Oncology
- Contact Person Name
- Fabio Puglisi
- Contact Person Email
- fabio.puglisi@cro.it
- Site Name
- Fondazione IRCCS San Gerardo Dei Tintori
- Department Name
- Oncology
- Contact Person Name
- Marina Elena Cazzaniga
- Contact Person Email
- marinaelena.cazzaniga@irccs-sangerardo.it
- Site Name
- IRCCS Centro di Riferimento Oncologico (other listed site)
- Department Name
- Oncology
Spain
- Earliest CTIS Part Ii Submission Date
- 02-02-2024
- Latest Decision Or Authorization Date
- 11-03-2025
- Processing Time Days
- 403
- Number Of Sites
- 12
- Number Of Participants
- 16
Sites
- Site Name
- Hospital Quironsalud Barcelona
- Department Name
- Oncology
- Contact Person Name
- Fabricio Racca Bussano
- Contact Person Email
- fracca@nextoncology.eu
- Site Name
- Institut Catala D'oncologia
- Department Name
- Oncology
- Contact Person Name
- Juan Miguel Gil Gil
- Contact Person Email
- mgilgil@iconcologia.net
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Oncology
- Contact Person Name
- Cristina Saura Manich
- Contact Person Email
- cristina.saura@vallhebron.cat
- Site Name
- Hospital Clinico San Carlos
- Department Name
- Oncology
- Contact Person Name
- Jose Angel Garcia Saenz
- Contact Person Email
- jgsaenz@salud.madrid.org
- Site Name
- Hospital Universitario De Canarias
- Department Name
- Oncology
- Contact Person Name
- Josefina Cruz Jurado
- Contact Person Email
- jcruzjurado@gmail.com
- Site Name
- Hospital Universitario 12 De Octubre
- Department Name
- Oncology
- Contact Person Name
- Eva Ciruelos Gil
- Contact Person Email
- eva.ciruelos@gmail.com
- Site Name
- Hospital Universitario Virgen De La Macarena
- Department Name
- Oncology
- Contact Person Name
- Esteban Nogales Fernández
- Contact Person Email
- esteban.nogales@gmail.com
- Site Name
- Hospital Clinic De Barcelona
- Department Name
- Oncology
- Contact Person Name
- Aleix Prat
- Contact Person Email
- alprat@clinic.cat
- Site Name
- Hospital Universitario De Badajoz
- Department Name
- Oncology
- Contact Person Name
- Marta González Cordero
- Contact Person Email
- martagcordero@gmail.com
- Site Name
- Hospital General Universitario Gregorio Maranon
- Department Name
- Oncology
- Contact Person Name
- Sara Lopez-Tarruella Cobo
- Contact Person Email
- sltc21@hotmail.com
- Site Name
- Complexo Hospitalario Universitario A Coruna
- Department Name
- Oncology
- Contact Person Name
- Silvia Antolin Novoa
- Contact Person Email
- silvia.antolin.novoa@sergas.es
- Site Name
- University Hospital Virgen Del Rocio S.L.
- Department Name
- Oncology
- Contact Person Name
- Francisco Javier Salvador Bofill
- Contact Person Email
- jsalvad2002@yahoo.es
Sponsor
Primary sponsor
- Full Name
- Daiichi Sankyo Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- Icon Laboratory Services Inc.
- Responsibilities
- Manage local lab reports for safety labs
- Name
- PPD Development L.P.
- Name
- IQVIA Limited
- Name
- Fortrea Inc.
- Name
- Guardant Health Inc.
- Name
- Labcorp Central Laboratory Services SARL
- Name
- Labcorp Central Laboratory Services LP
- Name
- Almac Clinical Technologies LLC
- Name
- Azenta US Inc.
- Responsibilities
- Long-term storage of biosamples
Third parties
- {"country":"United States","full_name":"Icon Laboratory Services Inc.","duties_or_roles":"Manage local lab reports for safety labs","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"PPD Development L.P.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"Long-term storage of biosamples","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- DS-8201a
- Active Substance
- TRASTUZUMAB DERUXTECAN
- Modality
- ADC
- Routes Of Administration
- INTRAVENIOUS INFUSION
- Route
- INTRAVENIOUS INFUSION
- Maximum Dose
- 5.4 mg/Kg
- Investigational Product Name
- Kadcyla (ado-trastuzumab emtansine, T-DM1)
- Active Substance
- TRASTUZUMAB EMTANSINE
- Modality
- ADC
- Routes Of Administration
- INTRAVENIOUS INFUSION
- Route
- INTRAVENIOUS INFUSION
- Authorisation Status
- Authorised (EU marketing authorisation EU/1/13/885/001)
- Maximum Dose
- 3.6 mg/Kg
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