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    The EU Clinical Trials Register currently displays   39363   clinical trials with a EudraCT protocol, of which   6448   are clinical trials conducted with subjects less than 18 years old.
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    EudraCT Number:2016-004986-18
    Sponsor's Protocol Code Number:DS8201-A-U201
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2017-10-02
    Trial results View results
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    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2016-004986-18
    A.3Full title of the trial
    A Phase 2, Multicenter, Open-Label Study of DS-8201a, an
    Anti-HER2-Antibody Drug Conjugate (ADC) for HER2-Positive,
    Unresectable and/or Metastatic Breast Cancer Subjects Who are
    Resistant or Refractory to T-DM1.
    Estudio abierto y multicéntrico en fase II de DS-8201a, un anti-HER2 conjugado anticuerpo-fármaco (CAF) para sujetos con cáncer de mama HER2 positivo irresecable y/o metastásico que son resistentes o refractarios a T-DM1.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 2 study of DS-8201a for HER2-Positive breast cancer that has either spread and/or cannot be treated with surgery and is resistant or non-responsive to T-DM1 treatment.
    Estudio de fase 2 de DS-8201a para el cáncer de mama HER2-positivo que se ha diseminado y / o no puede ser tratado con cirugía y es resistente o no responde al tratamiento con T-DM1.
    A.4.1Sponsor's protocol code numberDS8201-A-U201
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03248492
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorDaiichi Sankyo Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportDaiichi Sankyo Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationDaiichi Sankyo Inc.
    B.5.2Functional name of contact pointNot Available
    B.5.3 Address:
    B.5.3.1Street Address211 Mt Airy Rd
    B.5.3.2Town/ cityBasking Ridge
    B.5.3.3Post codeNJ 07920-2311
    B.5.3.4CountryUnited States
    B.5.4Telephone number+34955013068
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code DS-8201a
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNtbd
    D.3.9.1CAS number tbd
    D.3.9.2Current sponsor codeMAAA-1162a
    D.3.9.3Other descriptive nameDS-8201A
    D.3.9.4EV Substance CodeSUB188940
    D.3.10 Strength
    D.3.10.1Concentration unit mg/kg milligram(s)/kilogram
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number5.4 to 7.4
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Unresectable/metastatic breast cancer with HER2 positive expression
    Cáncer de mama irresecable/metastásico con expresión positiva de HER2
    E.1.1.1Medical condition in easily understood language
    Breast cancer
    Cáncer de mama
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10027475
    E.1.2Term Metastatic breast cancer
    E.1.2System Organ Class 100000020826
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    •Objective response rate (ORR) per imaging assessment - Percentage of participants with objective response is assessed every six weeks from Cycle 1 Day 1 through disease progression, by independent central imaging facility review based on RECIST version 1.1
    Tasa de respuesta objetiva (TRO) por evaluación de imagen - El porcentaje de participantes con respuesta objetiva se evalúa cada seis semanas desde el Ciclo 1 Día 1 a través de la progresión de la enfermedad, mediante una revisión central independiente basada en RECIST versión 1.1
    E.2.2Secondary objectives of the trial
    ●Duration of response
    ●Best percent change in the sum of the longest diameters (SLD) of measurable tumors
    ●Disease control rate (DCR)
    ●Clinical benefit rate (CBR)
    ●Progression-free survival
    ●Overall survival (OS)
    ●ORR assessed by the investigator based on RECIST version 1.1

    The following apply to categories; DS-8201a, total anti-HER2 antibody and MAAA-1181a:
    ●Maximum plasma/serum concentration (Cmax)
    ●Time to Cmax (Tmax)
    ●Area under the concentration-time curve (AUC) from dosing until the last quantifiable concentration (AUClast)
    ●AUC from the time of dosing until day 21 (AUC0-21d)
    • Evaluar la duración de la respuesta
    • el mejor cambio porcentual en la suma de los diámetros mayores (SDM) de los tumores medibles
    • la tasa de control de la enfermedad (TCE),
    • la tasa de beneficio clínico (TBC)
    • a supervivencia sin progresión (SSP)
    • la supervivencia general (SG)
    • TSO evaluado por el investigador basado en RECIST versión 1.1

    Lo siguiente se aplica a las categorías; DS - 8201a, anticuerpo anti - HER2 total y MAAA - 1181a:
    ● Concentración plasmática / sérica máxima (Cmax)
    ● Tiempo hasta Cmax (Tmax)
    ● Área bajo la curva concentración-tiempo (AUC) desde la dosificación hasta la última concentración cuantificable (AUClast)
    ● AUC desde el momento de la dosificación hasta el día 21 (AUC0-21d)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    •Men or women the age of majority in their country
    •Has pathologically documented breast cancer that:
    1.is unresectable or metastatic
    2.has HER2 positive expression confirmed per protocol
    •Has an adequate tumor sample
    •Has at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
    •Has protocol-defined adequate cardiac, renal and hepatic function
    •Agrees to follow protocol-defined method(s) of contraception
    • Varones o mujeres ≥20 años de Japón y Corea, ≥18 años en otros países.
    • Cáncer de mama documentado patológicamente que:
     sea irresecable o metastásico;
     presente expresión positiva de HER2 (los pacientes que sean positivos para el receptor de estrógenos (RE)/receptor de progesterona (RP) pueden inscribirse si son positivos para HER2) determinada según las directrices de la American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) evaluada en un laboratorio central. Consulte los detalles en el Manual de laboratorio.
    • Los pacientes deben tener una muestra de tumor adecuada disponible para la confirmación del estado de HER2 por el laboratorio central (basado en la muestra de tejido tumoral más reciente).
    • El paciente debe tener cáncer de mama que sea resistente primario o secundario a T-DM1 (todas las partes excepto la parte 2b).
     Para la parte 2b, una parte exploratoria del estudio, los pacientes deben haber interrumpido el tratamiento con T-DM1 por motivos distintos a la resistencia primaria o secundaria de la enfermedad.
    • Presencia de al menos una lesión medible según los Criterios de evaluación de la respuesta en tumores sólidos (RECIST) versión 1.1.
    • Fracción de eyección del ventrículo izquierdo (FEVI) ≥50 %
    • Tanto varones como mujeres en edad reproductiva/fértil deben aceptar seguir las instrucciones sobre métodos anticonceptivos.
    • Función renal adecuada, definida como:
    • Aclaramiento de creatinina ≥30 ml/min, calculado usando la ecuación de Cockcroft Gault modificada, ([{140 – edad en años} × {peso real en kg}] dividido entre [{72 × creatinina sérica en mg/dl} multiplicado por 0,85 si es una mujer]), o creatinina sérica ≤1,5 veces el límite superior de la normalidad (LSN).
    • Función hepática adecuada, definida como:
    • Bilirrubina total ≤3 × LSN; aspartato aminotransferasa (AST)/alanina aminotransferasa (ALT) ≤5 x LSN
    E.4Principal exclusion criteria
    •Has a medical history of myocardial infarction, symptomatic congestive heart failure (CHF) (NYHA classes II-IV), unstable angina or serious cardiac arrhythmia
    •Has a QTc prolongation to > 450 millisecond (ms) in males and > 470 ms in females
    •Has a medical history of clinically significant lung disease
    •Is suspected to have certain other protocol-defined diseases based on imaging at screening period
    •Has history of any disease, metastatic condition, drug/medication use or other condition that might, per protocol or in the opinion of the investigator, compromise:
    1.safety or well-being of the participant or offspring
    2.safety of study staff
    3.analysis of results
    • Antecedentes médicos de infarto de miocardio en los 6 meses previos al registro, insuficiencia cardíaca congestiva sintomática ([ICC], clases II a IV de la New York Heart Association), niveles de troponina indicativos de infarto de miocardio según se define en las directrices del American College of Cardiology (ACC), angina inestable o arritmia cardíaca grave que requiera tratamiento.
    • Tiene prolongación del intervalo QT corregido (QTc) a >470 ms (mujeres) o >450 ms (varones) según un electrocardiograma (ECG) de 12 derivaciones por triplicado en la selección.
    • Ha tenido enfermedad pulmonar clínicamente significativa que requirió un tratamiento con corticoesteroides sistémicos en los últimos 6 meses previos a la aleatorización/registro (por ejemplo, neumonía intersticial, neumonitis, fibrosis pulmonar y neumonitis severa por radiación) o que se sospeche que tienen estas enfermedades en el estudio por imagen en el periodo de selección.
    • Metástasis cerebrales no tratadas, sintomáticas o que requieran tratamiento para controlar los síntomas, así como antecedentes de radioterapia, cirugía u otro tratamiento, incluidos corticoesteroides o anticonvulsivos, para controlar los síntomas de las metástasis cerebrales en los 2 meses (60 días) previos a la aleatorización/el registro. Después de que aproximadamente 30 pacientes con estas características [el 20 % de los 150 que se espera que reciban la dosis recomendada para la fase 2 (DRF2)] se hayan inscrito en la DRF2, los siguientes pacientes con metástasis cerebrales actuales o antecedentes de metástasis cerebrales serán excluidos.
    • Tiene enfermedad de la córnea clínicamente significativa.
    E.5 End points
    E.5.1Primary end point(s)
    ORR assessed by independent central imaging facility review based on RECIST version 1.1.
    TRO evaluada mediante revisión en el centro de estudios por imagen central independiente según los criterios RECIST versión 1.1.
    E.5.1.1Timepoint(s) of evaluation of this end point
    22 months
    22 meses
    E.5.2Secondary end point(s)
    Secondary endpoints include:
    a) Duration of response, best percent change in the SLD of measurable tumors, DCR, clinical benefit ratio (CBR), PFS, OS, and ORR assessed by the investigator based on RECIST version 1.1.
    b) Maximum plasma/serum concentration (Cmax), Time to Cmax (Tmax), Area under the concentration-time curve (AUC) from dosing until the last quantifiable concentration (AUClast), AUC from the time of dosing until day 21 (AUC0-21d)
    Los criterios de valoración secundarios incluyen:
    a) Duración de la respuesta, Mejor cambio porcentual en la SDM de tumores medibles, TCE, TBC, SSP, SG , TRO evaluada por el investigador según los criterios RECIST versión 1.
    b) concentración máxima en suero/plasma (Cmáx), tiempo hasta la Cmáx (Tmáx), área bajo la curva de concentración-tiempo desde la administración hasta la última concentración cuantificable (ABCúlt), ABC desde el momento de la administración hasta el día 21 (ABC0 21d)
    E.5.2.1Timepoint(s) of evaluation of this end point
    For endpoints:
    a) 22 months
    b) 21 days
    Para valoración final:
    a) 22 meses
    b) 21 días
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E. trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E. description
    As per protocol
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA42
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Korea, Republic of
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months12
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months12
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 230
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 23
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state8
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 75
    F.4.2.2In the whole clinical trial 230
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    As defined in protocol
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2017-11-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-10-27
    P. End of Trial
    P.End of Trial StatusOngoing
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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