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    Summary
    EudraCT Number:2016-004513-27
    Sponsor's Protocol Code Number:MedOPP127
    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:2017-07-21
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2016-004513-27
    A.3Full title of the trial
    A phase II study of pembrolizumab and eribulin in patients with HR-positive/HER2-negative metastatic breast cancer previously treated with anthracyclines and taxanes
    Estudio de fase II de pembrolizumab y eribulina en pacientes con cáncer de mama metastásico receptor hormonal positivo/HER2 negativo previamente tratados con antraciclinas y taxanos
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A phase II study of pembrolizumab and eribulin in patients with HR-positive/HER2-negative metastatic breast cancer previously treated with anthracyclines and taxanes
    Estudio de fase II de pembrolizumab y eribulina en pacientes con cáncer de mama metastásico receptor hormonal positivo/HER2 negativo previamente tratados con antraciclinas y taxanos
    A.3.2Name or abbreviated title of the trial where available
    KELLY study (KEytruda and EribuLin in Luminal breast cancer)
    Estudio KELLY (KEytruda y EribuLin en cancer de mama luminal)
    A.4.1Sponsor's protocol code numberMedOPP127
    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 SponsorMedica Scientia Innovation Research (MedSIR)
    B.1.3.4CountrySpain
    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 supportMerck Sharp & Dohme de España, S.A.
    B.4.2CountrySpain
    B.4.1Name of organisation providing supportEISAI Farmacéutica S.A.
    B.4.2CountrySpain
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMedica Scientia Innovation Research (MedSIR)
    B.5.2Functional name of contact pointMaria Sió Modrego
    B.5.3 Address:
    B.5.3.1Street AddressRambla Cataluña, 2-4, 2D,
    B.5.3.2Town/ cityBarcelona
    B.5.3.3Post code08007
    B.5.3.4CountrySpain
    B.5.4Telephone number0034932214135
    B.5.6E-mailmaria.sio@medsir.org
    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.3.1Product namePembrolizumab
    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 INNPEMBROLIZUMAB
    D.3.9.3Other descriptive namePEMBROLIZUMAB
    D.3.9.4EV Substance CodeSUB167136
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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.IMP: 2
    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 Yes
    D.2.1.1.1Trade name HALAVEN
    D.2.1.1.2Name of the Marketing Authorisation holderEisai Europe Ltd
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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.3.4Pharmaceutical form Solution for injection
    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 INNERIBULIN
    D.3.9.1CAS number 253128-41-5
    D.3.9.4EV Substance CodeSUB31134
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.44
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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 No
    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
    Hormone receptor-(HR)positive/HER2-negative metastatic breast cancer (MBC)
    Cáncer de mama metastásico (CMM) con receptor hormonal (RH) positivo/HER2 negativo
    E.1.1.1Medical condition in easily understood language
    Metastatic breast cancer
    Cáncer de mama metastásico
    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
    To assess the efficacy -as determined by the clinical benefit rate
    (CBR) (total number of objective responses plus stable disease for at least 24 weeks) based on RECIST v.1.1- of MK3475 (pembrolizumab) in combination with eribulin in patients with HR-positive/HER2-negative MBC who have previously received an anthracycline and a taxane (for either early or advanced disease), unless contraindicated, and between one to two lines of chemotherapy in the metastatic setting.
    Evaluar la eficacia (determinada mediante la tasa de beneficio
    clínico [TBC] [número total de respuestas objetivas más
    enfermedad estable durante al menos 24 semanas] basada en
    RECIST v.1.1 de MK3475 (pembrolizumab) en combinación con
    eribulina en pacientes con CMM RH positivo/HER2 negativo
    que hayan recibido anteriormente una antraciclina y un taxano
    (para enfermedad inicial o avanzada), salvo que esté
    contraindicado, y entre una y dos líneas de quimioterapia en
    enfermedad metastásica.
    E.2.2Secondary objectives of the trial
    To determine the CBR based on RECIST v.1.1 in subjects with programmed death ligand-1 (PD-L1) positive tumors.
    - To determine the progression-free survival (PFS) based on RECIST v.1.1.
    - To determine the PFS based on RECIST v.1.1 in subjects with PD-L1 positive tumors.
    - To determine the overall survival (OS) (OS will be determined at the end of the study).
    - To determine the OS in subjects with PD-L1 positive tumors.
    - To determine the overall response rate (ORR) based on RECIST v.1.1.
    - To determine the ORR based on RECIST v.1.1 in subjects with PD-L1 positive tumors.
    - To determine the duration of response (DoR) based on RECIST v.1.1.
    - To determine the DoR based on RECIST v.1.1 in subjects with PD-L1 positive tumors.
    - To assess the safety and tolerability of MK3475 (pembrolizumab) in combination with eribulin according to the US National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.3.
    Determinar la TBC basada en RECIST v.1.1 en sujetos con
    tumores con ligando 1 de muerte programada (PD-L1) positivo.
    -Determinar la supervivencia libre de progresión (SLP) basada en RECIST v.1.1.
    - Determinar la SLP basada en RECIST v.1.1 en sujetos con
    tumores con PD-L1 positivo.
    - Determinar la supervivencia global (SG) (la SG se determinará
    al final del estudio).
    - Determinar la SG en sujetos con tumores con PD-L1 positivo.
    -Determinar la tasa de respuesta global (TRG) basada en
    RECIST v.1.1.
    - Determinar la TRG basada en RECIST v.1.1 en sujetos con
    tumores con PD-L1 positivo.
    - Determinar la duración de respuesta (DR) basada en RECIST
    v.1.1.
    - Determinar la DR basada en RECIST v.1.1 en sujetos con
    tumores con PD-L1 positivo.
    - Evaluar la seguridad y tolerabilidad de MK3475
    (pembrolizumab) en combinación con eribulina según los
    criterios de terminología común de acontecimientos adversos
    (CTCAE) del NCI (Instituto Nacional del Cáncer de EE. UU.),
    versión 4.03.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Written informed consent prior to beginning specific protocol procedures.
    2. Female patients ≥ 18 years of age. 3. Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1 which the Investigator believes is stable at the time of screening.
    4. Life expectancy ≥ 12 weeks.
    5. Patients have a histologically and/or cytologically confirmeddiagnosis of breast cancer.
    6. Patients have radiologic evidence of inoperable locally recurrent or MBC.
    7. Patients have HER2-negative breast cancer (based on most recently analyzed biopsy) defined as a negative in situ hybridization (ISH) test or an immunohistochemistry (IHC) status of 0, 1+, or 2+ (if IHC 2+, a negative ISH test is required) by local laboratory testing.
    8. Patients have HR-positive breast cancer defined as estrogen receptor (ER) and/or progesterone receptor (PR) with >1% of tumor cells positive for ER and/or PR by IHC irrespective of staining intensity.
    9. Available tumor tissue for PD-L1 biomarker analysis from a newly obtained core or excisional biopsy since last progression of a metastatic tumor lesion not previously irradiated.
    Note: Subjects for whom tumor biopsies cannot be obtained (e.g., inaccessible tumor or subject safety concern) may submit an archived metastatic tumor specimen only upon agreement from the Sponsor.
    10. Patients have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 as assessed by site Investigator and local radiology review.
    11. Patients have received at least one, but not more than two, prior chemotherapeutic regimens for locally recurrent and/or metastatic disease. Prior therapy must have included an anthracycline and a taxane in any combination or order and either in the early or metastatic disease setting unless contraindicated for a given patient. Prior anti-hormonal therapy is mandatory.
    12. Patients have adequate bone marrow and organ function as defined by the following laboratory values:
    - Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
    - Platelets ≥ 100 x 109/L.
    - Hemoglobin ≥ 9 g/dL.
    - Potassium, calcium (corrected for serum albumin), and magnesium within normal limits for the institution.
    Serum creatinine ≤ 1.5 x upper limit of normal (ULN).
    - Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) ≤ 2.5 x ULN (or ≤ 5.0 x ULN if liver metastases are present).
    - Total serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases are present). Patients with known Gilbert disease who have serum bilirubin ≤ 3 x ULN may be enrolled.
    13. Patients must be accessible for treatment and follow-up
    1. Consentimiento informado por escrito antes de iniciar los procedimientos específicos del protocolo.
    2. Pacientes mujeres ≥ 18 años de edad.
    3. Estado funcional del Eastern Cooperative Oncology Group (ECOG) de 0 o 1 que el investigador considere estable en el momento de la selección.
    4. Esperanza de vida ≥ 12 semanas
    5. Pacientes con un diagnóstico histológica o citológicamente confirmado de cáncer de mama.
    6. Pacientes con pruebas radiológicas de CMM o localmente recurrente no operable.
    7. Pacientes con cáncer de mama HER2 negativo (basado en la biopsia analizada más recientemente) definido como prueba de hibridación in situ (ISH) con un resultado negativo o estado de inmunohistoquímica (IHQ) de 0, 1+ o 2+ (en caso de IHQ 2+, será necesario realizar una prueba de hibridación in situ con un resultado negativo) mediante pruebas analíticas locales.
    8. Pacientes con cáncer de mama HR positivo definido como receptor de estrógeno (ER) o receptor de progesterona (PR) con > 1 % de células tumorales con un resultado positivo en ER o PR por IHQ, independientemente de la intensidad de tinción.
    9. Tejido tumoral disponible para el análisis de biomarcadores PD-L1 de una biopsia reciente con aguja gruesa o excisional obtenida desde la última progresión de una lesión tumoral metastásica que no se haya irradiado anteriormente.
    Nota: los sujetos de quienes no se puedan obtener biopsias tumorales (p. ej., tumor inaccesible o problema de seguridad para el sujeto) pueden entregar una muestra tumoral metastásica archivada solo previo acuerdo con el promotor.
    10. Pacientes con enfermedad medible basándose en los criterios de evaluación de respuesta en tumores sólidos (RECIST) versión 1.1 evaluada por el investigador del centro y mediante una revisión radiológica local.
    11. Pacientes que hayan recibido al menos uno, pero no más de dos, regímenes previos de quimioterapia para la enfermedad localmente recurrente o metastásica. El tratamiento previo debe haber incluido una antraciclina y un taxano, en cualquier combinación u orden, y en el estadio inicial o metastásico de la enfermedad, salvo que esté contraindicado para una paciente determinada. Es obligatorio un tratamiento antihormonal previo.
    12. Pacientes con una función adecuada de los órganos y médula ósea, según la definición de los siguientes parámetros de laboratorio:
    Recuento absoluto de neutrófilos (RAN) ≥ 1,5 x 109/l.
    - Plaquetas ≥ 100 x 109/l.
    - Hemoglobina ≥ 9 g/dl.
    - Potasio, calcio (corregido para la albúmina sérica) y magnesio dentro de los límites normales del centro.
    - Creatinina sérica ≤ 1,5 x límite superior normal (LSN).
    - Alanina aminotransferasa (AST) y aspartato aminotransferasa (ALT) ≤ 2,5 x LSN (o ≤ 5,0 x LSN en caso de metástasis hepáticas).
    - Bilirrubina sérica total en el intervalo normal (o ≤ 1,5 x LSN en caso de metástasis hepáticas). Pueden ser incluidas en el estudio pacientes con enfermedad de Gilbert conocida con bilirrubina sérica ≤ 3 x LSN.
    13. Pacientes con capacidad para cumplir con el tratamiento y el seguimiento.
    E.4Principal exclusion criteria
    1. Patients have received previous treatment with eribulin and an/or anti-PD1 or anti-PD-L1 agents.
    2. Patients have a known hypersensitivity to any of the excipients of MK3475 (pembrolizumab) or eribulin.
    3. Patients who have received chemotherapy, targeted small molecule therapy, or radiotherapy within two weeks of first dose of study treatment.
    4. Patients who have received monoclonal antibodies for direct antineoplastic treatment or an investigational agent/device within four weeks of first dose of study treatment.
    5. Patients have known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
    Note: Known brain metastases are considered active, if any of the following criteria is applicable:
    a. Brain imaging during screening demonstrates progression of existing metastases and/or appearance of new lesions compared to brain imaging performed at least four weeks earlier.
    b. Neurological symptoms attributed to brain metastases have not returned to baseline.
    c. Steroids were used for brain metastases within 28 days of first dose of study treatment.
    6. Patients have peripheral neuropathy grade 2 or more.
    7. Patients have a concurrent malignancy or malignancy within five years of study enrollment (with the exception of adequately treated, basal or squamous cell skin carcinoma or curatively resected cervical cancer).
    8. Patients have not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy.
    9. Patients have had a major surgical procedure within 28 days prior to starting study drug.
    10. Patients have an active cardiac disease or a history of cardiac dysfunction including any of the following:
    - Unstable angina pectoris or documented myocardial infarction within six months prior to study entry.
    - Symptomatic pericarditis.
    - History of documented congestive heart failure (New York Heart Association functional classification III-IV).
    - Patients have a left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO).
    11. Patients have any of the following cardiac conduction abnormalities:
    - Ventricular arrhythmias except for benign premature ventricular contractions.
    - Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication.
    - Conduction abnormality requiring a pacemaker.
    - Other cardiac arrhythmia not controlled with medication.
    12. Uncontrolled hyper/hypothyroidism or type 1 diabetes mellitus (T1DM). Patients with hypothyroidism stable on hormone replacement will not be excluded from the trial. Patients with controlled T1DM on a stable insulin regimen may be eligible for this study.
    13. Active autoimmune disease or a documented history of autoimmune disease, or a syndrome that has required systemic treatment (steroids or immunosuppressiveagents) in the past two years.
    14. Prior allogenic stem cell or solid organ transplantation.
    15. Active/history of pneumonitis requiring treatment with steroids or active/history of interstitial lung disease.
    16. Active uncontrolled infection at the time of screening
    17. Active tuberculosis.
    18. Current known infection with HIV.
    19. Active hepatitis B (HBV) [patients with negative hepatitis B surface antigen (HBsAg) test and a positive antibody to HBsAg (anti-HBsAg) test at screening are eligible] or hepatitis C (HCV) [patients with a positive antibody to hepatitis C (anti-HCV) are eligible only if polymerase chain reaction (PCR) is negative for virus hepatitis C RNA].
    20. Patients have any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator‟s judgment contraindicate patient participation in the clinical study.
    21. Treatment with systemic steroids (standard premedication for chemotherapy/contrast reactions, inhaled steroids, and local applications are allowed) or another immunosuppressive agent within seven days prior to study treatment initiation.
    22. Has received live vaccines within 30 days prior to first dose of study treatment.
    23. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, are not allowed to participate in this study unless they are using highly effective methods of contraception during dosing and up to 120 days after study drugs discontinuation.
    1.Pacientes que hayan recibido tratamiento previo con eribulina o fármacos anti-PD1 o anti-PD-L1.
    2.Pacientes con una hipersensibilidad conocida a cualquiera de los excipientes de MK3475 (pembrolizumab) o eribulina.
    3.Pacientes que hayan recibido quimioterapia, terapia dirigida con moléculas pequeñas o radioterapia durante las dos semanas previas a la primera dosis del tratamiento del estudio.
    4.Pacientes que hayan recibido anticuerpos monoclonales para el tratamiento antineoplásico directo o un fármaco o dispositivo en investigación durante las cuatro semanas previas a la primera dosis del tratamiento del estudio.
    5.Pacientes con metástasis activas conocidas en el sistema nervioso central (SNC) o meningitis carcinomatosa.
    Nota:las metástasis cerebrales conocidas se consideran activas si reúnen alguno de los siguientes criterios:a.La RM cerebral realizada durante la selección demuestra progresión de metástasis existentes o aparición de nuevas lesiones en comparación con la RM realizada al menos cuatro semanas antes. b. Los síntomas neurológicos atribuidos a las metástasis cerebrales no han remitido a sus niveles basales. c.Se han tomado esteroides para las metástasis cerebrales durante los 28 días previos a la primera dosis del tratamiento del estudio.
    6.Pacientes con neuropatía periférica de grado 2 o superior.
    7.Pacientes con un tumor maligno concurrente o tumor maligno durante los cinco años anteriores a la inclusión en el estudio(salvo carcinoma cutáneo de células basales o escamosas adecuadamente tratado o cáncer de cuello uterino resecado de forma curativa)
    8.Pacientes cuyos efectos secundarios de cualquier tratam. antineoplásico previo no haya remitido a grado 1 o mejor(excepto alopecia) 9.Pacientes que se hayan sometido a una intervención
    quirúrgica importante durante los 28 días previos al inicio del fármaco del estudio.10.Pacientes con una enfermedad cardíaca activa o antecedentes de disfunción cardíaca, incluyendo
    cualquiera de los siguientes: Angina de pecho inestable o infarto de miocardio documentado durante los seis meses anteriores a su
    entrada en el estudio;Pericarditis sintomática;Antecedentes de insuficiencia cardíaca congestiva documentada(clasificación funcional III-IV de la NewYork Heart Association);Pacientes con una FEVI< 50 % según determina una MUGA o un ECO.11. Pacientes con alguna de las siguientes anomalías cardíaca:Arritmias ventriculares excepto contracciones ventriculares prematuras benignas; Arritmias supraventriculares y nodulares que requieren un marcapasos o que no controladas con medicación;Anomalía de conducción que requiere un marcapasos;Otra arritmia cardíaca no controlada con
    medicación.12. Hipertiroidismo o hipotiroidismo no controlado o DMT1. Las pacientes con hipotiroidismo estable tras terapia hormonal sustitutiva no quedarán excluidas del ensayo.Las pacientes con DMT1 controlada que reciban un régimen estable de insulina pueden ser elegibles.13.Enfermedad autoinmune activa o antecedentes documentados de enfermedad autoinmune,o síndrome que haya requerido tratamiento sistémico(esteroides o
    fármacos inmunosupresores)en los dos últimos años.
    14. Trasplante alogénico previo de células madre o de
    órganos sólidos.
    15. Neumonitis activa o antecedentes de neumonitis que
    requieran tratamiento con esteroides, o enfermedad
    pulmonar intersticial activa o antecedentes de
    enfermedad pulmonar intersticial.
    16. Infección activa no controlada en el momento de la
    selección.
    17. Tuberculosis activa.
    18. Infección actual conocida por VIH.
    19. Hepatitis B (VHB) activa [las pacientes con un resultado
    negativo en la prueba de antígeno de superficie de la
    hepatitis B (HBsAg) y con un resultado positivo en la
    prueba de anticuerpos al HBsAg (anti-HBsAg) en la
    selección son elegibles] o hepatitis C (VHC) [las
    pacientes con un resultado positivo en la prueba de anticuerpos a la hepatitis C (anti-VHC) solo son elegibles
    si la reacción en cadena de la polimerasa (RPC) es
    negativa para el virus de la hepatitis C [ARN].
    20. Pacientes con cualquier otra patología no controlada o
    grave concurrente que, según el criterio del investigador,
    estaría contraindicada para la participación de la
    paciente en el estudio clínico.
    21. Tratamiento con esteroides sistémicos (premedicación
    estándar para quimioterapia/reacciones al contraste,
    esteroides inhalados y aplicaciones locales están
    permitidos) u otro fármaco inmunosupresor durante los
    siete días anteriores al inicio del tratamiento del estudio.
    22. Pacientes que hayan recibido vacunas vivas durante los
    30 días anteriores a la primera dosis del tratamiento del
    estudio.
    23. Las mujeres en edad fértil, definidas como todas las
    mujeres fisiológicamente capaces de quedarse
    embarazadas, no podrán participar en este estudio salvo
    que accedan a utilizar métodos anticonceptivos
    altamente eficaces durante la administración de la dosis
    y hasta 120 días después de la retirada de los fármacos
    del estudio.
    E.5 End points
    E.5.1Primary end point(s)
    CBR based on RECIST v.1.1.
    TBC basada en RECIST v.1.1.
    E.5.1.1Timepoint(s) of evaluation of this end point
    1 year
    1 año
    E.5.2Secondary end point(s)
    CBR based on RECIST v.1.1 in subjects with PD-L1 positive tumors.
     PFS based on RECIST v.1.1.
     PFS based on RECIST v.1.1 in subjects with PD-L1 positive tumors.
     OS (OS will be determined at the end of the study).
     OS in subjects with PD-L1 positive tumors.
     ORR based on RECIST v.1.1.
     ORR based on RECIST v.1.1 in subjects with PD-L1 positive tumors.
     DoR based on RECIST v.1.1.
     DoR based on RECIST v.1.1 in subjects with PD-L1 positive tumors.
     Safety.
    Exploratory endpoints:
     PFS based on irRECIST.
     ORR based on irRECIST.
     New predictive factors of response to MK3475 (pembrolizumab) and eribulin.
     TBC basada en RECIST v.1.1 en sujetos con tumores con PDL1
    positivo.
     SLP basada en RECIST v.1.1.
     SLP basada en RECIST v.1.1 en sujetos con tumores con PDL1
    positivo.
     SG (la SG se determinará al final del estudio).
     SG en sujetos con tumores con PD-L1 positivo.
     TRG basada en RECIST v.1.1.
     TRG basada en RECIST v.1.1 en sujetos con tumores con PDL1
    positivo.
     DR basada en RECIST v.1.1.
     DR basada en RECIST v.1.1 en sujetos con tumores con PD-L1
    positivo.
     Seguridad.
    Variables exploratorias:
     SLP basada en irRECIST.
     TRG basada en irRECIST.
     Nuevos factores predictivos de respuesta a MK3475 (pembrolizumab) y eribulina.
    E.5.2.1Timepoint(s) of evaluation of this end point
    2 years
    2 años
    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 No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Survival
    Response
    Tolerability
    Supervivencia
    Respuesta
    Tolerabilidad
    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.7.1.3.1Other 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 No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    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 No
    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 concerned11
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    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
    The end of study will be 12 months after last study dose or progressive disease experienced in all patients or when the trial is terminated by the Sponsor, whichever is earlier. This data point will be considered LPLV (Last Patient Last Visit).
    El final del estudio será 12 meses después de la última dosis del estudio o progresión experimentada en todas las pacientes o cuando el promotor finalice el estudio, aquello que ocurra primero. Esta función de datos se considerará UPUV (última paciente última visita).
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    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: 44
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 44
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male No
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state44
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 44
    F.4.2.2In the whole clinical trial 44
    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)
    None
    Ninguno
    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 Decision2017-09-04
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-08-31
    P. End of Trial
    P.End of Trial StatusOngoing
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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