Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   42869   clinical trials with a EudraCT protocol, of which   7063   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2018-001757-27
    Sponsor's Protocol Code Number:MK-3475-859
    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:2018-09-17
    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 number2018-001757-27
    A.3Full title of the trial
    A Phase 3, randomized, double-blind clinical study of pembrolizumab (MK-3475) plus chemotherapy versus placebo plus chemotherapy as first-line treatment in participants with HER2 negative, previously untreated, unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma (KEYNOTE-859)
    Estudio clínico de fase 3, aleatorizado y doble ciego de pembrolizumab (MK-3475) más quimioterapia en comparación con placebo más quimioterapia como tratamiento de primera línea en participantes con adenocarcinoma gástrico o de la unión gastroesofágica irresecable o metastásico, sin tratamiento previo y con HER2 negativo (KEYNOTE-859)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Pembrolizumab/placebo plus chemotherapy as first-line therapy in participants with HER2 negative advanced gastric or GEJ adenocarcinoma
    Pembrolizumab/placebo más quimioterapia como tratamiento de primera línea en participantes con adenocarcinoma gástrico o de la UGE avanzado con HER2 negativo
    A.4.1Sponsor's protocol code numberMK-3475-859
    A.5.4Other Identifiers
    Name:Other indentificationNumber:123 482
    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 SponsorMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., 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 supportMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMerck Sharp Dohme de España S.A.
    B.5.2Functional name of contact pointInvestigación Clínica
    B.5.3 Address:
    B.5.3.1Street AddressC/ Josefa Valcárcel, 38
    B.5.3.2Town/ cityMadrid
    B.5.3.3Post code28027
    B.5.3.4CountrySpain
    B.5.4Telephone number+34913210600
    B.5.5Fax number+34913210590
    B.5.6E-mailensayos_clinicos@merck.com
    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.3.2Product code MK-3475
    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.3.9.1CAS number 1374853-91-4
    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) Yes
    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 KEYTRUDA (pembrolizumab, MK-3475)
    D.2.1.1.2Name of the Marketing Authorisation holderMerck Sharp & Dohme B.V.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 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.3.9.1CAS number 1374853-91-4
    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) Yes
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    HER2 negative, previously untreated, unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma
    Adenocarcinoma gástrico o de la unión gastroesofágica (UGE) irresecable o metastásico, sin tratamiento previo y con receptor tipo 2 del factor de crecimiento epidérmico humano (HER2) negativo
    E.1.1.1Medical condition in easily understood language
    Gastric or gastric esophageal junction (GEJ) adenocarcinoma
    adenocarcinoma gástrico o de la unión gastroesofágica (UGE)
    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 10071114
    E.1.2Term Metastatic gastric adenocarcinoma
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10058526
    E.1.2Term Oesophageal adenocarcinoma metastatic
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare the overall survival (OS) of the participants following administration of pembrolizumab versus placebo when each is combined with chemotherapy
    To compare the progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), as assessed by blinded independent central review (BICR), following administration of pembrolizumab versus placebo when each is combined with chemotherapy
    Comparar la supervivencia global (SG) de los participantes tras la administración de pembrolizumab o de placebo al combinar cada uno de ellos con quimioterapia.
    tumores sólidos, versión 1.1 (RECIST 1.1), según una revisión central independiente y enmascarada (RCIE), tras la administración de pembrolizumab o de placebo al combinar cada uno de ellos con quimioterapia
    E.2.2Secondary objectives of the trial
    To compare the objective response rate (ORR) per RECIST 1.1, as assessed by BICR, following administration of pembrolizumab versus placebo when each is combined with chemotherapy
    To compare the duration of response (DOR) per RECIST 1.1, as assessed by BICR, following administration of pembrolizumab versus placebo when each is combined with chemotherapy in all participants and in participants with PD-L1-positive tumors (CPS ≥1)
    To evaluate the safety and tolerability of pembrolizumab plus chemotherapy versus placebo plus chemotherapy
    Comparar la tasa de respuestas objetivas (TRO) conforme a los criterios RECIST 1.1, según una RCIE, tras la administración de pembrolizumab o de placebo al combinar cada uno de ellos con quimioterapia.
    Comparar la duración de la respuesta (DR) conforme a los criterios RECIST 1.1, según una RCIE, tras la administración de pembrolizumab o de placebo al combinar cada uno de ellos con quimioterapia en todos los participantes y en los participantes con tumores con PD-L1 positivo (PPC ≥ 1).
    Evaluar la seguridad y la tolerabilidad de pembrolizumab más quimioterapia en comparación con placebo más quimioterapia.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Merck will conduct Future Biomedical Research on DNA (blood and tissue specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time.
    Meck llevará a cabo investigaciones biomédicas futuras (Sangre,y tejidos) con las muestras obtenidas de forma sistemática y específica durante este ensayo clínico. Estas investigaciones tendrán por objeto el análisis de biomarcadores para abordar aspectos nuevos que
    no se describen en otras partes del protocolo (como parte del ensayo principal) y solo se llevarán a cabo en muestras de los sujetos que hayan otorgado el consentimiento correspondiente. El objetivo de la obtención de muestras para investigación biomédica futura consiste en estudiar e
    identificar biomarcadores que proporcionen información a los científicos sobre las enfermedades y sus tratamientos. El objetivo último es utilizar tal información para desarrollar vacunas y fármacos más seguros y eficaces o para garantizar que los sujetos reciban la dosis correcta del fármaco o
    la vacuna adecuados en el momento preciso.
    E.3Principal inclusion criteria
    1. Has histologically- or cytologically-confirmed diagnosis of locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma, with known PD-L1 expression status.
    2. Has HER2 negative cancer. HER2 negative is defined as: IHC (0, or 1+) or fluorescence in situ hybridization (FISH) negative (HER2:CEP17 ratio <2). FISH can be replaced with locally available in situ hybridization (ISH) methods acceptable as per institutional guidelines (eg, DISH).
    3. Is Male or Female.
    4. Is at least 18 years of age at the time of signing the informed consent (or acceptable age according to local regulations, whichever is older).
    5. A male participant must agree to use contraception as detailed in Appendix 5 of this protocol during the treatment period and through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater, and must refrain from donating sperm during this period.
    6. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
    a. Not a woman of childbearing potential (WOCBP) as defined in Appendix 5.
    OR
    b. A WOCBP who agrees to follow the contraceptive guidance in Appendix 5 during the treatment period and through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater.
    7. The participant (or legally acceptable representative if applicable) provides written informed consent for the study. The participant may also provide consent for future
    biomedical research. However, the participant may participate in the main study without participating in future biomedical research.
    8. Has measurable disease per RECIST 1.1 as assessed by investigator assessment. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
    9. Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
    10. Has provided tumor tissue sample deemed adequate for PD-L1 biomarker analysis.
    11. Has provided tumor tissue sample for MSI biomarker analysis.
    12. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (within 3 days prior to the start of study intervention).
    13. Has adequate organ function, as defined in the protocol. Specimens must be collected within 10 days prior to the start-of-study intervention.
    1. Diagnóstico confirmado histológica o citológicamente de adenocarcinoma gástrico o de la UGE localmente avanzado irresecable o metastásico, con estado conocido respecto a la expresión de PD-L1.
    2. Cáncer con HER2 negativo. La negatividad para HER2 se define como: IHQ (0 o 1+) o hibridación in situ con fluorescencia (FISH) negativa (cociente HER2:CEP17 < 2). La FISH puede sustituirse por métodos de hibridación in situ (HIS) de disponibilidad local y aceptables conforme a las normas del centro (por ejemplo, DISH).
    3. Varón o mujer.
    4. Edad mínima de 18 años el día de la firma del consentimiento informado (o la edad legal conforme a las normas locales, lo que sea mayor).
    5. Los varones deberán comprometerse a utilizar métodos anticonceptivos, según se indica en el apéndice 5 de este protocolo, durante el período de tratamiento y hasta 180 días después de la última dosis de quimioterapia o hasta 120 días después de la última dosis de pembrolizumab, lo que suponga más tiempo, y deberán abstenerse de donar semen durante este período.
    6. Una mujer podrá participar si no está embarazada, no está amamantando y cumple al menos una de las condiciones siguientes:
    a. No es una mujer en edad fértil (MEF), según la definición del apéndice 5.
    O
    b. Es una MEF que se compromete a seguir las normas sobre métodos anticonceptivos que se recogen en el apéndice 5 durante el período de tratamiento y hasta 180 días después de la última dosis de quimioterapia o hasta 120 días después de la última dosis de pembrolizumab, lo que suponga más tiempo
    7. El participante (o su representante legal cuando proceda) otorga su consentimiento informado por escrito para el estudio. El participante también podrá otorgar su consentimiento para las investigaciones biomédicas futuras. No obstante, el participante podrá participar en el estudio principal sin necesidad de hacerlo en las investigaciones biomédicas futuras.
    8. Enfermedad mensurable conforme a los criterios RECIST 1.1, según la evaluación del investigador. Las lesiones ubicadas en una zona previamente irradiada se considerarán mensurables siempre que se haya constatado progresión en dichas lesiones
    9. Disponibilidad de una muestra de tejido tumoral de archivo o de una biopsia reciente, con aguja gruesa o por escisión, de una lesión tumoral no irradiada previamente. Se prefiere el uso de bloques de tejido fijados en formol e incluidos en parafina (FFIP) a los cortes para microscopio. Se prefiere el uso de biopsias recientes al tejido de archivo.
    10. Donación de una muestra de tejido tumoral que se considere suficiente para el análisis del biomarcador PD-L1.
    11. Donación de una muestra de tejido tumoral para el análisis del biomarcador de IMS.
    12. Estado funcional del Eastern Cooperative Oncology Group (ECOG) de 0 o 1 (en los 3 días previos al comienzo de la intervención del estudio).
    13. Presencia de una función orgánica adecuada, según se define en el protocolo. Las muestras se obtendrán en los 10 días previos al comienzo de la intervención del estudio.
    E.4Principal exclusion criteria
    1. Has squamous cell or undifferentiated gastric cancer.
    2. Has had major surgery, open biopsy, or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of study intervention.
    3. Has pre-existing peripheral neuropathy >Grade 1.
    4. Is a WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization or treatment allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
    5. Has had previous therapy for locally advanced, unresectable or metastatic gastric/GEJ cancer. Participants may have received prior neoadjuvant or adjuvant therapy as long as it was completed at least 6 months prior to randomization.
    6. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
    7. Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to randomization.
    8. Has received prior radiotherapy within 2 weeks prior to start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
    9. Has received a live vaccine within 30 days prior to the first dose of study intervention. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
    10. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
    11. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention.
    12. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
    13. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression) for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
    14. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
    15. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
    16. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
    17. Has an active infection requiring systemic therapy.
    18. Has a known history of human immunodeficiency virus (HIV) infection.
    19. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
    20. Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
    21. Has a history or current evidence of any condition (eg, known deficiency of the enzyme dihydropyrimidine dehydrogenase), therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
    22. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.
    23. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater.
    24. Has had an allogenic tissue/solid organ transplant
    1. Presencia de un cáncer gástrico epidermoide o indiferenciado.
    2. Práctica de una intervención de cirugía mayor o biopsia abierta o traumatismo importante en los 28 días previos a la aleatorización o previsión de la necesidad de una intervención de cirugía mayor durante la intervención del estudio.
    3. Neuropatía periférica preexistente de grado > 1.
    4. Mujer en edad fértil que dé positivo en una prueba de embarazo en orina realizada en las 72 horas previas a la aleatorización o asignación del tratamiento (véase el apéndice 5). Si el resultado de la prueba en orina es positivo o no puede confirmarse que sea negativo, será necesario hacer una prueba de embarazo en suero.
    5. Recepción de tratamiento previo para el cáncer gástrico o de la UGE localmente avanzado irresecable o metastásico. Los participantes podrán haber recibido tratamiento neoadyuvante o adyuvante previo siempre que haya finalizado al menos seis meses antes de la aleatorización.
    6. Tratamiento previo con un fármaco anti-PD-1, anti-PD-L1 o anti-PD-L2 o con un fármaco dirigido contra otro receptor de los linfocitos T estimulador o coinhibidor (como CTLA-4, OX-40 o CD137).
    7. Recepción de un tratamiento antineoplásico sistémico previo, incluidos fármacos en investigación, en las cuatro semanas previas a la aleatorización.
    8. Recepción de radioterapia en las dos semanas previas al comienzo de la intervención del estudio. Los participantes deberán haberse recuperado de toda la toxicidad relacionada con la radioterapia, no precisar corticoides y no haber sufrido una neumonitis por radiación. Se permite un lavado de una semana en caso de radioterapia paliativa (≤ 2 semanas de radioterapia) por enfermedad que no afecta al sistema nervioso central (SNC).
    9. Recepción de una vacuna de microorganismos vivos en los 30 días previos a la administración de la primera dosis de la intervención del estudio. Algunos ejemplos de vacunas de microorganismos vivos son, entre otros, los siguientes: vacuna contra el sarampión, antiparotídica, antirrubeólica, contra la varicela, contra la fiebre amarilla, antirrábica, bacilo de Calmette-Guérin (BCG) y antitifoidea. Las vacunas inyectables contra la gripe estacional contienen, por lo general, virus muertos y están permitidas; en cambio, las vacunas antigripales intranasales (p. ej., FluMist®) son vacunas de virus vivos atenuados y no están permitidas.
    10. Participación activa o pasada en un estudio de un fármaco en investigación o uso de un dispositivo en investigación en las cuatro semanas previas a la administración de la primera dosis de la intervención del estudio.
    11. Diagnóstico de inmunodeficiencia o recepción de tratamiento sistémico crónico con esteroides (en dosis superiores a 10 mg diarios de prednisona o un equivalente) o cualquier otra forma de tratamiento inmunodepresor en los siete días previos a la primera dosis de la intervención del estudio.
    12. Presencia de otra neoplasia maligna conocida que está en progresión o que ha necesitado tratamiento activo en los últimos tres años.
    13. Presencia de metástasis activas en el SNC o de meningitis carcinomatosa. Los participantes con metástasis cerebrales tratadas anteriormente podrán participar siempre que se encuentren radiológicamente estables, es decir, sin signos de progresión durante al menos cuatro semanas en estudios de imagen repetidos (hay que señalar que durante la selección para el estudio deberán realizarse nuevos estudios de imagen), clínicamente estables y sin necesidad de tratamiento con esteroides durante al menos 14 días antes de la primera dosis de la intervención del estudio.
    14. Presencia de hipersensibilidad grave (grado ≥ 3) a pembrolizumab o a cualquiera de sus excipientes.
    15. Presencia de una enfermedad autoinmunitaria activa que ha precisado tratamiento sistémico (es decir, fármacos modificadores de la enfermedad, corticoides o inmunodepresores) en los dos últimos años. El tratamiento de reposición (por ejemplo, tiroxina, insulina o corticoides en dosis fisiológicas por insuficiencia suprarrenal o hipofisaria) no se considera una forma de tratamiento sistémico y se permitirá su uso.
    16. Antecedentes de neumonitis (no infecciosa) que precisó la administración de esteroides o presencia de una neumonitis activa.
    17. Infección activa con necesidad de tratamiento sistémico.
    18. Antecedentes de infección por el virus de la inmunodeficiencia humana (VIH). Nota: No es necesario realizar pruebas de VIH a menos que lo exijan las autoridades sanitarias locales.
    19. Antecedentes de infección por el virus de la hepatitis B (reactividad del antígeno de superficie del virus de la hepatitis B [HBsAg]) o de infección activa por el virus de la hepatitis C (definida como detección de ARN del virus de la hepatitis C [VHC] [cualitativo]).
    20. Antecedentes de tuberculosis activa (Bacillus tuberculosis).

    Leer en el protocolo
    E.5 End points
    E.5.1Primary end point(s)
    - Overall survival (OS), defined as the time from randomization to death due to any cause
    - Progression-free Survival (PFS), defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first
    – Supervivencia Global (SG) definido como el tiempo transcurrido entre la aleatorización y la muerte por cualquier causa.
    - Supervivencia Sin Progresión (SSP) definido como el tiempo transcurrido entre la aleatorización y la primera progresión documentada de la enfermedad o la muerte por cualquier causa, lo que antes ocurra
    E.5.1.1Timepoint(s) of evaluation of this end point
    Overall survival (OS) = time from randomization to death due to any cause; Progression-free survival (PFS) = time from randomization to the first documented disease progression per RECIST 1.1 by (blinded independent central review (BICR) or death due to any cause, whicherver occurs first
    - Supervivencia Global (SG) = tiempo transcurrido entre la aleatorización y la muerte por cualquier causa; Supervivencia Sin Progresión (SSP) = tiempo transcurrido entre la aleatorización y la primera progresión documentada de la enfermedad conforme a los Criterios de evaluación de la respuesta en tumores sólidos, versión 1.1 (RECIST 1.1) (según una revisión central independiente y enmascarada (RCIE)), o la muerte por cualquier causa, lo que antes ocurra
    E.5.2Secondary end point(s)
    - Objective response (OR), defined as Complete response (CR) or partial response (PR)
    - Duration of Response (DOR), defined as the time from first response (CR or PR) to subsequent disease progression, or death from any cause, whichever occurs first
    - Respuesta objetiva (RO) definida como respuesta completa (RC) o parcial (RP).
    - Duración de la Respuesta (DR), definida como tiempo transcurrido entre la primera respuesta (RC o RP) y la progresión posterior de la enfermedad o la muerte por cualquier causa, lo que antes ocurra
    E.5.2.1Timepoint(s) of evaluation of this end point
    - Objective Response Rate (ORR) = proportion of participants who have an overall response – complete response (CR) or partial response (PR);
    - Duration of Response (DOR) =time from first response (CR or PR) to subsequent disease progression or death from any cause, whichever occurs first
    - Tasa de respuestas objetivas (TRO) = Proporción de participantes que tienen un respuesta global - respuesta completa (RC) o parcial (RP) .
    - Duración de la respuesta (DR), definido como el tiempo entre la primera respuesta (RC o RP) y la progresión posterior de la enfermedad o la muerte por cualquier causa, lo que antes ocurra.
    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 Yes
    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 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.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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 No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    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 Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA76
    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
    Australia
    Brazil
    Canada
    Chile
    China
    Colombia
    France
    Guatemala
    Hong Kong
    Ireland
    Israel
    Japan
    Korea, Republic of
    Mexico
    New Zealand
    Peru
    Poland
    Russian Federation
    South Africa
    Spain
    Switzerland
    Taiwan
    Turkey
    Ukraine
    United Kingdom
    United States
    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 overall study ends when the last participant completes the last study-related telephone-call or visit, withdraws from the study, or is lost to follow-up (ie, the participant is unable to be contacted by the investigator).
    El estudio en su conjunto finalizará cuando el último participante complete la última llamada telefónica o visita del estudio, se retire del estudio o se pierda para el seguimiento (es decir, cuando el investigador no pueda ponerse en contacto con el participante).
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months6
    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: 550
    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 state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 396
    F.4.2.2In the whole clinical trial 780
    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
    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 Decision2018-10-31
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-10-30
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    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
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA