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    Summary
    EudraCT Number:2012-004391-19
    Sponsor's Protocol Code Number:3475-010
    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:2013-03-01
    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 number2012-004391-19
    A.3Full title of the trial
    A Phase II/III Randomized Trial of Two Doses of MK-3475 (SCH900475) versus Docetaxel in Previously Treated Subjects with Squamous Histology Non-Small Cell Lung Cancer
    Ensayo de fase II/III aleatorizado de dos dosis de MK 3475 (SCH900475) frente a docetaxel en sujetos con cáncer de pulmón no microcítico de histología epidermoide tratados previamente
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    MK-3475 vs. Docetaxel in Second-Line Squamous Non-Small Cell Lung Cancer
    MK 3475 frente a docetaxel en sujetos con cáncer de pulmón no microcítico tratados previamente
    A.4.1Sponsor's protocol code number3475-010
    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., (Merck)
    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., (Merck)
    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 pointCristina Alzina Fernández-Figares
    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+34682-341968
    B.5.5Fax number913210 590
    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 nameMK-3475; SCH900475
    D.3.2Product code 1374853-91-4
    D.3.4Pharmaceutical form Powder 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 INNambrolizumab
    D.3.9.1CAS number 1374853-91-4
    D.3.9.2Current sponsor codeMK-3475
    D.3.9.3Other descriptive nameAnti-PD-1 monoclonal antibody
    D.3.9.4EV Substance CodeSUB91641
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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 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 nameMK-3475; SCH900475
    D.3.2Product code 1374853-91-4
    D.3.4Pharmaceutical form Powder 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 INNambrolizumab
    D.3.9.1CAS number 1374853-91-4
    D.3.9.2Current sponsor codeMK-3475
    D.3.9.3Other descriptive nameAnti-PD-1 monoclonal antibody
    D.3.9.4EV Substance CodeSUB91641
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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: 3
    D.1.2 and D.1.3IMP RoleComparator
    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 Docetaxel-Actavis
    D.2.1.1.2Name of the Marketing Authorisation holderActavis Deutschland GmbH & Co. KG
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameDocetaxel--Actavis
    D.3.2Product code L01CD02
    D.3.4Pharmaceutical form Solution for injection/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 INNdocetaxel
    D.3.9.1CAS number 114977-28-5
    D.3.9.3Other descriptive nameANHYDROUS DOCETAXEL
    D.3.9.4EV Substance CodeSUB22289
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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
    Non-Small Cell Lung Cancer
    cáncer de pulmón no microcítico
    E.1.1.1Medical condition in easily understood language
    lung cancer
    Cáncer de pulmón
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 15.1
    E.1.2Level LLT
    E.1.2Classification code 10066490
    E.1.2Term Progression of non-small cell lung cancer
    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
    1)Objective: To compare the overall survival (OS) of previously-treated subjects with SCC NSCLC treated with MK-3475 compared to docetaxel.
    Hypothesis: MK-3475 prolongs OS in previously-treated subjects with SCC NSCLC compared to docetaxel.
    2)Objective: To compare overall response rate (ORR) as determined by immune-related response criteria of previously-treated subjects with SCC NSCLC treated with MK-3475 compared to docetaxel.
    Hypotheses: MK-3475 yields a higher ORR as determined by immune-related response criteria in previously-treated subjects with SCC NSCLC than docetaxel
    3)Objective: Evaluate safety and tolerability profile of MK-3475 in previously-treated subjects with SCC NSCLC.
    1)Objetivo: comparar la SG de sujetos con CPNM de histología epidermoide tratados previamente que reciban MK 3475 en comparación con docetaxel.
    Hipótesis: MK 3475 prolonga la SG en los sujetos con CPNM de histología epidermoide tratados previamente en comparación con docetaxel.
    2)Objetivo: comparar la TRG, determinada mediante los criterios de respuesta relacionados con el sistema inmunológico, de sujetos con CPNM de histología epidermoide tratados previamente que reciban MK 3475 en comparación con docetaxel.
    Hipótesis: MK 3475 depara una mayor TRG, determinada mediante los criterios de respuesta relacionados con el sistema inmunológico, en los sujetos con CPNM de histología epidermoide tratados previamente en comparación con docetaxel.
    3)Objetivo: evaluar la seguridad y la tolerabilidad de MK 3475 en sujetos con CPNM de histología epidermoide tratados previamente.
    E.2.2Secondary objectives of the trial
    1)Objective: To investigate the correlation of clinical outcome (OS and ORR) with expression of a potential predictive biomarker, PD-L1.
    2)Objective: To evaluate progression free survival (PFS) as determined by immune-related response criteria of previously-treated subjects with SCC NSCLC treated with MK-3475 compared to docetaxel.
    3)Objective: To evaluate response duration of previously-treated subjects with SCC NSCLC treated with MK-3475 compared to docetaxel
    1)Objetivo: investigar la correlación entre la evolución clínica (SG y TRG) y la expresión de un posible biomarcador predictivo, PD L1.
    2)Objetivo: comparar la SSP, determinada mediante los criterios de respuesta relacionados con el sistema inmunológico, de sujetos con CPNM de histología epidermoide tratados previamente que reciban MK 3475 en comparación con docetaxel.
    3)Objetivo: evaluar la duración de la respuesta en sujetos con CPNM de histología epidermoide tratados previamente que reciban MK 3475 en comparación con docetaxel.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1)Be willing and able to provide written informed consent/assent for the trial.
    2)Be ?18 years of age on day of signing informed consent.
    3)Have a life expectancy of at least 3 months.
    4)Have a histologically or cytologically confirmed diagnosis of squamous cell non-small cell lung cancer (NSCLC) and have at least one measurable lesion as defined by RECIST 1.1. For those subjects whose tumors have a mixed histologic component of squamous and another histology, they will be considered eligible for this protocol.
    5)Have experienced investigator determined radiographic progression per RECIST 1.1 of SCC NSCLC after treatment with a platinum-containing doublet for stage IIIB/IV or recurrent disease. The site?s study team must have reviewed pre-trial images that are of diagnostic quality from at least 2 dates to confirm that radiographic progression has occurred per RECIST 1.1 following initiation of the first-line platinum-containing doublet. The central imaging vendor must have received these scans prior to randomization in this trial for a possible retrospective analysis of this eligibility criterion. The central vendor will not be confirming eligibility prior to randomization. Completion of treatment with a platinum-containing doublet as adjuvant therapy within one year of signing informed consent will satisfy the prior treatment requirement.
    6)Have a performance status of 0 or 1 on the ECOG Performance Scale.
    7)Have provided tissue for biomarker analysis from an archival tissue sample or fresh biopsy of a tumor lesion not previously irradiated. Tissue sample must be received by the central vendor prior to randomization.
    8)Have resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or less (except alopecia). If subject received major surgery or radiation therapy of > 30 Gy, they must have recovered from the toxicity and/or complications from the intervention.
    Refer to Protocol for the complete list.
    1)Estar dispuesto a otorgar su consentimiento/asentimiento informado por escrito para el ensayo y ser capaz de hacerlo.
    2)Tener una edad mínima de 18 años el día de firma del consentimiento informado.
    3)Tener una esperanza de vida de al menos 3 meses.
    4)Tener un diagnóstico confirmado mediante técnicas histológicas o citológicas de CPNM epidermoide y presentar al menos una lesión mensurable según se define en los criterios RECIST 1.1. Los sujetos cuyos tumores tengan un componente histológico mixto, epidermoide y de otro tipo, podrán participar en este protocolo.
    5)Haber presentado progresión radiológica del CPNM epidermoide, determinada por el investigador con arreglo a los criterios RECIST 1.1, después del tratamiento con un doblete con platino por enfermedad en estadio IIIB/IV o recurrente. El equipo del estudio del centro tendrá que haber revisado imágenes previas al ensayo, de calidad diagnóstica, correspondientes a al menos dos fechas, para confirmar que se ha producido progresión radiológica conforme a los criterios RECIST 1.1 tras el inicio de la administración del doblete con platino de primera línea. El proveedor central de estudios de imagen tendrá que haber recibido estas pruebas antes de la aleatorización en este ensayo para un posible análisis retrospectivo de este criterio de elegibilidad. El proveedor central no confirmará la elegibilidad antes de la aleatorización. La finalización del tratamiento con un doblete con platino como tratamiento adyuvante en el año previo a la firma del consentimiento informado satisfará el requisito de tratamiento previo.
    6)Tener un estado funcional de 0 o 1 en la escala del ECOG.
    7)Haber facilitado tejido para efectuar un análisis de biomarcadores a partir de una muestra de tejido de archivo o una biopsia reciente de una lesión tumoral no irradiada previamente. La muestra de tejido deberá ser recibida por el proveedor central antes de la aleatorización.
    8)Presentar resolución de los efectos tóxicos de la quimioterapia previa más reciente hasta un grado 1 o inferior (salvo alopecia). Cuando el sujeto se haya sometido a cirugía mayor o haya recibido >30 Gy de radioterapia, tendrá que haberse recuperado de la toxicidad o las complicaciones de la intervención.
    (Leer lista completa en el protocol)
    E.4Principal exclusion criteria
    1)Is known to have an EGFR mutation or the AML4-ALK translocation.
    2)Has received prior therapy with docetaxel for NSCLC.
    3)Is receiving systemic steroid therapy within three days prior to the first dose of trial treatment or receiving any other form of immunosuppressive medication (corticosteroid use on study for management of ECI-ies or as a pre-medication for docetaxel is allowed).
    4)Is expected to require any other form of systemic or localized antineoplastic therapy while on trial (including maintenance therapy with another agent for NSCLC or radiation therapy).
    5)Has received maintenance chemotherapy (chemotherapy for subjects with a stable or better response to the prior line of treatment) with an additional agent other than that used in the first-line regimen ("switch maintenance").
    6)Has received prior systemic cytotoxic chemotherapy, biological therapy (e.g., cetuximab), major surgery or received radiation therapy of > 30 Gy within 3 weeks of the first dose of trial treatment; received prior kinase inhibitor therapy or palliative radiotherapy of 30Gy or less within 7 days of the first dose of trial treatment.
    7)Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
    8)Has a known history of prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ cervical cancer, and has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.
    -Note: The time requirement for no evidence of disease for 5 years does not apply to the tumor for which a subject is enrolled in the trial. The time requirement also does not apply to subjects who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ cervical cancer.
    9)Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by MRI for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are using no steroids for at least three days prior to study medication..
    10)Has an active autoimmune disease, or a documented history of autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement will not be excluded from the study.
    11)Has interstitial lung disease.
    12)Has symptomatic ascites or pleural effusion. A subject who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
    13)Has an active infection requiring intravenous systemic therapy.
    14)Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
    15)Has known active Hepatitis B or C.
    Refer to Protocol for the complete list.
    1)Se sepa que tiene una mutación de EGFR o la translocación AML4 ALK.
    2)Haya recibido tratamiento previo con docetaxel para el CPNM.
    3)Esté recibiendo tratamiento con esteroides sistémicos en los tres días previos a la primera dosis del tratamiento del ensayo o cualquier otra forma de medicación inmunodepresora (se permitirá el uso de corticoides durante el estudio para tratar AIC-ei o como premedicación con docetaxel).
    4)Se prevea que precise cualquier otra formas de tratamiento antineoplásico localizado o sistémico durante el ensayo (incluido el tratamiento de mantenimiento con otro fármaco contra el CPNM o radioterapia).


    5)Haya recibido quimioterapia de mantenimiento (quimioterapia para sujetos con enfermedad estable o una respuesta mejor a la línea previa de tratamiento) con otro fármaco distinto del utilizado en el régimen de primera línea (?switch maintenance?).

    6)Haya recibido quimioterapia citotóxica sistémica previa, tratamiento biológico (por ejemplo, cetuximab), cirugía mayor o radioterapia >30 Gy en las 3 semanas previas a la primera dosis del tratamiento del ensayo o haya recibido tratamiento previo con un inhibidor de cinasas o radioterapia paliativa ?30 Gy en los 7 días previos a la primera dosis del tratamiento del ensayo.
    7)Haya recibido tratamiento previo con un anticuerpo anti PD 1, anti PD L1, anti PD L2, anti CD137 o anti CTLA 4 (antígeno asociado a los linfocitos citotóxicos 4) (como ipilimumab o cualquier otro anticuerpo o fármaco dirigido específicamente contra la coestimulación de linfocitos T o contra vías que actúen de punto de control).

    8)Tenga antecedentes de una neoplasia maligna previa, a excepción de carcinoma basocelular de piel, cáncer de vejiga superficial, carcinoma espinocelular de piel o cáncer cervicouterino in situ, y se haya sometido a un tratamiento potencialmente curativo sin datos de recurrencia de la enfermedad durante 5 años desde el inicio del mismo.
    -Nota: el requisito temporal de cinco años de ausencia de datos de enfermedad no se aplica al tumor que motive la inclusión del sujeto en el ensayo. Dicho requisito temporal tampoco se aplica a los sujetos que se hayan sometido a una resección definitiva satisfactoria de un carcinoma basocelular de piel, cáncer de vejiga superficial, carcinoma espinocelular de piel o cáncer cervicouterino in situ.



    9)Tenga metástasis activas en el sistema nervioso central (SNC) y/o meningitis carcinomatosa. Los sujetos con metástasis cerebrales tratadas con anterioridad podrán participar siempre que se encuentren estables (sin signos de progresión en la RM durante al menos cuatro semanas antes de la primera dosis del tratamiento del ensayo y con regreso de todos los síntomas neurológicos a la situación basal), no presenten indicios de metástasis cerebrales nuevas o que estén aumentando de tamaño y no utilicen esteroides durante al menos tres días antes de recibir la medicación del estudio.
    10)Tenga una enfermedad autoinmunitaria activa, o antecedentes documentados de una enfermedad autoinmunitaria, o un síndrome que precise tratamiento con esteroides o inmunodepresores sistémicos. Son excepciones a esta regla los sujetos con vitíligo o con asma o atopia infantil resuelta. No se excluirá del estudio a los que requieran un uso intermitente de broncodilatadores o inyecciones locales de esteroides. No se excluirá del estudio a los sujetos con hipotiroidismo estable con tratamiento de reposición hormonal.
    11)Presente una neumopatía intersticial.
    12)Presente ascitis o derrame pleural sintomáticos. Podrán participar los sujetos que se encuentren clínicamente estable tras recibir tratamiento por estas enfermedades (como toracocentesis o paracentesis terapéuticas).
    13)Presente una infección activa con necesidad de tratamiento sistémico por vía intravenosa.
    14)Tenga antecedentes de infección por el virus de la inmunodeficiencia humana (VIH) (anticuerpos contra el VIH 1 o 2).
    15)Tenga antecedentes de hepatitis B o C activa.

    (Leer lista completa en el protocolo)
    E.5 End points
    E.5.1Primary end point(s)
    Overall Survival is the gold standard endpoint to demonstrate superiority of antineoplastic therapy. Objective Response Rate provides an initial suggestion of a drug?s potential activity and has been the basis of accelerated approval of an antineoplastic agent in NSCLC, Alimta, in the United States of America. Thus, large improvements in ORR relative to control therapy could be considered justification for accelerated approval of the product while OS data mature.
    La SG es el criterio de valoración de referencia para demostrar la superioridad de un tratamiento antineoplásico. La TRG ofrece una idea inicial de la actividad potencial de un fármaco y ha sido la base de la aprobación acelerada de un antineoplásico en el CPNM, Alimta, en los Estados Unidos de América. Así pues, unas mejorías importantes de la TRG con respecto al tratamiento de control podrían considerarse una justificación para la aprobación acelerada del producto mientras maduran los datos de SG.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Imaging scans will be performed every 9 weeks.
    Los estudios de imagen se realizarán cada 9 semanas
    E.5.2Secondary end point(s)
    This trial will look at the potential correlation of PD-L1 expression with the outcomes of OS and ORR. Since PD-L1 is a ligand for PD-1 and MK-3475 disrupts the interaction of the two proteins, it is reasonable to look for expression of PD-L1 to predict responsiveness to anti-PD-1 therapy. PD-L1 may be a predictive biomarker of anti-PD-1 activity, and will be tested in this study on the biopsy samples provided during screening.
    En este ensayo se analizará la posible correlación entre la expresión de PD L1 y los criterios de valoración de SG y TRG. Dado que PD L1 es un ligando de PD 1 y MK 3475 altera la interacción entre las dos proteínas, resulta razonable analizar la expresión de PD L1 para predecir la capacidad de respuesta al tratamiento anti PD 1. PD L1 podría ser un biomarcador predictivo de la actividad anti PD 1 y se evaluará en este estudio en las muestras de biopsia que se obtengan durante la selección .
    E.5.2.1Timepoint(s) of evaluation of this end point
    Biomarker testing will be occur during the course of the study. Evaluation of PFS and duration of response will be ongoing throughout the study.
    El analisis de los biomarcadores se hará a lo largo del estudio.
    La evaluación de la supervivencia sin progresión y la duración de la respuesta se harán a lo largo del estudio.
    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 Yes
    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) Yes
    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 Yes
    E.8.1.7.1Other trial design description
    El estudio es abierto para el MK3475 o el comparador sin embargo para la dosis MK3475 es doble ciego
    Study is open label for MK-3475 or comparator, however, dose of MK-3475 is double-blinded
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned9
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA90
    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
    Argentina
    Australia
    Belgium
    Brazil
    Canada
    Chile
    Czech Republic
    Denmark
    France
    Germany
    Greece
    Hungary
    Italy
    Japan
    Korea, Republic of
    Lithuania
    Netherlands
    New Zealand
    Portugal
    South Africa
    Spain
    Taiwan
    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
    LVLS
    LPLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days15
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months10
    E.8.9.2In all countries concerned by the trial days15
    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: 245
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 163
    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 state31
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 275
    F.4.2.2In the whole clinical trial 408
    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)
    Standard of Care
    Tratamientos habituales
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation CRF Health
    G.4.3.4Network Country United States
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2013-05-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-04-12
    P. End of Trial
    P.End of Trial StatusOngoing
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