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   38482   clinical trials with a EudraCT protocol, of which   6323   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).
     
    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:2018-003824-35
    Sponsor's Protocol Code Number:MK-7902-006
    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:2019-01-18
    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 number2018-003824-35
    A.3Full title of the trial
    A Phase 3 Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Pemetrexed + Platinum Chemotherapy + Pembrolizumab (MK-3475) with or without Lenvatinib (E7080/MK-7902) as First-line Intervention in Participants with Metastatic Nonsquamous Non-small Cell Lung Cancer (LEAP-006)
    Estudio de fase 3, aleatorizado y controlado con placebo para evaluar la seguridad y la eficacia de pemetrexed + quimioterapia a base de platino + pembrolizumab (MK-3475) con o sin lenvatinib (E7080/MK-7902) como intervención de primera línea en participantes con cáncer de pulmón no microcítico, no epidermoide, metastásico (LEAP-006)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 3 Study of Pemetrexed + Platinum Chemotherapy + Pembrolizumab with or without Lenvatinib in Participants with NSCLC
    Estudio de fase 3 de pemetrexed + quimioterapia a base de platino + pembrolizumab con o sin lenvatinib en participantes con CPNM
    A.3.2Name or abbreviated title of the trial where available
    LEAP-006
    LEAP-006
    A.4.1Sponsor's protocol code numberMK-7902-006
    A.5.4Other Identifiers
    Name:IND numberNumber:140221
    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.4.1Name of organisation providing supportEisai Limited
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMerck Sharp & Dohme de España SA
    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+3491 3210600
    B.5.5Fax number+3491 3210590
    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 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.3.1Product 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.3.9.2Current sponsor codeMK-3475
    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 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 nameLenvatinib
    D.3.2Product code E7080
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLENVATINIB MESILATE
    D.3.9.1CAS number 857890-39-2
    D.3.9.2Current sponsor codeMK-7902
    D.3.9.3Other descriptive nameLENVATINIB MESILATE
    D.3.9.4EV Substance CodeSUB72971
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4
    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.IMP: 3
    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.3.9.2Current sponsor codeMK-3475
    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: 4
    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 nameLenvatinib
    D.3.2Product code E7080
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLENVATINIB MESILATE
    D.3.9.1CAS number 857890-39-2
    D.3.9.2Current sponsor codeMK-7902
    D.3.9.3Other descriptive nameLENVATINIB MESILATE
    D.3.9.4EV Substance CodeSUB72971
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule, hard
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Metastatic Nonsquamous Non-small Cell Lung Cancer
    Cáncer de pulmón de células no pequeñas no escamosas metastásico
    E.1.1.1Medical condition in easily understood language
    Metastatic Nonsquamous Non-small Cell Lung Cancer
    Cáncer de pulmón de células no pequeñas no escamosas 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 PT
    E.1.2Classification code 10059515
    E.1.2Term Non-small cell lung cancer metastatic
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10079440
    E.1.2Term Non-squamous non-small cell lung cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Part 1: To evaluate the safety and tolerability of treatment with lenvatinib + platinum doublet chemotherapy + pembrolizumab.
    Part 2: To compare PFS as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1 as defined in Section 4.2.1.1.3) for lenvatinib + platinum doublet chemotherapy + pembrolizumab versus matching placebo + platinum doublet chemotherapy + pembrolizumab. - Hypothesis (H1): The combination of lenvatinib +platinum doublet chemotherapy + pembrolizumab prolongs PFS per RECIST 1.1 by BICR compared to matching placebo + platinum doublet chemotherapy +pembrolizumab.
    Part 2: To compare OS for the combinations of lenvatinib + platinum doublet chemotherapy + pembrolizumab versus matching placebo + platinum doublet chemotherapy +pembrolizumab.
    Parte 1: Evaluar la seguridad y la tolerabilidad del tratamiento con lenvatinib + quimioterapia doble a base de platino + pembrolizumab.
    Parte 2: Comparar la SSP, evaluada mediante una revisión central independiente y enmascarada (RCIE) conforme a los Criterios de evaluación de la respuesta en tumores sólidos, versión 1.1 (RECIST 1.1, según se define en la sección 4.2.1.1.3), entre las combinaciones de lenvatinib + quimioterapia doble a base de platino + pembrolizumab y placebo equivalente + quimioterapia doble a base de platino + pembrolizumab.
    Parte 2: Comparar la SG entre las combinaciones de lenvatinib + quimioterapia doble a base de platino + pembrolizumab y placebo equivalente + quimioterapia doble a base de platino + pembrolizumab.
    E.2.2Secondary objectives of the trial
    Part 2: To compare objective response rate (ORR) as assessed by BICR according to RECIST 1.1 for the combinations of lenvatinib + platinum doublet chemotherapy+pembrolizumab versus matching placebo + platinum doublet chemotherapy + pembrolizumab.
    Part 2: To compare duration of response (DOR) per RECIST 1.1 by BICR for the combinations of lenvatinib + platinum doublet chemotherapy + pembrolizumab versus matching placebo + platinum doublet chemotherapy + pembrolizumab.
    Part 2: To compare the safety and tolerability for the combinations of lenvatinib + platinum doublet chemotherapy + pembrolizumab versus matching placebo + platinum doublet chemotherapy + pembrolizumab.

    Read in the protocol
    Parte 2: Comparar la tasa de respuestas objetivas (TRO), evaluada mediante una RCIE conforme a los criterios RECIST 1.1, entre las combinaciones de lenvatinib + quimioterapia doble a base de platino + pembrolizumab y placebo equivalente + quimioterapia doble a base de platino + pembrolizumab.
    Parte 2: Comparar la duración de la respuesta (DR) conforme a los criterios RECIST 1.1, según una RCIE, entre las combinaciones de lenvatinib + quimioterapia doble a base de platino + pembrolizumab y placebo equivalente + quimioterapia doble a base de platino + pembrolizumab.
    - Parte 2: Comparar la seguridad y la tolerabilidad de las combinaciones de lenvatinib + quimioterapia doble a base de platino + pembrolizumab y placebo equivalente + quimioterapia doble a base de platino + pembrolizumab.

    Leer en el protocolo
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Participant must:
    1. Have a histologically or cytologically confirmed diagnosis of Stage IV (American Joint Committee on Cancer [AJCC], version 8 or current version) nonsquamous NSCLC.
    2. Have confirmation that EGFR-, ALK-, or ROS1-directed therapy is not indicated as
    primary treatment (documentation of absence of tumor-activating EGFR mutations AND absence of ALK and ROS1 gene rearrangements OR presence of a KRAS mutation).
    3. Have measurable disease based on RECIST 1.1.
    4. Have provided an evaluable archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion (that was not previously irradiated) for central PD L1 testing. Formalin fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.
    Newly obtained biopsies are preferred to archived tissue. Formalin fixed specimens after the participant has been diagnosed with metastatic disease are preferred. Biopsies obtained prior to receipt of adjuvant/neoadjuvant chemotherapy are permitted if recent biopsy is not feasible.
    5. Be male or female ≥18 years of age inclusive, at the time of signing the informed consent form (ICF).
    6. Have a life expectancy of at least 3 months.
    7. Have an ECOG performance status of 0 or 1 within 7 days prior to the first dose of study intervention but before randomization.
    8. A male participant must agree to use contraception as detailed in Appendix 5 of this protocol during the treatment period and for at least 120 days after the last dose of pembrolizumab and/or lenvatinib/matching placebo and up to 180 days after the last dose of chemotherapeutic agents.
    A male participant must also agree to the following:
    Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
    OR
    Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause as detailed below:
    - Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant.
    9. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
    Is not a woman of childbearing potential (WOCBP)
    OR
    Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), as described in Appendix 5 during the intervention period and for at least 120 days after the last dose of study intervention The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
    A WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 24 hours before the first dose of study intervention.
    If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
    10. The participant (or legally acceptable representative if applicable) provides written informed consent for the study.
    11. Have adequate organ function as indicated by the laboratory values.
    Specimens must be collected and reviewed within 10 days prior to the first dose of study intervention.
    12. Have adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg and no change in antihypertensive medications within 1 week prior to randomization.
    Un participante deberá:
    1. Tener un diagnóstico confirmado histológica o citológicamente de CPNM no epidermoide en estadio IV (American Joint Committee on Cancer [AJCC], versión 8 o versión actual).
    2. Confirmación de que no está indicado el tratamiento dirigido contra EGFR, ALK o ROS1 como tratamiento primario (ausencia documentada de mutaciones de EGFR activadoras del tumor Y ausencia de reordenamientos génicos de ALK y ROS1 O presencia de una mutación de KRAS).
    3. Tener enfermedad mensurable conforme a los criterios RECIST 1.1
    4. Haber facilitado una muestra de tejido tumoral de archivo evaluable o haberse sometido a una biopsia reciente, con aguja gruesa o por escisión, de una lesión tumoral no irradiada previamente para un análisis centralizado de PD-L1. 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. Se prefiere el uso de muestras fijadas en formol después de que el participante haya sido diagnosticado de enfermedad metastásica. Se admitirán biopsias obtenidas antes de que el participante reciba quimioterapia adyuvante o neoadyuvante cuando no sea factible una biopsia reciente.
    5. Varón o mujer y edad mínima de 18 años en el momento de firmar el documento de consentimiento informado (DCI).
    6. Esperanza de vida mínima de tres meses.
    7. Estado funcional del ECOG de 0 o 1 en los 7 días previos a la primera dosis de la intervención del estudio pero antes de la aleatorización
    8. Los varones deben comprometerse a utilizar métodos anticonceptivos tal como se detalla en el apéndice 5 de este protocolo durante el período de tratamiento y hasta, como mínimo, 120 días después de la última dosis de pembrolizumab y/o lenvatinib/placebo equivalente, así como hasta 180 días después de la última dosis de quimioterápicos.
    Los varones participantes también deberán comprometerse a lo siguiente:
    • Abstinencia de relaciones heterosexuales como modo de vida habitual y preferido (abstinencia a largo plazo y persistente) y compromiso de mantenerla O
    • Uso de métodos anticonceptivos a menos que se confirme que presentan azoospermia (por vasectomía o secundaria a una causa médica [apéndice 5]) tal como se detalla a continuación:
    - Compromiso de utilizar preservativo masculino más uso por parte de la pareja de un método anticonceptivo adicional cuando se mantengan relaciones sexuales con mujeres en edad fértil que no estén embarazadas
    9. Una mujer podrá participar si no está embarazada, no está amamantando y cumple al menos una de las condiciones siguientes:
    • No es una mujer en edad fértil (MEF).
    • Es una MEF y utiliza un método anticonceptivo muy eficaz (con un índice de fallos < 1% anual), con baja dependencia de la usuaria, o practica abstinencia de relaciones heterosexuales como modo de vida preferido y habitual (abstinencia a largo plazo y persistente), según se describe en el apéndice 5, durante el período de intervención y hasta al menos 120 días después de la última dosis de la intervención del estudio. El investigador deberá evaluar la posibilidad de fracaso del método anticonceptivo (es decir, incumplimiento, inicio reciente) en relación con la primera dosis de la intervención del estudio.
    • Las MEF deberán dar negativo en una prueba de embarazo de alta sensibilidad (en orina o suero, según exija la normativa local) en las 24 horas previas a la primera dosis de la intervención del estudio.
    • Cuando el resultado de una prueba en orina no pueda confirmarse que es negativo (por ejemplo, resultado ambiguo), será necesario hacer una prueba de embarazo en suero. En tal caso, la participante será excluida si el resultado de la prueba de embarazo en suero es positivo.
    10. El participante (o su representante legal cuando proceda) otorga su consentimiento informado por escrito para el estudio.
    11. Función orgánica adecuada, conforme a lo indicado por los valores analíticos . Las muestras se obtendrán y analizarán en los 10 días previos a la primera dosis de la intervención del estudio.
    12. Presión arterial (PA) debidamente controlada, con o sin antihipertensivos, definida como una PA ≤ 150/90 mm Hg y sin modificaciones de la medicación antihipertensiva en la semana previa a la aleatorización.
    E.4Principal exclusion criteria
    If Participant:
    1. Has known untreated central nervous system (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 [the repeat imaging must be performed during the screening period]), clinically stable, and have not required steroids for at least 14 days prior to the first dose of study intervention.
    2. Has a history of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
    3. Radiographic evidence of major blood vessel invasion/infiltration. The degree of tumor invasion/infiltration of major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis after treatment with lenvatinib.
    4. Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy.
    5. Has an active autoimmune disease that has required systemic treatment in the 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, etc.) is allowed.
    6. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention.
    7. Has had an allogeneic tissue/solid organ transplant.
    8. Has a known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by the local health authority.
    9. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive or HBV-DNA detected) or known active Hepatitis C virus (defined as HCV
    RNA [qualitative] detected or HCV antibody reactive, if HCV-RNA is not the local SOC) infection. No testing for Hepatitis B or Hepatitis C is required unless mandated by the
    local health authority.
    10. Has a history of a gastrointestinal condition or procedure that in the opinion of the investigator may affect oral drug absorption.
    11. Has active hemoptysis (at least 0.5 tsp of bright red blood) within 2 weeks prior to the first dose of study intervention.
    12. Has significant cardiovascular impairment within 12 months prior to the first dose of study intervention, including history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, cerebrovascular accident (CVA)/stroke, or cardiac arrhythmia associated with hemodynamic instability.
    13. Has a known history of active tuberculosis.
    14. Has an active infection requiring systemic therapy.
    15. Has not recovered adequately from any toxicity and/or complication from major surgery prior to the first dose of study intervention.
    16. Has known psychiatric or substance abuse disorders that would interfere with the participant’s cooperation to meet with the requirements of the study.
    17. Previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has a known sensitivity to any component of lenvatinib or pembrolizumab, or as applicable, carboplatin, cisplatin, or pemetrexed.
    18. WOCBP who has a positive urine pregnancy test within 72 hours prior to the first dose of study intervention. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
    19. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of pembrolizumab and/or lenvatinib/matching placebo and up to 180 days after last dose of chemotherapeutic agents.
    20. Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC.

    Read in the protocol
    Si el Participante:
    1. Presencia de metástasis no tratadas conocidas en el sistema nervioso central (SNC) y/o 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 4 semanas en estudios de imagen repetidos [durante la fase de selección deberán realizarse nuevos estudios de imagen]) y clínicamente estables y no hayan precisado esteroides durante al menos 14 días antes de la primera dosis de la intervención del estudio.
    2. Antecedentes de neumonitis (no infecciosa) que precisó la administración de esteroides sistémicos o presencia de una neumonitis o neumopatía intersticial activa.
    3. Signos radiológicos de invasión/infiltración de vasos sanguíneos importantes. El grado de invasión/infiltración tumoral de vasos sanguíneos importantes debe tenerse en cuenta debido al posible riesgo de hemorragia grave asociada a una reducción o necrosis tumoral después del tratamiento con lenvatinib.
    4. Antecedentes de otras neoplasias malignas, salvo si el participante se ha sometido a un tratamiento potencialmente curativo y no ha habido signos de recidiva de la enfermedad durante al menos tres años desde el comienzo de ese tratamiento.
    5. 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. Están permitido los tratamientos de sustitución (p. ej., tiroxina, insulina o corticoides en dosis fisiológicas para una insuficiencia suprarrenal o hipofisaria, etc.).
    6. Diagnóstico de inmunodeficiencia o recepción de tratamiento sistémico crónico con esteroides (en dosis superiores a 10 mg diarios de prednisona o equivalente) o cualquier otra forma de tratamiento inmunodepresor en los siete días previos a la primera dosis de la intervención del estudio.
    7. Recepción de un alotrasplante de órgano sólido o tejidos.
    8. Antecedentes de infección por el virus de la inmunodeficiencia humana (VIH). No es necesario realizar pruebas de VIH a menos que lo exijan las autoridades sanitarias locales.
    9. Antecedentes de infección por el virus de la hepatitis B (reactividad del antígeno de superficie del virus de la hepatitis B [HBsAg] o detección de ADN del VHB) o de infección activa por el virus de la hepatitis C (detección de ARN del virus de la hepatitis C [VHC] [cualitativo] o anticuerpos contra el VHC cuando la determinación de ARN-VHC no sea la norma asistencial local). No es necesario realizar pruebas de hepatitis B o C a menos que lo exijan las autoridades sanitarias locales.
    10. Antecedentes de un trastorno o procedimiento gastrointestinal que, en opinión del investigador, podría afectar a la absorción oral de fármacos.
    11. Hemoptisis activa (al menos 2,5 ml de sangre roja brillante) en las dos semanas previas a la primera dosis de la intervención del estudio.
    12. Insuficiencia cardiovascular significativa en los 12 meses previos a la primera dosis de la intervención del estudio, como antecedentes de insuficiencia cardíaca congestiva de clase superior a la II según la New York Heart Association (NYHA), angina inestable, infarto de miocardio, accidente cerebrovascular (ACV)/ictus o arritmia cardíaca asociada a inestabilidad hemodinámica.
    13. Antecedentes de tuberculosis activa.
    14. Infección activa con necesidad de tratamiento sistémico.
    15. Ausencia de recuperación suficiente de cualquier toxicidad y/o complicación de una intervención de cirugía mayor antes de la primera dosis de la intervención del estudio.
    16. Presencia de un trastorno psiquiátrico o por abuso de sustancias que podría dificultar la capacidad del participante para colaborar en el cumplimiento de los requisitos del estudio.
    17. Antecedentes de una reacción de hipersensibilidad grave al tratamiento con un anticuerpo monoclonal o presencia de sensibilidad conocida a cualquier componente de lenvatinib o pembrolizumab o, según proceda, carboplatino, cisplatino o pemetrexed.
    18. Mujer en edad fértil que da positivo en una prueba de embarazo en orina realizada en las 72 horas previas a la primera dosis de la intervención del estudio. 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.
    19. Embarazo, en período de lactancia o intención de concebir o engendrar un hijo durante el período previsto del estudio, desde la visita de selección hasta 120 días después de la última dosis de pembrolizumab y/o lenvatinib/placebo equivalente y hasta 180 días después de la última dosis de los quimioterápicos.
    20. Recepción de quimioterapia sistémica previa u otro tratamiento antineoplásico dirigido o biológico contra el CPNM metastásico

    Leer en el protoclo
    E.5 End points
    E.5.1Primary end point(s)
    1. Part 1: Number of Participants with a Dose-limiting Toxicity
    2. Part 1: Number of Participants with One or More Adverse Events
    3. Part 2: Progression-free Survival (PFS) as Assessed by BICR according to RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ
    4. Part 2: Overall Survival (OS)
    1. Parte 1: Número de participantes con toxicidad limitante de la dosis
    2. Part 1: Número de participantes con uno o más acontecimientos adversos
    3. Part 2: Supervivencia sin progression (SSP) evaluada mediante una RCIE (Revisión de imagen independiente y enmascarada) conforme a los criterios RECIST 1.1, para el seguimiento de un máximo de 10 lesiones diana y un máximo de 5 lesiones diana por órgano.
    4. Part 2: Supervivencia global
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. Cycle 1; each cycle is 21 days (up to 21 days)
    2. Through 90 days post last dose of study treatment (Up to approximately 27 months)
    3. Up to approximately 24 months
    4. Up to approximately 60 months
    1. Ciclo 1; cada ciclo son 21 días (hasta 21 días)
    2. Durante 90 días a partir de la última dosis del tratamiento de studio (hasta aproximadamente 27 meses)
    3. Hasta aproximadamente 24 meses
    4. Hasta aproximadamente 60 meses
    E.5.2Secondary end point(s)
    1. Part 2: Objective Response Rate (ORR) as Assessed by BICR
    according to RECIST 1.1, modified to follow a maximum of 10 target
    lesions and a maximum of 5 target lesions per organ
    2. Part 2; Duration of Response (DOR) as Assessed by BICR according
    to RECIST 1.1, modified to follow a maximum of 10 target lesions and a
    maximum of 5 target lesions per organ
    3. Part 2: Number of Participants with One or More Adverse Events
    4. Part 2: Number of Participants Who Discontinue Study Treatment
    Due to an Adverse Event
    5. Part 2: Change from Baseline in European Organization for Research
    and Treatment of Cancer Quality of Life Questionnaire C-30 [EORTC
    QLQ-C30] Global Health Status/Quality of Life (QoL)(EORTC QLQ-C30
    Items 29 and 30); Cough (EORTC QLQ-Lung Cancer Module [LC13] Item
    31); Chest Pain (EORTC QLQ-LC13 Item 40); Dyspnea (EORTC QLQ-C30
    Item 8); and Physical Functioning (EORTC QLQ-C30 Items 1-5)
    Combined Score
    6. Part 2: Time to True Deterioration as Assessed by Change from
    Baseline in Global Health Status/QoL (EORTC QLQ-C30 Items 29 and
    30), Cough (EORTC QLQ-LC13 Item 31), Chest Pain (EORTC QLQ-LC13
    Item 40), Dyspnea (EORTC QLQ-C30 Item 8), and Physical Functioning
    (EORTC QLQ-C30 Items 1-5) Combined Score
    1. Part 2: Tasa de respuestas objetivas (TRO), evaluada mediante una RCIE conforme a los criterios RECIST 1.1, para el seguimiento de un máximo de 10 lesiones diana y un máximo de 5 lesiones diana por órgano.
    2. Part 2; Duración de la respuesta (DR), evaluada mediante una RCIE conforme a los criterios RECIST 1.1, para el seguimiento de un máximo de 10 lesiones diana y un máximo de 5 lesiones diana por órgano
    3. Part 2: Número de participantes con uno o más acontecimientos adversos.
    4. Part 2: Número de participantes que abandona el tratamiento debido a un acontecimiento adverso.
    5. Part 2: Variación media con respecto al momento basal del estado de salud general/calidad de vida (apartados 29 y 30 del cuestionario QLQ-C30 de la EORTC), tos (apartado 31 del cuestionario QLQ-LC13 de la EORTC), dolor torácico (apartado 40 del cuestionario QLQ-LC13 de la EORTC), disnea (apartado 8 del cuestionario QLQ-C30 de la EORTC) y función física (apartados 1-5 del cuestionario QLQ-C30 de la EORTC).
    6. Part 2: Tiempo hasta un deterioro real del estado de salud general/calidad de vida (apartados 29 y 30 del cuestionario QLQ-C30 de la EORTC), tos (apartado 31 del cuestionario QLQ-LC13 de la EORTC), dolor torácico (apartado 40 del cuestionario QLQ-LC13 de la EORTC), disnea (apartado 8 del cuestionario QLQ-C30 de la EORTC) y función física (apartados 1-5 del cuestionario QLQ-C30 de la EORTC).
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Up to approximately 24 months
    2. Up to approximately 24 months
    3. Up to approximately 24 months
    4. Up to approximately 24 months
    5. Baseline (Cycle 1 Day 1) and at designated timepoints up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)
    6. Baseline (Cycle 1 Day 1) and at designated timepoints up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)
    1. Hasta aproximadamente 24 meses.
    2. Hasta aproximadamente 24 meses.
    3. Hasta aproximadamente 24 meses.
    4. Hasta aproximadamente 24 meses.
    5. Momento basal (ciclo 1 día 1) y en los momentos definidos hasta 30 días después de la última dosis. Cada ciclo son 21 días (hasta aproximadamente 25 meses).
    6. ) Momento basal (ciclo 1 día 1) y en los momentos definidos hasta 30 días después de la última dosis. Cada ciclo son 21 días (hasta aproximadamente 25 meses).
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Yes
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic Yes
    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 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 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 concerned12
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA66
    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
    Canada
    Chile
    China
    France
    Germany
    Israel
    Japan
    Korea, Republic of
    New Zealand
    Poland
    Russian Federation
    Spain
    Turkey
    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
    LVLP
    LVLP
    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 months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    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: 430
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 285
    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 No
    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 state65
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 372
    F.4.2.2In the whole clinical trial 714
    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 Decision2019-02-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-02-05
    P. End of Trial
    P.End of Trial StatusOngoing
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA