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    Summary
    EudraCT Number:2019-003582-18
    Sponsor's Protocol Code Number:20190009
    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:2020-03-06
    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 number2019-003582-18
    A.3Full title of the trial
    A Phase 3 Multicenter, Randomized, Open Label, Active-controlled, Study of AMG 510 Versus Docetaxel for the Treatment of Previously Treated Locally Advanced and Unresectable or Metastatic NSCLC Subjects With Mutated KRAS p.G12C
    Estudio de fase III multicéntrico, aleatorizado, abierto y con control activo de AMG 510 frente a docetaxel en el tratamiento de sujetos con CPNM tratado previamente, localmente avanzado y no resecable o metastásico con la mutación p.G12C en el KRAS
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 3 Study to Compare AMG 510 With Docetaxel in NSCLC Subjects With KRAS p.G12C Mutation (CodeBreak 200)
    Estudio de fase III para comparar AMG 510 con docetaxel en sujetos con CPNM con la mutación p.G12C en el KRAS (CodeBreak 200)
    A.4.1Sponsor's protocol code number20190009
    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 SponsorAmgen 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 supportAmgen Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAmgen S.A.
    B.5.2Functional name of contact pointIHQ medical Info-Clinical Trials
    B.5.3 Address:
    B.5.3.1Street AddressWTC Barcelona, Moll de Barcelona s/n, Edifici Sud,7ª planta
    B.5.3.2Town/ cityBarcelona
    B.5.3.3Post code08039
    B.5.3.4CountrySpain
    B.5.4Telephone number+3493 6001860
    B.5.6E-mailinformacion.medica.es@amgen.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 nameAMG 510
    D.3.2Product code AMG 510
    D.3.4Pharmaceutical form Film-coated tablet
    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 INNPending
    D.3.9.3Other descriptive nameAMG 510
    D.3.9.4EV Substance CodeSUB193887
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number120
    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: 2
    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.2.1.2Country 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
    D.3.2Product code docetaxel
    D.3.4Pharmaceutical form Concentrate for 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 INNdocetaxel
    D.3.9.3Other descriptive nameDOCETAXEL
    D.3.9.4EV Substance CodeSUB12492MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    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
    Previously treated locally advanced and unresectable or metastatic non-small cell lung cancer (NSCLC) with KRAS p.G12C mutation
    Cáncer de pulmón no microcítico (CPNM) tratado previamente, localmente avanzado y no resecable o metastásico con la mutación p.G12C en el KRAS
    E.1.1.1Medical condition in easily understood language
    Previously treated locally advanced and unresectable or metastatic non-small cell lung cancer (NSCLC) with KRAS p.G12C mutation
    Cáncer de pulmón no microcítico (CPNM) tratado previamente, localmente avanzado y no resecable o metastásico con la mutación p.G12C en el KRAS
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10061873
    E.1.2Term 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
    •To compare the efficacy of AMG 510 versus docetaxel as assessed by progression-free survival (PFS) in previously treated subjects with KRAS p.G12C mutated nonsmall cell lung cancer (NSCLC)
    •Comparar la eficacia de AMG 510 frente a docetaxel, evaluada mediante la supervivencia libre de progresión (SLP) en sujetos tratados previamente con cáncer de pulmón no microcítico (CPNM) con la mutación p.G12C en el KRAS.
    E.2.2Secondary objectives of the trial
    •To compare the efficacy of AMG 510 Versus docetaxel as assessed by:
    - Overall Survival (OS)
    - Objective response rate (ORR)
    •To compare patient-reported outcomes (PRO) as assessed by:
    - European Organization for Research and Treatment of Cancer Quality-of life Questionnaire Core 13 (EORTC QLQ-LC13) and European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC QLQ-C30)
    •To compare efficacy of AMG 510 versus docetaxel as assessed by:
    - duration of response (DOR), time to response (TTR), and disease control rate (DCR)
    •To compare the safety and tolerability of AMG 510 versus docetaxel
    •To compare the effect of treatment with AMG 510 on other treatment and disease related symptoms, and health related quality of life relative to docetaxel
    •To characterize the pharmacokinetics (PK) of AMG 510 and its major metabolites
    •Comparar eficacia de AMG 510 frente a docetaxel, evaluada mediante:
    -Supervivencia global (SG).
    -Tasa de respuesta objetiva (TRO).
    •Comparar los resultados notificados por los pacientes (PRO), evaluados mediante:
    -Cuestionario de calidad de vida Core 13 de la Organización Europea para la Investigación y el Tratamiento del Cáncer (EORTC QLQ-LC13) y cuestionario de calidad de vida Core 30 de la Organización Europea para la Investigación y el Tratamiento del Cáncer (EORTC QLQ-C30).
    •Comparar eficacia de AMG 510 frente a docetaxel, evaluada mediante:
    -duración de respuesta (DR), tiempo hasta respuesta (THR) y tasa de control de enfermedad (TCE).
    •Comparar la seguridad y tolerabilidad de AMG 510 frente a docetaxel.
    •Comparar el efecto del tratamiento con AMG 510 sobre otros síntomas relacionados con el tratamiento y enfermedad, y la calidad de vida relacionada con la salud en relación con docetaxel.
    •Caracterizar la farmacocinética (FC) de AMG 510 y sus metabolitos principales.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Subject or subject’s legally acceptable representative has provided informed consent prior to initiation of any study specific activities/procedures.
    • Age ≥ 18 years of age
    • Have documentation of KRAS p.G12C mutation confirmed by central testing through the current protocol or Amgen Study 20190294 prior to enrollment.
    • Subjects will have received and progressed or experienced disease recurrence on or after receiving at least 1 prior systemic therapy for locally advanced and unresectable or metastatic disease. Prior treatment must include a platinum-based doublet chemotherapy and checkpoint inhibitor for advanced or metastatic disease, either given as one line of therapy or as individual lines of therapy unless the subject has a medical contraindication to one of the required therapies. If the subject has a medical contraindication to a required therapy, the subject may be enrolled only after the investigator discusses and obtains approval from the Amgen medical monitor.
    a) Adjuvant therapy will count as a line of therapy if the subject progressed on or within 6 months of adjuvant therapy administration.
    b) In locally advanced and unresectable NSCLC, disease progression on or within 6 months of end of prior curatively intended multimodal therapy will count as a line of therapy. If chemoradiation is followed by planned systemic therapy without documented progression between chemoradiation and systemic therapy, the entire treatment course counts as one line of therapy.
    • Subjects must have archived tumor tissue samples (formalin fixed, paraffin embedded [FFPE] sample [FFPE of excisional, core needle, or fine needle aspirates] collected within 5 years) or be willing to undergo pre-treatment tumor biopsy (excisional, core needle, or fine needle aspirates) prior to enrollment.
    • Measurable disease per RECIST v1.1 criteria. Lesions previously radiated are not considered measurable unless they have progressed after radiation.
    • ECOG Performance Status of ≤ 1
    • Adequate hematologic laboratory assessments
    • Life expectancy of > 3 months, in the opinion of the investigator
    • Adequate liver function
    • International normalized ratio (INR) and activated partial thromboplastin time ≤ 1.5 x ULN
    • Serum creatinine ≤ 1.5 x ULN OR creatinine clearance ≥ 60 mL/min. Cockcroft-Gault formula will be used for creatinine clearance calculation. Twenty-four hour urine collection is not required but is allowed.
    • QTc ≤ 470 msec in females and ≤ 450 msec in males
    • Ability to take oral medications and willing to record daily adherence to investigational product
    • El sujeto o su representante legal autorizado ha proporcionado su consentimiento informado antes de iniciar cualquier procedimiento/actividad específico del estudio.
    • Edad ≥ 18 años.
    • Disponer de documentación sobre la mutación p.G12C en el KRAS confirmada mediante pruebas realizadas en el laboratorio central según el protocolo actual o el estudio 20190294 de Amgen antes de la inclusión.
    • Los sujetos deberán haber progresado o experimentado recurrencia de la enfermedad mientras recibían o después de haber recibido al menos un tratamiento sistémico previo para la enfermedad localmente avanzada y no resecable o metastásica. El tratamiento previo debe incluir un doblete de quimioterapia basada en platino y un inhibidor de los puntos de control para la enfermedad avanzada o metastásica, ambos administrados como una única línea de tratamiento o como líneas de tratamiento individuales, a no ser que el sujeto presente una contraindicación médica a uno de los tratamientos requeridos. Si el sujeto presenta una contraindicación médica a un tratamiento requerido, el sujeto solo se podrá incluir en el estudio cuando el investigador haya hablado con el monitor médico de Amgen y haya obtenido su aprobación.
    a) El tratamiento adyuvante contará como una línea de tratamiento si el sujeto progresa en los 6 meses posteriores a la administración del tratamiento adyuvante.
    b) En el CPNM localmente avanzado y no resecable, la progresión de la enfermedad en los 6 meses posteriores al final del tratamiento multimodal con intención curativa previo contará como una línea de tratamiento. Si la quimiorradiación va seguida de un tratamiento sistémico planificado sin progresión documentada entre la quimiorradiación y el tratamiento sistémico, toda la tanda de tratamiento cuenta como una línea de tratamiento.
    • Los sujetos deben tener muestras de tejido tumoral archivado (muestra incluida en parafina y fijada con formol [FFPE] [aspiraciones por escisión, con aguja gruesa o con aguja fina incluidas en parafina y fijadas con formol] recogida durante los primeros 5 años) o estar dispuestos a someterse a una biopsia tumoral previa al tratamiento (aspiraciones por escisión, con aguja gruesa o con aguja fina) antes de la inclusión.
    • Enfermedad medible según los criterios RECIST v. 1.1. Las lesiones previamente radiadas no se consideran medibles, a no ser que hayan progresado tras la radiación.
    • Estado funcional ECOG ≤ 1.
    • Evaluaciones analíticas hematológicas adecuadas
    • Esperanza de vida > 3 meses, en opinión del investigador.
    • Función hepática adecuada
    • Cociente internacional normalizado (INR) y tiempo de tromboplastina parcial activada ≤ 1,5 x LSN.
    • Creatinina sérica ≤ 1,5 x LSN o aclaramiento de creatinina ≥ 60 ml/min. Se utilizará la fórmula de Cockcroft-Gault para calcular el aclaramiento de creatinina. No es necesario recoger una muestra de orina de 24 horas, pero está permitido.
    • QTc ≤ 470 ms en mujeres y ≤ 450 ms en hombres
    • Tener la capacidad de recibir medicamentos por vía oral y estar dispuesto a registrar diariamente la adherencia al producto en investigación.
    E.4Principal exclusion criteria
    • Subjects have received prior docetaxel in unresectable or metastatic setting.
    • Mixed small-cell lung cancer and NSCLC histology
    • Previously identified driver mutation other than KRAS p.G12C for which an approved therapy is available (including EGFR, ALK, etc).
    • Active brain metastases. Subjects who have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to study day 1 are eligible if they meet all of the following criteria: a) residual neurological symptoms grade ≤ 2; b) on stable doses of dexamethasone or equivalent for at least 2 weeks, if applicable; and c) follow-up MRI performed within 30 days prior to enrollment shows no progression or new lesions appearing.
    • Leptomeningeal disease.
    • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures at a frequency greater than monthly. Patients with PleurX catheters in place may be considered for the study with Medical Monitor approval.

    Other Medical Conditions
    • Known history of Human Immunodeficiency Virus (HIV) infection
    • Exclusion of hepatitis infection based on the following results and/or criteria:
    a) Positive hepatitis B surface antigen (HepBsAg)
    b) Negative HepBsAg with a positive for hepatitis B core antibody (Hepatitis B core antibody testing is not required for screening, however if this is done and is positive, then hepatitis B surface antibody [Anti-HBs] testing is necessary. Undetectable anti HBs in this setting would suggest unclear and possible infection, and needs exclusion).
    c) Positive Hepatitis C virus antibody: Hepatitis C virus RNA by polymerase chain reaction is necessary. Detectable Hepatitis C virus RNA renders the subject ineligible.
    • Malignancy other than NSCLC within 3 years prior to randomization, with the exception of those with a negligible risk of metastases or death and treated with expected curative outcome.
    • Major surgery within 28 days of study day 1
    • Significant gastrointestinal disorder that results in significant malabsorption, requirement for intravenous alimentation, or inability to take oral medication.
    • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 6 months prior to study day 1, unstable arrhythmias or unstable angina.
    • Severe infections within 4 weeks prior to randomization including, but not limited to hospitalization for complications of infection, bacteremia or severe pneumonia.
    • Therapeutic oral or intravenous antibiotics within 2 weeks prior to randomization. Prophylactic antibiotics are allowed with Amgen medical monitor approval.
    • Current CTCAE version 5.0 grade ≥ 2 peripheral neuropathy
    Prior/Concomitant Therapy
    • Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to CTCAE version 5.0 grade 0 or 1, or to levels dictated in the eligibility criteria with the exception of alopecia (any grade allowed) or toxicities from prior anti-tumor therapy that are considered irreversible (defined as having been present and stable for > 6 months), endocrine adverse events that are stably maintained on appropriate replacement therapy.
    • Anti-tumor therapy within 4 weeks of study day 1; Please note that bisphosphonates or anti-Receptor Activator of Nuclear Factor Kappa Beta Ligand (anti RANKL) antibody therapy is allowed if needed for management of hypercalcemia or for prevention of skeletal events.
    • Therapeutic or palliative radiation therapy within 2 weeks of study day 1. Subjects must have recovered from all radiotherapy related toxicity to CTCAE version 5.0 grade 1 or less with the exception of alopecia (any grade of alopecia allowed).
    • Other investigational procedures are excluded
    • Previous treatment with AMG 510 or other KRAS G12C inhibitor
    • History of severe hypersensitivity to docetaxel or to other drugs formulated with polysorbate 80, or known sensitivity to any of the products or components to be administered during dosing.
    • Los sujetos han recibido tratamiento previo con docetaxel en el contexto no resecable o metastásico.
    • Cáncer de pulmón microcítico mixto e histología de CPNM.
    • Mutación impulsora, identificada anteriormente, que no sea la p.G12C del KRAS y para la que se disponga de un tratamiento aprobado (incluidos EGFR, ALK, etc.).
    • Metástasis cerebrales activas. Los sujetos con metástasis cerebrales resecadas o que han recibido radioterapia hasta al menos 4 semanas antes del día 1 del estudio son elegibles si cumplen todos los criterios siguientes: a) presentan síntomas neurológicos residuales de grado ≤ 2, b) han recibido tratamiento con dosis estables de dexametasona o equivalente durante al menos 2 semanas, si procede, y c) la RM de seguimiento realizada en los 30 días previos a la inclusión no muestra progresión ni nuevas lesiones.
    • Enfermedad leptomeníngea.
    • Derrame pleural no controlado, derrame pericárdico o ascitis que requiera procedimientos de drenaje recurrentes con una frecuencia superior a una vez al mes. Se puede considerar la posibilidad de incluir a los pacientes con catéteres PleurX implantados tras la aprobación del monitor médico.

    Otras enfermedades
    • Antecedentes conocidos de infección por el virus de la inmunodeficiencia humana (VIH).
    • Exclusión de la infección por hepatitis según los resultados y/o criterios siguientes:
    a) Positivo para el antígeno de superficie de la hepatitis B (HepBsAg)
    b) Negativo para el HepBsAg y positivo para el anticuerpo del núcleo de la hepatitis B (no es necesario realizar pruebas para detectar el anticuerpo del núcleo de la hepatitis B en la selección, pero si se realizan y dan positivo, entonces se deben realizar pruebas para detectar el anticuerpo de superficie de la hepatitis B [anti-HBs]. En este contexto, la no detección del anti-HBs sugiere una posible infección incierta que se debe descartar).
    c) Positivo para anticuerpos del virus de la hepatitis C: se requiere determinar el ARN del virus de la hepatitis C mediante reacción en cadena de la polimerasa. La detección del ARN del virus de la hepatitis C hace inelegible al sujeto.
    • Tumores malignos distintos del CPNM en los 3 años previos a la aleatorización, salvo los que presentan un riesgo mínimo de metástasis o muerte y tratados con expectativas curativas.
    • Cirugía mayor en los 28 días previos al día 1 del estudio.
    • Trastorno gastrointestinal significativo que produce una malabsorción significativa, necesidad de alimentación por vía intravenosa o incapacidad de recibir medicación por vía oral.
    • Enfermedad cardiovascular significativa, como cardiopatía (de clase II o superior) de acuerdo con los criterios de la New York Heart Association, infarto de miocardio en los 6 meses previos al día 1 del estudio, arritmias inestables o angina inestable.
    • Infecciones graves en las 4 semanas previas a la aleatorización, incluidas, entre otras, hospitalización por complicaciones de la infección, bacteriemia o neumonía grave.
    • Antibióticos intravenosos u orales terapéuticos en las 2 semanas previas a la aleatorización. Se permite el uso de antibióticos profilácticos tras la
    aprobación del monitor médico de Amgen.
    • Neuropatía periférica de grado ≥ 2 actual según los criterios CTCAE
    Tratamiento previo/concomitante
    • Toxicidades no resueltas derivadas de un tratamiento antitumoral previo, definidas por no haberse resuelto hasta el grado 0 o 1 de los criterios CTCAE, versión 5.0, o hasta los niveles dictados en los criterios de elegibilidad, con la excepción de alopecia (se permite cualquier grado de alopecia), o toxicidades derivadas de un tratamiento antitumoral previo que se consideren irreversibles (definidas por haber estado presentes y estables durante > 6 meses) y acontecimientos adversos endocrinos que se mantengan estables con el tratamiento sustitutivo adecuado.
    • Tratamiento antitumoral en las 4 semanas previas al día 1 del estudio. Debe tenerse en cuenta que se permite el tratamiento con bisfosfonatos o un anticuerpo antiligando del receptor activador del factor nuclear kappa-β (anti-RANKL) si es necesario para el tratamiento de la hipercalcemia o para la prevención de acontecimientos esqueléticos.
    • Radioterapia terapéutica o paliativa en las 2 semanas previas al día 1 del estudio. Los sujetos se deben haber recuperado de todas las toxicidades
    relacionadas con la radioterapia hasta el grado 1 o inferior de los criterios CTCAE, versión 5.0, con la excepción de la alopecia (se permite cualquier grado de alopecia).
    • Se excluyen otros procedimientos de investigación.
    • Tratamiento previo con AMG 510 u otro inhibidor del KRASG12C.
    • Antecedentes de hipersensibilidad grave a docetaxel o a otros fármacos formulados con polisorbato 80 o sensibilidad conocida a alguno de los productos o componentes que se van a administrar durante el tratamiento.
    E.5 End points
    E.5.1Primary end point(s)
    • PFS - defined as time from randomization until disease progression or death from any cause, whichever occurs first for all subjects.
    • SLP - definida como el tiempo desde la aleatorización hasta la progresión de la enfermedad o la muerte por cualquier causa, lo que ocurra primero para cada sujeto.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The timing for the PA of PFS will be event driven. If PFS early success is achieved in the IA, the IA will serve the purpose of PA of PFS.
    The final analysis of the study will be done when the last subject completes LTFU.
    La cadencia de la AP de la SLP será controlada por eventos. Si se logra el éxito temprano de SLP en la AI, la AI servirá para el propósito de PA de PFS.
    El análisis final del estudio se realizará cuando el último sujeto complete la pérdida de seguimiento.
    E.5.2Secondary end point(s)
    • Overall survival - defined as time from randomization until death from any cause.
    • Objective response (complete response [CR] + partial response [PR]), assessed per RECIST v1.1. Response will be assessed by BICR.
    • Change from baseline over time to week 12 in disease related symptoms of:
    o Dyspnea as measured by a 4 item dyspnea domain from QLQ-C30 and QLQ-LC13
    o Cough as measured by QLQ-LC13
    o Chest Pain as measured by QLQ-LC13
    • Change from baseline over time to week 12 in
    o Physical functioning as measured by QLQ-C30
    o Global health status as measured by QLQ-C30
    • Duration of response - defined as time from first evidence of PR or CR to disease progression or death due to any cause, whichever occurs first.
    • Supervivencia global, definida como el tiempo desde la aleatorización hasta la muerte por cualquier causa.
    • Respuesta objetiva (respuesta completa [RC] + respuesta parcial [RP]), evaluada según los criterios RECIST v 1.1. La respuesta se evaluará mediante la RCEI.
    • Cambio con el tiempo desde el valor basal hasta la semana 12 en los síntomas relacionados con la enfermedad de:
    o Disnea, medida según un dominio de disnea de 4 elementos del QLQ-C30 y QLQ-LC13.
    o Tos, medida con el QLQ-LC13.
    o Dolor torácico, medido con el QLQ-LC13.
    • Cambio con el tiempo desde el valor basal hasta la semana 12 en:
    o Función física, medida con el QLQ-C30.
    o Estado de salud global, medido con el QLQ-C30.
    • Duración de la respuesta, definida como el tiempo desde la primera evidencia de RP o RC hasta la progresión de la enfermedad o la muerte por cualquier causa, lo que ocurra primero.
    E.5.2.1Timepoint(s) of evaluation of this end point
    The timing for the PA of PFS will be event driven. If PFS early success is achieved in the IA, the IA will serve the purpose of PA of PFS.
    The final analysis of the study will be done when the last subject completes LTFU.
    La cadencia de la AP de la SLP será controlada por eventos. Si se logra el éxito temprano de SLP en la AI, la AI servirá para el propósito de PA de PFS.
    El análisis final del estudio se realizará cuando el último sujeto complete la pérdida de seguimiento.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Docetaxel
    Docetaxel
    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 EEA160
    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
    Belgium
    Brazil
    Canada
    China
    Denmark
    Finland
    France
    Germany
    Greece
    Hungary
    Italy
    Japan
    Korea, Democratic People's Republic of
    Netherlands
    Poland
    Portugal
    Russian Federation
    Spain
    Sweden
    Switzerland
    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
    The end of study visit for an individual subject is defined as the date of the final study contact (eg, LFTU visit) when assessments or procedures are done.
    La visita de fin de estudio para un sujeto individual se define como la fecha del contacto final del estudio (por ejemplo, visita de LFTU) cuando se realizan evaluaciones o procedimientos.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days16
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months6
    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: 500
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 150
    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 state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 400
    F.4.2.2In the whole clinical trial 650
    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)
    N/A
    N/A
    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 Decision2020-05-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-05-07
    P. End of Trial
    P.End of Trial StatusOngoing
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