E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced or metastatic non-small cell lung cancer (NSCLC) |
Cáncer de pulmón no microcítico (CPNM) localmente avanzado irresecable o metastásico |
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E.1.1.1 | Medical condition in easily understood language |
NSCLC is a type of lung cancer |
CPNM es un tipo de cáncer de pulmón |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059515 |
E.1.2 | Term | Non-small cell lung cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•To evaluate the efficacy of MTIG7192A plus atezolizumab compared with placebo plus atezolizumab |
•Evaluar la eficacia de MTIG7192A más atezolizumab en comparación con placebo más atezolizumab |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the safety and tolerability of MTIG7192A plus atezolizumab compared with placebo plus atezolizumab •To characterize the pharmacokinetic (PK) profile of MTIG7192A and atezolizumab •To evaluate the immune response to MTIG7192A and atezolizumab |
•Evaluar la seguridad y la tolerabilidad de MTIG7192A más Atezolizumab en comparación con placebo más Atezolizumab. •Determinar el perfil farmacocinético de MTIG7192A y atezolizumab. •Evaluar la respuesta inmunitaria a MTIG7192A y atezolizumab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age >= 18 years - Eastern Cooperative Oncology Group Performance Status of 0 or 1 - Histologically or cytologically documented locally advanced unresectable NSCLC, recurrent, or metastatic NSCLC - No prior systemic treatment for locally advanced unresectable or metastatic NSCLC - Tumor PD-L1 expression on previously obtained archival tumor tissue or tissue obtained from a biopsy at screening - Confirmed availability of representative tumor specimens, along with an associated pathology report. - Measurable disease as defined by RECIST v1.1 - Life expectancy >=12 weeks - Adequate hematologic and end-organ function - For women of childbearing potential: Women must remain abstinent or use contraceptive methods during the treatment period and for at least 5 months after the last dose of study drugs - For men: men must remain abstinent or use a condom during the treatment period and for at least 90 days after the last dose of study treatment |
-Edad >= 18 años. -Estado funcional según la escala del ECOG de 0 o 1. -CPNM irresecable localmente avanzado,recidivante o metastásico -No haber recibido tratamiento sistémico previo para el CPNM localmente avanzado irresecable o metastásico. -Expresión tumoral de PD-L1 en tejido tumoral de archivo o reciente obtenido mediante biopsia durante la selección. -Disponibilidad confirmada de muestras tumorales representativas, con el informe anatomopatológico correspondiente -Enfermedad mensurable, definida conforme a los criterios RECIST, versión 1.1. -Esperanza de vida >= 12 semanas. -Función hematológica y de órganos efectores adecuada -Mujeres en edad fértil: compromiso de practicar abstinencia sexual o usar de métodos anticonceptivos durante el período de tratamiento y hasta al menos 5 meses después de la última dosis de los fármacos del estudio -Varones: compromiso de practicar abstinencia sexual o uso de métodos anticonceptivos durante el período de tratamiento y hasta al menos 90 días después de la última dosis del tratamiento del estudio |
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E.4 | Principal exclusion criteria |
- Patients with NSCLC known to have a sensitizing mutation in the EGFR gene or an ALK fusion oncogene - Symptomatic, untreated, or actively progressing CNS metastases - Spinal cord compression not definitively treated with surgery and/or radiation - History of leptomeningeal disease - Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures - Uncontrolled tumor-related pain - Uncontrolled hypercalcemia or symptomatic hypercalcemia - Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and/or treated with expected curative outcome General Medical Exclusions - Inability to comply with study and/or follow-up procedures - Pregnant, lactating, or breastfeeding women - Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results - Known clinically significant liver disease or current alcohol abuse - Significant cardiovascular disease - Severe infections within 4 weeks prior to initiation of study treatment - Received oral or IV antibiotics (including antifungals) within 2 weeks prior to randomization - Major surgical procedure within 4 weeks prior to randomization, or anticipation of need for a major surgical procedure during the study - Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug that may affect the interpretation of the results, or that may render the patient at high risk from treatment complications Treatment-Specific Exclusions - History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins - Known hypersensitivity or allergy to CHO cell products or any component of the atezolizumab formulation - Active or history of autoimmune disease - Prior allogeneic bone marrow transplantation or prior solid organ transplantation - History of idiopathic pulmonary fibrosis (including pneumonitis), organizing pneumonia drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis - Positive test for HIV at screening - Patients with active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection - Active tuberculosis - Administration of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment - Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to randomization |
-Pacientes portadores de mutaciones sensibilizadoras del gen EGFR o de un oncogén de fusión de ALK -Metástasis en el sistema nervioso central (SNC) sintomáticas, no tratadas o en progresión activa. -Compresión medular no tratada de forma definitiva con cirugía o radioterapia -Antecedentes de afectación leptomeníngea -Derrame pleural, derrame pericárdico o ascitis no controlados que necesitan procedimientos de drenaje repetidos -Dolor no controlado relacionado con el tumo -Hipercalcemia no controlada o hipercalcemia sintomática -Tumores malignos distintos del CPNM en los 5 años previos a la aleatorización, a excepción de aquellos con un riesgo insignificante de metástasis o muerte o tratados con intención curativa
*Criterios de exclusión médicos generales -Incapacidad para cumplir los procedimientos del estudio o del seguimiento. -Mujeres embarazadas, lactantes o que están amamantando. -Signos de enfermedad concomitante importante y no controlada que pueda afectar al cumplimiento del protocolo o a la interpretación de los resultados -Hepatopatía conocida con importancia clínica o alcoholismo activo. -Enfermedad cardiovascular importante -Infecciones graves en las 4 semanas previas al inicio del tratamiento del estudio -Tratamiento con antibióticos orales o IV (incluidos antifúngicos) en las 2 semanas previas a la aleatorización. - Intervención de cirugía mayor practicada en las 4 semanas previas a la aleatorización o previsión de la necesidad de una intervención de este tipo durante el estudio. -Cualquier otra enfermedad, disfunción metabólica, signo en la exploración física o dato analítico que suscite sospechas razonables de una enfermedad o proceso que contraindique el uso de un fármaco en investigación o que pueda afectar a la interpretación de los resultados o suponer un riesgo elevado de sufrir complicaciones del tratamiento para el paciente.
*Exclusiones relacionados con el tratamiento -Antecedentes de reacciones alérgicas, anafilácticas o de hipersensibilidad graves a proteínas de fusión o anticuerpos humanizados o quiméricos. -Hipersensibilidad o alergia conocida a productos procedentes de células ováricas de hámster chino (CHO) o a cualquier componente de la formulación de atezolizumab -Enfermedad autoinmunitaria activa o previa -Antecedente de alotrasplante de médula ósea o trasplante de órgano sólido. -Antecedentes de fibrosis pulmonar idiopática (incluida neumonitis), neumonía organizada , neumonitis de origen medicamentoso, neumonitis idiopática o signos de neumonitis activa -Resultado positivo en las pruebas de VIH en la selección -Pacientes con infección activa por el VHB ó con infección activa por el VHC -Tuberculosis activa. -Administración de una vacuna de virus vivos atenuados en las 4 semanas previas al inicio del tratamiento del estudio -Tratamiento con corticosteroides sistémicos u otros inmunodepresores sistémicos en las 2 semanas previas a la aleatorización. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Objective response rate 2. Progression-free survival |
1. Tasa de respuesta Objetiva(TRO) 2. Supervivencia libre de progresión (SSP) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1-2. Up to 5 years |
1-2. Hasta 5 años |
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E.5.2 | Secondary end point(s) |
1. Duration of objective response 2. Overall survival 3. Incidence, nature, and severity of adverse events, graded according to the NCI CTCAE v4.0 4. Clinically significant changes from baseline in vital signs, physical findings, and clinical laboratory results 5. Serum concentrations of MTIG7192A or atezolizumab 6. Incidence of treatment-emergent Anti-drug antibody |
1. Duración de la respuesta Objetiva 2. Supervivencia global 3.Incidencia, naturaleza e intensidad de los acontecimientos adversos, clasificados conforme a los CTCAE del NCI, versión 4.0. 4.Variaciones clínicamente significativas con respecto al momento basal de las constantes vitales, los hallazgos físicos y los resultados analíticos durante 5.Concentración sérica de MTIG7192A o atezolizumab 6.Incidencia de ACF (anticuerpos contra el fármaco)surgidos durante el tratamiento |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-4. Up to 5 years 5-6. Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1, at treatment discontinuation visit |
1-4. Hasta 5 años 5.6 Ciclo 1 día 1, Ciclo 2 día 1, Ciclo 4 día 1, Ciclo 12 día 1 y en la visita de discontinuación de tratamiento |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Brazil |
France |
Korea, Republic of |
Poland |
Romania |
Serbia |
Spain |
Taiwan |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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 this study is defined as the date when the last data required for all study analysis are collected. |
El final de este estudio se define como la fecha en que se recojan los últimos datos necesarios para todos los análisis del estudio. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |