| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| First Line Non-Small Cell Lung Cancer |
| Primera línea del cáncer de pulmón |
|
| E.1.1.1 | Medical condition in easily understood language |
| First Line Non-Small Cell Lung Cancer |
| primera línea del cáncer de pulmón |
|
| 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 | 18.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10029522 |
| E.1.2 | Term | Non-small cell lung cancer stage IV |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 18.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10029515 |
| E.1.2 | Term | Non-small cell lung cancer recurrent |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 18.1 |
| 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) |
|
| 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 demonstrate superiority with regard to PFS based on an Independent Review Committee assessment of avelumab versus platinum-based doublet in NSCLC subjects with PD-L1+ |
| Demostrar, basándose en la evaluación de un Comité de revisión independiente, la superioridad con respecto a la SSP de avelumab frente a un doblete con base de platino en sujetos con CPNM con PD-L1+ |
|
| E.2.2 | Secondary objectives of the trial |
Secondary objectives are as follows:
? To demonstrate superiority with regard to PFS of avelumab in PD-L1++ (at least 25% PD L1 positive tumor cells with at least 2+ staining intensity) subjects
? To demonstrate superiority in the objective response rate (ORR) by RECIST 1.1 of avelumab versus chemotherapy in PD-L1+ subjects
? To demonstrate superiority in overall survival (OS) of avelumab versus chemotherapy in PD-L1+ subjects
? To compare the subject-reported outcomes / quality of life when treated with avelumab versus chemotherapy using the European Quality of Life (EuroQOL) 5-dimensions questionnaire (EQ 5D), and the European Organization for Research and Treatment of Cancer (EORTC) QLQ C30 and module QLQ-LC13 in the intent to treat (ITT) population
? To determine the safety and tolerability of avelumab |
Los objetivos secundarios son los siguientes:
- Demostrar la superioridad de avelumab con respecto a la SSP en sujetos con PD-L1++ (cuando al menos el 25 % de las células tumorales presentan PD-L1 con una intensidad en la tinción a partir de grado 2)
- Demostrar la superioridad de la tasa de respuesta objetiva (TRO) según los RECIST
1.1 de avelumab frente a la quimioterapia en sujetos con PD-L1+
- Demostrar la superioridad de la supervivencia general (SG) de avelumab frente a la quimioterapia en sujetos con PD-L1+
- Comparar los resultados comunicados por el sujeto y la calidad de vida cuando se ha tratado con avelumab frente a la quimioterapia, mediante el cuestionario europeo sobre calidad de vida (EuroQoL) de 5 dimensiones (EQ-5D), el QLQ-C30 de la Organización Europea para la Investigación y el Tratamiento del Cáncer (EORTC) y el módulo QLQ-LC13 entre la población con intención de tratar (ITT)
- Determinar la seguridad y la tolerabilidad de avelumab |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Key inclusion criteria:
Male or female subjects ? 18 years, with an ECOG PS of 0 to 1 at trial entry, with the availability of a formalin-fixed, paraffin-embedded block containing tumor tissue or 7 (preferably 10) unstained tumor slides with PD-L1+, at least 1 measurable tumor lesion, and with histologically confirmed metastatic or recurrent NSCLC. Subjects must not have received any treatment for systemic lung cancer, and have an estimated life expectancy of more than 12 weeks.
Other protocol defined criteria could apply |
Criterios de inclusión principales:
Hombres o mujeres a partir de 18 años, con EG ECOG entre 0 y 1 al incorporarse al ensayo, de los que se disponga un bloque de biopsia fijada con formol e incluida en parafina de tejido tumoral o 7 (preferentemente 10) secciones de tumor sin tinción con PD-L1+, al menos 1 lesión medible, y CPNM metastásico o recidivante confirmado por histología. Los sujetos no podrán haber recibido ningún tratamiento sistémico para el cáncer de pulmón y su esperanza de vida estimada deberá ser superior a 12 semanas. |
|
| E.4 | Principal exclusion criteria |
Key exclusion criteria:
Subjects whose disease harbors an activating EFGR mutation, or with non-squamous cell NSCLC whose disease harbors and anaplastic lymphoma kinase (ALK) rearrangement are not eligible. Other exclusion criteria include prior therapy with any antibody or drug targeting T cell coregulatory proteins, concurrent anticancer treatment, or immunosuppressive agents, known severe hypersensitivity reactions to monoclonal antibodies (Grade ? 3 NCI CTCAE v 4.03), history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma), and persisting toxicity related to prior therapy of Grade > 1 NCI-CTCAE v 4.03. Subjects with brain metastases are excluded, except those meeting the following criteria: brain metastases that have been treated locally and have not been progressing at least 2 months after completion of therapy, do not require steroid maintenance therapy, and do not have ongoing neurological symptoms that are related to the brain localization of the disease.
Other protocol defined criteria could apply |
Criterios de exclusión principales:
No son aptos los sujetos portadores de mutaciones activadoras del gen EGFR, ni aquellos con CPNM no epidermoide que presenten reordenación del gen de la cinasa del linfoma anaplásico (ALK). Otros criterios de exclusión incluyen tratamiento previo con cualquier anticuerpo o fármaco dirigido a las proteínas correguladoras de los linfocitos T, tratamiento concurrente contra el cáncer o inmunosupresores, reacciones conocidas de hipersensibilidad grave a los anticuerpos monoclonales (de grado ? 3 según de los CTCAE del NCI), antecedentes de anafilaxia o asma incontrolable (es decir, con 3 o más características de asma parcialmente controlado) y toxicidades persistentes relacionadas con tratamientos anteriores de grado > 1 según la v 4.03 de los CTCAE del NCI. Se excluirá a los sujetos con metástasis cerebral, excepto a aquellos que cumplan los siguientes criterios: metástasis cerebrales tratadas que se encuentren clínicamente estables durante al menos 2 semanas antes de inscribirse. Los sujetos deberán haber dejado de tomar esteroides o sino, deberán estar tomando una dosis estable o en disminución < 10 mg diarios de prednisona (o equivalente), y que no presenten síntomas neurológicos continuados que estén relacionados con la ubicación de la enfermedad en el cerebro. Todas las posibles excepciones deben discutirse con el monitor médico de estudio antes de inscribirse. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression free survival time |
| Duración de la supervivencia |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Time from date of randomization until date of the first documentation of PD or death due to any cause in the absence of documented PD, whichever occurs first |
| Periodo entre la fecha de la aleatorización hasta la primera PE confirmada o la muerte por cualquier causa en ausencia de PE confirmada, lo que ocurra primero. |
|
| E.5.2 | Secondary end point(s) |
Secondary endpoints:
? Progression-free Survival in PD-L1++ ITT Subjects
? Best Overall Response
? Overall Survival
? Changes in Subject-reported Outcomes/Quality of Life (QoL) |
Los criterios de valoración secundarios son:
- la duración de la SSP en los sujetos con PD-L1++;
- la MRG según los criterios RECIST 1.1 y lo determinado por el CRI;
- la SG (el periodo desde la fecha de la aleatorización hasta la fecha de la muerte);
-cambios en los resultados comunicados por el sujeto y la calidad de vida (evaluados mediante los cuestionarios EQ-5D, EORTC QLQ-C30 y el módulo QLQ-LC13);
- los criterios de valoración de la seguridad (como los AA, las evaluaciones analíticas clínicas, las constantes vitales, la exploración física, los parámetros de ECG y el EG ECOG). |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Time from date of randomization until date of the first documentation of PD or death due to any cause in the absence of documented PD, whichever occurs first |
| Periodo entre la fecha de la aleatorización hasta la primera PE confirmada o la muerte por cualquier causa en ausencia de PE confirmada, lo que ocurra primero. |
|
| 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 | Yes |
| 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 | Yes |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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 | No |
| 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 | 114 |
| 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 |
| Australia |
| Belgium |
| Bulgaria |
| Canada |
| Chile |
| Colombia |
| Croatia |
| Czech Republic |
| Denmark |
| Estonia |
| France |
| Germany |
| Hungary |
| Ireland |
| Israel |
| Italy |
| Japan |
| Korea, Republic of |
| Latvia |
| Lithuania |
| Malaysia |
| Mexico |
| Netherlands |
| New Zealand |
| Peru |
| Poland |
| Portugal |
| Romania |
| Russian Federation |
| Singapore |
| Slovakia |
| South Africa |
| Spain |
| Taiwan |
| Thailand |
| Turkey |
| United Kingdom |
| United States |
|
| E.8.7 | Trial 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
|
| last patient last follow-up (5 years after last subject receives last dose of avelumab) |
| último paciente último seguimiento (5 años después del último sujeto recibe última dosis de avelumab) |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 7 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 23 |
| E.8.9.2 | In all countries concerned by the trial years | 7 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 23 |
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