E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage III non-small cell lung cancer |
Cáncer de pulmón no microcítico en fase III |
|
E.1.1.1 | Medical condition in easily understood language |
Non-small cell lung cancer |
Cáncer de pulmón no microcítico |
|
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 | 10029519 |
E.1.2 | Term | Non-small cell lung cancer stage III |
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 |
Clinical activity - To compare the antitumor activity of durvalumab alone vs durvalumab in combination with novel agents. |
Actividad Clínica - Comparar la actividad antitumoral de durvalumab en monoterapia frente a durvalumab en combinación con fármacos novedosos. |
|
E.2.2 | Secondary objectives of the trial |
Safety - To evaluate the safety and tolerability of durvalumab alone and durvalumab in combination with novel agents.
Clinical activity - To further compare the efficacy of durvalumab alone vs durvalumab in combination with novel agents.
Pharmacokinetics (a) To describe the pharmacokinetics (PK) of durvalumab alone and durvalumab in combination with novel agents. (b) To describe the PK of novel agents in combination with durvalumab.
Immunogenicity (a) To assess the immunogenicity of durvalumab alone or in combination with novel agents (b) To assess the immunogenicity of novel biologic agents in combination with durvalumab |
Seguridad - Evaluar la seguridad y la tolerabilidad de durvalumab en monoterapia y en combinación con fármacos novedosos.
Actividad clínica Comparar con más detenimiento la eficacia de durvalumab en monoterapia frente a durvalumab en combinación con fármacos novedosos. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent and any locally required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluation 2. Age 18 years or older 3. Body weight ≥ 35 kg 4. Subjects must have histologically or cytologically documented NSCLC who present with locally advanced, unresectable, Stage III disease 5. Subjects must have completed, without progressing, definitive cCRT within 28 days prior to being randomized into the study. 6. Subjects must have at least one previously irradiated tumor lesion that can be measured by RECIST v1.1 7. Provision of tumor tissue sample, when available, from original diagnosis obtained before initiation of chemoradiotherapy 8. Life expectancy ≥ 12 weeks 9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 |
1. Consentimiento informado por escrito, así como cualquier autorización local requerida, obtenidos del sujeto antes de la realización de cualquier procedimiento relacionado con el protocolo, incluidas las evaluaciones para la selección. 2. Tener 18 años o más. 3. Peso corporal ≥35 kg. 4. Los sujetos deberán padecer cáncer de pulmón no microcítico (CPNM) documentado histológica o citológicamente que se presente como enfermedad en estadio III, localmente avanzada y no resecable. 5. Los sujetos deberán haber completado, sin progresión de la enfermedad, un tratamiento de quimiorradioterapia concomitante (QRTc) en los 28 días previos a la aleatorización para el estudio. 6. Los sujetos deberán presentar al menos una lesión tumoral previamente irradiada, que se pueda medir mediante los criterios RECIST v1.1. 7. Disponibilidad de una muestra de tejido tumoral del diagnóstico original, cuando esté disponible, obtenida antes del inicio de la quimiorradioterapia. 8. Esperanza de vida ≥12 semanas. 9. Estado funcional de 0 o 1 según la puntuación del Grupo Oncológico Cooperativo (ECOG). |
|
E.4 | Principal exclusion criteria |
1. Mixed small cell and non-small cell lung cancer histology 2. Current or prior use of immunosuppressive medication within 14 days before the first dose of study drug. 3. Subjects with history of ≥ Grade 2 pneumonitis from prior chemoradiation therapy 4. Subjects with a history of venous thrombosis within the past 3 months 5. Subjects with history of myocardial infarction, transient ischemic attack, or stroke in the past 6 months 6. Congestive heart failure 7. Active or prior documented autoimmune or inflammatory disorders 8. History of active primary immunodeficiency 9. Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) 10. History of allogenic organ transplantation 11. QTcF interval ≥ 470 ms 12. History of another primary malignancy 13. Concurrent enrollment in another therapeutic clinical study or during the follow-up period of an interventional study. Enrollment in observational studies will be allowed 14. Females who are pregnant, lactating, or intend to become pregnant during their participation in the study |
1. Histología mixta microcítica y no microcítica del cáncer de pulmón. 2. Uso simultáneo o previo de medicación inmunosupresora en los 14 días previos a la primera dosis del fármaco del estudio. 3. Sujetos con antecedentes de neumonitis de grado ≥2 debido a la quimiorradioterapia previa. 4. Sujetos con antecedentes de flebotrombosis en los últimos 3 meses. 5. Sujetos con antecedentes de infarto de miocardio, accidente isquémico transitorio o accidente cerebrovascular en los últimos 6 meses. 6. Insuficiencia cardíaca congestiva. 7. Trastornos autoinmunitarios o inflamatorios activos o previos documentados. 8. Antecedentes de inmunodeficiencia primaria activa. 9. Infección activa, incluidas tuberculosis, hepatitis B, hepatitis C o por el virus de la inmunodeficiencia humana (VIH). 10. Antecedentes de trasplante alogénico de órganos. 11. Intervalo QTcF ≥470 ms. 12. Antecedentes de otra neoplasia maligna primaria. 13. Inclusión simultánea en otro estudio clínico terapéutico o durante el periodo de seguimiento de un estudio de intervención. Se permitirá la inclusión en estudios observacionales. 14. Mujeres embarazadas, en periodo de lactancia o que tengan intención de quedarse embarazada durante su participación en el estudio. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Clinical activity - Objective response (OR) per Response Evaluation Criteria for Solid Tumors version 1.1 (RECIST v1.1) |
Actividad clínica La respuesta objetiva (RO) según los Criterios de evaluación de la respuesta en tumores sólidos, versión 1.1 (RECIST v1.1). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From randomization until documention of disease progression, or the last evaluable disease assessment in the absence of PD prior to the initiation of subsequent anticancer therapy or discontinuation from the study, whichever occurs first. |
Desde la aleatorización hasta la documentación de la progresión de la enfermedad, o la última evaluación de la enfermedad evaluable en ausencia de progresión de la enfermedad antes del inicio de un tratamiento antineoplásico posterior o de la interrupción del estudio, lo que ocurra primero. |
|
E.5.2 | Secondary end point(s) |
Safety - Presence of adverse events (AEs), serious adverse events (SAEs), and abnormal laboratory parameters and vital signs.
Clinical activity - Duration of response (DoR), disease control (DC), progression-free survival (PFS) at 12 months, and PFS per RECIST v1.1 and overall survival (OS).
Pharmacokinetics - Concentration of durvalumab or novel agents in serum.
Immunogenicity - Antidrug antibody (ADA) incidence of durvalumab or novel biologic agents |
Seguridad - La presencia de acontecimientos adversos (AA), acontecimientos adversos graves (AAG), y constantes vitales y parámetros analíticos anómalos.
Actividad clínica - La duración de la respuesta (DdR), el control de la enfermedad (CE), la supervivencia sin progresión (SSP) a los 12 meses y la SSP según los RECIST v1.1, así como la supervivencia global (SG).
Farmacocinética - La concentración de durvalumab o de fármacos novedosos en suero.
Inmunogenia - La incidencia de anticuerpos antifármaco (AAF) contra durvalumab o biofármacos novedosos. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Safety - From time of informed consent through treatment period (12 months) or up to 3 months post last dose of study treatment.
DoR - From randomization until documention of disease progression.
DC - From randomization until progression, or the last evaluable disease assessment in the absence of PD prior to the initiation of subsequent anticancer therapy or discontinuation from the study, whichever occurs first.
PFS and OS - From start of treatment until study completion or death, whichever comes first.
Pharmacokinetics and immunogenicity - During the treatment period and follow-up. |
Seguridad: desde el consentimiento informado a lo largo del periodo de tratamiento (12 meses) o hasta 3 meses después de la última dosis del tratamiento del estudio. DR: desde la aleatorización hasta la documentación de progresión de la enfermedad. Control de la enfermedad (CE): desde la aleatorización hasta la progresión, o la última evaluación de la enfermedad evaluable en ausencia de progresión de la enfermedad antes del inicio de un tratamiento antineoplásico posterior o de la interrupción del estudio, lo que ocurra primero.
Supervivencia sin progresión (SSP) y supervivencia global (SG): desde el inicio del tratamiento hasta la finalización del estudio o la muerte, lo que suceda primero.
Farmacocinética e inmunogenicidad: durante el periodo de tratamiento y el seguimiento. |
|
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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity |
Inmunogenia |
|
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 | 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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Estudio de plataforma |
Platform study |
|
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 | 3 |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 42 |
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 |
Canada |
France |
Germany |
Hong Kong |
Italy |
Poland |
Portugal |
Spain |
Taiwan |
United States |
|
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 the study (“study completion”) is defined as the date of the last protocol-specified visit/assessment (including telephone contact) for the last subject in the study. This date will be 5 years after the final subject is entered into the study or when the sponsor stops the study, whichever occurs first. |
El fin del estudio (“conclusión del estudio”) se define como la fecha de la última visita o evaluación especificada en el protocolo (incluidos los contactos telefónicos) del último sujeto del estudio. Esta fecha será 5 años después de la entrada en el estudio del último sujeto o cuando el promotor detenga el estudio, lo que suceda antes. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |