E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced or metastatic squamous or nonsquamous non- small cell lung cancer (NSCLC) |
Cáncer de Pulmón no microcítico escamoso o no escamoso, metastásico o localmente avanzado (CPNM) |
|
E.1.1.1 | Medical condition in easily understood language |
NSCLC is a common type of lung cancer and can be defined as squamous or non-squamous, depending on the type of cells involved. Locally advanced or metastatic is cancer starting to spread. |
Cáncer Pulmón no microcítico:tipo frecuente cáncer de pulmón que se define como escamoso/no escamoso según las células implicadas.Cáncer metastásico/localmente avanzado es el que empieza a extenderse |
|
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 | 10029520 |
E.1.2 | Term | Non-small cell lung cancer stage IIIA |
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 | 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 | LLT |
E.1.2 | Classification code | 10066490 |
E.1.2 | Term | Progression of non-small cell lung cancer |
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 | 10029521 |
E.1.2 | Term | Non-small cell lung cancer stage IIIB |
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 | 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) |
|
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
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 |
Expansion Phase: Cohort B (sequential administration): determine antitumor activity of MEDI4736 in combination with tremelimumab in subjects who have received 1 prior line of treatment who are immunotherapy naïve, with non-EGFR mutation +ve/non-ALK rearrangement +ve, PD-L1-negative advanced non-squamous NSCLC Cohort C: determine the safety profile of MEDI4736/ tremelimumab combination at the recommended dose, using the Q4W dosing schedule in subjects with NSCLC who have received up to 3 prior lines of systemic therapy and failed PD-1/PD-L1 monotherapy Cohort C: determine antitumor activity of MEDI4736 in combination with tremelimumab at the recommended dose using Q4W dosing schedule in subjects with advanced NSCLC who have received up to 3 prior lines of systemic therapy and failed PD-1/PD-L1 monotherapy. Dose-expansion Cohorts: evaluate the safety profile of MEDI4736 monotherapy in subjects who have experienced irAEs after discontinuing MEDI4736 in combination with tremelimumab |
fase ampliación dosis: Cohorte B (administr. secuencial): Det. actividad antitumoral MEDI4736 y tremelimumab en politerapia en pacs. que han recibido 1 línea tto. anterior, que no han recibido inmunoterapia,sin mut. + RFCE y sin reordenamiento + ALK, con CPNM avanzado no escamoso y PD-L1 negativos . Cohorte C: Det. perfil seguridad MEDI4736 y tremelimumab en politerapia a dosis recomendada usando pauta C4S administrada a pacs. con CPNM que han recibido un máx. 3 líneas anteriores tto. sistémico y cuya monoterapia con PD-1/PD-L1 ha fracasado. Cohorte C: Det. actividad antitumoral MEDI4736 y tremelimumab en politerapia a dosis recomendada usando pauta C4S administrada a pacs. con CPNM que han recibido un máx. de 3 líneas anteriores tto. sistémico y cuya monoterapia con PD-1/PD-L1 ha fracasado. Cohortes ampliación dosis: det. perfil seguridad MEDI4736 en monoterapia en pacs. que han experimentado un AAni tras interrumpir tto. con MEDI4736 y tremelimumab en politerapia |
|
E.2.2 | Secondary objectives of the trial |
Cohort B (sequential admin): ?Evaluate antitumor activity of the MEDI4736/tremelimumab recommended dose combination (Q4W schedule) in subjects with 1 prior line of treatment, non-EGFR mutation +ve/non-ALK rearrangement +ve advanced non-squamous NSCLC regardless of PD-L1 status ?Determine the safety profile of the MEDI4736/tremelimumab combination in non-squamous NSCLC subjects ?Evaluate candidate, predictive, and/or prognostic biomarkers in immunotherapy-naïve, non-EGFR mutation +ve/non-ALK rearrangement +ve, advanced non-squamous NSCLC subjects for correlation with MEDI4736/tremelimumab combination activity Cohort C: Evaluate antitumor activity of the MEDI4736/tremelimumab combination in advanced NSCLC subjects who failed PD-1/PD-L1 monotherapy PK of: ?MEDI4736 in combination with tremelimumab ?tremelimumab in combination with MEDI4736 Determine the immunogenicity of MEDI4736 in combination with Tremelimumab and of tremelimumab in combination with MEDI473 |
Cohorte B (adm.secuencial): evaluar actividad antitumoral MEDI4736/tremelimumab politerapia dosis recomendada y usando pauta C4S en pacs. que han recibido 1 línea tto. anterior,CPNM avanzado no escamoso sin mut.+ RFCE y sin reordenamiento+ ALK,independientemente estado PD-L1 Det. perfil seguridad MEDI4736/tremelimumab politerapia en pacs. CPNM no escamoso Evaluar biomarcadores candidatos,predictivos y/o pronósticos en la población total pacs. con tumores CPNM avanzados no escamosos que no habían recibido inmunoterapia con anterioridad, sin mut.+ RFCE/reordenamiento + ALK, que se pueden correlacionar con la actividad MEDI4736/tremelimumab en politerapia Cohorte C: evaluar actividad antitumoral MEDI4736/tremelimumab politerapia en pacs. cuyo CPNM avanzado no ha respondido a monoterapia con PD-1/PD-L1 FC MEDI4736/tremelimumab en politerapia FC tremelimumab en combinación con MEDI4736 Det. inmunogenicidad MEDI4736/tremelimumab en politerapia y tremelimumab/MEDI4736 en politerapia |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ? 18 years 2. Histologically confirmed locally advanced or metastatic squamous or nonsquamous NSCLC 3. ECOG performance status of 0 or 1 4. At least 1 measurable lesion according to RECIST Version 1.1 5. At least 1 lesion amenable to biopsy at screening 6. Adequate organ and marrow function |
1. Edad > =18 años 2. Padecer un CPNM metastásico o localmente avanzado confirmado histológicamente (escamoso y no escamoso) 3. Estado funcional del Eastern Cooperative Oncology Group (ECOG) de 0 o 1 4. Al menos 1 lesión mensurable según RECIST v1.1. 5. Al menos 1 lesión apta para biopsia durante la selección 6. Deben conservar unas funciones orgánicas y de médula ósea adecuadas |
|
E.4 | Principal exclusion criteria |
1. Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment 2. Current or prior use of immunosuppressive medication within 14 days before the first dose of study drug 3. Active or prior documented autoimmune disease within the last 2 years 4. Major surgical procedure within 28 days prior to the first dose of study drug |
1. Cualquier quimioterapia, inmunoterapia, terapia biológica u hormonal concomitante para el tratamiento del cáncer 2. Uso previo o actual de medicamentos inmunosupresores durante los 14 días anteriores a la administración primera dosis de medicación del estudio 3. Trastornos autoinmunitarios activos o previos documentados durante los últimos 2 años 4. Cirugía mayor durante los 28 días anteriores a la administración de la primera dosis de medicación del estudio |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Cohort C: The endpoints for safety will include adverse events (AEs), serious adverse events (SAEs), laboratory evaluations, vital signs, physical examinations, and electrocardiogram (ECG) results.
Cohort B (sequential administration) and Cohort C: Objective response (OR) based on RECIST Version 1.1 |
Cohorte C: Los criterios de valoración de la seguridad serán: los acontecimientos adversos (AA), los acontecimientos adversos graves (AAG), los análisis de laboratorio, las constantes vitales, las exploraciones físicas y los resultados del electrocardiograma (ECG). Cohorte B (administración secuencial) y cohorte C: Respuesta objetiva (RO) determinada según RECIST v1.1. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Cohort C: Safety Evaluations take place at Screening, Cycle 1 (Days 1,2, 8, 15 and 22) then Day 1 and Day 22 of each cycle through Cycle 13. ECG testing takes place at Screening, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 7 Day 1, and Cycle 13 Day 1
Cohort B: Objective response as determined by radiographic disease assessment per RECIST Version 1.1 at Screening and every 8 weeks thereafter as per protocol |
Cohorte C: las evaluaciones de seguridad tendrán lugar en la selección, Ciclo 1 (días 1, 2, 8, 15 y 22), y el día 1 y 22 de cada ciclo hasta el ciclo 13. Los ECG se realizarán en la selección, ciclo 3 día 1, ciclo 4 día 1, ciclo 7 día 1 y ciclo 13 día 1. Cohorte B: respuesta objetiva documentada mediante evaluación radiográfica de la enfermedad según RECIST versión 1.1 en la selección y cada 8 semanas de acuerdo con el protocolo |
|
E.5.2 | Secondary end point(s) |
The endpoints for assessment of antitumor activity include: ? Dose-expansion Cohort B (sequential administration) and Cohort C: - OR as determined by the investigator based on RECIST v1.1. - Duration of response (DoR), disease control (DC), and progression-free survival (PFS) based on RECIST v1.1 by investigator and BICR, and overall survival (OS). ? Dose-expansion Cohort B (sequential administration) ? The endpoints for safety will include AEs, SAEs, laboratory evaluations, vital signs, physical examinations, and electrocardiogram (ECG) results. ? The endpoints related to candidate predictive and/or prognostic biomarkers in dose-expansion Cohort B (sequential administration) are likely to focus on tissue-based, protein or gene expression measures and peripheral gene signatures including, but not limited to: ? PD-L1 expression / localization on tumor membrane and tumor-infiltrating immune cells within the tumor microenvironment ? IHC measures of markers associated with infiltrating immune cells (eg, Cluster of Differentiation 8) ? Gene expression signatures associated with adaptive response (eg, IFNGamma and related genes) ? The endpoints for assessment of PK of MEDI4736 and tremelimumab include individual MEDI4736 and tremelimumab concentrations in serum and PK parameters including CmaxAUC), clearance, and half-life (t½). ? The endpoints for assessment of immunogenicity of MEDI4736 and tremelimumab include the number and percentage of subjects who develop detectable ADAs. |
Los criterios de valoración de la actividad antitumoral son: Cohorte B (administración secuencial) y cohorte C de ampliación de la dosis: - RO determinada por el investigador según RECIST v1.1. - Duración de la respuesta (DdR), control de la enfermedad (CE) y la supervivencia sin progresión (SSP) de acuerdo con los criterios RECIST v.1.1 determinados por el investigador y RCIE, así como la supervivencia global (SG). Cohorte B de ampliación de la dosis (administración secuencial) Los criterios de valoración de la seguridad serán los AA, los AAG, los análisis de laboratorio, las constantes vitales, las exploraciones físicas y los resultados del electrocardiograma (ECG). Es probable que los criterios de valoración relacionados con los biomarcadores candidatos, predictivos y/o pronósticos en la cohorte B de ampliación de la dosis (administración secuencial) se centren en las medidas de la expresión génica, tisular o proteínica y en los patrones génicos periféricos, entre otros: Expresión de PD-L1 / ubicación en la membrana tumoral y los inmunocitos infiltrantes de tumor dentro del microambiente tumoral Medidas IHQ de marcadores asociados con inmunocitos infiltrantes (p. ej., grupo de diferenciación 8) Patrones de expresión génica asociado con la respuesta de adaptación (p. ej., IFN-? y genes relacionados). Los criterios de valoración de la FC de MEDI4736 y tremelimumab son las concentraciones individuales de MEDI4736 y tremelimumab en suero, así como parámetros farmacocinéticos tales como la concentración máxima (Cmax), el área bajo la curva de concentración y tiempo (AUC), el aclaramiento y la semivida (t½). Los criterios de valoración de la inmunogenicidad de MEDI4736 y tremelimumab son el número y porcentaje de pacientes que desarrollen ACF detectables |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Screening through 5 years after the last subject receives the first dose of study medication |
Durante el período de 5 años desde que el último paciente inicie el tratamiento del estudio |
|
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 | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Phase Ib - Including exploratory therapy |
Fase 1b incluyendo terapia exploratoria |
|
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 | No |
E.8.1.1 | Randomised | No |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 37 |
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 |
Canada |
France |
Germany |
Italy |
Korea, Republic of |
Spain |
United Kingdom |
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
|
As per protocol: The end of the study (?study completion?) is defined as 5 years after the last subject begins treatment or the date the study is closed by the sponsor, whichever occurs first. |
De acuerdo con el protocolo: El final del estudio («finalización del estudio») se entiende como el transcurso de 5 años desde que el último paciente inicie el tratamiento o desde la fecha en que el promotor concluya el estudio, lo que ocurra primero |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 | 0 |