| 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) in treatment naiive patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild type tumour pathology. |
| Pacientes con CPNM avanzado o metastásico sin mutaciones en el receptor del factor de crecimiento epidérmico (EGFR) ni en la cinasa del linfoma anaplásico (ALK). |
|
| E.1.1.1 | Medical condition in easily understood language |
| Specific type of lung cancer called "non-small cell lung cancer" (NSCLC) |
| Un tipo específico de cáncer de pulmón llamado "Cáncer de pulmón no microcítico) (CPNM) |
|
| 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 | LLT |
| E.1.2 | Classification code | 10025055 |
| E.1.2 | Term | Lung cancer non-small cell stage IV |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of PFS in patients with NSCLC |
| Evaluar la eficacia del tratamiento de combinación de MEDI4736 + tremelimumab en comparación con el Tratamiento Standar en términos de SLP en pacientes con CPNM. |
|
| E.2.2 | Secondary objectives of the trial |
To assess the efficacy of MEDI4736 + tremelimumab combination therapy or MEDI4736 monotherapy compared to SoC in terms of PFS, ORR, DoR, APF12, PFS2, and OS
To assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to MEDI4736 monotherapy in terms of PFS and ORR
To assess disease-related symptoms and HRQoL in patients treated with MEDI4736 + tremelimumab and MEDI4736 therapies compared to SoC using the EORTC QLQ C30 v3 and the LC13 module
To assess the PK of MEDI4736 + tremelimumab and MEDI4736 therapies
To investigate the immunogenicity of MEDI4736 and tremelimumab
To explore irRECIST as an assessment methodology for clinical benefit of MEDI4736 + tremelimumab compared to SoC with assessment by BICR
To assess the safety and tolerability profile of MEDI4736 + tremelimumab and MEDI4736 therapies compared to SoC in the first-line setting for treatment of locally advanced or metastatic NSCLC patients |
Evaluar en más detalle eficacia del tto. de combinación de MEDI4736 + tremelimumab o MEDI4736 en monoterapia en comp. con el TR en términos de SLP, TRO, DdR, VSP12, SLP2 y SG.
Evaluar eficacia tto. de comb. de MEDI4736 + tremelimumab en comp. con MEDI4736 en monoterapia en términos de SLP y TRO.
Evaluar sínt. relacionados con la enf. y la CdVRS en pac. tratados con tto. combinación de MEDI4736 + tremelimumab y MEDI4736 en monoterapia en comp. con TR usando el QLQ-C30 v3 de la EORTC y módulo LC13.
Evaluar FC del tto. de comb. de MEDI4736 + tremelimumab y de MEDI4736 en monoterapia.
Investigar la inmunogenicidad de MEDI4736 y tremelimumab.
Explorar los RECISTri como metodología de eval. del benef. clínico de MEDI4736 + tremelimumab en comp. con TR con
evaluación RCIE.
Evaluar el perfil de seg. y tolerab. del tto. de combinación de MEDI4736 + tremelimumab y de MEDI4736 en monot. en comp. con el TR en el contexto de primera línea para el tto. de pac. con CPNM avanzado o metastásico. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
? Aged at least 18 years
? Documented evidence of Stage IV NSCLC
? No activating EGFR mutation or ALK rearrangement
? No prior chemotherapy or any other systemic therapy for
advanced/metastatic NSCLC
? World Health Organization (WHO) Performance Status of 0 or 1 |
1. Edad > o = 18 años en el momento de la selección
2. CPNM en estadio IV documentado histológicamente o citológicamente con enfermedad no susceptible de cirugía o radioterapia curativas
3. Los pacientes deben presentar tumores que carezcan de mutación activadora de EGFR y reordenación de ALK.
4. Ninguna quimioterapia previa o cualquier otro tratamiento sistémico previo para CPNM avanzado o metastásico.
5. Estado funcional de la Organización Mundial de la Salud (OMS)/Eastern Cooperative Oncology Group (ECOG) de 0 o 1 al reclutamiento. |
|
| E.4 | Principal exclusion criteria |
Patients should not enter the study if any of the
following exclusion criteria are fulfilled:
? Mixed small-cell lung cancer and NSCLC histology or not otherwise specified (NSCLC NOS)
? Brain metastases or spinal cord compression unless asymptomatic, treated and stable (not requiring steroids)
? Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis) |
Los pacientes no deben entrar en el ensayo si cumplen cualquiera de los siguientes criterios de exclusión:
1. Histología mixta de cáncer microcítico de pulmón y CPNM o no especificada (CPNM NE)
2. Metástasis cerebrales o compresión de la médula espinal a menos que el paciente esté asintomático y estable sin esteroides ni anticonvulsivantes durante al menos 1 mes antes del tratamiento del ensayo.
3. Trastornos autoinmunitarios o inflamatorios documentados, activos o previos (incluida enfermedad inflamatoria intestinal [p. ej., colitis o enfermedad de Crohn], |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression Free Survival (PFS) using investigator assessments according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1). |
| El análisis principal de la SLP se basará en los RECIST 1 -1 derivados programáticamente usando las evaluaciones tumorales por el investigador. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| At baseline, after that every 6 weeks for the first 48 weeks relative to the date of randomization, and then every 8 weeks until progression. |
La eficacia en todos los pacientes se evaluará mediante evaluaciones objetivas del tumor cada 6 semanas durante las primeras 48 semanas y
después cada 8 semanas hasta progresión de la enfermedad. |
|
| E.5.2 | Secondary end point(s) |
PFS in patients with PD-L1 negative NSCLC using Investigator assessments according to RECIST 1.1
PFS in patients with PD-L1 positive NSCLC using Investigator assessments according to RECIST 1.1
ORR, DoR, and APF12 using Investigator assessments according to RECIST 1.1
PFS2 using local standard clinical practice OS
PFS and ORR using Investigator assessments according to RECIST 1.1
EORTC QLQ-C30: Questionnaire consisting of 30 items measuring subjects general cancer
symptoms and functioning.
EORTC QLQ-LC13: A complementary questionnaire measuring lung cancer symptoms and
side effects from conventional chemo- and radiotherapy.
Changes in World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status will also be assessed.
Concentration of MEDI4736 and tremelimumab in blood and non-compartmental PK parameters, such as peak concentration and trough (as data allow; sparse sampling)
Presence of ADAs for MEDI4736 and tremelimumab
PFS and ORR using BICR assessment according to irRECIST
AEs, physical examinations, laboratory findings, and vital signs |
SLP en pacientes con CPNM negativo para PD-L1 usando las evaluaciones del investigador de acuerdo con los RECIST 1.1.
SLP en pacientes con CPNM positivo para PD-L1 usando las evaluaciones por el investigador de acuerdo con los RECIST 1.1.
TRO, DdR y VSP12 usando las evaluaciones por el investigador de acuerdo con los RECIST 1.1.
SLP2 según la práctica clínica habitual local 00SG.
SLP y TRO usando las evaluaciones por el investigador de acuerdo con los RECIST 1.1.
QLQ-C30 de la EORTC: Cuestionario de calidad de vida fundamental de 30 apartados.
QLQ-LC13 de la EORTC: Cuestionario de calidad de vida para el cáncer de pulmón de 13 apartados.
Se evaluarán también los cambios en el estado funcional de la Organización Mundial de la Salud (OMS)/el Eastern Cooperative Oncology Group (ECOG).
Concentración de MEDI4736 y tremelimumab en sangre y parámetros FC no compartimentales, como la concentración máxima y en el valle (según lo permitan los datos; toma de muestras dispersa).
Presencia de AAF frente a MEDI4736 y tremelimumab.
SLP y TRO usando la evaluación por RCIE de acuerdo con los RECISTri.
AA, exploraciones físicas, hallazgos de laboratorio y constantes vitales. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
For PFS - At baseline, then every 6 weeks for the first 48 weeks relative to the date of randomization, and then every 8 weeks until progression.
EORTC QLQ-C30- Every 4 weeks for the first 8 weeks relative to randomization, then every 8 weeks until second progression/death (whichever comes first).
EORTC QLQ-LC13 - Every 2 weeks for the first 8 weeks relative to randomization, then every 4 weeks until second progression (PFS2)/death (whichever comes first).
WHO/ECOG - At timepoints consistent with tumor assessments; at 30, 60, and 90 days following confirmation of progression; and then at initiation of subsequent anticancer therapy
PK (MEDI4736) - 12 and 24 weeks from randomization.
PK (Tremelimumab) - 12 weeks from randomization.
ADAs - 12 and 24 weeks from randomization. |
- SLP- Se realizarán evaluaciones tumorales cada 6 sem. durante las primeras 48 sem. y luego cada 8 sem. hT la progresión confirmada de la enf..
- EORTC QLQ-C30 - Cada 4 sem. durante las primeras 8 sem. en relación con la fecha de aleatorización, luego cada 8 sem. en adelante hasta segunda progresión/muerte (lo que suceda antes)
EORTC QLQ-LC13 - Cada 2 sem. durante las primeras 8 sem. en relación con la fecha de aleator., luego cada 4 sem. en adelante ht la segunda progresión/muerte (lo que suceda antes)
OMS/ECOG- En momentos coherentes con las eval. tumorales; a los 30, 60 y 90 días; y luego al inicio del tto. oncológico posterior.
- FC (MEDI4736) ? 12 y 24 sem. tras la aleatorización.
- FC (Tremelimumab) ? 12 sem. tras la randomización.
- ADAs ? 12 y 24 sem. tras la random.. |
|
| 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 | Yes |
| E.8.2.3.1 | Comparator description |
| Quimioterapia en doblete basado en platino |
| Platinum-based doublet chemotherapy |
|
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 48 |
| 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 |
| Hungary |
| Italy |
| Japan |
| Korea, Republic of |
| Netherlands |
| Russian Federation |
| Spain |
| Taiwan |
| Thailand |
| United States |
| Vietnam |
|
| 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
|
| LVLS |
| Última visita del último paciente. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | |
| 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 |
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