E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
stages AJCC v.8 IB-IIIA non-small cell lung cancer (NSCLC) |
cáncer de pulmón de células no pequeñas (NSCLC) en estadio IB-IIIA (según el American Joint Committee on Cancer [AJCC] |
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E.1.1.1 | Medical condition in easily understood language |
resectable non-small cell lung cancer (NSCLC) |
cáncer de pulmón de células no pequeñas (NSCLC) resecable. |
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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.1.3 | 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 MPR rate (≤10% of residual viable tumor cells) at the time of surgery in evaluable subjects treated with canakinumab alone and in combination with pembrolizumab |
Evaluar la tasa de RPM (</=10 % de células tumorales viables residuales) en la muestra de resección, en el momento de la cirugía, en los pacientes evaluables tratados con canakinumab en monoterapia o en combinación con pembrolizumab. |
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E.2.2 | Secondary objectives of the trial |
1. To assess the prevalence and incidence of IG (ADA) of canakinumab and pembrolizumab 2. To assess ORR in randomized subjects treated with canakinumab or pembrolizumab as monotherapy or in combination 3. To assess PK of canakinumab and pembrolizumab as monotherapy and in combination 4. To assess surgical feasibility rate in each treatment arm based on randomized subjects 5. To assess the rate of MPR at the time of surgery in (a)evaluable subjects in pembrolizumab monotherapy arm, (b)evaluable subjects based on local review in each treatment arm, (c)randomized subjects based on both central and local review in each treatment arm and (d)to estimate the difference in MPR and posterior probability of the difference in MPR≥10% between canakinumab + pembrolizumab combination and pembrolizumab alone 6. To evaluate safety and tolerability of canakinumab and pembrolizumab as monotherapy or in combination 7. To assess the relationship between key blood or tissue based biomarkers and MPR |
1. Evaluar la prevalencia e incidencia de inmunogenicidad (IG)/anticuerpos contra el fármaco(ADA)de canakinumab y pembrolizumab. 2. Evaluar la ORR en los pacientes aleatorizados tratados con canakinumab o pembrolizumab en monoterapia o en combinación. 3. Evaluar la farmacocinética (PK) de canakinumab y pembrolizumab en monoterapia y en combinación. 4. Evaluar la tasa de viabilidad quirúrgica en cada grupo de tratamiento basándose en pacientes aleatorizados. 5. Evaluar la tasa de RPM en el momento de la cirugía en (a) pacientes evaluables en el grupo de pembrolizumab en monoterapia, (b) pacientes evaluables basándose en la revisión local en cada grupo de tratamiento, c) pacientes aleatorizados basándose en las revisiones central y local en cada grupo de tratamiento y (d) estimar la diferencia en RPM y la probabilidad posterior de la diferencia en RPM >/=10 % entre la combinación de canakinumab + pembrolizumab y pembrolizumab en monoterapia. Para más objetivos ver protocolo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically confirmed NSCLC stage IB-IIIA (per American Joint Committee on Cancer (AJCC) 8th edition), deemed suitable for primary resection by treating surgeon, except for N2 and T4 tumors. 2. Subject must be eligible for surgery and with a planned surgical resection in approximately 4-6 weeks (from the first dose of study treatment). 3. A mandatory newly obtained tissue biopsy is required for study enrollment. An archival biopsy is also acceptable if obtained up to 6 months before first day of study treatment and if the subject did not go through antineoplastic systemic therapies between biopsy collection date and beginning of study treatment. 4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. 5. Other protocol-defined inclusion criteria may apply. |
1. NSCLC histológicamente confirmado en estadio IB-IIIA (según el American Joint Committee on Cancer [AJCC], 8ª edición), que el cirujano considere adecuado para resección primaria, salvo los tumores N2 y T4. 2. El paciente debe ser elegible para la cirugía y con una resección quirúrgica programada en aproximadamente 4 o 6 semanas (desde la primera dosis del tratamiento del estudio). 3. Para participar en el estudio será obligatoria una biopsia de tejido obtenida recientemente. También se aceptará una biopsia archivada si se ha obtenido hasta 6 meses antes del primer día del tratamiento del estudio y si el paciente no se ha sometido a ninguna terapia antineoplásica sistémica entre la fecha de recogida de la biopsia y el inicio del tratamiento del estudio. 4. Estado funcional (PS) del Grupo Cooperativo Oncológico del Este (ECOG) de 0 o 1. 5. Otros criterios de inclusión pueden aplicar |
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E.4 | Principal exclusion criteria |
1. Subjects with unresectable or metastatic disease. All subjects should have brain imgaing (either Magnetic Resonance Imaging [MRI] brain or Computed Tomography [CT] brain with contrast) prior to enrollment to exclude brain metastasis. 2. History of severe hypersensitivity reactions to monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction. 3. Presence or history of a malignant disease that has been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include the following: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type. Subjects who received prior systemic therapy (including chemotherapy, other anti-cancer therapies and any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) in the past 3 years before screening. 4. Other protocol-defined exclusion criteria may apply. |
1. Pacientes con una enfermedad no resecable o metastásica. Todos los pacientes deberán someterse a un diagnóstico por imagen del cerebro (resonancia magnética (RM) cerebral o tomografía computarizada (TC) cerebral con contraste) antes del reclutamiento para descartar la metástasis cerebral. 2. Antecedentes de reacciones graves de hipersensibilidad a anticuerpos monoclonales, que según la opinión del investigador puedan suponer un mayor riesgo de reacción grave a la perfusión. 3. Presencia o antecedentes de enfermedad maligna que haya sido diagnosticada o que haya requerido tratamiento durante los últimos 3 años. Las excepciones a esta exclusión son las siguientes: cáncer de piel de células basales y escamosas resecado completamente y cualquier tipo de carcinoma in situ resecado completamente. Pacientes que hayan recibido tratamiento sistémico previo (incluyendo quimioterapia, otros tratamientos contra el cáncer y cualquier otro anticuerpo o fármaco dirigido específicamente a las vías de coestimulación de células T o de puntos de control inmunitario) en los 3 años anteriores a la selección. 4. Otros criterios de exclusión pueden aplicar |
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E.5 End points |
E.5.1 | Primary end point(s) |
MPR rate based on central review |
RPM: la respuesta se evaluará centralmente |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary efficacy analysis will be performed after all subjects have had surgical resection or have discontinued study treatment earlier due to any reason. |
El análisis de eficacia principal se realizará después de que todos los sujetos se hayan sometido a una resección quirúrgica o hayan discontinuado el tratamiento del estudio prematuramente por cualquier motivo. |
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E.5.2 | Secondary end point(s) |
1. ADA prevalence at baseline and ADA incidence on-treatment 2. Overall response rate based on local investigator assessment per RECIST 1.1 3. Concentrations of canakinumab, pembrolizumab 4. Surgical feasibility rate 5. (a) MPR based on central review (b) MPR based on local review (c) MPR based on both central and local review (d) Difference in MPR rate based on central review 6. Type, frequency and severity of AEs (Common Terminology Criteria for Adverse Events [CTCAE] v5.0), vital signs and laboratory abnormalities 7. MPR based on the levels of biomarkers (PD-L1, CD8, hs-CRP, hs-IL-6) assessed at baseline and on treatment |
1. Prevalencia de ADA en la basal e incidencia de ADA durante el tratamiento. 2. Tasa de respuesta global basada en la evaluación local del investigador según RECIST 1.1. 3. Concentraciones de canakinumab y pembrolizumab. 4. Tasa de viabilidad quirúrgica. 5. (a) RPM basada en una revisión central (b) RPM basada en una revisión local (c) RPM basada en una revisión central y una revisión local (d) Diferencia en la tasa de RPM basada en una revisión central. 6. Tipo, frecuencia e intensidad de AA (Criterios de terminología común de acontecimientos adversos [CTCAE] v5.0), constantes vitales y anomalías de laboratorio. 7. RPM basada en los niveles de biomarcadores (PD-L1, CD8, PCRus, IL-6us) evaluados en la basal y durante el tratamiento. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secondary endpoint analyses will be performed at the same time as the primary endpoint analysis (after all subjects have had surgical resection or have discontinued study treatment earlier due to any reason). |
Los análisis de las variables secundarias se realizarán a la vez que el análisis de las variables principales (después de que todos los sujetos se hayan sometido a una resección quirúrgica o hayan discontinuado el tratamiento del estudio prematuramente por cualquier motivo). |
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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 | 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 | 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 | No |
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 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 |
Austria |
Canada |
France |
Germany |
Greece |
Hungary |
Netherlands |
Russian Federation |
Spain |
Taiwan |
Turkey |
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
|
When the last subject finishes their last safety follow-up visit at 130 days after last administration of study treatment and any repeat assessments associated with this visit have been documented and followed-up appropriately by the Investigator or, in the event of an early study termination decision, the date of that decision (each subject will be required to complete the study in its entirety and thereafter no further study treatment will be made available to them) |
Cuando el último pte haya finalizado su última visita de seguimiento de seguridad 130 días después de la última administración del tto del estudio y el investigador haya documentado y realizado de manera adecuada el seguimiento de cualquier evaluación de esta visita que se haya repetido o, en el caso de que se haya decidido finalizar el estudio prematuramente, la fecha de dicha decisión (será necesario que cada pte complete el estudio y posteriormente ya no dispondrá de más tto 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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 16 |