E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent or Refractory pediatric cancer |
Cáncer pediátrico recidivante o refractario |
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E.1.1.1 | Medical condition in easily understood language |
Recurrent or Refractory Pediatric Malignancies |
Neoplasias malignas pediátricas recidivantes o refractarias |
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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 | 10029260 |
E.1.2 | Term | Neuroblastoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10015560 |
E.1.2 | Term | Ewing's sarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10039022 |
E.1.2 | Term | Rhabdomyosarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049280 |
E.1.2 | Term | Solid tumour |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10025322 |
E.1.2 | Term | Lymphomas non-Hodgkin's unspecified histology |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024329 |
E.1.2 | Term | Leukemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10065443 |
E.1.2 | Term | Malignant glioma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10027107 |
E.1.2 | Term | Medulloblastoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 | 10014967 |
E.1.2 | Term | Ependymoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10007958 |
E.1.2 | Term | Central nervous system neoplasm |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary - Part A Safety Lead-in: - Safety Lead-in: To estimate the safety and tolerability of study treatment in pediatric participants with malignant neoplasms that are refractory, relapsed, or participants for whom curative treatments are lacking. - To characterize the pharmacokinetics (PK) of bempegaldesleukin and nivolumab in pediatric participants with malignant neoplasms that are refractory, relapsed, or participants for whom curative treatments are lacking.
Primary - Part B Expansion
To estimate the preliminary efficacy (eg, ORR of study treatment separately in the following disease cohorts): B1: Neuroblastoma B2: Ewing sarcoma B3: Rhabdomyosarcoma B4: Miscellaneous solid tumors B5: Non-Hodgkin lymphoma (NHL)/leukemia B6: High-grade glioma B7: Medulloblastoma and embryonal tumors B8: Ependymoma B9: Miscellaneous central nervous system (CNS) tumors |
Principal - Parte A, Preinclusión de seguridad - Preinclusión de seguridad: estimar la seguridad y la tolerabilidad del tratamiento del estudio en participantes pediátricos con neoplasias malignas que sean refractarias, recidivantes o participantes para los que no haya tratamientos curativos. - Caracterizar la farmacocinética (FC) de bempegaldesleukin y nivolumab en participantes pediátricos con neoplasias malignas que sean refractarias, recidivantes o participantes para los que no haya tratamientos curativos.
Principal – Parte B, expansión Estimar la eficacia preliminar (p. ej. TRO del tratamiento del estudio por separado en las siguientes cohortes de enfermedad): B1: Neuroblastoma B2: Sarcoma de Ewing B3: Rabdomiosarcoma B4: Tumores sólidos variados B5: Linfoma no Hodgkin (LNH)/leucemia B6: Glioma de alto grado B7: Meduloblastoma y tumores embrionarios B8: Ependimoma B9: Tumores variados del sistema nervioso central (SNC) |
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E.2.2 | Secondary objectives of the trial |
Secondary - Part B Expansion - To estimate the safety of study therapy in pediatric participants. - To estimate the progression-free survival (PFS) and overall survival (OS) of study therapy in pediatric participants. |
Secundarios - Parte B, Expansión - Estimar la seguridad del tratamiento del estudio en participantes pediátricos. - Estimar la supervivencia libre de progresión (SLP) y la supervivencia global (SG) del tratamiento del estudio en participantes pediátricos |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age < 18 years for Part A and Part B - Age up to 30 years for Part B Cohorts B2, B3 and B4 - Must have received standard of care therapy and there must be no potentially curative treatment available - Histologically confirmed with malignant neoplasms that are refractory, relapsed, or curative treatments are lacking - Must have measurable or evaluable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for solid tumors, Response Assessment in Neuro-Oncology (RANO) or Response Assessment in Pediatric Neuro-Oncology (RAPNO) for central nervous system tumors, International Pediatric Non-Hodgkin Lymphoma Response Criteria for non-Hodgkin lymphoma (NHL), revised International Neuroblastoma Response Criteria (INRC) for neuroblastoma, modified National Comprehensive Cancer Network (NCCN) Criteria for acute lymphoblastic leukemia, and modified Cheson et al International Working Group criteria for acute myeloid leukemia - Lansky play score for age ≤ 16 years or Karnofsky performance score for age > 16 years assessed within 2 weeks of enrollment must be ≥ 60 |
- Edad < 18 años para la Parte A y Parte B - Edad hasta 30 años para las Cohortes B2, B3 y B4 de la Parte B - Deben haber recibido el tratamiento de referencia actual y no debe haber tratamiento potencialmente curativo disponible - Neoplasias malignas confirmadas histológicamente que son refractarias, recidivantes o pacientes para los que faltan tratamientos curativos - Deben tener enfermedad medible o evaluable según los Criterios de Evaluación de la Respuesta en Tumores Sólidos (RECIST) v1.1 para tumores sólidos, Evaluación de la Respuesta en Neuro-Oncología (RANO) o Evaluación de la Respuesta en Neuro-Oncología Pediátrica (RAPNO) para tumores del sistema nervioso central, Criterios Internacionales de Respuesta en el Linfoma no Hodgkin Pediátrico (LNH) para el LNH, Criterios Internacionales de Respuesta en el Neuroblastoma (INRC) revisados para el neuroblastoma, Criterios de la National Comprehensive Cancer Network (NCCN) modificados para la leucemia linfoblástica aguda y criterios del Grupo de Trabajo Internacional de Cheson et al modificados para la leucemia mieloide aguda - Puntuación de Lansky para edades ≤ 16 años o puntuación de estado funcional de Karnofsky para edades > 16 años evaluada en el plazo de 2 semanas previas al reclutamiento debe ser ≥ 60 |
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E.4 | Principal exclusion criteria |
- Osteosarcoma, T-cell/NK-cell leukemia/lymphoma, and Hodgkin lymphoma - Need for > 2 antihypertensive medications for management of hypertension (including diuretics) - Known cardiovascular history, including unstable or deteriorating cardiac disease, within the previous 12 months prior to screening - Inadequately treated adrenal insufficiency - Active, known, or suspected autoimmune disease - Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of start of study treatment - Prior allogeneic stem cell transplant - Previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection either suspected or confirmed within 4 weeks prior to screening |
- Osteosarcoma, leucemia/linfoma de células T/células NK y linfoma de Hodgkin - Necesidad de > 2 medicamentos antihipertensivos para el manejo de la hipertensión (incluidos diuréticos) - Antecedentes cardiovasculares conocidos, como enfermedad cardíaca inestable o en deterioro, dentro de los 12 meses previos a la selección - Insuficiencia suprarrenal tratada de forma inadecuada - Enfermedad autoinmunitaria activa conocida o sospecha de ella. - Problema que precise tratamiento sistémico con corticosteroides u otros medicamentos inmunodepresores dentro de los 14 días previos al comienzo del tratamiento del estudio - Trasplante alogénico de células progenitoras - Infección previa por SARS-CoV-2 ya sea de sospecha o confirmada dentro de las 4 semanas previas a la selección |
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E.5 End points |
E.5.1 | Primary end point(s) |
Part A: 1. Incidence of dose-limiting toxicities, adverse events (AEs), serious AEs (SAEs), drug-related AEs, AEs leading to discontinuation and death. 2. Pharmacokinetic (PK) parameters: Peak concentration, trough concentration, time-averaged concentration, clearance (CL) and volume of distribution (Vd).
Part B: 3. Investigator-assessed objective response rate (ORR) |
Parte A: 1. Incidencia de toxicidades limitantes de la dosis, acontecimientos adversos (AA), AA graves (AAG), AA relacionados con el fármaco, AA que condujeron a la suspensión y muerte. 2. Parámetros farmacocinéticos FC: Concentración máxima, concentración valle, tiempo promedio de concentración, aclaramiento (CL) y volumen de distribución (Vd).
Parte B: 3. Tasa de respuestas objetivas (TRO) evaluada por el investigador |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to 2 years and 100 days 2. Up to 2 years 3. Up to 5 years |
1. Hasta 2 años y 100 días 2. Hasta 2 años 3. Hasta 5 años |
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E.5.2 | Secondary end point(s) |
Part B: - Incidence of AEs, SAEs, drug-related AEs, AEs leading to discontinuation and death. - Incidence of laboratory abnormalities: Hematology tests and clinical chemistry tests. - Progression-free survival (PFS) - Overall survival (OS) |
Parte B: - Incidencia de AA, AAG, AA relacionados con el fármaco, AA que conduzcan a la suspensión y muerte. - Incidencia de anomalías de laboratorio: pruebas de hematología y pruebas de química clínicas - Supervivencia libre de progresión (SLP) - Supervivencia global (SG) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to 5 years |
Hasta 5 años |
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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) | 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 - Dose-finding study design |
Fase IB - Diseño de estudio de búsqueda de dosis |
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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 | 1 |
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 | 14 |
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 |
Canada |
United States |
France |
Germany |
Italy |
Netherlands |
Spain |
United Kingdom |
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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
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LVLS |
Última visita del último sujeto |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 10 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 10 |