E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent or Refractory pediatric cancer |
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E.1.1.1 | Medical condition in easily understood language |
Recurrent or Refractory Pediatric Malignancies |
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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 |
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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. |
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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 |
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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). Participants with hypertension must be on a stable antihypertensive regimen for the 14 days prior to treatment assignment. - 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 first dose of study drug. |
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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) |
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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 |
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E.5.2 | Secondary end point(s) |
Part B: - Incidence of AEs, SAEs, toxicities, 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) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 |
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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 | 13 |
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 | 4 |
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 |
France |
Germany |
Italy |
Netherlands |
Spain |
United Kingdom |
United States |
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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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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 | |
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 |