E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed Solid Tumor Refractory Solid Tumor Relapsed Central Nervous System Tumor Refractory Central Nervous System Tumor Diffuse Intrinsic Pontine Glioma High Grade Glioma |
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E.1.1.1 | Medical condition in easily understood language |
Central Nervous System (CNS) Tumors |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To confirm the safety, characterize the pharmacokinetics (PK) and anticipate recommended phase 2 dose (RP2D) of REGN2810 for children with recurrent or refractory solid or CNS tumors To confirm the safety and anticipated RP2D of REGN2810 given concomitantly with conventionally fractionated or hypofractionated radiation among patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG) and high-grade glioma (HGG) and with re-irradiation in patients with recurrent HGG To assess PK of REGN2810 in pediatric patients with newly diagnosed DIPG, newly diagnosed HGG, or recurrent HGG when given in combination with radiation To assess anti-tumor activity of REGN2810 in combination with radiation in improving overall survival at 12 months (OS12) among patients with newly diagnosed DIPG and recurrent HGG and in improving progression-free survival at 12 months (PFS12) among patients with newly diagnosed HGG |
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E.2.2 | Secondary objectives of the trial |
To assess anti-tumor activity of REGN2810 monotherapy as identified by objective response in children with recurrent or refractory solid or CNS tumors To assess immunogenicity To assess safety and tolerability profiles of REGN2810 given in combination with conventionally fractionated or hypofractionated radiation among patients with newly diagnosed DIPG To assess safety and tolerability profiles of REGN2810 given in combination with conventionally fractionated or hypofractionated radiation among patients with newly diagnosed HGG To assess safety and tolerability profiles of REGN2810 given in combination with re-irradiation among patients with recurrent HGG To assess immunogenicity |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age 0 to <18 years of age (Phase 1) 2. Age ≥3 and ≤25 years of age (Efficacy Phase) 3. Karnofsky performance status ≥50 (patients >16 years) or Lansky performance status ≥50 (patients ≤ 16 years) 4. Life expectancy >8 weeks 5. Adequate Bone Marrow Function 6. Adequate Renal Function 7. Adequate Liver Function 8. Adequate Neurologic Function
Note: Other protocol-defined Inclusion criteria apply |
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E.4 | Principal exclusion criteria |
1. Patients with bulky metastatic disease of the CNS causing Uncal herniation or symptomatic midline shift, significant, symptomatic mass effect, or uncontrolled neurological symptoms such as seizures or altered mental status 2. Patients with metastatic spine disease and gliomatosis as documented by diffuse involvement of >2 lobes 3. Patients who are receiving any other investigational anticancer agent(s) 4. Patients on greater than dexamethasone 0.1 mg/kg/day (maximum 4 mg/day) or equivalent dose in alternate corticosteroid, or actively undergoing corticosteroid dose escalation in the last 7 days 5. Patients with a history of allogeneic stem cell transplant 6. Prior treatment with an agent that blocks the PD-1/PD-L1/PD-L2 pathway
Note: Other protocol-defined Exclusion criteria apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Incidence and severity of treatment-emergent adverse events (TEAEs) 2. Incidence and severity of immune-related adverse events (irAEs) 3. Incidence and severity of adverse events of special interest (AESIs) 4. Incidence and severity of serious adverse events (SAEs) 5. Incidence of deaths 6. Incidence of laboratory abnormalities 7. Incidence of dose limiting toxicities (DLTs) 8. PK for REGN2810 estimated Observed terminal half-life (t1/2) 9. PK for REGN2810 Concentration at end of infusion (Ceoi) 10. PK for REGN2810 Area under the curve (AUC2w) 11. Overall survival among newly diagnosed DIPG and recurrent HGG patients 12. Progression-free survival among newly diagnosed HGG patients |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1-6; 11-12 - Up to 36 months 7 - Baseline to 28 days; up to 4 weeks post radiation therapy 8-10 - Up to 24 months |
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E.5.2 | Secondary end point(s) |
1. Objective response rate (ORR) 2. Incidence of anti-drug antibodies (ADA) to REGN2810 given as monotherapy 3. Incidence of anti-drug antibodies (ADA) to REGN2810 given in combination with radiation |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. approximately 24 months 2 - 3 - 1st follow-up visit, approximately 25 months |
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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 | No |
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 | 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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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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.8.9.2 | In all countries concerned by the trial years | 5 |
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 | 13 |