REGN2810 in Pediatric Patients With Relapsed, Refractory Solid, or Central Nervous System (CNS) Tumors and Safety and Efficacy of REGN2810 in Combination With Radiotherapy in Pediatric Patients With Newly Diagnosed or Recurrent Glioma

Study Overview
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Brief Summary
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Phase 1: To confirm the safety and anticipated recommended phase 2 dose (RP2D) of REGN2810 (cemiplimab) for children with recurrent or refractory solid or Central Nervous System (CNS) tumors To characterize the pharmacokinetics (PK) of REGN2810 given in children with recurrent or refractory solid or CNS tumors Phase 2 (Efficacy Phase): To confirm the safety and anticipated RP2D of REGN2810 to be given concomitantly with conventionally fractionated or hypofractionated radiation among patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG) To confirm the safety and anticipated RP2D of REGN2810 given concomitantly with conventionally fractionated or hypofractionated radiation among patients with newly diagnosed high-grade glioma (HGG) To confirm the safety and anticipated RP2D of REGN2810 given concomitantly 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 To assess anti-tumor activity of REGN2810 in combination with radiation in improving progression-free survival at 12 months (PFS12) among patients with newly diagnosed HGG To assess anti-tumor activity of REGN2810 in combination with radiation in improving overall survival at OS12 among patients with recurrent HGG

Official Title
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A Safety and Pharmacokinetic Study of Single Agent REGN2810 in Pediatric Patients With Relapsed or Refractory Solid or Central Nervous System (CNS) Tumors and a Safety and Efficacy Trial of REGN2810 in Combination With Radiotherapy in Pediatric Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma, Newly Diagnosed High-Grade Glioma, or Recurrent High-Grade Glioma

Conditions
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Relapsed Solid Tumor, Refractory Solid Tumor, Relapsed Central Nervous System Tumor, Refractory Central Nervous System Tumor, Diffuse Intrinsic Pontine Glioma, High Grade Glioma

Intervention / Treatment
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* Drug: cemiplimab (monotherapy)
* Drug: cemiplimab (maintenance)
* Radiation: Conventional or hypofractionated
* Radiation: Re-irradiation


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Age 0 to <18 years of age (Phase 1) Age ≥3 and ≤25 years of age (Efficacy Phase) Karnofsky performance status ≥50 (patients >16 years) or Lansky performance status ≥50 (patients ≤ 16 years) Life expectancy >8 weeks Adequate Bone Marrow Function Adequate Renal Function Adequate Liver Function Adequate Neurologic Function Key Exclusion Criteria: 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 Patients with metastatic spine disease and gliomatosis as documented by diffuse involvement of >2 lobes Patients who are receiving any other investigational anticancer agent(s) 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 Patients with a history of allogeneic stem cell transplant Prior treatment with an agent that blocks the PD-1/PD-L1/PD-L2 pathway Note: Other protocol-defined Inclusion/Exclusion criteria apply

Ages Eligible for Study
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Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1<br>Patients in both the Solid Tumor Cohort and the CNS Cohort will receive cemiplimab monotherapy. Each Cohort will have 2 subgroups by age (0 to <12 years, 12 to <18 years). | Drug: cemiplimab (monotherapy)<br>* To be administered intravenously as monotherapy in Phase 1<br>* Other names: Libtayo;|
| Experimental: Efficacy with Newly Diagnosed DIPG<br>≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy | Drug: cemiplimab (maintenance)<br>* To be administered intravenously in combination with radiation and then used as maintenance therapy<br>* Other names: Libtayo;Radiation: Conventional or hypofractionated<br>* Combined with cemiplimab IV administration<br>|
| Experimental: Efficacy with Newly Diagnosed HGG<br>≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy | Drug: cemiplimab (maintenance)<br>* To be administered intravenously in combination with radiation and then used as maintenance therapy<br>* Other names: Libtayo;Radiation: Conventional or hypofractionated<br>* Combined with cemiplimab IV administration<br>|
| Experimental: Efficacy with Recurrent HGG<br>≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy | Drug: cemiplimab (maintenance)<br>* To be administered intravenously in combination with radiation and then used as maintenance therapy<br>* Other names: Libtayo;Radiation: Re-irradiation<br>* Combined with cemiplimab IV administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of treatment-emergent adverse events (TEAEs) | Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy | Up to 36 months | 
| Incidence and severity of immune-related adverse events (irAEs) | Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy | Up to 36 months | 
| Incidence and severity of adverse events of special interest (AESIs) | Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy | Up to 36 months | 
| Incidence and severity of serious adverse events (SAEs) | Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy | Up to 36 months | 
| Incidence of deaths | Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy | Up to 36 months | 
| Incidence of laboratory abnormalities | Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy Grade 3 or higher per CTCAE v4.0 | Up to 36 months | 
| Incidence of dose limiting toxicities (DLTs) | Phase 1: given as monotherapy | Baseline to 28 days | 
| Incidence of dose limiting toxicities (DLTs) | Efficacy Phase: given in combination with radiation therapy | Up to 4 weeks post radiation therapy | 
| PK for REGN2810 estimated Observed terminal half-life (t1/2) | Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy | Up to 24 months | 
| PK for REGN2810 Concentration at end of infusion (Ceoi) | Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy | Up to 24 months | 
| PK for REGN2810 Area under the curve (AUC2w) | Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy | Up to 24 months | 
| Overall survival among newly diagnosed DIPG and recurrent HGG patients | Efficacy Phase: given in combination with radiation therapy | Up to 36 months | 
| Progression-free survival among newly diagnosed HGG patients | Efficacy Phase: given in combination with radiation therapy | Up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Phase 1: given as monotherapy | Approximately 24 months | 
| Incidence of anti-drug antibodies (ADA) to REGN2810 given as monotherapy | Phase 1: given as monotherapy | 1st follow-up visit, approximately 25 months | 
| Incidence of anti-drug antibodies (ADA) to REGN2810 given in combination with radiation | Efficacy Phase: given in combination with radiation therapy | 1st follow-up visit, approximately 25 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Newly Diagnosed, Recurrent, Refractory