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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

NCT03690869

Description:

Phase 1: To confirm the safety and anticipated recommended phase 2 dose (RP2D) of the PD-1 inhibitor REGN2810 (cemiplimab) for children with recurrent or refractory solid or CNS tumors and to characterize the pharmacokinetics (PK) of REGN2810 given in children with recurrent or refractory solid or Central Nervous System (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

Related Conditions:
  • Diffuse Intrinsic Pontine Glioma
  • Malignant Glioma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: R2810-ONC-1690
  • SECONDARY ID: PNOC 013 (CC#160825)
  • NCT ID: NCT03690869

Conditions

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

Interventions

DrugSynonymsArms
REGN2810 (monotherapy)cemiplimabPhase 1
REGN2810 (maintenance)cemiplimabEfficacy with Newly Diagnosed DIPG

Purpose

Phase 1: To confirm the safety and anticipated recommended phase 2 dose (RP2D) of the PD-1 inhibitor REGN2810 (cemiplimab) for children with recurrent or refractory solid or CNS tumors and to characterize the pharmacokinetics (PK) of REGN2810 given in children with recurrent or refractory solid or Central Nervous System (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

Trial Arms

NameTypeDescriptionInterventions
Phase 1ExperimentalPatients in both the Solid Tumor Cohort and the CNS Cohort will receive REGN2810 monotherapy. Each Cohort will have 2 subgroups by age (0 to <12 years, 12 to <18 years).
  • REGN2810 (monotherapy)
Efficacy with Newly Diagnosed DIPGExperimental≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of REGN2810 and radiation therapy
  • REGN2810 (maintenance)
Efficacy with Newly Diagnosed HGGExperimental≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of REGN2810 and radiation therapy
  • REGN2810 (maintenance)
Efficacy with Recurrent HGGExperimental≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of REGN2810 and radiation therapy
  • REGN2810 (maintenance)

Eligibility Criteria

        Key Inclusion Criteria:

          1. Age 0 to <18 years of age (Phase 1)

          2. Age ≥3 and ≤25 years of age (Efficacy Phase)

          3. Karnofsky ≥50 for patients >16 years of age and Lansky ≥50 for patients ≤ 16 years of
             age

          4. Patients who are receiving corticosteroids must be on a stable or decreasing dose for
             at least 7 days prior to enrollment

          5. Adequate Bone Marrow Function

          6. Adequate Renal Function

          7. Adequate Liver Function

          8. Adequate Neurologic Function

        Key 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 greater than 2 lobes

          3. Patients who are receiving any other investigational agents

          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

          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

          7. Prior treatment with idelalisib

        Note: Other protocol Inclusion/Exclusion criteria apply
      
Maximum Eligible Age:25 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of dose limiting toxicities (DLTs)
Time Frame:Baseline to 28 days
Safety Issue:
Description:Phase 1

Secondary Outcome Measures

Measure:Anti-tumor activity of REGN2810 monotherapy as identified by objective response in children with recurrent, refractory solid, or CNS tumors
Time Frame:Up to 36 months
Safety Issue:
Description:Phase 1
Measure:Immunogenicity (Anti-REGN2810 antibody)
Time Frame:Up to 25 months
Safety Issue:
Description:Phase 1 and Efficacy Phase; assessed by measurement of anti-drug antibodies (ADAs)
Measure:Tolerability profiles of REGN2810 given in combination with conventionally fractionated or hypofractionated radiation among patients with newly diagnosed DIPG
Time Frame:Up to 36 months
Safety Issue:
Description:Efficacy Phase; as assessed by number of patients with DLTs and /or treatment emergent adverse events (AEs) as assessed by CTCAE v4.0
Measure:Tolerability profiles of REGN2810 given in combination with conventionally fractionated or hypofractionated radiation among patients with newly diagnosed HGG
Time Frame:Up to 36 months
Safety Issue:
Description:Efficacy Phase; as assessed by number of patients with DLTs and /or treatment emergent adverse events (AEs) as assessed by CTCAE v4.0
Measure:Tolerability profiles of REGN2810 given in combination with re-irradiation among patients with recurrent HGG
Time Frame:Up to 36 months
Safety Issue:
Description:Efficacy Phase; as assessed by number of patients with DLTs and /or treatment emergent adverse events (AEs) as assessed by CTCAE v4.0

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Regeneron Pharmaceuticals

Trial Keywords

  • Newly Diagnosed
  • Recurrent
  • Refractory

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