Clinical Trials /

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 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

Related Conditions:
  • Central Nervous System Neoplasm
  • 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 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

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 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

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

Primary Outcome Measures

Measure:Incidence and severity of treatment-emergent adverse events (TEAEs)
Time Frame:Up to 36 months
Safety Issue:
Description:Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy

Secondary Outcome Measures

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

Details

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

Trial Keywords

  • Newly Diagnosed
  • Recurrent
  • Refractory

Last Updated

December 24, 2020