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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

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ClinicalTrials.gov Identifier: NCT03690869
Recruitment Status : Recruiting
First Posted : October 1, 2018
Last Update Posted : December 24, 2020
Sponsor:
Collaborator:
Pacific Pediatric Neuro-Oncology Consortium
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Brief Summary:

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

Condition or disease Intervention/treatment Phase
Relapsed Solid Tumor Refractory Solid Tumor Relapsed Central Nervous System Tumor Refractory Central Nervous System Tumor Diffuse Intrinsic Pontine Glioma High Grade Glioma Drug: REGN2810 (monotherapy) Drug: REGN2810 (maintenance) Radiation: Conventional or hypofractionated Radiation: Re-irradiation Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 3, 2018
Estimated Primary Completion Date : January 28, 2025
Estimated Study Completion Date : January 28, 2025


Arm Intervention/treatment
Experimental: Phase 1
Patients 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).
Drug: REGN2810 (monotherapy)
To be administered intravenously as monotherapy in Phase 1
Other Name: cemiplimab

Experimental: Efficacy with Newly Diagnosed DIPG
≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of REGN2810 and radiation therapy
Drug: REGN2810 (maintenance)
To be administered intravenously in combination with radiation and then used as maintenance therapy
Other Name: cemiplimab

Radiation: Conventional or hypofractionated
Combined with REGN2810 IV administration

Experimental: Efficacy with Newly Diagnosed HGG
≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of REGN2810 and radiation therapy
Drug: REGN2810 (maintenance)
To be administered intravenously in combination with radiation and then used as maintenance therapy
Other Name: cemiplimab

Radiation: Conventional or hypofractionated
Combined with REGN2810 IV administration

Experimental: Efficacy with Recurrent HGG
≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of REGN2810 and radiation therapy
Drug: REGN2810 (maintenance)
To be administered intravenously in combination with radiation and then used as maintenance therapy
Other Name: cemiplimab

Radiation: Re-irradiation
Combined with REGN2810 IV administration




Primary Outcome Measures :
  1. Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 36 months ]
    Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy

  2. Incidence and severity of immune-related adverse events (irAEs) [ Time Frame: Up to 36 months ]
    Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy

  3. Incidence and severity of adverse events of special interest (AESIs) [ Time Frame: Up to 36 months ]
    Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy

  4. Incidence and severity of serious adverse events (SAEs) [ Time Frame: Up to 36 months ]
    Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy

  5. Incidence of deaths [ Time Frame: Up to 36 months ]
    Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy

  6. Incidence of laboratory abnormalities [ Time Frame: Up to 36 months ]
    Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy Grade 3 or higher per CTCAE v4.0

  7. Incidence of dose limiting toxicities (DLTs) [ Time Frame: Baseline to 28 days ]
    Phase 1: given as monotherapy

  8. Incidence of dose limiting toxicities (DLTs) [ Time Frame: Up to 4 weeks post radiation therapy ]
    Efficacy Phase: given in combination with radiation therapy

  9. PK for REGN2810 estimated Observed terminal half-life (t1/2) [ Time Frame: Up to 24 months ]
    Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy

  10. PK for REGN2810 Concentration at end of infusion (Ceoi) [ Time Frame: Up to 24 months ]
    Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy

  11. PK for REGN2810 Area under the curve (AUC2w) [ Time Frame: Up to 24 months ]
    Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy

  12. Overall survival among newly diagnosed DIPG and recurrent HGG patients [ Time Frame: Up to 36 months ]
    Efficacy Phase: given in combination with radiation therapy

  13. Progression-free survival among newly diagnosed HGG patients [ Time Frame: Up to 36 months ]
    Efficacy Phase: given in combination with radiation therapy


Secondary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: Approximately 24 months ]
    Phase 1: given as monotherapy

  2. Incidence of anti-drug antibodies (ADA) to REGN2810 given as monotherapy [ Time Frame: 1st follow-up visit, approximately 25 months ]
    Phase 1: given as monotherapy

  3. Incidence of anti-drug antibodies (ADA) to REGN2810 given in combination with radiation [ Time Frame: 1st follow-up visit, approximately 25 months ]
    Efficacy Phase: given in combination with radiation therapy



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Ages Eligible for Study:   up to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03690869


Contacts
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Contact: Clinical Trials Administrator 844-734-6643 clinicaltrials@regeneron.com

Locations
Show Show 18 study locations
Sponsors and Collaborators
Regeneron Pharmaceuticals
Pacific Pediatric Neuro-Oncology Consortium
Investigators
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Study Director: Clinical Trial Management Regeneron Pharmaceuticals
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Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03690869    
Other Study ID Numbers: R2810-ONC-1690
PNOC 013 (CC#160825) ( Other Identifier: Pacific Pediatric Neuro-Oncology Consortium (PNOC) )
First Posted: October 1, 2018    Key Record Dates
Last Update Posted: December 24, 2020
Last Verified: July 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Regeneron Pharmaceuticals:
Newly Diagnosed
Recurrent
Refractory
Additional relevant MeSH terms:
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Neoplasms
Glioma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Nervous System Diseases
Neoplasms by Site
Cemiplimab
Antineoplastic Agents, Immunological
Antineoplastic Agents