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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 : May 9, 2019
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 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

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 : 150 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 2, 2018
Estimated Primary Completion Date : January 27, 2025
Estimated Study Completion Date : January 27, 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. Rate of dose limiting toxicities (DLTs) [ Time Frame: Baseline to 28 days ]
    Phase 1

  2. Rate of dose limiting toxicities (DLTs) [ Time Frame: Up to 4 weeks post radiation therapy ]
    Phase 2

  3. Anticipated recommended phase 2 dose (RP2D) of REGN2810 (cemiplimab) for children with recurrent, refractory solid, or CNS tumors [ Time Frame: Up to 36 months ]
    Phase 1; as assessed by DLTs

  4. PK of REGN2810 estimated Observed terminal half-life (t1/2) [ Time Frame: Up to 24 months ]
    Phase 1 in children with recurrent, refractory solid, or CNS tumors

  5. PK of REGN2810 Concentration at end of infusion (Ceoi) [ Time Frame: Up to 24 months ]
    Phase 1 in children with recurrent, refractory solid, or CNS tumors

  6. PK of REGN2810 Area under the curve (AUC2w) [ Time Frame: Up to 24 months ]
    Phase 1 in children with recurrent, refractory solid, or CNS tumors

  7. Anticipated RP2D of REGN2810 given concomitantly with conventionally fractionated or hypofractionated radiation among patients with newly diagnosed DIPG [ Time Frame: Up to 36 months ]
    Efficacy Phase; as assessed by DLTs

  8. Anticipated RP2D of REGN2810 given concomitantly with conventionally fractionated or hypofractionated radiation among patients with newly diagnosed HGG [ Time Frame: Up to 36 months ]
    Efficacy Phase; as assessed by DLTs

  9. Anticipated RP2D of REGN2810 given concomitantly with re-irradiation in patients with recurrent HGG [ Time Frame: Up to 36 months ]
    Efficacy Phase; as assessed by DLTs

  10. PK of REGN2810 estimated Observed terminal half-life (t1/2) [ Time Frame: Up to 24 months ]
    Efficacy Phase in pediatric patients with newly diagnosed DIPG, newly diagnosed HGG, or recurrent HGG when given in combination with radiation

  11. PK of REGN2810 Concentration at end of infusion (Ceoi) [ Time Frame: Up to 24 months ]
    Efficacy Phase in pediatric patients with newly diagnosed DIPG, newly diagnosed HGG, or recurrent HGG when given in combination with radiation

  12. PK of REGN2810 Area under the curve (AUC2w) [ Time Frame: Up to 24 months ]
    Efficacy Phase in pediatric patients with newly diagnosed DIPG, newly diagnosed HGG, or recurrent HGG when given in combination with radiation

  13. Anti-tumor activity of REGN2810 in combination with radiation in improving overall survival at 12 months (OS12) among patients with newly diagnosed DIPG [ Time Frame: Up to 36 months ]
    Efficacy Phase; as assessed by CT of MRI

  14. Anti-tumor activity of REGN2810 in combination with radiation in improving progression-free survival at 12 months (PFS12) among patients with newly diagnosed HGG [ Time Frame: Up to 36 months ]
    Efficacy Phase

  15. Anti-tumor activity of REGN2810 in combination with radiation in improving OS12 among patients with recurrent HGG [ Time Frame: Up to 36 months ]
    Efficacy Phase


Secondary Outcome Measures :
  1. 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 ]
    Phase 1

  2. Immunogenicity (Anti-REGN2810 antibody) [ Time Frame: Up to 25 months ]
    Phase 1 and Efficacy Phase; assessed by measurement of anti-drug antibodies (ADAs)

  3. 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 ]
    Efficacy Phase; as assessed by number of patients with DLTs and /or treatment emergent adverse events (AEs) as assessed by CTCAE v4.0

  4. 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 ]
    Efficacy Phase; as assessed by number of patients with DLTs and /or treatment emergent adverse events (AEs) as assessed by CTCAE v4.0

  5. Tolerability profiles of REGN2810 given in combination with re-irradiation among patients with recurrent HGG [ Time Frame: Up to 36 months ]
    Efficacy Phase; as assessed by number of patients with DLTs and /or treatment emergent adverse events (AEs) as assessed by CTCAE v4.0



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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 ≥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


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
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United States, District of Columbia
Children's National Health System (Children's National Medical Center) Recruiting
Washington, District of Columbia, United States, 20010
United States, Maryland
Johns Hopkins - Pediatric Oncology Recruiting
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Dana Farber Cancer Institute/ Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02215
United States, Minnesota
Children's Hospitals and Clinics of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55404
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
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     History of Changes
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: May 9, 2019
Last Verified: May 2019

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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
Neurologic Manifestations
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
Signs and Symptoms
Neoplasms by Site
Cemiplimab
Antineoplastic Agents, Immunological
Antineoplastic Agents