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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

Primary Purpose

Relapsed Solid Tumor, Refractory Solid Tumor, Relapsed Central Nervous System Tumor

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
cemiplimab (monotherapy)
cemiplimab (maintenance)
Conventional or hypofractionated
Re-irradiation
Sponsored by
Regeneron Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed Solid Tumor focused on measuring Newly Diagnosed, Recurrent, Refractory

Eligibility Criteria

undefined - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Children's Hospital Los Angeles (CHLA)
  • Rady Children's Hospital
  • UCSF Benioff Children's Hospital
  • Children's National Health System (Children's National Medical Center)
  • University of Florida- Neurosurgery
  • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Johns Hopkins - Pediatric Oncology
  • Massachusetts General Hospital
  • Dana Farber Cancer Institute/ Boston Children's Hospital
  • C. S. Mott/University of Michigan
  • Children's Hospitals and Clinics of Minnesota
  • University of Minnesota / Masonic Cancer Center
  • Washington University School of Medicine
  • Nationwide Children's Hospital
  • Oregon Health & Science University (OHSU) - Doernbecher Children's Hospital
  • The Children's Hospital of Philadelphia
  • St. Jude Children's Research Hospital
  • Texas Children's Cancer & Hematology Centers Baylor College of Medicine
  • University of Utah
  • Seattle Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Phase 1

Efficacy with Newly Diagnosed DIPG

Efficacy with Newly Diagnosed HGG

Efficacy with Recurrent HGG

Arm Description

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).

≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy

≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy

≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy

Outcomes

Primary Outcome Measures

Incidence and severity of treatment-emergent adverse events (TEAEs)
Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy
Incidence and severity of immune-related adverse events (irAEs)
Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy
Incidence and severity of adverse events of special interest (AESIs)
Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy
Incidence and severity of serious adverse events (SAEs)
Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy
Incidence of deaths
Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy
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
Incidence of dose limiting toxicities (DLTs)
Phase 1: given as monotherapy
Incidence of dose limiting toxicities (DLTs)
Efficacy Phase: given in combination with 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
PK for REGN2810 Concentration at end of infusion (Ceoi)
Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy
PK for REGN2810 Area under the curve (AUC2w)
Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy
Overall survival among newly diagnosed DIPG and recurrent HGG patients
Efficacy Phase: given in combination with radiation therapy
Progression-free survival among newly diagnosed HGG patients
Efficacy Phase: given in combination with radiation therapy

Secondary Outcome Measures

Objective response rate (ORR)
Phase 1: given as monotherapy
Incidence of anti-drug antibodies (ADA) to REGN2810 given as monotherapy
Phase 1: given as monotherapy
Incidence of anti-drug antibodies (ADA) to REGN2810 given in combination with radiation
Efficacy Phase: given in combination with radiation therapy

Full Information

First Posted
September 17, 2018
Last Updated
July 7, 2023
Sponsor
Regeneron Pharmaceuticals
Collaborators
Pacific Pediatric Neuro-Oncology Consortium
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1. Study Identification

Unique Protocol Identification Number
NCT03690869
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Terminated
Why Stopped
Sponsor Decision
Study Start Date
September 24, 2018 (Actual)
Primary Completion Date
May 10, 2023 (Actual)
Study Completion Date
May 10, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals
Collaborators
Pacific Pediatric Neuro-Oncology Consortium

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed Solid Tumor, Refractory Solid Tumor, Relapsed Central Nervous System Tumor, Refractory Central Nervous System Tumor, Diffuse Intrinsic Pontine Glioma, High Grade Glioma
Keywords
Newly Diagnosed, Recurrent, Refractory

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
57 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 1
Arm Type
Experimental
Arm Description
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).
Arm Title
Efficacy with Newly Diagnosed DIPG
Arm Type
Experimental
Arm Description
≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy
Arm Title
Efficacy with Newly Diagnosed HGG
Arm Type
Experimental
Arm Description
≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy
Arm Title
Efficacy with Recurrent HGG
Arm Type
Experimental
Arm Description
≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy
Intervention Type
Drug
Intervention Name(s)
cemiplimab (monotherapy)
Other Intervention Name(s)
REGN2810, Libtayo
Intervention Description
To be administered intravenously as monotherapy in Phase 1
Intervention Type
Drug
Intervention Name(s)
cemiplimab (maintenance)
Other Intervention Name(s)
REGN2810, Libtayo
Intervention Description
To be administered intravenously in combination with radiation and then used as maintenance therapy
Intervention Type
Radiation
Intervention Name(s)
Conventional or hypofractionated
Intervention Description
Combined with cemiplimab IV administration
Intervention Type
Radiation
Intervention Name(s)
Re-irradiation
Intervention Description
Combined with cemiplimab IV administration
Primary Outcome Measure Information:
Title
Incidence and severity of treatment-emergent adverse events (TEAEs)
Description
Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy
Time Frame
Up to 36 months
Title
Incidence and severity of immune-related adverse events (irAEs)
Description
Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy
Time Frame
Up to 36 months
Title
Incidence and severity of adverse events of special interest (AESIs)
Description
Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy
Time Frame
Up to 36 months
Title
Incidence and severity of serious adverse events (SAEs)
Description
Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy
Time Frame
Up to 36 months
Title
Incidence of deaths
Description
Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy
Time Frame
Up to 36 months
Title
Incidence of laboratory abnormalities
Description
Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy Grade 3 or higher per CTCAE v4.0
Time Frame
Up to 36 months
Title
Incidence of dose limiting toxicities (DLTs)
Description
Phase 1: given as monotherapy
Time Frame
Baseline to 28 days
Title
Incidence of dose limiting toxicities (DLTs)
Description
Efficacy Phase: given in combination with radiation therapy
Time Frame
Up to 4 weeks post radiation therapy
Title
PK for REGN2810 estimated Observed terminal half-life (t1/2)
Description
Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy
Time Frame
Up to 24 months
Title
PK for REGN2810 Concentration at end of infusion (Ceoi)
Description
Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy
Time Frame
Up to 24 months
Title
PK for REGN2810 Area under the curve (AUC2w)
Description
Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy
Time Frame
Up to 24 months
Title
Overall survival among newly diagnosed DIPG and recurrent HGG patients
Description
Efficacy Phase: given in combination with radiation therapy
Time Frame
Up to 36 months
Title
Progression-free survival among newly diagnosed HGG patients
Description
Efficacy Phase: given in combination with radiation therapy
Time Frame
Up to 36 months
Secondary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
Phase 1: given as monotherapy
Time Frame
Approximately 24 months
Title
Incidence of anti-drug antibodies (ADA) to REGN2810 given as monotherapy
Description
Phase 1: given as monotherapy
Time Frame
1st follow-up visit, approximately 25 months
Title
Incidence of anti-drug antibodies (ADA) to REGN2810 given in combination with radiation
Description
Efficacy Phase: given in combination with radiation therapy
Time Frame
1st follow-up visit, approximately 25 months

10. Eligibility

Sex
All
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trial Management
Organizational Affiliation
Regeneron Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Children's Hospital Los Angeles (CHLA)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90054
Country
United States
Facility Name
Rady Children's Hospital
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
UCSF Benioff Children's Hospital
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Children's National Health System (Children's National Medical Center)
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
University of Florida- Neurosurgery
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Johns Hopkins - Pediatric Oncology
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana Farber Cancer Institute/ Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
C. S. Mott/University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Children's Hospitals and Clinics of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
University of Minnesota / Masonic Cancer Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Oregon Health & Science University (OHSU) - Doernbecher Children's Hospital
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
St. Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
Texas Children's Cancer & Hematology Centers Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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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