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

High Grade Glioma Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT03690869
• Other study ID #: R2810-ONC-1690
• Secondary ID: PNOC 013 (CC#160
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: September 24, 2018
• Est. completion date: May 10, 2023

Study information

• Verified date: June 2023
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 57
• Est. completion date: May 10, 2023
• Est. primary completion date: May 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 25 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• cemiplimab (monotherapy)
To be administered intravenously as monotherapy in Phase 1
• cemiplimab (maintenance)
To be administered intravenously in combination with radiation and then used as maintenance therapy

Radiation:
• Conventional or hypofractionated
Combined with cemiplimab IV administration
• Re-irradiation
Combined with cemiplimab IV administration

Locations

Country	Name	City	State
United States	C. S. Mott/University of Michigan	Ann Arbor	Michigan
United States	Johns Hopkins - Pediatric Oncology	Baltimore	Maryland
United States	Dana Farber Cancer Institute/ Boston Children's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of Florida- Neurosurgery	Gainesville	Florida
United States	Texas Children's Cancer & Hematology Centers Baylor College of Medicine	Houston	Texas
United States	Children's Hospital Los Angeles (CHLA)	Los Angeles	California
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Children's Hospitals and Clinics of Minnesota	Minneapolis	Minnesota
United States	University of Minnesota / Masonic Cancer Center	Minneapolis	Minnesota
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Oregon Health & Science University (OHSU) - Doernbecher Children's Hospital	Portland	Oregon
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	Rady Children's Hospital	San Diego	California
United States	UCSF Benioff Children's Hospital	San Francisco	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Children's National Health System (Children's National Medical Center)	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals	Pacific Pediatric Neuro-Oncology Consortium

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of treatment-emergent adverse events (TEAEs)	Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy	Up to 36 months
Primary	Incidence and severity of immune-related adverse events (irAEs)	Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy	Up to 36 months
Primary	Incidence and severity of adverse events of special interest (AESIs)	Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy	Up to 36 months
Primary	Incidence and severity of serious adverse events (SAEs)	Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy	Up to 36 months
Primary	Incidence of deaths	Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy	Up to 36 months
Primary	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	Up to 36 months
Primary	Incidence of dose limiting toxicities (DLTs)	Phase 1: given as monotherapy	Baseline to 28 days
Primary	Incidence of dose limiting toxicities (DLTs)	Efficacy Phase: given in combination with radiation therapy	Up to 4 weeks post radiation therapy
Primary	PK for REGN2810 estimated Observed terminal half-life (t1/2)	Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy	Up to 24 months
Primary	PK for REGN2810 Concentration at end of infusion (Ceoi)	Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy	Up to 24 months
Primary	PK for REGN2810 Area under the curve (AUC2w)	Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy	Up to 24 months
Primary	Overall survival among newly diagnosed DIPG and recurrent HGG patients	Efficacy Phase: given in combination with radiation therapy	Up to 36 months
Primary	Progression-free survival among newly diagnosed HGG patients	Efficacy Phase: given in combination with radiation therapy	Up to 36 months
Secondary	Objective response rate (ORR)	Phase 1: given as monotherapy	Approximately 24 months
Secondary	Incidence of anti-drug antibodies (ADA) to REGN2810 given as monotherapy	Phase 1: given as monotherapy	1st follow-up visit, approximately 25 months
Secondary	Incidence of anti-drug antibodies (ADA) to REGN2810 given in combination with radiation	Efficacy Phase: given in combination with radiation therapy	1st follow-up visit, approximately 25 months