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

Phase 1

Terminated

• Conditions: Relapsed Central Nervous System Tumor; Diffuse Intrinsic Pontine Glioma; Refractory Central Nervous System Tumor; Relapsed Solid Tumor; High Grade Glioma; Refractory Solid Tumor
• Interventions: Drug: cemiplimab (monotherapy); Drug: cemiplimab (maintenance); Radiation: Conventional or hypofractionated; Radiation: Re-irradiation

• Registration Number: NCT03690869
• Lead Sponsor: 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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-09-17
• Study Start: 2018-09-24
• Study First Submitted QC: 2018-09-28
• Study First Posted: 2018-10-01
• Primary Completion: 2023-05-10
• Study Completion: 2023-05-10
• Results First Submitted: 2024-05-07
• Results First Submitted QC: 2024-10-01
• Results First Posted: 2024-10-09
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-04
• Last Update Posted: 2025-04-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 57

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 1	cemiplimab (monotherapy)	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).
Efficacy with Newly Diagnosed HGG	cemiplimab (maintenance)	≥ 3 to \< 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy
Efficacy with Newly Diagnosed DIPG	Conventional or hypofractionated	≥ 3 to \< 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy
Efficacy with Newly Diagnosed DIPG	cemiplimab (maintenance)	≥ 3 to \< 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy
Efficacy with Recurrent HGG	Re-irradiation	≥ 3 to \< 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy
Efficacy with Recurrent HGG	cemiplimab (maintenance)	≥ 3 to \< 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy
Efficacy with Newly Diagnosed HGG	Conventional or hypofractionated	≥ 3 to \< 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy

Primary Outcome Measures

Name	Time	Method
Number of Treatment-emergent Adverse Events (TEAEs)	From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)	TEAEs are AEs that developed or worsened during the on-treatment period and any treatment-related AEs that occur during the post-treatment period but prior to initiation of other anticancer therapy. Number of TEAEs reported.
Number of Severe (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] Grade 3/4/5) TEAEs	From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)	NCI CTCAE version 4.0 was utilized for AE grading of severity: Grade 1 (Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated); Grade 2 (Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL); Grade 3 (Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL); Grade 4 (Life-threatening consequences; urgent intervention indicated); Grade 5 (Death related to AE). Number of NCI grade 3/4/5 Treatment-Emergent Adverse Events (AEs) reported
Number of Treatment-emergent Sponsor Identified Immune-related Adverse Events (irAEs)	From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)	Number of sponsor-identified irAEs (all grades) reported.
Number of Severe (NCI CTCAE Grade 3/4/5) Treatment-emergent Sponsor Identified irAEs	From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)	Number of severe treatment-emergent sponsor-identified irAEs reported.
Number of Treatment-emergent AEs of Special Interest (AESI)	From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)	AEs of special interest (AESI) are AEs required to be monitored, documented, and managed in a pre-specified manner as described in the protocol. Number of treatment-emergent AESI reported.
Number of NCI Grade 3/4/5 Treatment-emergent AESI	From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)	Number of NCI grade 3/4/5 treatment-emergent AESI reported
Number of Participants With Any TEAE Resulting in Death	From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)	Number of participants with any TEAE resulting in death reported
Number of Participants With at Least One Lab Abnormality (NCI-CTCAE All Grades) in Hematology, Electrolytes, Liver, Chemistry	Up to 36 months	Number of participants with new or worsened laboratory abnormalities (NCI-CTCAE All Grades) reported in Hematology, Electrolytes, Liver, Chemistry; Grade 1 (Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated); Grade 2 (Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL); Grade 3 (Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL); Grade 4 (Life-threatening consequences; urgent intervention indicated); Grade 5 (Death related to AE).
Number of Participants Who Developed Dose Limiting Toxicities (DLTs) (Phase 1)	Baseline to 28 days	Number of participants who developed dose limiting toxicities (DLTs) in phase 1 reported
Number of Participants Who Developed DLTs (Efficacy Phase)	Up to 4 weeks post radiation therapy
Elimination Half-life (t1/2) of Functional Cemiplimab (REGN2810) in Serum	Up to 24 months
Trough Concentration (Ctrough) of Functional Cemiplimab (REGN2810) in Serum	Up to Week 16	Ctrough (trough concentration) of functional cemiplimab in serum reported.
Peak Concentration (Cmax) of Functional Cemiplimab (REGN2810) in Serum	Up to Week 16	Cmax (peak concentration) of functional cemiplimab in serum reported.
Area Under the Concentration-time Curve (AUC) of Functional Cemiplimab (REGN2810) in Serum	Up to 24 months
Percentage of Progression-free Survival (PFS) at 12 Months for Participants With Newly Diagnosed HGG (ndHGG)	At 12 months	PFS was defined as the time from randomization to the date of the first documented tumor progression, as determined per Response Assessment in Neuro-Oncology (RANO)/Immunotherapy Response Assessment in Neuro-Oncology (iRANO) criteria, or death due to any cause.
Percentage of Overall Survival (OS) at 12 Months for Participants With ndDIPG and Recurrent HGG (rHGG)	Up to 12 months	OS was defined as the time from randomization to the date of death due to any cause. A participant who had not died was censored at the last date that participant was documented to be alive. 95% CI is based on Kaplan-Meier method.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) for Participants Who Have a Confirmed Complete Response (CR) or Partial Response (PR)	Approximately 24 months	ORR was defined as the percentage of participants who have a confirmed complete response (CR) or partial response (PR), as determined per standard criteria between the date of first study treatment and the date of the first objectively documented progression or the date of receiving another anti-cancer systemic therapy, whichever came first. Clopper-Person exact confidence interval
Number of Participants With Anti-REGN2810 Antibodies (ADA)	1st follow-up visit, approximately 25 months	ADA status classified as: Positive; Pre-existing (baseline \[BL\] sample positive \& all post BL ADA titers reported as \< 9-fold BL titer value); Negative (all samples negative); ADA positive: Treatment-boosted (positive result at BL with ≥1 post BL titer result ≥9-fold BL titer value); Treatment-emergent (TE) (negative result or missing result at BL with ≥1 positive post BL result); TE: Persistent (positive result detected in ≥2 consecutive post BL samples separated by ≥ a 12/16-week post BL period with no ADA-negative results in-between, regardless of any missing samples; Indeterminate (positive result in last collection, regardless of any missing samples); Transient (not persistent or indeterminate, regardless of any missing samples)

Trial Locations

Locations (20)

Children's Hospital Los Angeles (CHLA); 🇺🇸 Los Angeles, California, United States

Rady Children's Hospital; 🇺🇸 San Diego, California, United States

Ann & Robert H. Lurie Children's Hospital of Chicago; 🇺🇸 Chicago, Illinois, 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

Nationwide Children's Hospital; 🇺🇸 Columbus, Ohio, United States

The Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Texas Children's Cancer & Hematology Centers Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

UCSF Benioff Children's Hospital; 🇺🇸 San Francisco, California, United States

Children's National Health System (Children's National Medical Center); 🇺🇸 Washington, District of Columbia, United States

University of Florida- Neurosurgery; 🇺🇸 Gainesville, Florida, United States

C. S. Mott/University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

University of Minnesota / Masonic Cancer Center; 🇺🇸 Minneapolis, Minnesota, United States

Children's Hospitals and Clinics of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Oregon Health & Science University (OHSU) - Doernbecher Children's Hospital; 🇺🇸 Portland, Oregon, United States

St. Jude Children's Research Hospital; 🇺🇸 Memphis, Tennessee, United States

University of Utah; 🇺🇸 Salt Lake City, Utah, United States

Seattle Children's Hospital; 🇺🇸 Seattle, Washington, United States