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

NCT03690869 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: R2810-ONC-1690PNOC 013 (CC#160825)
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 20

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

Conditions

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

Outcome Measures

Primary Outcomes (16)

• Number of Treatment-emergent Adverse Events (TEAEs)

  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.

  From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)

• Number of Severe (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] Grade 3/4/5) TEAEs

  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

  From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)

• Number of Treatment-emergent Sponsor Identified Immune-related Adverse Events (irAEs)

  Number of sponsor-identified irAEs (all grades) reported.

  From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)

• Number of Severe (NCI CTCAE Grade 3/4/5) Treatment-emergent Sponsor Identified irAEs

  Number of severe treatment-emergent sponsor-identified irAEs reported.

  From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)

• Number of Treatment-emergent AEs of Special Interest (AESI)

  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.

  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

  Number of NCI grade 3/4/5 treatment-emergent AESI reported

  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

  Number of participants with any TEAE resulting in death reported

  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 at Least One Lab Abnormality (NCI-CTCAE All Grades) in Hematology, Electrolytes, Liver, Chemistry

  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).

  Up to 36 months

• Number of Participants Who Developed Dose Limiting Toxicities (DLTs) (Phase 1)

  Number of participants who developed dose limiting toxicities (DLTs) in phase 1 reported

  Baseline to 28 days

• 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

  Ctrough (trough concentration) of functional cemiplimab in serum reported.

  Up to Week 16

• Peak Concentration (Cmax) of Functional Cemiplimab (REGN2810) in Serum

  Cmax (peak concentration) of functional cemiplimab in serum reported.

  Up to Week 16

• 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)

  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.

  At 12 months

• Percentage of Overall Survival (OS) at 12 Months for Participants With ndDIPG and Recurrent HGG (rHGG)

  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.

  Up to 12 months

Secondary Outcomes (2)

• Objective Response Rate (ORR) for Participants Who Have a Confirmed Complete Response (CR) or Partial Response (PR)

  Approximately 24 months

• Number of Participants With Anti-REGN2810 Antibodies (ADA)

  1st follow-up visit, approximately 25 months

Study Arms (4)

Phase 1

EXPERIMENTAL

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).

Drug: cemiplimab (monotherapy)

Efficacy with Newly Diagnosed DIPG

EXPERIMENTAL

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

Drug: cemiplimab (maintenance); Radiation: Conventional or hypofractionated

Efficacy with Newly Diagnosed HGG

EXPERIMENTAL

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

Drug: cemiplimab (maintenance); Radiation: Conventional or hypofractionated

Efficacy with Recurrent HGG

EXPERIMENTAL

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

Drug: cemiplimab (maintenance); Radiation: Re-irradiation

Interventions

cemiplimab (monotherapy) DRUG

To be administered intravenously as monotherapy in Phase 1

Also known as: REGN2810, Libtayo

Phase 1

cemiplimab (maintenance) DRUG

To be administered intravenously in combination with radiation and then used as maintenance therapy

Also known as: REGN2810, Libtayo

Efficacy with Newly Diagnosed DIPG; Efficacy with Newly Diagnosed HGG; Efficacy with Recurrent HGG

Conventional or hypofractionated RADIATION

Combined with cemiplimab IV administration

Efficacy with Newly Diagnosed DIPG; Efficacy with Newly Diagnosed HGG

Re-irradiation RADIATION

Combined with cemiplimab IV administration

Efficacy with Recurrent HGG

Eligibility Criteria

• Age: Up to 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead
• Pacific Pediatric Neuro-Oncology Consortium: collaborator

Study Sites (20)

Children's Hospital Los Angeles (CHLA)

Los Angeles, California, 90054, United States

Location

Rady Children's Hospital

San Diego, California, 92123, United States

Location

UCSF Benioff Children's Hospital

San Francisco, California, 94158, United States

Location

Children's National Health System (Children's National Medical Center)

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida- Neurosurgery

Gainesville, Florida, 32610, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Johns Hopkins - Pediatric Oncology

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute/ Boston Children's Hospital

Boston, Massachusetts, 02215, United States

Location

C. S. Mott/University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Children's Hospitals and Clinics of Minnesota

Minneapolis, Minnesota, 55404, United States

Location

University of Minnesota / Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Oregon Health & Science University (OHSU) - Doernbecher Children's Hospital

Portland, Oregon, 97239, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Texas Children's Cancer & Hematology Centers Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84113, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Related Links

• A Plain Language Summary is available on TrialSummaries.com

MeSH Terms

Conditions

Central Nervous System Neoplasms; Diffuse Intrinsic Pontine Glioma; Glioma; Recurrence

Interventions

cemiplimab; Maintenance; Congresses as Topic; Re-Irradiation

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Brain Diseases; Central Nervous System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Health Care Facilities Workforce and Services; Organizations; Health Care Economics and Organizations; Radiotherapy; Therapeutics; Retreatment

Limitations and Caveats

As all efficacy cohorts for this study have now been closed due to the futility criteria, Regeneron as Sponsor in collaboration with PNOC made a decision to close the study to further enrollment.

Results Point of Contact

• Title: Clinical Trials Administrator
• Organization: Regeneron Pharmaceuticals Inc.

clinicaltrials@regeneron.com

844-734-6643

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2018
• First Posted: October 1, 2018
• Study Start: September 24, 2018
• Primary Completion: May 10, 2023
• Study Completion: May 10, 2023
• Last Updated: April 8, 2025
• Results First Posted: October 9, 2024

Record last verified: 2025-04

Locations

US (20)