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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
57
To be administered intravenously as monotherapy in Phase 1
To be administered intravenously in combination with radiation and then used as maintenance therapy
Combined with cemiplimab IV administration
Combined with cemiplimab IV administration
Children's Hospital Los Angeles (CHLA)
Los Angeles, California, United States
Rady Children's Hospital
San Diego, California, United States
UCSF Benioff Children's Hospital
San Francisco, California, United States
Children's National Health System (Children's National Medical Center)
Washington D.C., District of Columbia, United States
University of Florida- Neurosurgery
Gainesville, Florida, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
Johns Hopkins - Pediatric Oncology
Baltimore, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Dana Farber Cancer Institute/ Boston Children's Hospital
Boston, Massachusetts, United States
C. S. Mott/University of Michigan
Ann Arbor, Michigan, United States
...and 10 more locations
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.
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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).
Time frame: 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
Time frame: Baseline to 28 days
Number of Participants Who Developed DLTs (Efficacy Phase)
Time frame: Up to 4 weeks post radiation therapy
Elimination Half-life (t1/2) of Functional Cemiplimab (REGN2810) in Serum
Time frame: Up to 24 months
Trough Concentration (Ctrough) of Functional Cemiplimab (REGN2810) in Serum
Ctrough (trough concentration) of functional cemiplimab in serum reported.
Time frame: Up to Week 16
Peak Concentration (Cmax) of Functional Cemiplimab (REGN2810) in Serum
Cmax (peak concentration) of functional cemiplimab in serum reported.
Time frame: Up to Week 16
Area Under the Concentration-time Curve (AUC) of Functional Cemiplimab (REGN2810) in Serum
Time frame: 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.
Time frame: 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.
Time frame: Up to 12 months
Objective Response Rate (ORR) for Participants Who Have a Confirmed Complete Response (CR) or Partial Response (PR)
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
Time frame: Approximately 24 months
Number of Participants With Anti-REGN2810 Antibodies (ADA)
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)
Time frame: 1st follow-up visit, approximately 25 months
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