Clinical trial NCT03690869: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
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
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Pacific Pediatric Neuro-Oncology Consortium
First posted: 2018-10-01
Enrollment: 57
Sex: ALL
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Number of Treatment-emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)
measure: Number of Severe (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] Grade 3/4/5) TEAEs
timeFrame: From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)
measure: Number of Treatment-emergent Sponsor Identified Immune-related Adverse Events (irAEs)
timeFrame: From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)
measure: Number of Severe (NCI CTCAE Grade 3/4/5) Treatment-emergent Sponsor Identified irAEs
timeFrame: From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)
measure: Number of Treatment-emergent AEs of Special Interest (AESI)
timeFrame: From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)
measure: Number of NCI Grade 3/4/5 Treatment-emergent AESI
timeFrame: From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)
measure: Number of Participants With Any TEAE Resulting in Death
timeFrame: From first dose of study drug up to 90 days after the last dose of study treatment (up to 36 months)
measure: Number of Participants With at Least One Lab Abnormality (NCI-CTCAE All Grades) in Hematology, Electrolytes, Liver, Chemistry
timeFrame: Up to 36 months
measure: Number of Participants Who Developed Dose Limiting Toxicities (DLTs) (Phase 1)
timeFrame: Baseline to 28 days
measure: Number of Participants Who Developed DLTs (Efficacy Phase)
timeFrame: Up to 4 weeks post radiation therapy
measure: Elimination Half-life (t1/2) of Functional Cemiplimab (REGN2810) in Serum
timeFrame: Up to 24 months
measure: Trough Concentration (Ctrough) of Functional Cemiplimab (REGN2810) in Serum
timeFrame: Up to Week 16
measure: Peak Concentration (Cmax) of Functional Cemiplimab (REGN2810) in Serum
timeFrame: Up to Week 16
measure: Area Under the Concentration-time Curve (AUC) of Functional Cemiplimab (REGN2810) in Serum
timeFrame: Up to 24 months
measure: Percentage of Progression-free Survival (PFS) at 12 Months for Participants With Newly Diagnosed HGG (ndHGG)
timeFrame: At 12 months
measure: Percentage of Overall Survival (OS) at 12 Months for Participants With ndDIPG and Recurrent HGG (rHGG)
timeFrame: Up to 12 months
Secondary outcomes:
measure: Objective Response Rate (ORR) for Participants Who Have a Confirmed Complete Response (CR) or Partial Response (PR)
timeFrame: Approximately 24 months
measure: Number of Participants With Anti-REGN2810 Antibodies (ADA)
timeFrame: 1st follow-up visit, approximately 25 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles (CHLA)
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital
state: California
city: San Francisco
country: United States
facility: UCSF Benioff Children's Hospital
state: California
city: Washington
country: United States
facility: Children's National Health System (Children's National Medical Center)
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida- Neurosurgery
state: Florida
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins - Pediatric Oncology
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute/ Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: C. S. Mott/University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota / Masonic Cancer Center
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University (OHSU) - Doernbecher Children's Hospital
state: Oregon
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Houston
country: United States
facility: Texas Children's Cancer & Hematology Centers Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: