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

Regeneron Pharmaceuticals

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Relapsed Central Nervous System Tumor; Relapsed Solid Tumor; High Grade Glioma; Refractory Central Nervous System Tumor; Diffuse Intrinsic Pontine Glioma; Refractory Solid Tumor

Treatments: Radiation: Re-irradiation; Radiation: Conventional or hypofractionated; Drug: cemiplimab (monotherapy); Drug: cemiplimab (maintenance)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03690869

R2810-ONC-1690

PNOC 013 (CC#160825) (Other Identifier)

Details and patient eligibility

About

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

Enrollment: 57 patients

Sex: All

Ages: Under 25 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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57 participants in 4 patient groups

Phase 1

Experimental group

Description:

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).

Treatment:

Drug: cemiplimab (monotherapy)

Efficacy with Newly Diagnosed DIPG

Experimental group

Description:

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

Treatment:

Drug: cemiplimab (maintenance)

Radiation: Conventional or hypofractionated

Efficacy with Newly Diagnosed HGG

Experimental group

Description:

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

Treatment:

Drug: cemiplimab (maintenance)

Radiation: Conventional or hypofractionated

Efficacy with Recurrent HGG

Experimental group

Description:

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

Treatment:

Drug: cemiplimab (maintenance)

Radiation: Re-irradiation