Clinical trial

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

Name

R2810-ONC-1690

Description

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

Trial arms

Trial start

2018-09-24

Estimated PCD

2023-05-10

Trial end

2023-05-10

Status

Terminated

Phase

Early phase I

Treatment

cemiplimab (monotherapy)

To be administered intravenously as monotherapy in Phase 1

Arms:

Phase 1

Other names:

REGN2810, Libtayo

cemiplimab (maintenance)

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

Arms:

Efficacy with Newly Diagnosed DIPG, Efficacy with Newly Diagnosed HGG, Efficacy with Recurrent HGG

Other names:

REGN2810, Libtayo

Conventional or hypofractionated

Combined with cemiplimab IV administration

Arms:

Efficacy with Newly Diagnosed DIPG, Efficacy with Newly Diagnosed HGG

Re-irradiation

Combined with cemiplimab IV administration

Arms:

Efficacy with Recurrent HGG

Size

Primary endpoint

Incidence and severity of treatment-emergent adverse events (TEAEs)

Up to 36 months

Incidence and severity of immune-related adverse events (irAEs)

Up to 36 months

Incidence and severity of adverse events of special interest (AESIs)

Up to 36 months

Incidence and severity of serious adverse events (SAEs)

Up to 36 months

Incidence of deaths

Up to 36 months

Incidence of laboratory abnormalities

Up to 36 months

Incidence of dose limiting toxicities (DLTs)

Baseline to 28 days

Incidence of dose limiting toxicities (DLTs)

Up to 4 weeks post radiation therapy

PK for REGN2810 estimated Observed terminal half-life (t1/2)

Up to 24 months

PK for REGN2810 Concentration at end of infusion (Ceoi)

Up to 24 months

PK for REGN2810 Area under the curve (AUC2w)

Up to 24 months

Overall survival among newly diagnosed DIPG and recurrent HGG patients

Up to 36 months

Progression-free survival among newly diagnosed HGG patients

Up to 36 months

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

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 57, 'type': 'ACTUAL'}}

Updated at

2023-07-10

1 organization

1 product

6 indications

Organization

Regeneron Pharmaceuticals

Product

Cemiplimab

Indication

Relapsed Solid Tumor

Indication