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
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| ClinicalTrials.gov Identifier: NCT03690869 |
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Recruitment Status :
Terminated
(Sponsor Decision)
First Posted : October 1, 2018
Last Update Posted : July 10, 2023
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Sponsor:
Regeneron Pharmaceuticals
Collaborator:
Pacific Pediatric Neuro-Oncology Consortium
Information provided by (Responsible Party):
Regeneron Pharmaceuticals
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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
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Relapsed Solid Tumor Refractory Solid Tumor Relapsed Central Nervous System Tumor Refractory Central Nervous System Tumor Diffuse Intrinsic Pontine Glioma High Grade Glioma | Drug: cemiplimab (monotherapy) Drug: cemiplimab (maintenance) Radiation: Conventional or hypofractionated Radiation: Re-irradiation | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 57 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | September 24, 2018 |
| Actual Primary Completion Date : | May 10, 2023 |
| Actual Study Completion Date : | May 10, 2023 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Phase 1
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).
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Drug: cemiplimab (monotherapy)
To be administered intravenously as monotherapy in Phase 1
Other Names:
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Experimental: Efficacy with Newly Diagnosed DIPG
≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy
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Drug: cemiplimab (maintenance)
To be administered intravenously in combination with radiation and then used as maintenance therapy
Other Names:
Radiation: Conventional or hypofractionated Combined with cemiplimab IV administration |
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Experimental: Efficacy with Newly Diagnosed HGG
≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy
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Drug: cemiplimab (maintenance)
To be administered intravenously in combination with radiation and then used as maintenance therapy
Other Names:
Radiation: Conventional or hypofractionated Combined with cemiplimab IV administration |
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Experimental: Efficacy with Recurrent HGG
≥ 3 to < 12 years cohort and 12 to ≤ 25 years cohort with combination of cemiplimab and radiation therapy
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Drug: cemiplimab (maintenance)
To be administered intravenously in combination with radiation and then used as maintenance therapy
Other Names:
Radiation: Re-irradiation Combined with cemiplimab IV administration |
Primary Outcome Measures :
- Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 36 months ]Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy
- Incidence and severity of immune-related adverse events (irAEs) [ Time Frame: Up to 36 months ]Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy
- Incidence and severity of adverse events of special interest (AESIs) [ Time Frame: Up to 36 months ]Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy
- Incidence and severity of serious adverse events (SAEs) [ Time Frame: Up to 36 months ]Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy
- Incidence of deaths [ Time Frame: Up to 36 months ]Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy
- Incidence of laboratory abnormalities [ Time Frame: Up to 36 months ]Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy Grade 3 or higher per CTCAE v4.0
- Incidence of dose limiting toxicities (DLTs) [ Time Frame: Baseline to 28 days ]Phase 1: given as monotherapy
- Incidence of dose limiting toxicities (DLTs) [ Time Frame: Up to 4 weeks post radiation therapy ]Efficacy Phase: given in combination with radiation therapy
- PK for REGN2810 estimated Observed terminal half-life (t1/2) [ Time Frame: Up to 24 months ]Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy
- PK for REGN2810 Concentration at end of infusion (Ceoi) [ Time Frame: Up to 24 months ]Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy
- PK for REGN2810 Area under the curve (AUC2w) [ Time Frame: Up to 24 months ]Phase 1: given as monotherapy Efficacy Phase: given in combination with radiation therapy
- Overall survival among newly diagnosed DIPG and recurrent HGG patients [ Time Frame: Up to 36 months ]Efficacy Phase: given in combination with radiation therapy
- Progression-free survival among newly diagnosed HGG patients [ Time Frame: Up to 36 months ]Efficacy Phase: given in combination with radiation therapy
Secondary Outcome Measures :
- Objective response rate (ORR) [ Time Frame: Approximately 24 months ]Phase 1: given as monotherapy
- Incidence of anti-drug antibodies (ADA) to REGN2810 given as monotherapy [ Time Frame: 1st follow-up visit, approximately 25 months ]Phase 1: given as monotherapy
- Incidence of anti-drug antibodies (ADA) to REGN2810 given in combination with radiation [ Time Frame: 1st follow-up visit, approximately 25 months ]Efficacy Phase: given in combination with radiation therapy
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| Ages Eligible for Study: | up to 25 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Key Inclusion Criteria:
- 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
Key Exclusion Criteria:
- 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
Note: Other protocol-defined Inclusion/Exclusion criteria apply
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03690869
Locations
Show 20 study locations
Sponsors and Collaborators
Regeneron Pharmaceuticals
Pacific Pediatric Neuro-Oncology Consortium
Investigators
| Study Director: | Clinical Trial Management | Regeneron Pharmaceuticals |
| Responsible Party: | Regeneron Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT03690869 |
| Other Study ID Numbers: |
R2810-ONC-1690 PNOC 013 (CC#160825) ( Other Identifier: Pacific Pediatric Neuro-Oncology Consortium (PNOC) ) |
| First Posted: | October 1, 2018 Key Record Dates |
| Last Update Posted: | July 10, 2023 |
| Last Verified: | June 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Regeneron Pharmaceuticals:
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Newly Diagnosed Recurrent Refractory |
Additional relevant MeSH terms:
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Neoplasms Glioma Nervous System Neoplasms Central Nervous System Neoplasms Diffuse Intrinsic Pontine Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue |
Nervous System Diseases Neoplasms by Site Brain Stem Neoplasms Infratentorial Neoplasms Brain Neoplasms Brain Diseases Central Nervous System Diseases Cemiplimab Antineoplastic Agents, Immunological Antineoplastic Agents |