A Safety and Efficacy Study of Combined Fianlimab + Cemiplimab in Children and Young Adults With Recurrent or Progressive High-Grade Glioma or Posterior Fossa-A Ependymoma

A Phase 1/2 Open-Label, Safety and Efficacy Study of Neoadjuvant Fianlimab (Anti-LAG-3 Antibody) in Combination With Cemiplimab (Anti-PD-1 Antibody) and Cemiplimab Alone Followed by Adjuvant Fianlimab in Combination With Cemiplimab in Pediatric and Young Adult Participants With Recurrent or Progressive High-Grade Glioma or Pediatric and Adult Participants With Recurrent or Progressive Posterior Fossa-A Ependymoma

This study is researching an experimental drug called cemiplimab (called "study drug") and the combination of experimental drugs of fianlimab and cemiplimab (called "study drugs"). The study is focused on children and young adults with recurrent or progressive High-Grade Glioma (HGG) or ependymoma. "Recurrent" means that the cancer came back after treatment. "Progressive" means that the tumor has grown or spread.

The aim of the study is to see how safe, tolerable, and effective cemiplimab and the combination of fianlimab and cemiplimab are.

The study is looking at several other research questions, including:

• What side effects may happen from receiving the study drug(s)
• Do the study drug(s) help study participants live longer without their tumors growing or spreading
• How much of the study drug(s) is in the blood at different times
• Whether the body makes antibodies against the study drug(s) (which could make the study drug[s] less effective or lead to side effects)

Study Overview

• Status: Not yet recruiting
• Conditions: High-Grade Glioma (HGG); Posterior Fossa-A Ependymoma
• Intervention / Treatment: Drug: Cemiplimab; Drug: Cemiplimab+Fianlimab Fixed Dose Combination (FDC)

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Participant must be diagnosed with recurrent/progressive HGG or PF-A ependymoma with unequivocal progression on Magnetic Resonance Imaging (MRI) as described in the protocol
2. Participant must have histologically confirmed (at initial diagnosis or relapse) HGG or PF-A ependymoma
3. Participant must be an adequate medical candidate for surgical resection as described in the protocol
4. Karnofsky Performance Status (KPS) score ≥50 (in participants ≥16 years) or Lansky Performance Status (LPS) score ≥50 (in participants <16 years) as described in the protocol
5. Adequate organ function as described in the protocol

Key Exclusion Criteria:

1. Active autoimmune disease requiring systemic immunosuppressive therapy in the past 2 years
2. Active, serious medical illness, infection or other systemic illness which would limit participation in the trial
3. Has not yet recovered from any acute toxicities resulting from prior therapy
4. History of myocarditis
5. Prior treatment with antibodies to Programmed Cell Death Protein -1 (PD-1), Programmed Cell Death Protein Ligand -1 (PD-L1), Lymphocyte Activation Gene 3 (LAG3), or Cytotoxic T-Lymphocyte Associated protein 4 (CTLA-4)
6. Treatment with high dose systemic corticosteroids as described in the protocol
7. History of interstitial lung disease (eg, idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management

Note: Other protocol defined Inclusion/ Exclusion Criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 Arm A; Neoadjuvant Period: cemiplimab Adjuvant Period: fianlimab+cemiplimab	Drug: Cemiplimab; Administered per the protocol; Other Names: REGN2810; Libtayo®; Drug: Cemiplimab+Fianlimab Fixed Dose Combination (FDC); Administered per the protocol; Other Names: REGN3767; REGN 2810; Libtayo®
Experimental: Phase 1 Arm B; Neoadjuvant Period: fianlimab+cemiplimab Adjuvant Period: fianlimab+cemiplimab	Drug: Cemiplimab+Fianlimab Fixed Dose Combination (FDC); Administered per the protocol; Other Names: REGN3767; REGN 2810; Libtayo®
Experimental: Phase 2; Neoadjuvant Period: fianlimab+cemiplimab Adjuvant Period: fianlimab+cemiplimab	Drug: Cemiplimab+Fianlimab Fixed Dose Combination (FDC); Administered per the protocol; Other Names: REGN3767; REGN 2810; Libtayo®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Survival (OS)	12 months
Progression Free Survival (PFS)	12 months
Occurrence of Treatment Emergent Adverse Events (TEAEs)	Up to 26 months
Severity of TEAEs	Up to 26 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival	Up to 5 years
Progression Free Survival (PFS)	Up to 5 years
Severity of TEAEs	Up to 5 years
Concentrations of fianlimab in serum	Up to 5 years
Concentrations of cemiplimab in serum	Up to 5 years
Occurrence of Anti-Drug Antibody (ADA) to fianlimab	Up to 5 years
Occurrence of ADA to cemiplimab	Up to 5 years
Magnitude of ADA to fianlimab	Up to 5 years
Magnitude of ADA to cemiplimab	Up to 5 years
Death due to any cause	Up to 5 years
Occurrence of TEAEs	Up to 5 years

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): August 31, 2026
• Primary Completion (Estimated): August 27, 2032
• Study Completion (Estimated): August 17, 2034

Study Registration Dates

• First Submitted: April 28, 2026
• First Submitted That Met QC Criteria: April 28, 2026
• First Posted (Actual): May 5, 2026

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Ependymoma; Progressive; Recurrent; Pediatric Central Nervous System (CNS) tumors; Posterior Fossa A (PF-A)
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Pathological Conditions, Signs and Symptoms; Neoplasms; Recurrence; Glioma; Ependymoma; cemiplimab
• Other Study ID Numbers: R3767-ONC-2320; 2025-521485-96-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No