NCT07422363

Testing the Combination of Anti-cancer Drugs Actimab-A and Cemiplimab (REGN2810) to Improve Outcomes for Patients With Recurrent Glioblastoma

A Phase I Trial of 225Ac-anti-CD33 and PD1-Inhibitor in Recurrent Glioblastoma

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of Actimab-A when given together with cemiplimab (REGN2810) in treating patients with glioblastomas that have come back after a period of improvement (recurrent). Actimab-A consists of the monoclonal antibody lintuzumab combined with the radioactive drug actinium Ac 225. Lintuzumab specifically binds to the cell surface antigen CD33 which is found on the glioblastoma cells and delivers the actinium Ac 225. This may allow the glioblastoma to be found and treated by Actimab-A. Immunotherapy with monoclonal antibodies, such as cemiplimab (REGN2810), may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving Actimab-A with cemiplimab (REGN2810) may be safe, tolerable and/or effective in treating recurrent glioblastoma.

Detailed description

PRIMARY OBJECTIVE: I. To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of actinium Ac 225 lintuzumab (Actimab-A) in combination with cemiplimab (REGN2810) in recurrent glioblastoma. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To evaluate the impact of baseline tumor mutational burden on response. III. To evaluate the pharmacokinetics of cemiplimab (REGN2810). IV. To evaluate the alpha radiation dosimetry of Actimab-A. EXPLORATORY OBJECTIVES: I. To evaluate circulating tumor deoxyribonucleic acid (DNA) (ctDNA) as a predictor for treatment response. II. To evaluate the impact of baseline tumor expression signatures on response. III. To evaluate the correlation of changes in cytokine production and arginase activity with response. IV. To evaluate the impact of combination treatment on peripheral immune cells. V. To correlate adverse events (AEs) with absorbed doses of radiation to organs at risk (OARs) such as the kidneys. OUTLINE: This is a dose-escalation study of Actimab-A in combination with cemiplimab. Patients receive Actimab-A intravenously (IV) over 30 minutes on either days 1 and 22 of cycles 1-3, days 1 and 22 of cycles 1 and 2, or days 1 and 22 of cycle 1 and day 1 of cycle 2. Patients also receive cemiplimab IV over 30 minutes on days 1 and 22 of each cycle. Cycles repeat every 42 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and radiologic imaging throughout the study and positron emission tomography (PET)/computed tomography (CT) on study. Patients may also optionally undergo single-photon emission computed tomography (SPECT)/CT on study. After completion of study treatment, patients are followed up at 3 weeks, 30 days, and then every 3 months for up to 2 years.

Conditions

• Recurrent Glioblastoma, IDH-Wildtype
• Recurrent Gliosarcoma
• Recurrent WHO Grade 4 Glioma

Interventions

Type	Name	Description
RADIATION	Actinium Ac 225 Lintuzumab	Given IV
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
BIOLOGICAL	Cemiplimab	Given IV
PROCEDURE	Computed Tomography	Undergo PET/CT and/or SPECT/CT
PROCEDURE	Positron Emission Tomography	Undergo PET/CT
PROCEDURE	Radiologic Imaging Procedure	Undergo radiologic imaging
PROCEDURE	Single Photon Emission Computed Tomography	Undergo SPECT/CT

Timeline

• Start date: 2026-06-28
• Primary completion: 2027-02-28
• Completion: 2027-02-28
• First posted: 2026-02-20
• Last updated: 2026-04-13

Regulatory

• FDA-regulated drug study