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.
Patients must have histologically or cytologically confirmed glioblastoma isocitrate dehydrogenase wild type (IDH-WT) World Health Organization (WHO) grade 4 inclusive of gliosarcoma (Louis et al., 2021)
Note: Isocitrate dehydrogenase (IDH) status confirmed by immunohistochemistry (IHC) for IDH1 R132H + next-generation sequencing (NGS) for IDH1 and IDH2 hotspots
Evidence of recurrent disease (RD) that is measurable (1 x 1cm) at first or second relapse demonstrated by disease progression using Response Assessment in Neuro-Oncology 2.0 (RANO 2.0) criteria, unless the recurrence is outside the radiation field or has been histologically documented
Tumor O-6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) methylation status must be available from any prior GBM tumor specimen; results of routinely used methods for MGMT methylation testing (e.g., mutagenically separated polymerase chain reaction [MSPCR] or quantitative polymerase chain reaction [PCR] are acceptable)
Patients who have not recovered to grade 0 or 1 or pre-treatment baseline from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
Patients who are receiving any other investigational agents
Presence of extracranial metastatic or leptomeningeal disease
History of allergic reactions attributed to compounds of similar chemical or biologic composition to Actimab-A and cemiplimab (REGN2810)