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
3 other identifiers
interventional
30
0 countries
N/A
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Dec 2026
Shorter than P25 for phase_1
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 19, 2026
CompletedFirst Posted
Study publicly available on registry
February 20, 2026
CompletedStudy Start
First participant enrolled
December 4, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
February 28, 2027
Study Completion
Last participant's last visit for all outcomes
February 28, 2027
June 12, 2026
June 1, 2026
3 months
February 19, 2026
June 11, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
Dose limiting toxicities (DLTs)
DLT is defined as any grade ≥ 3 non-hematologic toxicity regardless of supportive care or grade ≥ 4 hematologic toxicity per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 that occurs during the first six (6) weeks after initiating treatment. DLTs per CTCAE version 5.0 will be tabulated for each dose level.
Up 6 weeks after initiating treatment
Maximum tolerated dose (MTD)
Will use a Bayesian optimal interval design to find the MTD. Recommended phase 2 dose determination will include both the DLT period for the MTD, as well as consideration of later cycle adverse events (AEs) and the overall safety profile, and available correlatives and will be determined by the study team and Cancer Therapy Evaluation Program collaborators.
Up to 18 months
Frequency of AEs
AEs per CTCAE version 5.0 will be tabulated for each dose level.
Up to 30 days after last dose of study drug
Secondary Outcomes (6)
Objective response rate (ORR)
Up to 2 years
Progression free survival
From randomization or initiation of treatment to the occurrence of disease progression or death, assessed up to 2 years
Overall survival
From date of diagnosis until the patient's death from any cause, assessed up to 2 years
Tumor mutational burden (TMB) (whole exome sequencing [somatic])
At baseline
Trough and post end of infusion concentrations of cemiplimab (REGN2810) in serum
At cycle (C) 1 day (D) 1, C1D22, C2D1, C2D22, C3D1, and C3D22 (Cycle = 42 days)
- +1 more secondary outcomes
Other Outcomes (9)
Change in variant allele frequencies (VAF) of tumor mutations in circulating tumor deoxyribonucleic acid (ctDNA)
Baseline to C3 (Cycle = 42 days)
Expression of immune checkpoint receptors and myeloid derived suppressor cells markers by ribonucleic acid sequencing (RNAseq) on archival tissue
At C1D1, C1D8, C1D22, C2D1, C2D22, C3D1, C3D22, and progression of disease (Cycle = 42 days)
Protein expression of CD33 and PD-L1 by immunohistochemistry on archival tissue
At baseline
- +6 more other outcomes
Study Arms (1)
Treatment (Actimab-A, cemiplimab)
EXPERIMENTALPatients receive Actimab-A 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 PET/CT on study. Patients may also optionally undergo SPECT/CT on study.
Interventions
Given IV
Undergo SPECT/CT
Given IV
Undergo blood sample collection
Undergo PET/CT and/or SPECT/CT
Undergo PET/CT
Eligibility Criteria
You may qualify if:
- 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)
- Previous first-line treatment with at least radiotherapy (prior dose ≥ 40 gray \[Gy\])
- Note: Prior temozolomide, prior tumor-treatment fields and/or Gliadel wafer (if placed at initial tumor resection) are allowed, but none of these are required
- Last radiation ≥ 6 months (182 days) prior to enrollment if received ≥ 60 Gy or ≥ 3 months (84 days) if received \< 60 Gy to limit the risk of radiation necrosis
- No previous treatment with anti PD1, PDL1, CTLA-4, or other immune checkpoint inhibitors
- No tumor-directed therapy for most recent progression
- Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of Actimab-A in combination with cemiplimab (REGN2810) in patients \< 18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
- Absolute neutrophil count ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Hemoglobin ≥ 9 g/dL
- Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled)
- +9 more criteria
You may not qualify if:
- 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)
- Patients being treated with systemic immunostimulatory agents (including, but not limited to, interferon \[IFN\]-α or interleukin \[IL\]-2) within four (4) weeks prior to cycle 1 day 1. The study principal investigator (PI) must be consulted if a patient was being treated with any antibody within four (4) half-lives of said antibody
- Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-alpha \[TNF-α\] agents) within two (2) weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:
- Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study
- Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study
- Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
- Pregnant women are excluded from this study because cemiplimab (REGN2810) is an anti-PD-1 agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cemiplimab (REGN2810), breastfeeding should be discontinued if the mother is treated with cemiplimab (REGN2810). These potential risks also apply to Actimab-A
- Early disease progression prior to three (3) months from the completion of radiotherapy
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy defined as dexamethasone \> 2 mg/day or bioequivalent for at least three (3) consecutive days within two (2) weeks of start of study drug
- Has active autoimmune disease that has required systemic treatment in the past two (2) years
- Prior administration of a radiopharmaceutical unless 10 or more effective half-lives have elapsed before injection of Actimab-A (Ac225-lintuzumab)
- Previous treatment with bevacizumab for the treatment of glioblastoma with therapeutic intent, or with bevacizumab as supportive therapy (e.g., edema reduction) within six (6) weeks (42 days) of initiation of study treatment. This is approximately two (2) half-lives which is justified based on median time to rebound tumor progression following bevacizumab discontinuation (6.1 weeks), median time to clinical deterioration following bevacizumab discontinuation after disease progression from multiple studies indicating that washout periods longer than eight (8) weeks are unlikely to be tolerated, and perioperative outcome data after neoadjuvant bevacizumab demonstrating relative safety of surgical intervention at least four (4) weeks after bevacizumab discontinuation (Sener et al., 2024)
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Megan Mantica
UPMC Hillman Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 19, 2026
First Posted
February 20, 2026
Study Start (Estimated)
December 4, 2026
Primary Completion (Estimated)
February 28, 2027
Study Completion (Estimated)
February 28, 2027
Last Updated
June 12, 2026
Record last verified: 2026-06
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.