Zr-89 Crefmirlimab Berdoxam and Immuno-Positron Emission Tomography for the Imaging of Patients With Resectable Brain Tumors

Biologic Validation of Zr-89 Crefmirlimab Berdoxam CD8+ Minibody ImmunoPET in Human Brain Tumors

This phase I trial studies how well zirconium (Zr)-89 crefmirlimab berdoxam and immuno-positron emission tomography (PET) identifies areas of immune cell activity in patients with brain tumors that can be removed by surgery (resectable). One important predictor of the immune response is the presence and change in CD8 positive (+) tumor infiltrating lymphocytes (TIL) cells. Identifying the presence and changes in CD8+ cells can be challenging, particularly for participants with central nervous system (CNS) tumors, and usually requires invasive procedures such as repeat tissue biopsies, which may not accurately represent the immune status of the entire tumor. Zr-89 crefmirlimab berdoxam is known as a radioimmunoconjugate which consists of a radiolabeled anti-CD8+ minibody whose uptake can be imaged with PET. Upon administration, Zr 89 crefmirlimab berdoxam specifically targets and binds to the CD8+ cells. This enables PET imaging and may detect CD8+ T-cell distribution and activity and may help determine the patient's response to cancer immunotherapeutic agents more accurately. Giving Zr-89 crefmirlimab berdoxam along with undergoing immuno-PET imaging may work better at identifying immune cell activity in patients with resectable brain tumors.

Study Overview

• Status: Recruiting
• Conditions: Glioma; Meningioma; Metastatic Malignant Neoplasm in the Brain; Malignant Brain Neoplasm
• Intervention / Treatment: Procedure: Magnetic Resonance Imaging; Other: Electronic Health Record Review; Procedure: Advanced Magnetic Resonance Imaging; Procedure: Brain Surgery; Procedure: Immuno-Positron Emission Tomography Scan; Procedure: Stereotactic Biopsy; Diagnostic test: Zirconium Zr 89 Crefmirlimab Berdoxam

Detailed Description

PRIMARY OBJECTIVE:

I. To verify the specificity of Zr-89 crefmirlimab berdoxam CD8+ minibody immunoPET in identifying regions of immune cell activity in human glioma patients using stereotactic image-guided biopsies and multiplexed immunohistochemistry (IHC).

EXPLORATORY OBJECTIVE:

I. To evaluate the associations between exploratory biomarkers, clinical outcomes, and adverse events which include:

Ia. Exploring whether changes in specific magnetic resonance imaging (MRI) parameters correlate with tumor and peripheral blood immune responses; Ib. Assessing the potential change in Zr-89 crefmirlimab berdoxam uptake in tumor tissue and correlation with CD8 infiltrate in tumor tissue; Ic. Explore the correlation of visual and semi-quantitative Zr-89 crefmirlimab berdoxam PET measurements with clinical outcome.

OUTLINE:

Patients receive Zr-89 crefmirlimab berdoxam intravenously (IV) over 5-10 minutes 3 days prior to scheduled surgical resection. Approximately 24 hours after receiving Zr-89 crefmirlimab berdoxam, patients undergo immuno-PET scans. Patients then undergo scheduled standard of care surgical resection of the brain tumor and brain biopsy. Additionally, patients undergo advanced physiologic and metabolic magnetic resonance imaging (MRI) and MRI prior to surgery on study.

After completion of study treatment, patients are followed up until death.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sichen Li; Phone Number: 310-592-9091; Email: sichenli@mednet.ucla.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA / Jonsson Comprehensive Cancer Center
      • Contact: Sichen Li; Phone Number: 310-794-5663; Email: sichenli@mednet.ucla.edu
      • Principal Investigator: Robert M. Prins, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female >= 18 years of age
• Documentation of a diagnosis of brain tumor including brain metastases, any grade of gliomas and meningiomas
• The participant is scheduled for standard of care surgical tumor resection
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial

Exclusion Criteria:

• Male or female < 18 years of age
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data
• Not medically cleared for surgery
• Individuals who cannot tolerate MRI scan or PET/CT scan
• Pregnant or breast-feeding women

• Serum creatinine OR measured or calculated creatinine clearance (Glomerular filtration rate [GFR] can be use in place of creatinine or creatinine clearance [CrCl]) =< 1.5 X institutional upper limit of normal (ULN) OR >= 60mL/min for subjects with creatinine levels > 1.5 X institutional ULN

  • Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin: =< 1.5 X institutional ULN OR direct bilirubin =< institutional ULN for subjects with total bilirubin levels > 1.5 institutional ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 X institutional ULN OR =< 5 X institutional ULN for subjects with Gilberts syndrome
• Albumin >= 2.5 mg/dL
• Patients with splenic dysfunction or post splenectomy
• Any abnormalities that would be a contraindication to gadolinium-based contrast agent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (Zr-89 crefmirlimab berdoxam + ImmunoPET); Patients receive Zr-89 crefmirlimab berdoxam IV over 5-10 minutes 3 days prior to scheduled surgical resection. Approximately 24 hours after receiving Zr-89 crefmirlimab berdoxam, patients undergo immuno-PET scans. Patients then undergo scheduled standard of care surgical resection of the brain tumor and brain biopsy. Additionally, patients undergo advanced physiologic and metabolic MRI and MRI prior to surgery.

Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Other: Electronic Health Record Review; Ancillary studies; Procedure: Advanced Magnetic Resonance Imaging; Undergo advanced MRI; Other Names: AMRI; Procedure: Brain Surgery; Undergo brain surgery; Procedure: Immuno-Positron Emission Tomography Scan; Undergo immuno-PET; Other Names: Immuno-PET Scan; Procedure: Stereotactic Biopsy; Undergo stereotactic image-guided biopsy; Diagnostic test: Zirconium Zr 89 Crefmirlimab Berdoxam; Undergo Zirconium Zr 89 Crefmirlimab Berdoxam PET; Other Names: 89Zr-Df-Crefmirlimab; 89Zr-Df-IAB22M2C; 89Zr-Crefmirlimab Berdoxam; 89Zr-Desferrioxamine-IAB22M2C; Zirconium Zr 89-Df-IAB22M2C; Zirconium Zr 89-Df-Crefmirlimab; Zirconium Zr-89 Crefmirlimab Berdoxam

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Analyses will be examined graphically and summarized by descriptive statistics. Data transformation may be applied to quantitative variables prior to analyses if deemed necessary.	Up to 1 month
Zirconium (Zr)-89 crefmirlimab berdoxam uptake	Will be determined by standardized uptake value-based quantitative measures relative to CD8+ tumor infiltrating lymphocytes density determined by immunohistochemistry from tumor biopsy samples. Analyses will be examined graphically and summarized by descriptive statistics. Data transformation may be applied to quantitative variables prior to analyses if deemed necessary. Will correlate immuno-positron emission tomography uptake with cytotoxic T-cell density across all tumor samples. Multivariate cox and log rank tests will be used to compare survival outcomes.	Up to 24 hours

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Robert M Prins, UCLA / Jonsson Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2024
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2028

Study Registration Dates

• First Submitted: October 17, 2024
• First Submitted That Met QC Criteria: October 17, 2024
• First Posted (Actual): October 21, 2024

Study Record Updates

• Last Update Posted (Actual): February 5, 2026
• Last Update Submitted That Met QC Criteria: February 3, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Glioma; Meningioma; Brain Neoplasms; Investigative Techniques; Chemistry Techniques, Analytical; Spectrum Analysis; Magnetic Resonance Spectroscopy
• Other Study ID Numbers: 24-000877 (Other Identifier: UCLA / Jonsson Comprehensive Cancer Center); P30CA016042 (U.S. NIH Grant/Contract); P50CA211015 (U.S. NIH Grant/Contract); NCI-2024-08388 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); R01CA267726 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No