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

Phase 1

Recruiting

• Conditions: Glioma; Malignant Brain Neoplasm; Meningioma; Metastatic Malignant Neoplasm in the Brain

• Registration Number: NCT06650163
• Lead Sponsor: Jonsson Comprehensive Cancer Center

Brief Summary

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.

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 Timeline

• Study First Submitted: 2024-10-17
• Study First Submitted QC: 2024-10-17
• Study First Posted: 2024-10-21
• Study Start: 2024-12-05
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-07
• Last Update Posted: 2025-01-09
• Primary Completion: 2027-01-31
• Study Completion: 2028-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events	Up to 1 month	Analyses will be examined graphically and summarized by descriptive statistics. Data transformation may be applied to quantitative variables prior to analyses if deemed necessary.
Zirconium (Zr)-89 crefmirlimab berdoxam uptake	Up to 24 hours	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.

Trial Locations

Locations (1)

UCLA / Jonsson Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States