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

Jonsson Comprehensive Cancer Center

Status and phase

Enrolling

Phase 1

Conditions

Malignant Brain Neoplasm

Glioma

Meningioma

Metastatic Malignant Neoplasm in the Brain

Treatments

Procedure: Brain Surgery

Procedure: Advanced Magnetic Resonance Imaging

Procedure: Magnetic Resonance Imaging

Other: Electronic Health Record Review

Procedure: Stereotactic Biopsy

Diagnostic Test: Zirconium Zr 89 Crefmirlimab Berdoxam

Procedure: Immuno-Positron Emission Tomography Scan

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT06650163

P50CA211015 (U.S. NIH Grant/Contract)

NCI-2024-08388 (Registry Identifier)

24-000877 (Other Identifier)

P30CA016042 (U.S. NIH Grant/Contract)

R01CA267726 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment

20 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Diagnostic

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

20 participants in 1 patient group

Treatment (Zr-89 crefmirlimab berdoxam + ImmunoPET)

Experimental group

Description:

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.