Imaging with Zr-89 Crefmirlimab Berdoxam for Brain Cancer

Overseen By Sichen Li

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Jonsson Comprehensive Cancer Center

Disqualifiers: Pregnancy, Breastfeeding, Splenic dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 3 days

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate a new imaging technique's ability to detect immune cell activity in individuals with surgically removable brain tumors. The technique employs Zr-89 crefmirlimab berdoxam, an experimental imaging agent, to visualize immune cells on a PET scan. This could enhance doctors' understanding of a patient's immune response to cancer treatments. Individuals diagnosed with a brain tumor and scheduled for surgery may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding the treatment's effects in humans, offering participants the opportunity to be among the first to experience this new imaging technique.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What prior data suggests that this imaging technique is safe for patients with brain tumors?

Research has shown that Zr-89 crefmirlimab berdoxam, used for brain cancer imaging, is generally safe. As this is an early trial, the primary goal is to ensure the treatment's safety for participants. So far, studies have not raised any safety concerns.

Zr-89 crefmirlimab berdoxam attaches to certain immune cells, allowing doctors to visualize these cells during PET scans. This is important because it can reveal how active the immune cells are in fighting the tumor. Although the study is in its early stages, the treatment is designed to be safe when used correctly. It focuses on imaging rather than directly attacking the tumor, which may reduce the risk of side effects.

While more research is needed to confirm long-term safety, current findings are promising. For those considering joining a trial, these early results suggest that the treatment is likely safe. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard of care for brain cancer, which typically involves surgery, radiation, and chemotherapy, Zr-89 crefmirlimab berdoxam introduces an innovative approach by combining targeted imaging with immuno-PET. This treatment uses a special radio-labeled antibody to highlight cancer cells in the brain, enabling more precise imaging before surgical resection. Researchers are excited because this method could potentially improve the accuracy of tumor removal and provide detailed insights into the tumor's behavior, which current imaging techniques might miss. This could lead to better surgical outcomes and personalized treatment strategies.

What evidence suggests that this imaging technique is effective for identifying immune cell activity in brain cancer?

In this trial, participants will receive Zr-89 crefmirlimab berdoxam combined with a special scan called immuno-PET. Research has shown that Zr-89 crefmirlimab berdoxam, when paired with immuno-PET, can effectively detect immune cell activity in brain tumors. This treatment targets CD8+ cells, key indicators of the body's fight against cancer. By attaching to these cells, the treatment enables PET scans to reveal where immune cells are active in the tumor. Early results suggest this method might identify these cells more effectively than traditional, more invasive methods. This could help doctors assess how well a patient's immune system responds to treatment. ^{1 2 4 5 6}

Who Is on the Research Team?

Robert M Prins

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with brain tumors that can be surgically removed. It's suitable for those who need their immune cell activity checked without invasive procedures like repeat biopsies, which may not show the full picture.

Inclusion Criteria

I have been diagnosed with a brain tumor, including brain metastases, gliomas, or meningiomas.

The participant (or legally acceptable representative if applicable) provides written informed consent for the trial

I am scheduled for surgery to remove my tumor.

Exclusion Criteria

Pregnant or breast-feeding women

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

Individuals who cannot tolerate MRI scan or PET/CT scan

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive Zr-89 crefmirlimab berdoxam intravenously over 5-10 minutes 3 days prior to scheduled surgical resection, followed by immuno-PET scans approximately 24 hours later.

3 days

1 visit (in-person)

Surgical Resection and Biopsy

Patients undergo scheduled standard of care surgical resection of the brain tumor and brain biopsy.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment until death.

Up to 1 month

What Are the Treatments Tested in This Trial?

Interventions

• Immuno-Positron Emission Tomography Scan
• Zr-89 Crefmirlimab Berdoxam

Trial Overview The study tests Zr-89 crefmirlimab berdoxam combined with immuno-PET scans to track CD8+ T-cell activity in the tumor. This could help assess how well a patient might respond to cancer immunotherapy more accurately than current methods.

How Is the Trial Designed?

Group I: Treatment (Zr-89 crefmirlimab berdoxam + ImmunoPET) Experimental Treatment 7 Interventions

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.

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study involving 18 patients with advanced melanoma or non-small-cell lung cancer, the uptake of 89Zr-labeled pembrolizumab in tumors was found to correlate with treatment response and patient survival, suggesting it could be a useful predictor of therapy effectiveness.

The optimal dose for 89Zr-pembrolizumab was determined to be 5 mg, with the best imaging results observed on day 7 after administration, indicating a potential timeline for monitoring treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

89Zr-pembrolizumab imaging as a non-invasive approach to assess clinical response to PD-1 blockade in cancer. Kok, IC., Hooiveld, JS., van de Donk, PP., et al.[2022]

The bispecific antibody Adu-8D3 showed a 7-fold higher brain uptake compared to Aducanumab and effectively targeted amyloid-β plaques in a mouse model of Alzheimer's disease, indicating its potential as a more effective treatment option.

The 89Zr-immuno-PET imaging technique successfully detected low levels of amyloid plaques in young mice, suggesting it could be a valuable tool for early diagnosis and monitoring of Alzheimer's disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of 89Zr-DFO*-immuno-PET to assess improved target engagement of a bispecific anti-amyloid-ß monoclonal antibody. Stergiou, N., Wuensche, TE., Schreurs, M., et al.[2023]

The study developed a novel imaging technique using 89Zr-labeled avelumab to non-invasively characterize PD-L1 expression in breast cancer, showing high specificity and effectiveness in tumor imaging.

PET imaging revealed significant uptake of the tracer in tumors, spleen, and lymph nodes, indicating its potential for evaluating treatment responses in breast cancer patients undergoing immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo characterization of PD-L1 expression in breast cancer by immuno-PET with 89Zr-labeled avelumab. Li, M., Ehlerding, EB., Jiang, D., et al.[2020]

In a first-in-human study involving 22 patients with various tumor types, PET imaging using zirconium-89-labeled atezolizumab showed promise in predicting responses to PD-L1 blockade therapy, with better correlation to clinical outcomes than traditional biopsy-based methods.

The imaging revealed high and heterogeneous uptake of the tracer in tumors, suggesting that molecular PET imaging could be a more effective tool for assessing PD-L1 status and guiding treatment decisions compared to current diagnostics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

89Zr-atezolizumab imaging as a non-invasive approach to assess clinical response to PD-L1 blockade in cancer. Bensch, F., van der Veen, EL., Lub-de Hooge, MN., et al.[2019]

The NANO-RAD study is a phase I clinical trial investigating the safety and tolerability of AGuIX nanoparticles combined with whole brain radiotherapy (WBRT) in patients with multiple brain metastases, aiming to determine the maximum-tolerated dose.

This study will assess the pharmacokinetics and distribution of AGuIX in brain metastases and surrounding tissue, with a total of 15-18 patients planned for recruitment, highlighting its potential as a radiosensitizer in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of multiple brain metastases using gadolinium nanoparticles and radiotherapy: NANO-RAD, a phase I study protocol. Verry, C., Sancey, L., Dufort, S., et al.[2020]

The monoclonal antibody ramucirumab (RAM) was successfully radiolabelled with zirconium-89, allowing for effective targeting and imaging of VEGFR2-positive tumors in prostate and ovarian cancer models.

In vivo studies demonstrated significant uptake of the radiolabelled RAM in tumors, with high tumor-to-muscle ratios observed over several days, indicating its potential for use in imaging and possibly treating angiogenesis-related cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of anti-VEGFR2 monoclonal antibody ramucirumab labelled with zirconium-89 for tumour imaging. Novy, Z., Janousek, J., Barta, P., et al.[2022]

Bexmarilimab, a monoclonal antibody targeting CLEVER-1, shows promise in cancer immunotherapy and fibrosis treatment, with preclinical studies in rabbits indicating effective targeting of fibrotic tissues.

The study demonstrated that 89Zr-labeled bexmarilimab has a favorable distribution profile, with significant uptake in fibrotic renal tissue, supporting its potential use in human PET studies for patient stratification and treatment monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of 89Zr-Desferrioxamine-Bexmarilimab, a Humanized Antibody Against Common Lymphatic Endothelial and Vascular Endothelial Receptor-1, in a Rabbit Model of Renal Fibrosis. Moisio, O., Virta, J., Yatkin, E., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06650163?cond=%22Meningioma%22&intr=%22Chelating%20Agents%22&viewType=Table&rank=3

NCT06650163 | Zr-89 Crefmirlimab Berdoxam and ... Giving Zr-89 crefmirlimab berdoxam along with undergoing immuno-PET imaging may work better at identifying immune cell activity in patients with resectable ...

2. trialx.com trialx.com/clinical-trials/listings/314715/zr-89-crefmirlimab-berdoxam-and-immuno-positron-emission-tomography-for-the-imaging-of-patients-with-resectable-brain-tumors/

Zr-89 Crefmirlimab Berdoxam and Immuno-Positron ... This phase I trial studies how well zirconium (Zr)-89 crefmirlimab berdoxam and immuno-positron emission tomography (PET) identifies areas of immune cell ...

3. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/zirconium-zr-89-crefmirlimab-berdoxam?pn=1

Clinical Trials Using Zirconium Zr 89 Crefmirlimab Berdoxam Review the clinical trials studying zirconium zr 89 crefmirlimab berdoxam on this list and use the filters to refine the results by age and location.

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/547795

Zr-89 Crefmirlimab Berdoxam and Immuno-Positron ... This phase I trial studies how well zirconium (Zr)-89 crefmirlimab berdoxam and immuno-positron emission tomography (PET) identifies areas ...

5. trials.braintumor.org trials.braintumor.org/trials/NCT05279027

Zr89 + PET Companion Trial - National Brain Tumor Society This is a single institution, prospective cohort study of Zirconium Zr 89 Crefmirlimab Berdoxa PET/CT as an early measure of response in patients with melanoma.

6. uclahealth.org uclahealth.org/clinical-trials/zr-89-crefmirlimab-berdoxam-and-immuno-positron-emission

Zr-89 Crefmirlimab Berdoxam and Immuno-Positron ... This phase I trial studies how well zirconium (Zr)-89 crefmirlimab berdoxam and immuno-positron emission tomography (PET) identifies areas of immune cell ...