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

Trial Summary

What is the purpose of this trial?

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.

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 data supports the effectiveness of the treatment Zr-89 Crefmirlimab Berdoxam for brain cancer?

Research on similar treatments using zirconium-89 (Zr-89) labeled antibodies, like pembrolizumab and atezolizumab, shows that PET imaging can help predict patient responses to cancer therapies by highlighting areas of high antibody uptake in tumors. This suggests that Zr-89 Crefmirlimab Berdoxam might also be effective in identifying and monitoring brain cancer treatment responses. ^{1 2 3 4 5}

What makes the drug Zr-89 Crefmirlimab Berdoxam unique for brain cancer?

Zr-89 Crefmirlimab Berdoxam is unique because it uses a radioactive element, zirconium-89, to help visualize brain cancer through imaging. This approach allows doctors to see how the drug targets specific cancer cells, which can be different from traditional treatments that do not provide this imaging capability. ^{2 3 5 6 7}

Research Team

Robert M Prins

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

89Zr-pembrolizumab imaging as a non-invasive approach to assess clinical response to PD-1 blockade in cancer. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

In vivo characterization of PD-L1 expression in breast cancer by immuno-PET with 89Zr-labeled avelumab. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of anti-VEGFR2 monoclonal antibody ramucirumab labelled with zirconium-89 for tumour imaging. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

89Zr-atezolizumab imaging as a non-invasive approach to assess clinical response to PD-L1 blockade in cancer. [2019]

5. United States 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. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Treatment of multiple brain metastases using gadolinium nanoparticles and radiotherapy: NANO-RAD, a phase I study protocol. [2020]

7. Germany pubmed.ncbi.nlm.nih.gov

Application of 89Zr-DFO*-immuno-PET to assess improved target engagement of a bispecific anti-amyloid-ß monoclonal antibody. [2023]