89Zr-DFO-YS5 Imaging for Prostate Cancer

Overseen By Maya Aslam

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Robert Flavell, MD, PhD

Disqualifiers: Inability to consent, others

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

Compensation: Varies

Number of Visits: 5

37 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new imaging method to better understand a protein called CD46, found in aggressive prostate cancer that resists traditional hormone therapy. Participants will receive a special imaging agent, 89Zr-DFO-YS5 (a radiolabeled compound), along with a YS5 antibody, to help doctors assess CD46 levels in their cancer. This could guide future treatments targeting this protein. The trial seeks men with metastatic castration-resistant prostate cancer, especially those whose cancer continues to grow despite treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new imaging method.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the treatment 89Zr-DFO-YS5, used for imaging prostate cancer, has undergone early testing to assess its safety. This treatment involves a small amount of radioactive material, zirconium-89, linked to an antibody targeting prostate cancer cells. Early results from these studies have not revealed any serious side effects, suggesting the treatment is generally safe.

The YS5 antibody, used with 89Zr-DFO-YS5, has also been included in these studies. So far, no strong evidence of harmful side effects has emerged, indicating that this combination is generally safe as well.

Since both components of the treatment remain in early testing stages, safety information is limited. The primary goal of this trial phase is to evaluate safety, so researchers closely monitor participants for any adverse reactions. It is important to consult healthcare providers to understand the potential risks and benefits before deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the 89Zr-DFO-YS5 imaging technique for prostate cancer because it offers a new way to visualize cancer progression in the body. Unlike traditional imaging methods, this technique uses a radiolabeled antibody, 89Zr-DFO-YS5, which specifically targets prostate cancer cells, potentially providing clearer and more precise images. This unique targeting ability could help doctors detect cancer earlier and more accurately track how it responds to treatment, which is a big step forward from conventional methods. Additionally, the YS5 antibody used alongside this imaging agent may enhance the precision of the scans, allowing for even better detection and monitoring of prostate cancer.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Studies have shown that the imaging agent 89Zr-DFO-YS5 effectively detects prostate cancer with the protein CD46. This protein often appears in more aggressive prostate cancers, making it an important treatment target. Research indicates that 89Zr-DFO-YS5, when used in PET scans, successfully highlights areas where CD46 is present, aiding doctors in seeing the cancer more clearly. In this trial, participants in different cohorts will receive varying doses of the YS5 antibody, a component of this imaging method that has shown promise in targeting CD46. These findings suggest that focusing on CD46 could be a powerful strategy in managing advanced prostate cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Robert Flavell, MD, PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

Men over 18 with advanced prostate cancer that's resistant to hormone therapy can join. They should be fairly active (able to care for themselves) and have good organ function, including liver and kidneys. Men who've had other cancers might qualify if it doesn't affect this trial's safety or results.

Inclusion Criteria

I am mostly self-sufficient and can carry out daily activities.

Demonstrates adequate organ function: Total bilirubin <1.5 X upper limit of normal (ULN), Aspartate aminotransferase (AST) <= 3 X institutional ULN, Alanine aminotransferase (ALT) <= 3 X institutional ULN, Creatinine clearance >= 60 mL/min, Ability to understand a written informed consent document, and the willingness to sign it, Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

My prostate cancer has spread and does not respond to hormone therapy.

Exclusion Criteria

Any condition that, in the opinion of the Principal Investigator, would impair the patient's ability to comply with study procedures

I have previously received the YS5 antibody.

I am unable to give informed consent due to my age, health, or mental condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants receive a microdose of the imaging agent and undergo whole body PET imaging to determine tumor and normal tissue uptake and dosimetry.

1-2 weeks

Up to 4 visits (in-person)

Follow-up

Participants are monitored for adverse events and imaging outcomes after the initial scan.

5 weeks

1-2 visits (in-person)

Optional Repeat Imaging

Participants have the option to receive a repeat PET scan at the time of disease progression.

What Are the Treatments Tested in This Trial?

Interventions

• 89Zr-DFO-YS5
• YS5 antibody

Trial Overview The study is testing a new imaging agent called 89Zr-DFO-YS5 used in PET/CT or PET/MRI scans to see if it can identify a protein linked to aggressive prostate cancer. This could help develop new treatments targeting this protein.

How Is the Trial Designed?

Group I: Cohort C: 89Zr-DFO-YS5, Optimal dose YS5 antibody Experimental Treatment 4 Interventions

Participants receive optimal dose of YS5 antibody prior to imaging and administration of one dose of up to 3 millicurie (mCi) 89Zr-DFO-YS5 and then complete a single whole body PET scan at the optimal time determined in Cohort A. Participants have the option to receive a repeat 89Zr-DFO-YS5 PET at the time of disease progression.

Group II: Cohort B: 89Zr-DFO-YS5, YS5 antibody Experimental Treatment 4 Interventions

Participants receive either a 20mg or 50mg dose of YS5 prior to imaging and administration of one dose of up to 3 millicurie (mCi) 89Zr-DFO-YS5 and then complete a single whole body PET scan at the optimal time determined in Cohort A. The optimal dose of unmodified YS5 antibody will be used in the following cohorts C \& D. Participants have the option to receive a repeat 89Zr-DFO-YS5 PET at the time of disease progression.

Group III: Cohort A: 89Zr-DFO-YS5 Experimental Treatment 3 Interventions

Participants receive one dose of 89Zr-DFO-YS5 up to 3 millicurie (mCi), and undergo a whole body PET performed at 1-4 hours, approximately 20-28 hours, 48-96 hours, and 120-168 hours post injection for up to 4 scans total. The optimized scan time will be used for imaging in cohorts B and C. Participants have the option to receive a repeat 89Zr-DFO-YS5 PET at the time of disease progression.

Who Is Running the Clinical Trial?

Robert Flavell, MD, PhD

Lead Sponsor

Trials

5

Recruited

90+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Fortis Therapeutics, Inc.

Industry Sponsor

Trials

4

Recruited

160+

Published Research Related to This Trial

The monoclonal antibody RM2, when labeled with iodine-125, effectively targets prostate cancer cells (PC-3 and LNCaP) in both in vitro and in vivo studies, demonstrating increased cellular uptake over time.

In animal models, RM2 showed significant accumulation in prostate tumors, indicating its potential as a radioimmunotracer for imaging prostate cancer, with optimal uptake observed up to 72 hours post-injection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibody RM2 as a potential ligand for a new immunotracer for prostate cancer imaging. Hasegawa, Y., Oyama, N., Nagase, K., et al.[2015]

The radiopharmaceutical [225Ac]DOTA-YS5 effectively targets prostate cancer, delivering high radiation levels to tumor tissues while minimizing exposure to healthy organs, as shown in biodistribution studies with xenograft models.

In preclinical tests, [225Ac]DOTA-YS5 not only reduced tumor size but also extended survival in both cell line-derived and patient-derived prostate cancer models, indicating its potential as a promising treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Prostate Cancer with CD46-targeted 225Ac Alpha Particle Radioimmunotherapy. Bidkar, AP., Wang, S., Bobba, KN., et al.[2023]

89Zr is an ideal radioisotope for PET imaging with antibodies due to its long half-life of 78.4 hours, which aligns well with the extended biological half-life of antibodies, allowing for better imaging of tumors over time.

The study demonstrates a method for labeling antibodies with 89Zr using the chelator desferrioxamine (DFO), and illustrates its application in PET imaging using a prostate-specific membrane antigen targeting antibody in a mouse model, showcasing its potential for enhanced cancer diagnostics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The bioconjugation and radiosynthesis of 89Zr-DFO-labeled antibodies. Zeglis, BM., Lewis, JS.[2018]

In a study involving 50 patients with advanced prostate cancer, (89)Zr-J591 PET/CT imaging was able to detect significantly more osseous metastases (491 sites) compared to conventional imaging methods (339 sites), demonstrating its superior efficacy in identifying bone lesions.

While (89)Zr-J591 showed high accuracy for detecting bone lesions (95.2%), its effectiveness for soft-tissue lesions was lower (60%), indicating that while it is a promising tool for bone metastasis detection, further optimization may be needed for soft-tissue imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I/II Study for Analytic Validation of 89Zr-J591 ImmunoPET as a Molecular Imaging Agent for Metastatic Prostate Cancer. Pandit-Taskar, N., O'Donoghue, JA., Durack, JC., et al.[2022]

(89)Zr-immuno-PET is a promising imaging technique that can visualize and quantify the distribution of monoclonal antibodies (mAbs) in tumors, helping to predict their efficacy and toxicity based on initial clinical trials.

Initial studies have shown that (89)Zr-immuno-PET correlates with target expression levels in tumors, indicating its potential as a predictive biomarker for personalized treatment, particularly in HER2-positive breast cancer with trastuzumab-emtansine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immuno-Positron Emission Tomography with Zirconium-89-Labeled Monoclonal Antibodies in Oncology: What Can We Learn from Initial Clinical Trials? Jauw, YW., Menke-van der Houven van Oordt, CW., Hoekstra, OS., et al.[2022]

The maximum-tolerated dose (MTD) of yttrium-90-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 ((90)Y-J591) was determined to be 17.5 mCi/m², with acceptable toxicity observed in 29 patients with androgen-independent prostate cancer.

Significant antitumor activity was noted, with two patients showing substantial declines in prostate-specific antigen (PSA) levels, indicating potential effectiveness of (90)Y-J591 in targeting prostate cancer metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of yttrium-90-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for androgen-independent prostate cancer. Milowsky, MI., Nanus, DM., Kostakoglu, L., et al.[2018]

The study demonstrated that [89Zr]-anti-PD-1 immuno-PET is a safe and effective imaging method to assess the response to PD-1 blockade in non-small cell lung cancer (NSCLC), showing higher uptake in responders compared to non-responders.

Conventional imaging methods like [18F]-FDG-PET were unable to detect the anti-tumor effects of PD-1 therapy, highlighting the potential of [89Zr]-anti-PD-1 as a more reliable tool for monitoring treatment response in immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel [89Zr]-anti-PD-1-PET-CT to assess response to PD-1/PD-L1 blockade in lung cancer. Puyalto, A., Rodríguez-Remírez, M., López, I., et al.[2023]

In a study involving ten patients with prostate cancer, including nine with metastatic disease, an Indium-111-labeled monoclonal antibody targeting prostate-specific antigen was evaluated for its effectiveness compared to standard technetium bone scans.

The results suggest that this radiolabeled antibody approach could potentially improve cancer staging and may be developed further as a therapeutic option, highlighting its promising role in managing prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of monoclonal antibody imaging of metastatic prostatic carcinoma. Meyers, FJ., Denardo, SJ., Macey, D., et al.[2019]

In a pilot study involving 11 patients with localized prostate cancer, (89)Zr labeled J591 monoclonal antibody positron emission tomography (PET) successfully identified 72.7% of significant lesions, particularly those with a Gleason score of 7 or higher, indicating its potential efficacy in detecting clinically significant disease.

The study suggests that larger lesions are more easily identified by PET imaging, and there is a correlation between standardized uptake values and Gleason scores, although further research is needed to confirm these findings in a larger clinical trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective pilot study of (89)Zr-J591/prostate specific membrane antigen positron emission tomography in men with localized prostate cancer undergoing radical prostatectomy. Osborne, JR., Green, DA., Spratt, DE., et al.[2021]

Citations

1. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT05245006

PET Imaging Study of 89Zr-DFO-YS5 in Men With Prostate ... A first-in-human, pilot PET imaging study of 89Zr-DFO-YS5, an immunoPET agent for detecting CD46 positive malignancy in men with prostate cancer.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05245006?term=AREA%5BBasicSearch%5D(AREA%5BConditionSearch%5D(%22Castration-Resistant%20Prostate%20Carcinoma%22)%20AND%20AREA%5BInterventionSearch%5D(%22immunoglobulins,%20intravenous%22))&rank=4

PET Imaging Study of 89Zr-DFO-YS5 in Men With Prostate ... CD46 is an exciting new therapeutic target in prostate cancer, with the antibody drug conjugate FOR46 under investigation in phase I clinical trials.

3. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/334077

PET Imaging Study of 89Zr-DFO-YS5 in Men with Prostate ... These data will provide crucial information about the feasibility of targeting cluster of differentiation 46 (CD46) in mCRPC, will be used guide the development ...

4. urotoday.com urotoday.com/clinical-trials/prostate-cancer/155011-a-first-in-human-pilot-pet-imaging-study-of-89zr-dfo-ys5-an-immunopet-agent-for-detecting-cd46-positive-malignancy-in-men-with-prostate-cancer.html

A First-in-Human, Pilot PET Imaging Study of 89Zr-DFO ... A First-in-Human, Pilot PET Imaging Study of 89Zr-DFO-YS5, an ImmunoPET Agent for Detecting CD46 Positive Malignancy in Men with Prostate Cancer ...

5. withpower.com withpower.com/trial/phase-1-prostate-cancer-2-2022-f0134

89Zr-DFO-YS5 Imaging for Prostate Cancer Trial Overview The study is testing a new imaging agent called 89Zr-DFO-YS5 used in PET/CT or PET/MRI scans to see if it can identify a protein linked to ...