A Phase 1 interventional study of 89Zr-DFO-YS5 and YS5 antibody in Prostate Cancer and Metastatic Castration-resistant Prostate Cancer, sponsored by Robert Flavell, MD, PhD. Active, not recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-03-17.
Sponsored by Robert Flavell, MD, PhD · Phase 1, Interventional, and Diagnostic
CD46 is an exciting new therapeutic target in prostate cancer, with the antibody drug conjugate FOR46 under investigation in phase I clinical trials. The hypothesis of the study is that CD46 expression, measured via our novel imaging biomarker, is a characteristic feature of mCRPC, and particularly common in the most lethal forms of the disease including adenocarcinoma and Small-cell neuroendocrine carcinoma (SCNC). These data will provide crucial information about the feasibility of targeting cluster of differentiation 46 (CD46) in mCRPC, will be used guide the development of novel therapeutic and theranostic agents, to help develop treatments that improve outcomes for men with the most lethal forms of prostate cancer.
This single center imaging study involves one microdose of the imaging agent, followed by whole body PET imaging. Imaging data will be acquired in up to four PET studies to determine tumor and normal tissue uptake and dosimetry.
PRIMARY OBJECTIVES:
SECONDARY OBJECTIVES:
OUTLINE: Participants were originally assigned to 1 of 3 cohorts. Cohort B is closed to accrual. Enrollment into Cohort A and C are ongoing.
Cohort A: PET imaging data will be acquired up to four times to determine tumor and normal tissue uptake and dosimetry. The optimized scan time will be used for imaging in Cohorts B and C.
(CLOSED) Cohort B: A dose of cold, non-radiolabeled antibody administered will be varied to determine the optimal antibody dose for image quality. The optimized antibody dose will be used in Cohort C. Participants will be followed for an additional 4-5 weeks after dose administration to assess for adverse events.
Cohort C: PET imaging will be acquired at the optimal time point and optimal antibody dose determined in Cohorts A \& B, and have the option to obtain an repeat scan at the time of disease progression.
All participants will be followed for up to 5 weeks after their first scan to assess for adverse events and will be followed-up until progression. At the time of progression, participants will have the option to receive a repeat scan.
6,370 studies on the registry are indexed under Prostatic Neoplasms; 1,400 are open to participants now.
This study's enrollment of 30 is below the median of 58 across 4,822 interventional studies indexed under Prostatic Neoplasms.
Browse Prostatic Neoplasms studies →Robert Flavell, MD, PhD is the lead sponsor of 6 studies on the registry; 3 are open to participants now.
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Demonstrates adequate organ function as defined below:
Exclusion Criteria:
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.
Drug: 89Zr-DFO-YS5 · Procedure: Positron Emission Tomography (PET)/Computerized tomography (CT) · Procedure: Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI)
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.
Drug: 89Zr-DFO-YS5 · Biological: YS5 antibody · Procedure: Positron Emission Tomography (PET)/Computerized tomography (CT) · Procedure: Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI)
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.
Drug: 89Zr-DFO-YS5 · Biological: YS5 antibody · Procedure: Positron Emission Tomography (PET)/Computerized tomography (CT) · Procedure: Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI)
3 mCi will be administered intravenously
Also known as: immunoPET agent, Imaging Agent
20 or 50 mg administered intravenously
Also known as: YS5, Unmodified YS5 antibody
Imaging which combines a CT scan and a PET scan
Also known as: PET/CT, PET/CT Scan, Whole Body PET/CT
Imaging which combines an MRI scan and a PET scan
Also known as: PET/CT, PET/MRI Scan, Whole Body PET/MRI
Optimal time point for imaging using 89Zr-DFO-YS5 PET post-injection (Cohort A)
For Cohort A, the optimal time point will be selected based on optimal maximun Standardized uptake value (SUVmax) of metastatic lesions, and ratio of SUVmax to blood pool. Due to the limited samples, the investigator will use all available lesions without considering the location of the lesions or the possible intra-correlation of the lesions from the same participant.
Time frame: Up to 7 days
Optimal antibody dose for imaging using 89Zr-DFO-YS5 PET (Cohort B)
For Cohort B, the optimal dose of antibody will be selected based on the optimal SUVmax of metastatic lesions, and ratio of SUVmax to blood pool. Due to the limited samples, the investigator will use all available lesions without considering the location of the lesions or the possible intra-correlation of the lesions from the same participant.
Time frame: Up to 7 days
Proportion of participants with metastatic lesions accurately detected in mCRPC using 89Zr-DFO-YS5 PET (sensitivity) (Cohort C)
Sensitivity is the probability that a test will indicate disease among those with the actual disease: True Positive / (True Positive + False Negative). Lesions will be graded on a semi-quantitative scale ranging from 1-5 as is common for 89Zr-antibody human imaging studies (1 = no uptake, 2 = probably no uptake, 3 = equivocal, 4 = probably positive, 5 = definitely positive). Using as a cut-off to 4 or 5 on the semi-quantitative scale, the sensitivity of 89Zr-DFO-YS5 PET will be descriptively reported on a lesion-per-lesion basis, using as reference standard staging scans including CT or MRI of the chest/abdomen/pelvis and whole body bone scan. The sensitivity estimate will be based on lesion level without considering the location of the lesions or the possible intra-correlation of the lesions from the same patient.
Time frame: Up to 24 months
Median SUVmax (Cohort C)
The median and range of SUVmax across all metastatic lesions per participant will be descriptively reported using mediastinal blood pool and normal organ as background uptake values will be reported with range of SUVmax.
Time frame: Up to 24 months
Average SUVmax (SUVmax-ave) (Cohort C)
The average SUVmax-ave across all metastatic lesions per participant will be descriptively reported using mediastinal blood pool and normal organ as background uptake values for all cohorts will be reported with 95% confidence intervals
Time frame: Up to 24 months
Proportion of participants with treatment-related Adverse Events
The frequency and severity of adverse events following Zr-DFO-YS5 injection will be descriptively reported, using CTCAE version 5.0
Time frame: Up to 3 weeks after last dose administration, approximately 35 days
Average organ uptake of 89Zr-DFO-YS5 (Cohort C)
Average organ uptake of 89Zr-DFO-YS5 on PET will be estimated.
Time frame: Up to 24 months
Intra-tumoral uptake of 89Zr-DFO-YS5 by tumor type (Cohort C)
The median and range for intra-tumoral SUVmax within metastatic lesions will be descriptively reported
Time frame: Up to 24 months
Intra-tumoral uptake of 89Zr-DFO-YS5 by Site of Disease (Cohort C)
The median and range for intra-tumoral SUVmax within metastatic lesions will be descriptively reported
Time frame: Up to 24 months
Inter-tumoral heterogeneity (Cohort C)
The median and range for intra-tumoral SUVmax within metastatic lesions will be descriptively reported to assess for Inter-tumoral heterogeneity.
Time frame: Up to 24 months
Inter-participant heterogeneity (Cohort C)
The median and range for intra-tumoral SUVmax within metastatic lesions will be descriptively reported to assess for Inter-participant heterogeneity
Time frame: Up to 24 months
Tumor-to-background signal (Cohort C)
The median and range for intra-tumoral SUVmax within metastatic lesions will be descriptively reported
Time frame: Up to 24 months
Plan to share: No
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Robert Flavell, MD, PhD