PET Imaging Study of 89Zr-DFO-YS5 in Men With Prostate Cancer
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 other identifiers
interventional
30
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 prostate-cancer
Started Mar 2022
Typical duration for phase_1 prostate-cancer
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 8, 2022
CompletedFirst Posted
Study publicly available on registry
February 17, 2022
CompletedStudy Start
First participant enrolled
March 18, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 31, 2027
March 17, 2026
March 1, 2026
5.4 years
February 8, 2022
March 13, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
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.
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.
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.
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.
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
Up to 24 months
Secondary Outcomes (7)
Proportion of participants with treatment-related Adverse Events
Up to 3 weeks after last dose administration, approximately 35 days
Average organ uptake of 89Zr-DFO-YS5 (Cohort C)
Up to 24 months
Intra-tumoral uptake of 89Zr-DFO-YS5 by tumor type (Cohort C)
Up to 24 months
Intra-tumoral uptake of 89Zr-DFO-YS5 by Site of Disease (Cohort C)
Up to 24 months
Inter-tumoral heterogeneity (Cohort C)
Up to 24 months
- +2 more secondary outcomes
Study Arms (3)
Cohort A: 89Zr-DFO-YS5
EXPERIMENTALParticipants 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.
Cohort B: 89Zr-DFO-YS5, YS5 antibody
EXPERIMENTALParticipants 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.
Cohort C: 89Zr-DFO-YS5, Optimal dose YS5 antibody
EXPERIMENTALParticipants 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.
Interventions
3 mCi will be administered intravenously
20 or 50 mg administered intravenously
Imaging which combines a CT scan and a PET scan
Imaging which combines an MRI scan and a PET scan
Eligibility Criteria
You may qualify if:
- Participants must have histologically or cytologically confirmed metastatic, castration resistant prostate cancer (mCRPC).
- Age \>=18 years
- Eastern Cooperative Oncology Group (ECOG) performance status \< 2 (Karnofsky \>60%).
- Demonstrates adequate organ function as defined below:
- Total bilirubin \<1.5 X upper limit of normal (ULN).
- Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase (SGOT)) \<= 3 X institutional upper limit of normal (ULN).
- Alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase (SGPT)) \<= 3 X institutional ULN.
- Serum creatinine \<=1,5 X institutional ULN or calculated creatinine clearance (Glomerular filtration rate (GFR)) \>= 60 mL/min, calculated using the Cockcroft-Gault equation.
- 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.
You may not qualify if:
- Patients who because of age, general medical, or psychiatric condition, or physiologic status cannot give valid informed consent.
- Any condition that, in the opinion of the Principal Investigator, would impair the patient's ability to comply with study procedures.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Robert Flavell, MD, PhDlead
- United States Department of Defensecollaborator
- Fortis Therapeutics, Inc.collaborator
Study Sites (1)
University of California, San Francisco
San Francisco, California, 94143, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Robert Flavell, MD, PhD
University of California, San Francisco
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- DIAGNOSTIC
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
February 8, 2022
First Posted
February 17, 2022
Study Start
March 18, 2022
Primary Completion (Estimated)
July 31, 2027
Study Completion (Estimated)
July 31, 2027
Last Updated
March 17, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share