This phase I trial tests 89Zr-DFO-YS5 positron emission tomography (PET) in imaging CD46 positive prostate cancer that continues to grow and spread despite interventions to block androgen production (castration resistant) and has spread to other places in the body (metastatic). 89Zr-DFO-YS5 is a type imaging agent called a radiopharmaceutical. A radiopharmaceutical involves a small amount of radioactive material that is injected into the vein to help in imaging different areas of the body. 89Zr-DFO-YS5 targets a specialized protein called CD46, which is in certain prostate tumor cells. A PET scan uses a special camera to detect energy given off from radioactive material to make detailed pictures of areas where the 89Zr accumulates in the body. Diagnostic procedures, such as PET, may help find prostate cancer and find out how far it has spread. Unmodified YS5 is an antibody that is targeted to prostate tumor cells in the body. An antibody is a type of protein that is made in the laboratory and can bind to certain targets in the body, such as antigens on the surface of tumor cells. The purpose of this trial is to determine the best timing for PET following 89Zr-DFO-YS5 injection and the best dose of unmodified YS5 antibody for imaging using 89Zr-DFO-YS5.
Additional locations may be listed on ClinicalTrials.gov for NCT05245006.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
I. To determine the optimal time point for imaging (based on analyzing the 4 scans of all Cohort A patients) using zirconium Zr 89-DFO-YS5 (89Zr-DFO-YS5) PET post-injection. (Cohort A)
II. To determine the optimal antibody dose for imaging using 89Zr-DFO-YS5 PET. (Cohort B)
III. To determine the sensitivity of metastatic lesion detection in metastatic castration resistant prostate cancer (mCRPC) using 89Zr-DFO-YS5 PET as compared with conventional imaging. (Cohort C)
SECONDARY OBJECTIVES:
I. To determine the safety of 89Zr-DFO-YS5 and anti-CD46 monoclonal antibody YS5 (YS5). (All Cohorts)
II. To determine the average organ uptake of 89Zr-DFO-YS5. (Cohort C)
III. To descriptively report the patterns of intra-tumoral uptake of 89Zr-DFO-YS5 on whole body PET, including by site of disease, uptake by tumor type, inter-tumoral and inter-patient heterogeneity, and tumor-to-background signal. (Cohort C)
EXPLORATORY OBJECTIVES:
I. To determine whether baseline uptake on 89Zr-DFO-YS5 PET is associated with subsequent clinical outcomes including objective response rate, progression-free survival, and >= 50% decline from baseline in prostate specific antigen levels (PSA50) response.
OUTLINE: Patients are assigned to 1 of 3 cohorts.
COHORT A (COMPLETE 08/09/2024): Patients receive 89Zr-DFO-YS5 intravenously (IV) on day 1. Patients then undergo PET at 1-4 hours, 20-28 hours, 48-96 hours, and 120-168 hours after receiving 89Zr-DFO-YS5. Patients also undergo computed tomography (CT)/magnetic resonance imaging (MRI) at screening, collection of blood samples throughout the trial, and an optional 89Zr-DFO-YS5 PET/CT or PET/MRI at the time of disease progression.
COHORT B (CLOSED TO ACCRUAL 08/09/2024): Patients receive 89Zr-DFO-YS5 IV and YS5 antibody IV on day 1. Patients then undergo PET at 120-168 hours after receiving 89Zr-DFO-YS5. Patients also undergo CT/MRI at screening, collection of blood samples throughout the trial, and an optional 89Zr-DFO-YS5 PET/CT or PET/MRI at the time of disease progression.
COHORT C: Patients receive 89Zr-DFO-YS5 IV on day 1. Patients then undergo PET at 120-168 hours after receiving 89Zr-DFO-YS5. Patients also undergo CT/MRI at screening, collection of blood samples throughout the trial, and an optional 89Zr-DFO-YS5 PET/CT or PET/MRI at the time of disease progression.
After completion of study intervention, patients are followed up at days 28-35 and then until disease progression.
Lead OrganizationUniversity of California San Francisco
Principal InvestigatorRobert Flavell
