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.
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
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: 1. To determine the optimal time point for imaging (based on analyzing the 4 scans of all participants using 89Zr-DFO-YS5 PET post-injection. (Cohort A) 2. To determine the optimal antibody dose for imaging using 89Zr-DFO-YS5 PET. (Cohort B). 3. To determine the sensitivity of metastatic lesion detection in mCRPC using 89Zr-DFO-YS5 PET as compared with conventional imaging.(Cohort C) SECONDARY OBJECTIVES: 1. To determine the safety of 89Zr-DFO-YS5. 2. To determine average organ uptake of 89Zr-DFO-YS5. 3. 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. ARMS: 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. Participants in Cohort A will be followed throughout the course of their scan(s). Cohort B: The dose of cold, non-radiolabeled antibody administered will be varied, to determine the optimal antibody dose for image quality and participants will be followed for an additional three weeks after dose administration to assess for adverse events. The optimized cold antibody dose will be used for imaging in Cohort C. Cohort C: PET imaging will be acquired at the optimal time point and antibody dose following 89Zr-DFO-YS5, and participants will be followed for an additional three weeks after dose administration to assess for adverse events, and until progression. Participants in this cohort will have the option to receive a repeat 89Zr-DFO-YS5 PET at the time of disease progression.