A Phase 2 Trial of 61Cu-NU101 PET/CT Compared Against Current Standard-of-care 18F-piflufolastat (Pylarify®) PET/CT.

This is an open, phase 2, two center, non-randomized trial. Total of 34 subjects are planned, based on a statistical analysis to provide 80% power to determine non-inferiority of 61Cu-NU101 as compared to 18F-piflufolastat PET/CT. Each participant will have biopsy-proven prostate cancer visualized on standard-of-care 18F-piflufolastat PET/CT performed within 30 days of trial accrual. If participants have not had a diagnostic quality CT and/or a bone scan within 30 days of trial accrual, then will undergo a diagnostic quality CT and/or bone scan, as needed. Participants will undergo a research 61Cu-NU101 PET/CT, as follows: Each subject will receive a single administration of 61Cu-NU101, followed by PET/CT imaging at 1 and 4 hours. There will be optional 5-minute dynamic scans at tracer administration and 20- and 40-minutes post injection. Safety of 61Cu-NU101 will be evaluated by monitoring for unlikely adverse events. Ability of 61Cu-NU101to visualize malignant lesions will be evaluated by comparing the number of suspicious lesions demonstrated on the standard-of-care 18F-piflufolastat PET/CT with the number of suspicious lesions demonstrated on the experimental 61Cu-NU101PET/CT. Positive lesions will be considered to be foci greater than local background that are not physiologic/benign by location. If there is a discrepancy between the number of lesions detected by 18F-piflufolastat PET/CT and 61Cu-NU101PET/CT, then a discrepant lesion will be selected for biopsy to provide pathologic proof as a reference standard, if possible.

Determination of lesions suspicious for malignancy on 18F-piflufolastat PET/CT and 61Cu-NU101: The previously performed standard-of-care 18F-piflufolastat PET/CT and the on-trial research 61Cu-NU101will be evaluated using the same methodology, by radiologists with expertise in the interpretation of PSMA-targeted PET/CT imaging. Abnormal tracer accumulation will be defined as areas of uptake outside of sites considered physiologic or inflammatory. The locations of focal tracer abnormalities will be recorded. Radiotracer uptake will be graded on a scale of 1-5 where 1 = definitely normal, 2 = probably normal, 3 = equivocal, 4 = probably abnormal, and 5 = definitely abnormal. Semiquantitative analysis of tracer uptake will be performed for grade 4 and 5 lesions. Three-dimensional regions of interest (ROIs) will be placed in areas of tracer uptake and used for quantification of standardized uptake value (SUV), calculated as: SUV = decay-corrected mean ROI activity (μCi/ml) / (injected dose (μCi)/ body weight (g)). SUVmax will be recorded. Lesions graded as 4 (probably abnormal) or 5 (definitely abnormal) for malignancy will be counted and included in the number on lesions suspicious for malignancy in each examination.

Determination of lesions suspicious for malignancy on CT and bone scan: As a secondary objective, the number of lesions suspicious for malignancy will be compared between 61Cu-NU101and standard-of-care CT/bone scan. CT and bone scan will be interpreted by radiologists with expertise in the interpretation in CT and bone scans. Abnormal findings on CT and bone scan will be graded on a scale of 1-5 where 1 = definitely normal, 2 = probably normal, 3 = equivocal, 4 = probably abnormal, and 5 = definitely abnormal. No quantitative measurements will be made on CT and bone scan. For osseous lesions, a corresponding lesion on CT and bone scan will be counted as only 1 lesion. Lesions graded as 4 (probably abnormal) or 5 (definitely abnormal) for malignancy will be counted and included in the number on lesions suspicious for malignancy.