The safety and efficacy of PYLARIFY were evaluated in two prospective, open-label, multi-center clinical studies in men with prostate cancer: OSPREY (NCT02981368) and CONDOR (NCT03739684).

OSPREY

OSPREY enrolled a cohort of 268 men with biopsy-proven prostate cancer who were considered candidates for radical prostatectomy and pelvic lymph node dissection. These patients were all considered to have high risk disease based on criteria such as Gleason score, PSA level, and tumor stage. Each patient received a single PYLARIFY PET/CT from mid-thigh to skull vertex.

Three central readers independently interpreted each PET scan for the presence of abnormal PYLARIFY uptake in pelvic lymph nodes in multiple subregions, including the common iliac lymph nodes. The readers were blinded to all clinical information. While readers also recorded the presence of PYLARIFY PET-positive lesions in the prostate gland and outside the pelvis, those results were not included in the primary efficacy analysis.

A total of 252 patients (94%) underwent standard-of-care prostatectomy and template pelvic lymph node dissection and had sufficient histopathology data for evaluation of the pelvic lymph nodes. Surgical specimens were separated into three regions: left hemipelvis, right hemipelvis, and other. For each patient, PYLARIFY PET results and histopathology results obtained from dissected pelvic lymph nodes were compared by surgical region. PET results in locations that were not dissected were excluded from analysis.

For the 252 evaluable patients, the mean age was 64 years (range 46 to 84 years), and 87% were white. The median serum PSA was 9.3 ng/mL. The total Gleason score was 7 for 19%, 8 for 46%, and 9 for 34% of the patients, with the remainder of the patients having Gleason scores of 6 or 10.

Table 5 shows PYLARIFY PET performance by reader through comparison to pelvic lymph node histopathology at the patient-level with region matching, such that at least one true positive region defines a true positive patient. Approximately 24% of the evaluable patients had pelvic lymph node metastases based on histopathology (95% confidence interval: 19%, 29%).

In exploratory analyses, there were numerical trends towards more true positive results among patients with total Gleason score of 8 or higher and among patients with tumor stage of T2c or higher relative to those patients with lower Gleason score or tumor stage.

CONDOR

CONDOR enrolled 208 patients with biochemical evidence of recurrent prostate cancer, defined by serum PSA of at least 0.2 ng/mL after radical prostatectomy (with confirmatory PSA level also at least

0.2 ng/mL) or by an increase in serum PSA of at least 2 ng/mL above the nadir after other therapies. The mean age was 68 years (range 43 to 91 years), and 90% of patients were white. The median serum PSA was 0.82 ng/mL. Prior treatment included radical prostatectomy in 85% of the patients.

All enrolled patients had conventional imaging evaluation (for most patients, CT or MRI) within 60 days prior to receiving PYLARIFY PET, and this evaluation was negative or equivocal for prostate cancer. All patients received a single PYLARIFY PET/CT from mid-thigh to skull vertex with optional imaging of the lower extremities.

Three central readers independently evaluated each PYLARIFY PET scan for the presence and location of positive lesions. Location of each lesion was categorized in one of 19 subregions that were grouped into 5 regions (prostate/prostate bed, pelvic lymph nodes, other lymph nodes, soft tissue, bone). The readers were blinded to all clinical information.

Depending on the reader, a total of 123 to 137 patients (59% to 66%) had at least one lesion that was identified as PYLARIFY PET-positive (Table 6, TP + FP + PET-Positive Without Reference Standard). The region most commonly observed to have a PYLARIFY PET-positive finding was pelvic lymph nodes (40% to 42% of all PET-positive regions) and the least common region was soft tissue (6% to 7%).

Depending on the reader, 99 to 104 patients with a PYLARIFY PET-positive region had location-matched composite reference standard information available (Evaluable Set, Table 6, TP + FP) that consisted of histopathology, imaging (CT, MRI, ultrasound, fluciclovine PET, choline PET, or bone scan) obtained within 60 days of the PYLARIFY PET scan, or response of serum PSA level to targeted radiotherapy. Reference standard information for PET-negative regions was not systematically collected in this study.

Table 6 shows patient-level performance results of PYLARIFY PET by reader, including location -matched positive predictive value [true positive / (true positive + false positive)], also known as Correct Localization Rate (CLR). For these results, a patient was considered true positive if they had at least one matching location positive on both PYLARIFY PET and the composite reference standard. In addition to calculating location-matched positive predictive value in the Evaluable Set (CLR), an exploratory analysis of positive predictive value in all scanned patients (Imputed CLR) was performed in which PYLARIFY PET-positive patients who lacked reference standard information were imputed using an estimated likelihood that at least one PET-positive lesion was reference standard positive, based on patient-specific factors.

An exploratory analysis of region-level positive predictive value using only PET-positive regions that had sufficient composite reference standard information to determine true positive or false positive status demonstrated results of 67% to 70% with the lower bound of the 95% confidence interval ranging from 59% to 63%.

The percentage of patients categorized as true positive in a location-matched analysis out of all patients scanned with PYLARIFY was an additional exploratory endpoint. Using the same imputation approach for PET-positive patients who lacked reference standard information as in Table 6 above, this value was 47% to 51%, with the lower bound of the 95% confidence interval ranging from 40% to 45%.

Table 7 shows patient-level PYLARIFY PET results from the majority read stratified by serum PSA level. Percent PET positivity was calculated as the proportion of patients with a positive PYLARIFY PET out of all patients scanned. Percent PET positivity includes patients determined to be either true positive or false positive as well as those in whom such determination was not made due to lack of composite reference standard information. The likelihood of a patient having at least one PYLARIFY PET-positive lesion generally increased with higher serum PSA level.