Study of Diagnostic Performance of [18F]CTT1057 in BCR

The current study aimed at evaluating the diagnostic performance of \[18F\]CTT1057 as a PET imaging agent for detection and localization of Prostate specific membrane antigen (PSMA) positivity in patients diagnosed of biochemical recurrence of prostate cancer (PCa), using a composite truth standard.

Approximately 190 participants were to be enrolled to ensure at least 152 participants were evaluable (i.e. have both an evaluable \[18F\]CTT1057 Positron emission tomography/Computed Tomography (PET/CT) scan imaging and at least one evaluable Composite Truth Standard (CTS) assessment and had not received any prohibited systemic antineoplastic therapy before the completion of PET/CTs and CTS procedures, which were required for the calculation of the co-primary endpoints.

This was a prospective, open-label, multi center, single-arm Phase III study to evaluate the diagnostic performance of \[18F\]CTT1057 as a PET imaging agent for detection and localization of PSMA positive tumors in PCa patients diagnosed with biochemical recurrence (BCR) after initial definitive therapy with either radical prostatectomy (RP) or curative intent radiation therapy (RT), using a CTS as reference.

The CTS to be used as reference were hierarchical in nature, with 3 levels of Standard of Truth (SoT) procedures, that were applied as follows:

CTS Level 1: Histopathology if available for the lesion (from prospective biopsy or salvage surgery performed within 8 weeks after the \[18F\]CTT1057 PET/CT scan); OR in case that histopathology was not available for a lesion, inconclusive or negative (for biopsy only).

CTS Level 2: Imaging diagnostic procedures performed on each patient as clinically indicated per SoC, which included at least a high resolution CT scan with contrast and a \[68Ga\]Ga-PSMA-11 PET/CT) performed within 8 weeks (either before or after) the \[18F\]CTT1057 PET/CT scan. Three-month follow-up imaging (from baseline) were also be used as part of the CTS level 2 in cases where it is clinically required for the diagnosis of particular lesion(s); OR if neither of the two above were feasible or deemed appropriate or they were inconclusive.

CTS Level 3: 50% or greater decline in PSA following radiation therapy (as long as no concomitant androgen deprivation therapy (ADT) was given) as per Prostate Cancer Working Group 3 (PCWG3) criteria.

All participants underwent 2 PET/CT scans: one with the investigational agent \[18F\]CTT1057 and another with \[68Ga\]Ga-PSMA-11 (as a component of the CTS Level 2 and for a secondary endpoint of assessment of concordance between the 2 PET/CT scans for detection of lesions). The 2 PET imaging procedures were performed at least 14 days apart, and the PET/CT scan sequence for each participant was assigned at random in a 1:1 ratio.

Eligibility Criteria:
Inclusion Criteria

* Signed informed consent must be obtained prior to participation in the study
* Biopsy proven prostate adenocarcinoma.
* Biochemical recurrence following initial definitive therapy (with either RP or curative intent radiation therapy) as defined:

by AUA criteria (Cookson et al 2007) for patients who have undergone RP: Initial serum PSA of ≥0.2 ng/ml measured at least 6 weeks after RP with a second confirmatory persistent PSA level of \>0.2 ng/ml, or by ASTRO-Phoenix criteria (Roach et al 2006) for patients who have undergone curative-intent radiation therapy (RT): Rise of serum PSA measurement of 2 or more ng/mL above the nadir PSA observed post RT.

* ECOG performance status 0-2
* Participants must be adults ≥ 18 years of age

Exclusion Criteria:

* Inability to complete the needed investigational and standard-of-care imaging examinations due to any reason (severe claustrophobia, inability to lie still for the entire imaging time, etc.)
* Any additional medical condition, serious intercurrent illness, concomitant cancer or other extenuating circumstance that, in the opinion of the Investigator, would indicate a significant risk to safety or impair study participation, including, but not limited to, current severe urinary incontinence, hydronephrosis, severe voiding dysfunction, need of indwelling/condom catheters, New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection, active hepatitis B or C, and COVID-19
* Prior major surgery undergone less than 12 weeks prior to screening (with the exception of any surgery related to prostatic cancer)
* Known allergy, hypersensitivity, or intolerance to \[18F\]CTT1057, \[68Ga\]Ga-PSMA-11, or to CT contrast
* Prior and current use of PSMA targeted therapies
* Prior ADT (first or second generation), including LHRH analogues (agonists or antagonists), within 9 months before screening
* Any 5-alpha reductase inhibitors within 30 days before screening
* Use of other investigational drugs within 30 days before screening
* Castration-resistant patients
* Patient with small cell or neuroendocrine PCa in more than 50% of biopsy tissue
* Prior salvage surgery or salvage radiation therapy