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

Phase 3

Completed

Conditions: Recurrence
Prostate Cancer
Prostatic Neoplasms

Interventions: Drug: [18F]CTT1057
Drug: [68Ga]Ga-PSMA-11

Registration Number: NCT04838613

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 190

Inclusion Criteria

Not provided

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
PET/CT imaging with [18F]CTT1057 followed by [68Ga]Ga-PSMA-11 or vice versa	[18F]CTT1057	All eligible participants were assigned to one of the following two PET/CT scan sequences at random in a 1:1 ratio: * Sequence 1: \[18F\]CTT1057 on Day 1 (investigational imaging agent of interest) followed by \[68Ga\]Ga-PSMA-11 at least 14 days apart (as part of CTS if required, and for secondary endpoint) * Sequence 2: \[68Ga\]Ga-PSMA-11 (as part of CTS if required, and for secondary endpoint) on Day 1 followed by \[18F\]CTT1057 (investigational imaging agent of interest) at least 14 days apart
PET/CT imaging with [18F]CTT1057 followed by [68Ga]Ga-PSMA-11 or vice versa	[68Ga]Ga-PSMA-11	All eligible participants were assigned to one of the following two PET/CT scan sequences at random in a 1:1 ratio: * Sequence 1: \[18F\]CTT1057 on Day 1 (investigational imaging agent of interest) followed by \[68Ga\]Ga-PSMA-11 at least 14 days apart (as part of CTS if required, and for secondary endpoint) * Sequence 2: \[68Ga\]Ga-PSMA-11 (as part of CTS if required, and for secondary endpoint) on Day 1 followed by \[18F\]CTT1057 (investigational imaging agent of interest) at least 14 days apart

Primary Outcome Measures

Name	Time	Method
Patient-level Positive Predictive Value (PPV) (With Anatomical Localization) of Vidoflufolastat (18F)	vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)	Patient-level positive predictive value (PPV) is defined as the percentage of participants who have at least one True Positive (TP) lesion (exactly localized correspondence between PET imaging and the reference standard), regardless of any co-existent False Positive (FP) findings, out of all participants who are PET/CT scan positive.
Region-level Correct Localization Rate (CLR) of Vidoflufolastat (18F)	vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)	Region-level correct localization rate (CLR) is defined as the percentage of regions containing at least one True Positive (TP) lesion (exactly localized correspondence between PET imaging and the reference standard), regardless of any co-existent False Positive (FP) findings within the same region, out of all regions containing at least one PET-positive finding.

Secondary Outcome Measures

Name	Time	Method
Patient-level Sensitivity of Vidoflufolastat (18F)	vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)	Patient-level sensitivity is defined as the percentage of participants who test positive on vidoflufolastat (18F) and Composite Truth Standard (CTS) (True Positive (TP)) among those that are CTS positive (True Positive (TP) or False Negative (FN)).
Patient-level Specificity of Vidoflufolastat (18F)	vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)	Patient-level specificity is defined as the percentage of participants who test negative on vidoflufolastat (18F) and CTS (True Negative (TN)) among those that are CTS negative (True Negative (TN) or False Positive (FP)).
Patient-level Negative Predictive Value (NPV) of Vidoflufolastat (18F)	vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)	Patient-level negative predictive value is defined as the percentage of participants who are both vidoflufolastat (18F) and CTS negative (True Negative (TN)) among those who test negative on vidoflufolastat (18F) (True Negative (TN) or False Negative (FN)).
Patient-level Accuracy of Vidoflufolastat (18F)	vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)	Patient-level accuracy is defined as the percentage of participants who are CTS and vidoflufolastat (18F) positive (True Positive (TP)) and negative (True Negative (TN)) among those participants that identified on vidoflufolastat (18F) (True Positive (TP), True Negative (TN), False Positive (FP) or False Negative (FN)).
Patient-level Correct Detection Rate (CDR)	vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)	Patient-level correct detection rate (CDR) is defined as the percentage of participants who have at least one True Positive (TP) lesion (exactly localized correspondence between PET imaging and the reference standard), regardless of any co-existent False Positive (FP) findings, out of all participants who are scanned.
Patient-level Detection Rate	vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)	Patient-level detection rate is defined as the percentage of participants who have at least one PET positive lesion, regardless of True Positive (TP) or False Positive (FP) findings, out of all participants who are scanned.
Region-level Sensitivity of Vidoflufolastat (18F) (Overall)	vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)	Region level sensitivity is defined as the percentage of regions that test positive on both vidoflufolastat (18F) and CTS (True Positive (TP)) among those regions that are CTS positive (True Positive (TP) or False Negative (FN)).
Region Level Specificity of Vidoflufolastat (18F)	vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)	Region level specificity is defined as the percentage of regions that test negative on both vidoflufolastat (18F) and CTS (True Negative (TN)) among those regions that are CTS negative (False Positive (FP) or True Negative (TN)).
Region Level Negative Predictive Value (NPV) of Vidoflufolastat (18F)	vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)	Region level negative predictive value is defined as the percentage of regions that are CTS and vidoflufolastat (18F) negative (True Negative (TN)) among those regions that test negative on vidoflufolastat (18F) (True Negative (TN) or False Negative (FN)).
Region Level Accuracy of Vidoflufolastat (18F)	vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)	Region level accuracy is defined as the percentage of regions that are CTS andvidoflufolastat (18F) positive (True Positive (TP)) and negative (True Negative (TN)) among those regions that identified on vidoflufolastat (18F) (True Positive (TP), True Negative (TN), False Positive (FP) and False Negative (FN)).
Patient-level Positive Predictive Value (PPV) of Vidoflufolastat (18F) Related to PSA Levels	vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)	Patient-level positive predictive value related to PSA levels is defined as the percentage of participants who have at least one True Positive (TP) lesion (exactly anatomically localized correspondence between vidoflufolastat (18F) PET imaging and the reference standard), regardless of any co-existent False Positive (FP) findings, out of all participants who are vidoflufolastat (18F) positive, stratified by PSA levels. This endpoint was analyzed in each of the following subgroups: PSA ≤ 0.5 ng/mL; 0.5 ng/mL\<PSA≤1 ng/mL; 1 ng/mL\<PSA≤2 ng/mL; 2 ng/mL\<PSA≤5 ng/mL; PSA \> 5 ng/mL.
Overview of Adverse Events (AEs) and Treatment Emergent Adverse Events (TEAEs)	From first dosing (Day 1) up to 14 days post dosing	An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject.
Vidoflufolastat (18F) Scan Inter-reader Variability	vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)	Inter-reader variability is defined as the agreement among three readers determination of vidoflufolastat (18F) images.
Vidoflufolastat (18F) Scan Intra-reader Variability	vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)	Intra-reader variability is defined as the within-reader agreement for two different time points of vidoflufolastat (18F) images.
Concordance Between Vidoflufolastat (18F) and Gallium (68Ga) Gozetotide for Detection of Lesions at Lesion Level Using Central Reads (Overall)	vidoflufolastat (18F) PET imaging acquired at Day 1 or Day 15 assessed against Composite Truth Standard (CTS) obtained within 8 weeks (before or after) of 18F-CTT PET scan or during follow-up (up to 90 days after radiotherapy for PSA level assessment)	Concordance between vidoflufolastat (18F) and gallium (68Ga) gozetotide for detection of PSMA-positive lesions (location and number) using central reads.
Change in Patient Management Plans Attributed to the Vidoflufolastat (18F) PET/CT Scan	From randomization up to 14 days after obtaining the results of the vidoflufolastat (18F) PET imaging	Change in patient management plans attributed to the PET/CT scan is defined as the percentage of participants who underwent a change in intended treatment plan attributed to the vidoflufolastat (18F) PET/CT scan as assessed by pre and post imaging questionnaires.