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

Novartis Pharmaceuticals190 enrolled

Overview

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

Sex: MALEMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

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

Locations (13)

Explorer Molecular Imaging center

Sacramento, California, United States

Novartis Investigative Site

Marseille, France

Novartis Investigative Site

Marseille, France

Novartis Investigative Site

Nîmes, France

Novartis Investigative Site

Pierre-Bénite, France

Novartis Investigative Site

Saint-Priest-en-Jarez, France

Novartis Investigative Site

Toulouse, France

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, Spain

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Barcelona, Spain

...and 3 more locations

Outcomes

Primary Outcomes

Region-level Correct Localization Rate (CLR) of Vidoflufolastat (18F)

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.

Time frame: 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) (With Anatomical Localization) of Vidoflufolastat (18F)

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.

Secondary Outcomes

Patient-level Sensitivity of Vidoflufolastat (18F)

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)

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)

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)

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)

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

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)

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)

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)

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)

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

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)

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.

Time frame: From first dosing (Day 1) up to 14 days post dosing

Vidoflufolastat (18F) Scan Inter-reader Variability

Inter-reader variability is defined as the agreement among three readers determination of vidoflufolastat (18F) images.

Vidoflufolastat (18F) Scan Intra-reader Variability

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)

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

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.

Time frame: From randomization up to 14 days after obtaining the results of the vidoflufolastat (18F) PET imaging

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

Overview

Conditions

Interventions

Eligibility

Locations (13)

Outcomes

Primary Outcomes

Secondary Outcomes