Study of Diagnostic Performance of [18F]CTT1057 for PSMA-positive Tumors Detection

Novartis Pharmaceuticals195 enrolled

Overview

The purpose of this study was to evaluate the diagnostic performance of \[18F\]CTT1057 as a PET imaging agent for detection and localization of PSMA positive tumors using histopathology as Standard of Truth (SoT). Tissue specimens from both the primary tumor and pelvic lymph nodes dissected during surgery from patients with newly-diagnosed high-risk prostate cancer (PCa) were used for the histopathology assessments.

This was a multi-center, single-arm, open-label prospective study to evaluate the diagnostic performance of vidoflufolastat (18F) as a positron emission tomography (PET) imaging agent for detection and localization of prostate specific membrane antigen (PSMA) positive tumors, using histopathology as standard of truth (SoT). in newly diagnosed high-risk prostate cancer (PCa) patients. A total of 195 participants were enrolled to ensure that at least 156 participants were evaluable for the co-primary endpoints. Surgery was performed after vidoflufolastat (18F) positron emission tomography/computerized tomography (PET/CT) scan. The co-primary endpoints of patient-level sensitivity and region-level specificity were assessed by comparing the central reading results of the vidoflufolastat (18F) PET/CT scan to the local histopathology results in the dissected tissue specimens, i.e. both the primary tumor and the dissected Pelvic Lymph Nodes (PLNs).

Study Type

INTERVENTIONAL

Allocation

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

195

Conditions

Prostatic Neoplasms Prostate Cancer

Interventions

[18F]CTT1057DRUG

PET/CT imaging with \[18F\]CTT1057

Eligibility

Sex: MALEMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Untreated high risk biopsy-proven PCa patients according to D'Amico classification (Stage ≥ T2c or PSA level \>20ng/ml or Gleason score ≥8) (D'Amico et al 1998) * Scheduled or planned radical prostatectomy and extended pelvic lymph node resection up to 6 weeks after the investigational PET/CT scan followed by histopathology assessment * ECOG performance status 0-2 * Signed informed consent must be obtained prior to participation in the study * 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. * Known allergy, hypersensitivity, or intolerance to \[18F\]CTT1057 * Prior and current use of PSMA targeted therapies * Prior and current treatment with any ADT (first or second generation), including LHRH analogues (agonists or antagonists) * Any 5-alpha reductase inhibitors within 30 days before screening * Patients with small cell or neuroendocrine PCa in more than 50% of biopsy tissue * Patients with incidental PCa after transurethral resection * Use of other investigational drugs within 30 days before screening

Locations (16)

Explorer Molecular Imaging center

Sacramento, California, United States

Novartis Investigative Site

Marseille, France

Novartis Investigative Site

Outcomes

Primary Outcomes

Patient-level Sensitivity of Vidoflufolastat (18F) - % Sensitivity

Sensitivity of vidoflufolastat (18F) Positron Emission Tomography (PET) imaging, considering Prostate Specific Membrane Antigen (PSMA) positive patients as those who show at least one pathological vidoflufolastat (18F) uptake either in the primary tumor and/or metastatic Pelvic Lymph Node (PLN) regions, with anatomically localized correspondence with the Standard of Truth (SoT).

Time frame: vidoflufolastat (18F)7 PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan

Region-level Specificity of Vidoflufolastat (18F) - % Specificity

Specificity of vidoflufolastat (18F) PET imaging, defined as proportion of PLN regions that test negative for lymph nodes on vidoflufolastat (18F) among those that are lymph node negative on the SoT.

Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan

Secondary Outcomes

Patient-level Specificity of Vidoflufolastat (18F) - % Specificity

Specificity of vidoflufolastat (18F) PET imaging, considering PSMA negative patients as those who do not show any pathological vidoflufolastat (18F) uptake either in the primary tumor or PLNs and will be confirmed not having primary tumor or metastatic PLNs with the SoT

Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan

Patient-level Positive Predictive Value of Vidoflufolastat (18F)

Proportion of patients who are both vidoflufolastat (18F) and SoT positive (true positives (TP) among those who test positive on vidoflufolastat (18F) (TP+ false positives (FP))

Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan

Data from ClinicalTrials.gov

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Novartis Investigative Site

Pierre-Bénite, France

Novartis Investigative Site

Toulouse, France

Novartis Investigative Site

Toulouse, France

Novartis Investigative Site

Bergamo, BG, Italy

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Milan, MI, Italy

...and 6 more locations

Patient-level Negative Predictive Value of Vidoflufolastat (18F)

Proportion of patients who are both vidoflufolastat (18F) and SoT negative (true negatives (TN)) among those who test negative on vidoflufolastat (18F) (TN+ false negatives (FN))

Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan

Patient-level Accuracy of Vidoflufolastat (18F)

Proportion of patients that are SoT and vidoflufolastat (18F) positive (TP) and negative (TN) among all patients in Efficacy Analysis Set (EFF) (TP+TN+FP+FN)

Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan

Region-level Sensitivity of Vidoflufolastat (18F) - % Sensitivity

Proportion of PLN regions that test positive on both vidoflufolastat (18F) and SoT (TP) among those that are SoT positive (TP+FN)

Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan

Region-level Positive Predictive Value of Vidoflufolastat (18F)

Proportion of Pelvic Lymph Node (PLN) regions that are Standard of Truth (SoT) and vidoflufolastat (18F) positive (TP) among those regions that test positive on vidoflufolastat (18F) (TP+False Positive (FP))

Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan

Region-level Negative Predictive Value of Vidoflufolastat (18F)

Proportion of PLN regions that are SoT and vidoflufolastat (18F) negative (TN) among those regions that test negative on vidoflufolastat (18F) (TN+FN)

Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan

Region-level Accuracy of Vidoflufolastat (18F)

Proportion of PLN regions that are SoT and vidoflufolastat (18F) positive (TP) and negative (TN) among all PLN regions assessed vidoflufolastat (18F)(TP+TN+FP+FN)

Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan

Region-level Sensitivity of Vidoflufolastat (18F) Scan With Standard of Truth Excluding Pelvic Lymph Node (PLN) Metastasis < 2 mm

Sensitivity of vidoflufolastat (18F) PET imaging in the PLN region, excluding from the analysis those lymph nodes showing metastasis \<2mm (micro-metastasis)

Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan

Detection of Distant Metastasis of Vidoflufolastat (18F) Scan - Participants With at Least One Distant Metastatic Lesion (%)

Number of distant metastasis identified at PET/CT scan in all patients, and percentage of patients with at least one distant metastatic lesion (extra-PLN, visceral or skeletal)identified by PET scan in all patients with an evaluable vidoflufolastat (18F) PET/CT scan.

Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan

Overview of Adverse Events

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: Adverse Events are reported from the single dose of study treatment administration until 14 days afterwards, for a maximum time frame of approx. 14 days.

Vidoflufolastat (18F) Scan Inter-reader Variability - %

Scan inter-reader variability is defined the agreement rate among reader determination of vidoflufolastat (18F) images.

Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan

Vidoflufolastat (18F) Scan Inter-reader Variability - Number of Scans Agreed

Scan inter-reader variability is defined the agreement rate among reader determination of vidoflufolastat (18F) images.

Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan

Vidoflufolastat (18F) Scan Intra-reader Variability

Scan intra-reader variability is defined as the within-reader agreement rate of vidoflufolastat (18F) images.

Time frame: vidoflufolastat (18F) PET imaging acquired at Day 1 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan

Observed Maximum Blood Concentration (Cmax) of Vidoflufolastat (18F)

Time frame: Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection)

Time of Maximum Observed Blood Concentration Occurrence (Tmax) of Vidoflufolastat (18F)

Time frame: Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection)

Area Under the Vidoflufolastat (18F) Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast)

Time frame: Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection)

Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUCinf) of Vidoflufolastat (18F)

Time frame: Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post infusion)

Half-Life Lambda z of Vidoflufolastat (18F)

Time frame: Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection)

Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) of Vidoflufolastat (18F)

Time frame: Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection)

Urinary Excretion of Radioactivity Expressed as a Percentage of Injected Activity (%IA) of Vidoflufolastat (18F)

Time frame: Day 1 (pre-injection/0 hour, 0 hour (injection) - T (image acquisition starting time), T (image acquisition starting time) to 3 hours, 3 hours to 5 hours post imaging)

Total Systemic Clearance for Intravenous Administration (CL) of Vidoflufolastat (18F)

Time frame: Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection)