Prostatic Neoplasms, Prostate Cancer
Conditions
Keywords
[18F]CTT1057, Positron Emission Tomography/Computerized Tomography, PET/CT, Radioligand, Imaging, Primary Staging, PS, Standard of Truth, SoT, Prostate Cancer, PCa
Brief summary
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.
Detailed description
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).
Interventions
DRUG[18F]CTT1057
PET/CT imaging with \[18F\]CTT1057
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
All participants will receive \[18F\]CTT1057 for PET/CT scan imaging, and surgery will be performed up to 6 weeks after \[18F\]CTT1057 PET for pathology assessment of the tissue specimens. Additional pharmacokinetics (PK) assessments will be performed on the date of imaging in a subset of approximately 10 patients at the same site.
Eligibility
Sex/Gender
MALE
Age
18 Years to 100 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient-level Sensitivity of Vidoflufolastat (18F) - % Sensitivity | 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 | 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). |
| Region-level Specificity of Vidoflufolastat (18F) - % Specificity | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient-level Negative Predictive Value of Vidoflufolastat (18F) | 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 | 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)) |
| Patient-level Accuracy of Vidoflufolastat (18F) | 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 | 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) |
| Region-level Sensitivity of Vidoflufolastat (18F) - % Sensitivity | 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 | Proportion of PLN regions that test positive on both vidoflufolastat (18F) and SoT (TP) among those that are SoT positive (TP+FN) |
| Region-level Positive Predictive Value of Vidoflufolastat (18F) | 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 | 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)) |
| Region-level Negative Predictive Value of Vidoflufolastat (18F) | 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 | Proportion of PLN regions that are SoT and vidoflufolastat (18F) negative (TN) among those regions that test negative on vidoflufolastat (18F) (TN+FN) |
| Region-level Accuracy of Vidoflufolastat (18F) | 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 | 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) |
| Region-level Sensitivity of Vidoflufolastat (18F) Scan With Standard of Truth Excluding Pelvic Lymph Node (PLN) Metastasis < 2 mm | 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 | Sensitivity of vidoflufolastat (18F) PET imaging in the PLN region, excluding from the analysis those lymph nodes showing metastasis \<2mm (micro-metastasis) |
| Detection of Distant Metastasis of Vidoflufolastat (18F) Scan - Participants With at Least One Distant Metastatic Lesion (%) | 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 | 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. |
| Overview of Adverse Events | 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. | 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 assessed against histopathology as Standard of Truth (SoT) obtained during surgery within 6 weeks from vidoflufolastat (18F) scan | Scan inter-reader variability is defined the agreement rate among reader determination of vidoflufolastat (18F) images. |
| Patient-level Specificity of Vidoflufolastat (18F) - % Specificity | 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 | 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 |
| Vidoflufolastat (18F) Scan Intra-reader Variability | 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 | Scan intra-reader variability is defined as the within-reader agreement rate of vidoflufolastat (18F) images. |
| Observed Maximum Blood Concentration (Cmax) of Vidoflufolastat (18F) | 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) | 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) | 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) | Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post infusion) | — |
| Half-Life Lambda z of Vidoflufolastat (18F) | 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) | 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) | 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) | Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection) | — |
| Vidoflufolastat (18F) Scan Inter-reader Variability - Number of Scans Agreed | 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 | Scan inter-reader variability is defined the agreement rate among reader determination of vidoflufolastat (18F) images. |
| Patient-level Positive Predictive Value of Vidoflufolastat (18F) | 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 | 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)) |
Countries
France, Italy, Spain, Switzerland, United States
Participant flow
Recruitment details
195 patients were enrolled. 184 participants received vidoflufolastat (18F) and 184 underwent PET/CT. 173 patients completed the study and 184 patients completed treatment.
Participants by arm
| Arm | Count |
|---|---|
| PET/CT Imaging With Vidoflufolastat (18F). Single intravenous dose of approximately 370 Mega-Becquerel (MBq) on Day 1 and subsequent PET/CT scan | 195 |
| Total | 195 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Physician Decision | 6 |
| Overall Study | Protocol Violation | 3 |
| Overall Study | Technical Problems | 2 |
| Overall Study | Withdrawal by Subject | 9 |
Baseline characteristics
| Characteristic | PET/CT Imaging With Vidoflufolastat (18F). |
|---|---|
| Age, Continuous | 64.5 Years STANDARD_DEVIATION 6.41 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 56 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 122 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 17 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 192 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 195 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 184 |
| other Total, other adverse events | 23 / 184 |
| serious Total, serious adverse events | 2 / 184 |
Outcome results
Primary
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
Population: The Efficacy Analysis Set (EFF) included all enrolled participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan and histopathology assessment, and had not received any prohibited systemic antineoplastic therapy before the completion of PET/CT and surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Patient-level Sensitivity of Vidoflufolastat (18F) - % Sensitivity | 86.8 % Sensitivity |
| Central Reader 2 | Patient-level Sensitivity of Vidoflufolastat (18F) - % Sensitivity | 90.0 % Sensitivity |
| Central Reader 3 | Patient-level Sensitivity of Vidoflufolastat (18F) - % Sensitivity | 86.9 % Sensitivity |
Primary
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
Population: The Efficacy Analysis Set (EFF) included all enrolled participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan and histopathology assessment, and had not received any prohibited systemic antineoplastic therapy before the completion of PET/CT and surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Region-level Specificity of Vidoflufolastat (18F) - % Specificity | 97.1 % Specificity |
| Central Reader 2 | Region-level Specificity of Vidoflufolastat (18F) - % Specificity | 97.1 % Specificity |
| Central Reader 3 | Region-level Specificity of Vidoflufolastat (18F) - % Specificity | 97.1 % Specificity |
Secondary
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)
Population: The Pharmacokinetic analysis set (PAS) included all participants who received the investigational treatment (i.e. vidoflufolastat (18F)) with valid results for the outcome measure.~For PK outcome measures, a subset of 10 patients maximum were analyzed. For this parameter, results for only 1 pt were evaluable.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Central Reader 1 | Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUCinf) of Vidoflufolastat (18F) | 50.0 h*kBq/mL |
Secondary
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)
Population: The Pharmacokinetic analysis set (PAS) included all participants who received the investigational treatment (i.e. vidoflufolastat (18F)) with valid results for the outcome measure.~For PK outcome measures, a subset of 10 patients maximum were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Central Reader 1 | Area Under the Vidoflufolastat (18F) Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) | 47.9 h*kBq/mL | Standard Deviation 11.9 |
Secondary
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
Population: Safety set - all treated patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Central Reader 1 | Detection of Distant Metastasis of Vidoflufolastat (18F) Scan - Participants With at Least One Distant Metastatic Lesion (%) | 6 Participants |
| Central Reader 2 | Detection of Distant Metastasis of Vidoflufolastat (18F) Scan - Participants With at Least One Distant Metastatic Lesion (%) | 9 Participants |
| Central Reader 3 | Detection of Distant Metastasis of Vidoflufolastat (18F) Scan - Participants With at Least One Distant Metastatic Lesion (%) | 10 Participants |
Secondary
Half-Life Lambda z of Vidoflufolastat (18F)
Time frame: Day 1 (0, 0-5, 15, 30, 60, 120, 180-240, 300 minutes post injection)
Population: The Pharmacokinetic analysis set (PAS) included all participants who received the investigational treatment (i.e. vidoflufolastat (18F)) with valid results for the outcome measure.~For PK outcome measures, a subset of 10 patients maximum were analyzed. For this parameter, results for only 1 pt were evaluable.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Central Reader 1 | Half-Life Lambda z of Vidoflufolastat (18F) | 1.34 h |
Secondary
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)
Population: The Pharmacokinetic analysis set (PAS) included all participants who received the investigational treatment (i.e. vidoflufolastat (18F)) with valid results for the outcome measure.~For PK outcome measures, a subset of 10 patients maximum were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Central Reader 1 | Observed Maximum Blood Concentration (Cmax) of Vidoflufolastat (18F) | 49.0 kBq/mL | Standard Deviation 19.2 |
Secondary
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.
Population: Safety set - all treated patients
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Central Reader 1 | Overview of Adverse Events | Adverse events | 24 Participants |
| Central Reader 1 | Overview of Adverse Events | Treatment-related Adverse events | 1 Participants |
| Central Reader 1 | Overview of Adverse Events | Serious adverse events | 2 Participants |
| Central Reader 1 | Overview of Adverse Events | Serious adverse events Treatment-related | 0 Participants |
| Central Reader 1 | Overview of Adverse Events | Fatal serious adverse events | 0 Participants |
| Central Reader 1 | Overview of Adverse Events | Fatal serious adverse events Treatment-related | 0 Participants |
| Central Reader 1 | Overview of Adverse Events | Adverse events leading to dose adjustment / interruption | 0 Participants |
| Central Reader 1 | Overview of Adverse Events | Adverse events requiring additional therapy | 5 Participants |
Secondary
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
Population: The Efficacy Analysis Set (EFF) included all enrolled participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan and histopathology assessment, and had not received any prohibited systemic antineoplastic therapy before the completion of PET/CT and surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Patient-level Accuracy of Vidoflufolastat (18F) | 84.9 % Accuracy |
| Central Reader 2 | Patient-level Accuracy of Vidoflufolastat (18F) | 89.0 % Accuracy |
| Central Reader 3 | Patient-level Accuracy of Vidoflufolastat (18F) | 85.5 % Accuracy |
Secondary
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
Population: The Efficacy Analysis Set (EFF) included all enrolled participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan and histopathology assessment, and had not received any prohibited systemic antineoplastic therapy before the completion of PET/CT and surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Patient-level Negative Predictive Value of Vidoflufolastat (18F) | 4.3 % Negative Predictive Value |
| Central Reader 2 | Patient-level Negative Predictive Value of Vidoflufolastat (18F) | 0.0 % Negative Predictive Value |
| Central Reader 3 | Patient-level Negative Predictive Value of Vidoflufolastat (18F) | 4.3 % Negative Predictive Value |
Secondary
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
Population: The Efficacy Analysis Set (EFF) included all enrolled participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan and histopathology assessment, and had not received any prohibited systemic antineoplastic therapy before the completion of PET/CT and surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Patient-level Positive Predictive Value of Vidoflufolastat (18F) | 97.3 % Positive Predictive Value |
| Central Reader 2 | Patient-level Positive Predictive Value of Vidoflufolastat (18F) | 98.7 % Positive Predictive Value |
| Central Reader 3 | Patient-level Positive Predictive Value of Vidoflufolastat (18F) | 98.0 % Positive Predictive Value |
Secondary
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
Population: The Efficacy Analysis Set (EFF) included all enrolled participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan and histopathology assessment, and had not received any prohibited systemic antineoplastic therapy before the completion of PET/CT and surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Patient-level Specificity of Vidoflufolastat (18F) - % Specificity | 20.0 % Specificity |
| Central Reader 2 | Patient-level Specificity of Vidoflufolastat (18F) - % Specificity | 0.0 % Specificity |
| Central Reader 3 | Patient-level Specificity of Vidoflufolastat (18F) - % Specificity | 25.0 % Specificity |
Secondary
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
Population: The Efficacy Analysis Set (EFF) included all enrolled participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan and histopathology assessment, and had not received any prohibited systemic antineoplastic therapy before the completion of PET/CT and surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Region-level Accuracy of Vidoflufolastat (18F) | 82.0 % Accuracy |
| Central Reader 2 | Region-level Accuracy of Vidoflufolastat (18F) | 82.0 % Accuracy |
| Central Reader 3 | Region-level Accuracy of Vidoflufolastat (18F) | 82.6 % Accuracy |
Secondary
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
Population: The Efficacy Analysis Set (EFF) included all enrolled participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan and histopathology assessment, and had not received any prohibited systemic antineoplastic therapy before the completion of PET/CT and surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Region-level Negative Predictive Value of Vidoflufolastat (18F) | 83.2 % Negative Predictive Value |
| Central Reader 2 | Region-level Negative Predictive Value of Vidoflufolastat (18F) | 83.2 % Negative Predictive Value |
| Central Reader 3 | Region-level Negative Predictive Value of Vidoflufolastat (18F) | 83.8 % Negative Predictive Value |
Secondary
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
Population: The Efficacy Analysis Set (EFF) included all enrolled participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan and histopathology assessment, and had not received any prohibited systemic antineoplastic therapy before the completion of PET/CT and surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Region-level Positive Predictive Value of Vidoflufolastat (18F) | 63.6 % Positive Predictive Value |
| Central Reader 2 | Region-level Positive Predictive Value of Vidoflufolastat (18F) | 63.6 % Positive Predictive Value |
| Central Reader 3 | Region-level Positive Predictive Value of Vidoflufolastat (18F) | 66.7 % Positive Predictive Value |
Secondary
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
Population: The Efficacy Analysis Set (EFF) included all enrolled participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan and histopathology assessment, and had not received any prohibited systemic antineoplastic therapy before the completion of PET/CT and surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Region-level Sensitivity of Vidoflufolastat (18F) Scan With Standard of Truth Excluding Pelvic Lymph Node (PLN) Metastasis < 2 mm | 26.9 % Sensitivity |
| Central Reader 2 | Region-level Sensitivity of Vidoflufolastat (18F) Scan With Standard of Truth Excluding Pelvic Lymph Node (PLN) Metastasis < 2 mm | 26.9 % Sensitivity |
| Central Reader 3 | Region-level Sensitivity of Vidoflufolastat (18F) Scan With Standard of Truth Excluding Pelvic Lymph Node (PLN) Metastasis < 2 mm | 30.8 % Sensitivity |
Secondary
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
Population: The Efficacy Analysis Set (EFF) included all enrolled participants who received the dose of investigational treatment (i.e. vidoflufolastat (18F)), had both an evaluable vidoflufolastat (18F) PET/CT scan and histopathology assessment, and had not received any prohibited systemic antineoplastic therapy before the completion of PET/CT and surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Region-level Sensitivity of Vidoflufolastat (18F) - % Sensitivity | 20.6 % Sensitivity |
| Central Reader 2 | Region-level Sensitivity of Vidoflufolastat (18F) - % Sensitivity | 20.6 % Sensitivity |
| Central Reader 3 | Region-level Sensitivity of Vidoflufolastat (18F) - % Sensitivity | 23.5 % Sensitivity |
Secondary
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)
Population: The Pharmacokinetic analysis set (PAS) included all participants who received the investigational treatment (i.e. vidoflufolastat (18F)) with valid results for the outcome measure.~For PK outcome measures, a subset of 10 patients maximum were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Central Reader 1 | Time of Maximum Observed Blood Concentration Occurrence (Tmax) of Vidoflufolastat (18F) | 0.0333 Hours |
Secondary
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)
Population: The Pharmacokinetic analysis set (PAS) included all participants who received the investigational treatment (i.e. vidoflufolastat (18F)) with valid results for the outcome measure.~For PK outcome measures, a subset of 10 patients maximum were analyzed. For this parameter, results for only 1 pt were evaluable.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Central Reader 1 | Total Systemic Clearance for Intravenous Administration (CL) of Vidoflufolastat (18F) | 7.70 L/h |
Secondary
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)
Population: The Pharmacokinetic analysis set (PAS) included all participants who received the investigational treatment (i.e. vidoflufolastat (18F)) with valid results for the outcome measure.~For PK outcome measures, a subset of 10 patients maximum were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Central Reader 1 | Urinary Excretion of Radioactivity Expressed as a Percentage of Injected Activity (%IA) of Vidoflufolastat (18F) | 0 HRS INJECTION/PRE-INJECTION | 0.000821 %IA | Standard Deviation 0.0012 |
| Central Reader 1 | Urinary Excretion of Radioactivity Expressed as a Percentage of Injected Activity (%IA) of Vidoflufolastat (18F) | 0 HRS (INJECTION) - T (IMAGE ACQUISITION STARTING TIME) | 15.8 %IA | Standard Deviation 11.9 |
| Central Reader 1 | Urinary Excretion of Radioactivity Expressed as a Percentage of Injected Activity (%IA) of Vidoflufolastat (18F) | IMAGE ACQUISITION STARTING TIME T - 3 H | 11.9 %IA | Standard Deviation 8.3 |
| Central Reader 1 | Urinary Excretion of Radioactivity Expressed as a Percentage of Injected Activity (%IA) of Vidoflufolastat (18F) | 3 H - 5 H | 10.5 %IA | Standard Deviation 8.06 |
Secondary
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
Population: Safety set - all treated patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Vidoflufolastat (18F) Scan Inter-reader Variability - % | 63.9 % variability |
Secondary
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
Population: Safety set - all treated patients
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Central Reader 1 | Vidoflufolastat (18F) Scan Inter-reader Variability - Number of Scans Agreed | Number of scans agreed by all three readers | 163 Participants |
| Central Reader 1 | Vidoflufolastat (18F) Scan Inter-reader Variability - Number of Scans Agreed | Number of scans agreed by two readers | 21 Participants |
Secondary
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
Population: Safety set - all treated patients with a valid measurement.~For this outcome measure, scans for a subset of 20 patients were read by each reader at 2 different time points.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Central Reader 1 | Vidoflufolastat (18F) Scan Intra-reader Variability | 100 variability (%) |
| Central Reader 2 | Vidoflufolastat (18F) Scan Intra-reader Variability | 100 variability (%) |
| Central Reader 3 | Vidoflufolastat (18F) Scan Intra-reader Variability | 89.4 variability (%) |
Secondary
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)
Population: The Pharmacokinetic analysis set (PAS) included all participants who received the investigational treatment (i.e. vidoflufolastat (18F)) with valid results for the outcome measure.~For PK outcome measures, a subset of 10 patients maximum were analyzed. For this parameter, results for only 1 pt were evaluable.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Central Reader 1 | Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) of Vidoflufolastat (18F) | 14.9 L |