Conditions: Biochemical Recurrence of Malignant Neoplasm of Prostate
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 52
Healthy volunteers: no

Brief summary:
The aim of this study is to determine the safety and efficacy of 64Cu-SAR-bisPSMA and determine the ability of 64Cu-SAR-bisPSMA Positron emission tomography (PET)/computed tomography (CT) to correctly detect the recurrence of prostate cancer in participants with biochemical recurrence of prostate cancer following definitive therapy.

Detailed description:
Participants with biochemical evidence of recurrence of PC were evaluated with 64CU-SAR-bisPSMA PET/CT (Day 0 and Day 1) and by conventional methodologies up to 180 days later, eg. Histopathology/biopsy, conventional imaging, PSA reduction post focal salvage therapy or radiotherapy with no concomitant androgen deprivation therapy. Three independent central readers blinded to the participant number, the time of the PET/CT scan and the results of the conventional methodologies assessed the 64Cu-SAR-bisPSMA PET/CT. Three separate independent readers assessed the results of the conventional methodologies.

Arms:
arm 1: Patients will receive a single administration of 200 megabecquerels (MBq) of 64Cu-SAR-bisPSMA.

Interventions: intervention 1: 64Cu-SAR-bisPSMA
Intervention descriptions: intervention 1: 64Cu-SAR-bisPSMA

Protocol document:
SAP_002.pdf: 
   
 
 
 
 
 
64Cu-SAR-bisPSMA Positron Emission Tomography: A Phase 1/2 Study of 
Participants with Biochemical Recurrence of Prostate Cancer 
Protocol: CLP06 
 
 
 
STATISTICAL ANALYSIS PLAN 
Version 1.0 
September 7, 2023 
 
 
NCT05249127 
 
 
 
 
 
 


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CONFIDENTIAL 
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STATISTICAL ANALYSIS PLAN APPROVAL 
Protocol: CLP06  
Version 1.0 
 
_____________________________________ 
 
           
           
_______________________ 
Sonia Minassian 
           
 
 
 
Date 
Principal Statistician 
Inclin, Inc. 
 
 
_____________________________________ 
 
           
           
_______________________ 
Kevin Butler                  
 
           
 
 Date 
Study Statistician 
Inclin, Inc 
 
 
_______________________________________  
           
           
_______________________ 
Glynn Morrish 
 
 
 
 
 
Date 
Statistician 
Clarity Pharmaceuticals Ltd. 
 
 
 
 
 
            
_______________________________________  
           
           
_______________________ 
Eva Lengyelova 
 
 
 
 
 
Date 
VP of Clinical Development 
Clarity Pharmaceuticals Ltd. 
 
 


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_______________________________________  
           
           
_______________________ 
Othon Gervasio 
 
 
 
 
 
Date 
Senior Medical Director 
Clarity Pharmaceuticals Ltd. 
 
 


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Table of Contents 
LIST OF ABBREVIATIONS .......................................................................................................7 
1.0 
INTRODUCTION............................................................................................................10 
2.0 
STUDY DESIGN ..............................................................................................................10 
3.0 
STUDY OBJECTIVES AND ENDPOINTS ..................................................................11 
3.1.1 
Primary Study Objectives and Endpoints .............................................11 
3.1.2 
Secondary Study Objectives and Endpoints .........................................11 
3.1.3 
Exploratory Study Objectives and Endpoints .......................................13 
4.0 
HYPOTHESIS TEST AND SAMPLE SIZE ESTIMATION ......................................14 
4.1 
Hypothesis Test ......................................................................................................14 
4.2 
Sample Size Estimation .........................................................................................14 
5.0 
RANDOMIZATION AND BLINDING .........................................................................15 
6.0 
ANALYSIS SETS.............................................................................................................15 
7.0 
STATISTICAL METHODS ...........................................................................................16 
7.1 
General Considerations ..........................................................................................16 
7.1.1 
Standard Calculations............................................................................16 
7.1.2 
Summarization Groupings ....................................................................17 
7.2 
General Comments on the Statistical Analyses .....................................................17 
7.3 
Handling of Missing Data ......................................................................................17 
7.4 
Reporting Conventions ..........................................................................................18 
7.5 
Replacement of Participants ..................................................................................18 
7.6 
Calculation of PSA Doubling Time and PSA Velocity .........................................18 
7.7 
Imaging Scans and Reference Standard .................................................................19 
7.8 
Definitions for Assessments of the Reference Standard against 64Cu-SAR-
bisPSMA PET/CT Results .....................................................................................22 
7.9 
Analysis Visit Windows for Reference Datapoints ...............................................23 
8.0 
DEVIATIONS FROM PROTOCOL ANALYSES .......................................................24 
9.0 
STATISTICAL ANALYSES ..........................................................................................24 
9.1 
Screened Participants .............................................................................................24 
9.2 
Patient Disposition .................................................................................................24 
9.3 
Analysis Sets ..........................................................................................................25 
9.4 
Protocol Deviations ................................................................................................25 
9.5 
Demographics and Baseline Characteristics ..........................................................25 


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9.6 
Medical and Surgical History ................................................................................25 
9.7 
Prostate Cancer Related History ............................................................................25 
9.8 
Prior and Concomitant Medications ......................................................................26 
9.9 
Cancer Surgery, Therapy, and Radiotherapy .........................................................26 
9.10 
Conventional Imaging and Histopathology ...........................................................26 
9.11 
Study Drug Administration ....................................................................................27 
9.12 
64Cu-SAR-bisPSMA PET/CT Imaging..................................................................27 
9.13 
Reference Standard ................................................................................................28 
9.14 
Efficacy Analyses ..................................................................................................28 
9.14.1 
Primary Efficacy Analyses ....................................................................28 
9.14.2 
Secondary Efficacy Analyses ................................................................30 
9.14.3 
Exploratory Efficacy Analyses .............................................................31 
9.14.4 
Intra and Inter-reader Variability ..........................................................34 
9.14.5 
Disease Management ............................................................................36 
9.15 
Safety Analyses ......................................................................................................36 
9.15.1 
Adverse Events......................................................................................37 
9.15.2 
Clinical Laboratory Evaluations ...........................................................38 
9.15.3 
Vital Signs .............................................................................................38 
9.15.4 
Electrocardiogram (ECG) Parameters...................................................38 
9.15.5 
Physical Examination ............................................................................39 
9.15.6 
Prostate Cancer Symptoms ...................................................................39 
9.16 
Biodistribution Analysis ........................................................................................39 
APPENDICES ..............................................................................................................................41 
 


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Table of Figures and Tables 
 
Table 1 Analysis Sets ....................................................................................................................15 
Table 2 Regions and Subregions Assessed on the 64Cu-SAR-bisPSMA PET/CT scans ...............20 
Table 3 Deviations from Protocol Analyses ..................................................................................24 
Table 4 Cohen’s Kappa Levels of Agreement ..............................................................................35 


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LIST OF ABBREVIATIONS  
Abbreviation 
Explanation 
64Cu-SAR-bisPSMA 64Copper-labelled bisCOSAR-(Lys-urea-Glu)2 
ADaM 
analysis data model 
AE 
adverse event 
AJCC 
American Joint Committee on Cancer 
ANPV 
Apparent Negative Predictive Value 
ATC 
Anatomical/Therapeutic/Chemical 
BMI 
body mass index 
bpm 
beats per minute 
CDISC 
Clinical Data Interchange Standards Consortium 
CDR 
correct detection rate 
CI 
confidence interval 
CSR 
Clinical Study Report 
CT 
Computed Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DR 
Detection rate 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDC 
Electronic Data Capture 
eGFR 
Estimated glomerular filtration rate 
FAS 
Full Analysis Set 
FP 
False positive 
FPR 
False positive rate 


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ICH 
International Council for Harmonisation 
MedDRA 
Medical Dictionary for Regulatory Activities 
NE 
non-evaluable 
PC 
prostate cancer 
PET 
Positron Emission Tomography 
PP 
Per Protocol 
PPV 
positive predictive value 
PSA 
prostate-specific antigen 
PSADT 
Prostate-specific antigen doubling time 
QT interval 
the time from the start of the Q wave to the end of the T wave 
QTc 
corrected QT interval 
QTcB 
QT interval corrected using the Bazett’s formula 
QTcF 
QT interval corrected using the Fridericia method 
RR interval 
the time between successive R waves 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
SDTM 
Study Data Tabulation Model 
SOC 
standard of care 
SUV 
Standardized uptake value 
SUVr 
Lesion-to-background Standardized Uptake Value Ratio 
TEAE 
treatment-emergent AE 
TN 
true negative 
TNR 
True negative rate 
TP 
true positive 
ULN 
upper limit of normal 


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WHO 
World Health Organization 


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1.0 
INTRODUCTION 
This Statistical Analysis Plan (SAP) provides the framework for the summarization and analysis 
of the clinical data from the “64Cu-SAR-bisPSMA Positron Emission Tomography: A Phase 1/2 
Study of Participants with Biochemical Recurrence of Prostate Cancer” study. Changes made to 
the SAP after it has been signed but prior to the database lock will be documented in an SAP 
amendment. Any important changes made to the analysis will be described in the Clinical Study 
Report (CSR).  
2.0 
STUDY DESIGN 
This is a phase 1/2, single-arm, open-label multi-center study of 64Cu-labelled SAR-bisPSMA 
(64Cu-SAR-bisPSMA) administered to participants with biochemical recurrence of Prostate 
Cancer (PC) following definitive therapy. The intent is to verify the diagnostic ability of 64Cu-
SAR-bisPSMA. 
The study consists of a single administration of 64Cu-SAR-bisPSMA on Day 0, followed by a 
Positron Emission Tomography (PET)/Computed Tomography (CT) scan at 1 to 4 hours post 
dose, and at 24 hours post dose. Participants will continue to follow-up for a maximum of 180 
days where the 64Cu-SAR-bisPSMA PET/CT findings will be verified by follow-up conventional 
imaging at Day 90 and 180 (if applicable), histopathology, and Prostate-Specific Antigen (PSA) 
levels.  
64Cu-SAR-bisPSMA PET/CT scans will undergo central review by 3 blinded reviewers. The 
composite Reference Standard will be determined by an independent, blinded, central expert panel 
and may consist of histopathology, conventional imaging modalities that are routinely used in the 
diagnosis and staging of PC and PSA levels.  


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3.0 
STUDY OBJECTIVES AND ENDPOINTS 
3.1.1 Primary Study Objectives and Endpoints 
Objective 
Endpoint 
▪ To investigate safety and 
tolerability of 64Cu-SAR-
bisPSMA. 
▪ Incidence and severity of treatment-emergent adverse 
events (AEs) and serious AEs (SAEs) following the 
administration of 64Cu-SAR-bisPSMA. 
▪ To investigate the ability of 
64Cu-SAR-bisPSMA PET/CT to 
correctly detect recurrence of 
PC. 
▪ Participant-level correct detection rate (CDR), 
defined as the proportion of true positive (TP) 
participants on the Day 0 scan out of all participants 
with a Day 0 scan. 
▪ Participant-level CDR, defined as the proportion of 
TP participants on the Day 1 scan out of all 
participants with a Day 1 scan. 
▪ Region-level positive predictive value (PPV), defined 
as the proportion of TP regions on the Day 0 scan out 
of all positive regions on the Day 0 scan. 
▪ Region-level PPV, defined as the proportion of TP 
regions on the Day 1 scan out of all positive regions 
on the Day 1 scan. 
 
3.1.2 Secondary Study Objectives and Endpoints 
Objective 
Endpoint 
▪ To investigate the 
biodistribution of 64Cu-SAR-
bisPSMA. 
Biodistribution of 64Cu-SAR-bisPSMA on the Day 0 and 
Day 1 scan:  
▪ Maximum and mean standardized uptake values 
(SUVs) in lesion(s), visceral/soft tissue, bone. 
▪ Lesion-to-background ratio. 
▪ To assess the participant-level 
positive predictive value (PPV) 
of 64Cu-SAR-bisPSMA 
PET/CT.  
▪ Participant-level positive predictive value (PPV), 
defined as the proportion of TP participants on the 
Day 0 scan out of all participants with a positive Day 
0 scan. 


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▪ Participant-level PPV, defined as the proportion of 
TP participants on the Day 1 scan out of all 
participants with a positive Day 1 scan. 
▪ To assess the participant-level 
detection rate (DR) of 64Cu-
SAR-bisPSMA PET/CT.  
▪ Participant-level detection rate (DR), defined as the 
proportion of participants with a positive Day 0 scan 
out of all participants with a Day 0 scan. 
▪ Participant-level DR, defined as the proportion of 
participants with a positive Day 1 scan out of all 
participants with a Day 1 scan. 
▪ To assess the false positive rate 
(FPR) 64Cu-SAR-bisPSMA 
PET/CT. 
▪ Participant-level false positive rate (FPR), defined as 
the proportion of FP participants on the Day 0 scan 
out of all participants with a positive Day 0 scan. 
▪ Participant-level FPR, defined as the proportion of 
FP participants on the Day 1 scan out of all 
participants with a positive Day 1 scan. 
▪ Region-level FPR, defined as the proportion of FP 
regions on the Day 0 scan out of all positive regions 
on the Day 0 scan. 
▪ Region-level FPR, defined as the proportion of FP 
regions on the Day 1 scan out of all positive regions 
on the Day 1 scan. 
▪ To assess the rate of discrepant 
PET negativity rate of the 64Cu-
SAR-bisPSMA PET/CT scans. 
▪ Participant-level discrepant PET negativity rate, 
defined as the proportion of participants with 
contradicting Day 0 and Day 1 results for whom the 
Reference Standard was positive. 
▪ To assess the true negative rate 
(TNR) of 64Cu-SAR-bisPSMA 
PET/CT. 
▪ Participant-level true negative rate (TNR), defined as 
the proportion of TN participants on the Day 0 scan 
out of all participants with a negative Day 0 scan. 
▪ Participant-level TNR, defined as the proportion of 
TN participants on the Day 1 scan out of all 
participants with a negative Day 1 scan. 
▪ Region-level TNR, defined as the proportion of TN 
regions on the Day 0 scan out of all negative regions 
on the Day 0 scan. 


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▪ Region-level TNR, defined as the proportion of TN 
regions on the Day 1 scan out of all negative regions 
on the Day 1 scan. 
 
3.1.3 Exploratory Study Objectives and Endpoints 
Objective 
Endpoint 
▪ To evaluate the reproducibility 
of the 64Cu-SAR-bisPSMA 
PET/CT readings and 
consistency among readers. 
▪ Intra-reader variability per reader. 
▪ Inter-reader variability expressed by kappa statistics. 
▪ To assess the impact of 64Cu-
SAR-bisPSMA PET/CT on 
disease management. 
▪ Proportion of participants with any change in 
intended PC treatment due to either the Day 0 or Day 
1 scan. 
▪ Composite performance of the 
Day 0 and Day 1 64Cu-SAR-
bisPSMA PET/CT scans. 
▪ Composite CDR defined as the proportion of TP 
participants on the Day 0 and/or Day 1 scan out of all 
participants with a Day 0 and/or Day 1 scan. 
▪ Composite participant/region-level PPV defined as 
the proportion of TP participants/regions on the Day 
0 and/or Day 1 scan out of all participants/regions 
with a positive Day 0 and/or Day 1 scan.  
▪ Composite DR defined as the proportion of 
participants with a positive Day 0 and/or Day 1 scan 
out of all participants with a Day 0 and/or Day 1 
scan. 
▪ To determine the effect of 
baseline variables on the CDR, 
PPV and DR of 64Cu-SAR-
bisPSMA PET/CT. 
▪ CDR, participant- and region-level PPV and DR of 
the Day 0 and/or Day 1 scan as a function of baseline 
variables. 
▪  To explore the correlation 
between 64Cu-SAR-bisPSMA 
PET-positivity and Reference 
Standard results. 
▪ Relationship between PET-positivity (biodistribution 
measures such as SUVs and lesion-to-background 
ratio), versus true/false positivity and as a function of 
lesion location and size. 


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▪ To assess the lesion-level 
performance of 64Cu-SAR-
bisPSMA PET/CT. 
▪ Difference in the number of lesions detected per 
participant on the Day 0 versus the Day 1 scan. 
▪ Overall agreement rate on the Day 0 and Day 1 
scans, defined as the number lesions with matching 
subregion divided by the total number of lesions 
identified across all scans by either imaging.  
▪ Overall agreement rate on the Day 0 and reference 
scans, defined as the number lesions with matching 
subregion divided by the total number of lesions 
identified across all scans by either imaging. 
▪ Overall agreement rate on the Day 1 and reference 
scans, defined as the number lesions with matching 
subregion divided by the total number of lesions 
identified across all scans by either imaging. 
 
4.0 
HYPOTHESIS TEST AND SAMPLE SIZE ESTIMATION 
4.1 
Hypothesis Test 
No formal hypothesis testing is planned. All statistical testing and associated p-values are 
presented without controlling for the alpha level. 
4.2 
Sample Size Estimation 
Approximately 50 participants are planned to be enrolled into the study. The assumed CDR of 
64Cu-SAR-bisPSMA PET/CT imaging is 42% in this population. A sample size of 40 participants 
is estimated to provide more than 85% power to achieve a lower boundary of a 2-sided 95% exact 
binomial confidence interval (CI) about the estimated CDR that exceeds 20%. Accounting for a 
20% non-evaluable rate, approximately 50 participants will need to undergo 64Cu-SAR-bisPSMA 
PET/CT in this study. 
Additionally, for the co-primary efficacy endpoint of region-level PPV, assuming 65% of 
participants are estimated to have 64Cu-SAR-bisPSMA PET/CT positive findings in this target 
population and each participant with positive findings has an average of 1.3 positive regions, then 
40 participants are expected to produce approximately 34 positive regions. The assumed region-
level PPV rate of 64Cu-SAR-bisPSMA PET/CT imaging is approximately 65% in all PET positive 
regions. Therefore, a sample size of 40 participants (i.e., approximately 34 positive regions) is 


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estimated to provide more than 80% power to achieve a lower boundary of a 2-sided 95% exact 
binomial CI about the estimated region-level PPV that exceeds 40%. 
5.0 
RANDOMIZATION AND BLINDING 
This study is single-arm so there is no randomization. 
There are multiple levels of blinding present in this study for the readers involved in determining 
PC from various imaging modalities, creating the composite reference standard, and evaluating the 
64Cu-SAR-bisPSMA scans. Blinding will not be applied to the analysis as this is a single-arm 
study. 
6.0 
ANALYSIS SETS 
For the purposes of defining the analysis sets, a participant is considered enrolled when they have 
a Day 0 visit. Unless otherwise specified, data for participants who were enrolled but did not 
receive a 64Cu-SAR-bisPSMA administration will be listed but will not be included in summary 
tables. For purposes of analysis, the following analysis sets are defined: 
Table 1 
Analysis Sets 
Analysis Set 
Description 
All Participants Set 
All screened participants who signed the informed consent form.  
Screen failure information will be summarized using the All 
Participants Set. 
Enrolled Analysis Set 
All participants who signed the informed consent form (ICF) and 
were enrolled into the study. This will be used for patient 
disposition and analysis set summaries. 
Safety Analysis Set 
All enrolled participants who receive any amount of 64Cu-SAR-
bisPSMA. This will be used to assess safety data. 
Full Analysis Set (FAS) 
All participants who receive any amount of 64Cu-SAR-bisPSMA 
and have 64Cu-SAR-bisPSMA PET/CT imaging results from at 
least one central reader. This will be used for all efficacy 
analyses. 
Per Protocol (PP) Analysis 
Set  
All participants in the FAS who have an evaluable assessment of 
the Reference standard against 64Cu-SAR-bisPSMA PET/CT 
imaging results for the participant-level and at least 1 region for 
the Day 0 and Day 1 64Cu-SAR-bisPSMA PET/CT scan and who 


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have no exclusionary protocol deviations that exclude them from 
PP analysis. Participants that were replaced on study will not be 
included. This will be used to repeat the primary and selected 
secondary efficacy analyses only. 
Biodistribution Analysis Set 
All participants in the Safety Analysis Set who have at least one 
biodistribution measure. This will be used to summarize 
biodistribution data. 
7.0 
STATISTICAL METHODS  
7.1 
General Considerations 
7.1.1 
Standard Calculations 
▪ Variables requiring calculation will be derived using the following formulas: 
▪ Baseline: A baseline value, unless specified otherwise, is the last non-missing value recorded 
prior to the 64Cu-SAR-bisPSMA administration. If an assessment has both a date and time that 
exactly match the date and time of first dose of study drug, the assessment will be counted as 
baseline. For participants who are enrolled, but not dosed, the last assessment collected on or 
prior to the enrollment date is considered baseline. 
▪ Change from Baseline: Change from baseline will be calculated for each patient at the 
specified time point as the value at the specified time point minus the baseline value. 
▪ Study Day: The day of 64Cu-SAR-bisPSMA administration will be on Day 0 as specified in 
the study protocol schedule of events, but for Clinical Data Interchange Standards Consortium 
(CDISC) compliance, the study day variables will consider this as “Day 1” as there cannot be 
a Day 0. Study listings will be presented as “Day 0” to match the protocol.   
▪ For a given date, study day is calculated in the SDTM data as days since the date of single 
dose of 64Cu-SAR-bisPSMA: 
• Study day = date – dose date + 1, where date ≥ dose date  
• Study day = date – dose date, where date < dose date 
▪ For a given date, study day is calculated in the TLF presentations as days since the date of 
single dose of 64Cu-SAR-bisPSMA: 
• 
Study day = date – dose date, where date ≥ dose date  
• 
Study day = date – dose date, where date < dose date 
▪ Days: Durations, expressed in days, between one date (date1) and another later date (date2) 
are calculated according to the following formula: duration in days = (date2 – date1 + 1). 


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▪ Body Mass Index (BMI): BMI (kg/m2) = weight (kg) / [[height (cm)/100]2]. 
7.1.2 Summarization Groupings 
The summary tables will be presented by visit, timepoint (when applicable), and central reader (for 
efficacy analyses). As this is a single-arm study, only 1 group will be reported per analysis set.  
7.2 
General Comments on the Statistical Analyses 
▪ Age will be computed from the informed consent date and the date of birth. 
▪ Continuous variables will be summarized using number (n), mean, standard deviation (SD), 
median, 25th quartile, 75th quartile, minimum, and maximum. 
▪ Categorical data will be reported with frequency counts and percentages.  
▪ All relevant data captured on the electronic case report forms (eCRFs) and from external 
laboratories including specific descriptions of ‘other’ and comments fields will be provided in 
by-participant listings. All listings will be sorted by participant number and visit in ascending 
order.   
▪ If a clinical laboratory result is reported relative to a lower/upper range of detection for an 
assay, for example, “<10”, the numeric portion of the result (10) will be used for statistical 
analyses and the full result, including any symbols, will be provided in the patient listings.   
▪ Analysis Data Model (ADaM) datasets will be prepared using CDISC ADaM Version 2.1 or 
later, and CDISC ADaM Implementation Guide Version 1.1 or later. Pinnacle 21 Community 
Validator Version 3.1.2 or later will be utilized to ensure compliance with CDISC standards. 
▪ Version 9.4 (or higher) of the SAS® statistical software package will be used to provide all 
tables, listings, and figures. 
▪ The analyses described in this plan are considered a priori, in that they have been defined prior 
to the first patient enrolled. Any changes to the planned analyses after first patient enrolled 
will be documented in this SAP and in the CSR. 
7.3 
Handling of Missing Data 
▪ Missing values for individual data points will remain as missing. Missing values will not be 
imputed and only observed values will be used in data analyses and presentations unless 
otherwise indicated. For the reference standard, expert panel adjudications will never be 
missing and will be assigned as “non-evaluable” if based on missing data. Sensitivity analyses 
will be performed for non-evaluable reference standard assessments. 
▪ Where individual data points are missing, categorical data will be summarized based on 
reduced denominators (i.e., only patients with available data will be included in the 
denominators) unless otherwise indicated. 


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7.4 
Reporting Conventions 
In general, the units provided for a result will mirror what is collected on the eCRF unless 
otherwise specified. Results collected will use the number of decimal places that are collected, 
with mean, SD, and median reported to 1 decimal place greater than the original data. Minimum, 
maximum, 25th quartile and 75th quartile values will be reported to the same number of decimal 
places as the collected data. 
P-values will be reported to 3 decimal places, with values less than 0.001 reported as “<0.001” and 
values greater than 0.999 reported as “>0.999”. 
7.5 
Replacement of Participants 
Participants who do not complete all required study visits (including those who receive prohibited 
treatment and are discontinued early) may be replaced if needed to achieve the target sample size. 
Participants who withdraw prior to receiving investigational product will be replaced. 
The study team will meet periodically to determine if such participants need to be replaced.  
7.6 
Calculation of PSA Doubling Time and PSA Velocity 
The following values of PSA are collecting for this study: 
• PSA at Initial Diagnosis 
• Nadir PSA after initial definitive treatment 
• Most Recent PSA prior to screening #1 and #2 
• Screening PSA 
• PSA taken during the study at day 90 and 180 (if appliable) or after start of salvage focal 
therapy (can vary) 
PSA doubling time (PSADT) and PSA velocity will be calculated at baseline and during the study 
and require different definitions. PSA at initial diagnosis will not be used for any calculations of 
PSA velocity or PSADT.  
For calculation of PSADT and PSA velocity at Baseline, which will be calculated for all 
participants: 
• PSA Velocity = Slope of the line of best fit using all available data within 12 months prior 
to screening as well as screening value (excluding at initial diagnosis). 
• PSADT = ln(2) / ((ln(PSA value at screening) – ln(oldest PSA value within 12 months 
prior to screening)) / (# of months from oldest PSA value within 12 months prior to PSA at 
screening)) 


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For calculation of PSADT and PSA velocity for on-study measurements, only the last measure of 
PSA taken during the study will be used. The following calculations will be done for PSA 
measurements Post-Baseline: 
• PSA Velocity = Slope of the line of best fit using all available data on-study, including 
screening value. 
o If the participant initiated radiation therapy on-study, the last PSA value is instead 
the last PSA value PRIOR to initiating radiation therapy. 
• PSADT = ln(2) / ((ln(Last on-study PSA value) – ln(PSA at screening)) / (# of months 
from last on-study PSA value to PSA at screening)) 
o If the participant initiated radiation therapy on-study, the last PSA value is instead 
the last PSA value PRIOR to initiating radiation therapy. 
• If a participant has no post-screening value prior to initiation of radiation therapy, they 
will be excluded from post-baseline calculations of PSADT and PSA velocity. 
For the calculation of the line of best fit for PSA Velocity, the following equations will be used for 
each participant, where xi is the date of the measurement in months from screening (screening is x 
= 0) for each value, yi is the PSA value, and n is the total number of datapoints for the participant 
for that calculation: 
𝑋=
∑
𝑥𝑖
𝑛
𝑖=1
𝑛
      𝑌=
∑
𝑦𝑖
𝑛
𝑖=1
𝑛
 
𝑃𝑆𝐴 𝑉𝑒𝑙𝑜𝑐𝑖𝑡𝑦= ∑
(𝑥𝑖−𝑋)(𝑦𝑖−𝑌)
𝑛
𝑖=1
∑
(𝑥𝑖−𝑋)2
𝑛
𝑖=1
 
 
7.7 
Imaging Scans and Reference Standard 
The 64Cu-SAR-bisPSMA PET/CT scans at Day 0 and Day 1 will be interpreted locally in a non-
blinded fashion, and centrally by 3 different independent blinded readers in a random order. Each 
reader will be required to evaluate the PET/CT scans individually for the presence of pathological 
64Cu-SAR-bisPSMA uptake in the prostate bed/gland, pelvic lymph nodes, extra pelvic lymph 
nodes, visceral/soft tissue and bone. Both local and central interpretations will determine the 
number of PET-positive lesions in each region and subregion. Table 2 lists the regions and 
subregions that will be assessed on the 64Cu-SAR-bisPSMA PET/CT scans. 


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Table 2 Regions and Subregions Assessed on the 64Cu-SAR-bisPSMA PET/CT scans 
 
Anatomic Region 
Subregions 
1 
Prostatic 
1. Prostate Gland or Prostate Bed 
2 
Pelvic lymph nodes 
1. Right Pelvic 
2. Left Pelvic 
3. Other Pelvic 
3 
Extra pelvic lymph 
nodes 
1. Retroperitoneal 
2. Supradiaphragmatic 
3. Other Extra-Pelvic 
4 
Visceral/soft tissue  
1. Lung / Pleura 
2. Liver 
3. Other Soft Tissue / Visceral 
5 
Bone  
1. Pelvic Bone – R 
2. Pelvic Bone – L 
3. Skull 
4. Clavicle – R 
5. Clavicle – L 
6. Scapula – R 
7. Scapula – L 
8. Sternum 
9. Ribcage – R 
10. Ribcage – L 
11. Spine 
12. Extremities 
13. Other bone lesion 
 
The 3 central reader interpretations will be used in the analysis. Subregion, region, and participant-
level 64Cu-SAR-bisPSMA status will be derived. A fourth reader may be used as a backup, and the 
backup reader results will replace missing reader results that they perform. 
For derivations of 64Cu-SAR-bisPSMA Day 0 or Day 1 positive status: 
• A subregion is considered 64Cu-SAR-bisPSMA PET/CT positive if it has at least one 
unequivocal PET-positive lesion. 
• A region is considered 64Cu-SAR-bisPSMA PET/CT positive if it has at least one 
subregion that is considered positive (at least one unequivocal PET-positive lesion). 
• A participant is considered 64Cu-SAR-bisPSMA PET/CT positive if they have at least one 
region that is considered positive.  


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The algorithm for determining the status of a subregion for the 64Cu-SAR-bisPSMA result on Day 
0 or Day 1 was changed during the study based on an amendment to the imaging database for 
collection of non-evaluable results for subregion-level data. This change occurred on 13-Feb-2023 
and participants will be flagged in listings as to whether their 64Cu-SAR-bisPSMA results were 
collected before or after this change. 
 
Prior to this amendment, subregion status is defined as the following: 
• A subregion is considered 64Cu-SAR-bisPSMA PET/CT positive if it has at least one 
unequivocal PET-positive lesion. 
• If a subregion has only equivocal lesions or no lesions present, the subregion is considered 
negative. 
 
After this amendment, subregion status is defined as the following: 
• A subregion is considered 64Cu-SAR-bisPSMA PET/CT positive if it has at least one 
unequivocal PET-positive lesion. 
• If a subregion has only equivocal lesions, the subregion is considered negative. 
• If a subregion is marked as non-evaluable, then the subregion is non-evaluable and cannot 
be used in the comparison with the reference standard, this will be excluded from the 
analysis for that participant. 
• If the subregion is not marked as non-evaluable but there are no lesions present, the 
subregion is considered negative. 
 
A reference datapoint is a follow-up histopathology assessment, PSA response, or imaging scan 
(with the exception of the 64Cu-SAR-bisPSMA PET/CT scans) occurring between Day 1 and Day 
180 that is used to confirm if PC is demonstrated on a participant, region and subregion level. All 
reference datapoints on study will be evaluated by the expert reference panel to determine the 
reference standard for each participant. The results will be indicated as “positive”, “negative”, 
“inconclusive/equivocal”, or “non-evaluable”. Additional details are provided in the Reference 
Standard Review Panel Charter. 
Note: An “inconclusive” finding (as described in the protocol and imaging manuals) was assigned 
to the value of “indeterminate” in the transfer dataset for the central reader histopathology results. 
As such, for the data analysis and presentation of histopathology findings the terms “inconclusive” 
and “indeterminate”, are considered to have the same meaning and will be used interchangeably. 
This was implemented in the central reader histopathology database, as for other CDISC SDTM 
variables that require controlled terminology, “indeterminate” is the defined submission value, 
with acknowledgement that “inconclusive” is a defined CDISC synonym for this term (to allow 
for the connection of NCI preferred terms with SDTM submission values).   


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The composite Reference Standard will be assessed against the 64Cu-SAR-bisPSMA results at a 
region-level and a participant-level. 
7.8 
Definitions for Assessments of the Reference Standard against 64Cu-SAR-bisPSMA 
PET/CT Results 
Assessment of the Reference Standard against 64Cu-SAR-bisPSMA PET/CT results (i.e., 
assignment of True Positive, True Negative, False Positive or Non-evaluable status) will be 
undertaken for Day 0 and Day 1 64Cu-SAR-bisPSMA PET/CT results separately. 
 
Assessments of Region-Level Reference Standard against the 64Cu-SAR-bisPSMA PET/CT 
results: 
• True Positive:  
o Histopathology: A region that is 64Cu-SAR-bisPSMA PET-positive (includes at 
least one unequivocal PET-positive lesion) and Reference Standard positive is 
considered a TP region. 
o Imaging: A subregion that is 64Cu-SAR-bisPSMA PET-positive (i.e., includes at 
least one unequivocal PET-positive lesion) and Reference Standard positive (i.e., 
includes at least one unequivocal lesion detected on conventional imaging in that 
subregion) is considered a TP subregion. The subregion must match between the 
two assessments. If any region has at least one TP subregion, the region-level status 
is considered TP. 
• True Negative: 
o A region that is 64Cu-SAR-bisPSMA PET-negative (no unequivocal PET-positive 
lesion or only equivocal lesion(s) detected within the subregions) and Reference 
Standard negative. 
• False Positive: 
o A region that is 64Cu-SAR-bisPSMA PET-positive (i.e., includes at least one 
unequivocal PET-positive lesion) and Reference Standard negative based on at 
least 1 evaluable timepoint. 
• Non-evaluable: 
o A region that has either non-evaluable (NE) 64Cu-SAR-bisPSMA PET/CT results 
for a specific timepoint (Day 0 or Day 1) or has a non-evaluable or inconclusive 
Reference Standard will not be assigned for that timepoint. 
 
Assessments of Participant-Level Reference Standard against the 64Cu-SAR-bisPSMA PET/CT 
results: 
• True Positive: 


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o A participant with at least one TP region and/or at least one unequivocal 64Cu-
SAR-bisPSMA positive lesion in any region and a confirmed PSA response to 
radiation or other salvage focal therapy. 
▪ Confirmed PSA response following radiation or other salvage focal therapy 
(as long as no concomitant ADT is given) = total PSA decline ≥50% from 
baseline, confirmed by a 2nd value within 4 weeks per Prostate Cancer 
Working Group 3 criteria. 
•  True Negative: 
o A participant with a negative 64Cu-SAR-bisPSMA PET/CT (i.e., no unequivocal 
PET-positive lesion or only equivocal lesion(s) detected) and negative Reference 
Standard. 
• False Positive: 
o A participant who does not meet the TP criteria and has at least one unequivocal 
64Cu-SAR-bisPSMA PET-positive lesion and has an evaluable Reference Standard. 
• Non-evaluable: 
o A participant that has either non-evaluable 64Cu-SAR-bisPSMA PET/CT results for 
a specific timepoint (Day 0 or Day 1) or has a non-evaluable or inconclusive 
Reference Standard will not be assigned for that timepoint. 
 
False negative results (region or participant-level) will not be assigned as there is no way to 
determine whether the disease was initially present, or whether the disease has developed since the 
acquisition of the baseline and 64Cu-SAR-bisPSMA imaging. For summarization purposes only, 
these will be considered “Test Negative” defined as a negative 64Cu-SAR-bisPSMA PET/CT 
result within region-level or participant-level and a positive Reference Standard within region-
level or participant-level.  
 
Full programmatic details of the algorithm listed above to define 64Cu-SAR-bisPSMA scan status, 
reference panel status, and the assessment comparing the two at the subregion-level, region-level, 
and participant-level will be given in a supplemental analysis document labelled: 
CLP06_Primary_Analysis_Supplement.xlsx.   
 
 
7.9 
Analysis Visit Windows for Reference Datapoints 
A reference datapoint defined in the previous sections can occur at anytime post-Day 1 on study. 
There are 2 reference timepoints of interest in the analysis, Day 90 and Day 180. These timepoints 
(visit labels) are the occasions at which information was collected on clinical events that occurred 
between the previous visit/reference timepoint and the current visit/reference timepoint i.e., the 
visit/reference timepoint represents events that occurred over a window of time up to that 


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visit/reference timepoint and does not represent only events which occurred at the specific 
timepoint/day. The following describes the analysis windows surrounding these analysis visits: 
1. The visit described in the visit form completed for the assessment will be used as the 
analysis visit. 
2. If the visit is considered unscheduled or out of the protocol defined visit windows (Day 75-
105 for Day 90 and 165-195 for Day 180), then the following analysis visit windows are 
used: 
a. Day 90 Analysis Visit: Day 2 – Day 120 (or first analysis visit post-baseline) 
b. Day 180 Analysis Visit (only if a Day 90 already exists): Day 121 – End of Study. 
8.0 
DEVIATIONS FROM PROTOCOL ANALYSES 
Table 3 
Deviations from Protocol Analyses 
Analysis 
Endpoint and 
SAP Section 
Protocol v3.0 Original 
Analysis 
Updated Analysis 
Rationale 
Exploratory 
Outcome: Function 
of Baseline 
Variables 
Section 9.14.3.2. 
This analysis includes 
Lesion-to-background 
ratio as per protocol. 
Lesion-to-background 
ratio not included in this 
exploratory analysis. 
Inclusion of lesion-to-
background ratio is not 
deemed necessary or 
informative in this 
analysis.  
 
9.0 
STATISTICAL ANALYSES 
9.1 
Screened Participants 
Using the All Participants Analysis set, the number of screened patients will be summarized as 
well as the number and percentage of patients who were enrolled and reasons for non-enrollment. 
Inclusion/exclusion findings will also be listed. 
9.2 
Patient Disposition 
Patient disposition will be summarized for the Enrolled Analysis Set. Summaries will include: 
▪ Number of patients who completed the study. 


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▪ Number of patients who discontinued from the study and reason for discontinuation. 
Patient disposition data will also be presented in listings.  
9.3 
Analysis Sets 
Using the Enrolled analysis set, the number and percent of patients in the Safety, FAS, PP, and 
Biodistribution analysis sets will be provided. Reasons for exclusion from the FAS, PP and 
Biodistribution analysis sets will be summarized and presented in listings. 
9.4 
Protocol Deviations 
In accordance with International Council for Harmonisation (ICH) E3, Sponsor-defined eligibility 
violations and important (major) protocol deviations will be identified and listed. Deviations that 
exclude a participant from the PP Population will also be identified. Protocol deviations will also 
be tabulated by type of deviation and major deviations will be summarized separately by type of 
deviation in the Enrolled Analysis Set. 
9.5 
Demographics and Baseline Characteristics 
Demographic and baseline characteristics will be listed and summarized descriptively for the 
Safety Analysis Set, FAS, and PP Analysis Set. The following demographic and baseline data will 
be summarized: sex, age, race, ethnicity, height, weight, BMI, and Eastern Cooperative Oncology 
Group (ECOG) status. Age is calculated in the Electronic Data Capture (EDC) from date of birth 
to date of informed consent. 
A demographic listing will also be provided.  
9.6 
Medical and Surgical History 
Medical and Surgical history collected at screening will be coded using Medical Dictionary for 
Regulatory Activities (MedDRA), version 25. Medical and Surgical history will be summarized 
for the Safety Analysis Set by system organ class and preferred name. 
Medical and Surgical history will be listed.  
9.7 
Prostate Cancer Related History  
Relevant medical history related to PC will be summarized for the Safety Analysis Set, including 
initial prostate cancer diagnosis (PC pathology results), location of metastasis (only locations that 
at least 1 participant had are included), initial diagnosis stage per American Joint Committee on 
Cancer (AJCC) classification, initial diagnosis staging (T, N and M), initial Gleason score, time 


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from initial diagnosis to Day 0, time from biochemical recurrence to Day 0,  and PSA levels at 
biochemical recurrence. 
All relevant PC related history will also be listed. 
9.8 
Prior and Concomitant Medications  
Verbatim terms on case report forms will be mapped to Anatomical/Therapeutic/Chemical (ATC) 
class and generic drug name using the World Health Organization (WHO) drug dictionary, WHO 
Drug – Global B3, March 2022. 
Prior medications are those medications started before the administration of 64Cu-SAR-bisPSMA. 
Concomitant medications are those medications taken after the administration of 64Cu-SAR-
bisPSMA. As such, prior medications continued after the use of study drug are also considered 
concomitant medications. Prior and concomitant medications will be summarized for the Safety 
Analysis Set by ATC class (level 3) and preferred name. Patients receiving the same medication 
more than once are counted only once for each ATC class and preferred name. 
All medications with partial or missing dates and times recorded on the concomitant medication 
eCRF will be considered concomitant unless a partial stop date and time clearly indicates it was 
stopped before the administration of 64Cu-SAR-bisPSMA. 
Prior and concomitant medications will be listed by patient.  
9.9 
Cancer Surgery, Therapy, and Radiotherapy 
PC-related treatments that occur before and on study will be summarized for the Safety Analysis 
Set by visit and treatment type. The number of historical and on-study cancer therapies, 
radiotherapies, and surgeries will be summarized by visit and type of treatment. 
Any cancer surgeries, therapies, and radiotherapies, including start and stop dates, treatment type, 
treatment regime, and response information will also be listed for each participant. 
9.10 
Conventional Imaging and Histopathology 
Standard of care (SOC) conventional imaging will be performed during screening as part of 
eligibility into the trial and at Day 90 and 180 (if applicable) to establish the Reference Standard. 
Furthermore, additional SOC conventional imaging can be completed at investigator discretion 
within 180 days (±15 days) of Day 0. Both local and central reads of these scans will be 
summarized and listed.  


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The type of imaging, modality of imaging, and recurrent PC status will be summarized as well as 
the results for each region and subregion, including evidence of lesions, equivocality, and number 
of lesions for the FAS. 
Similarly, local histopathology findings will be summarized for the FAS, including the type of 
histopathology procedure, scan type where the lesion was identified, imaging modality used to 
guide biopsy (if applicable), number of lesions biopsied, number of lesions per subject with 
histopathology, and results for the 5 anatomical regions (PC positivity, histologic type, Gleason 
Score, and Gleason Grade). Central histopathology results will be summarized from the expert 
reference panel CRF. 
Local and central SOC conventional imaging results and histopathology findings will be listed for 
all participants for the Enrolled Analysis Set. 
9.11 
Study Drug Administration 
Participants will receive a single dose of 64Cu-SAR-bisPSMA on Day 0. The following 
information will be summarized for the Safety analysis set: 
• Make and model of dose calibrator. 
• Reference vial activity. 
• Activity in syringe before and after injection in MBq.  
o 1 mCi = 37 MBq 
• Method of administration. 
• Number of participants with a complete dose administered and reasons for not completely 
administered doses. 
• Actual administered activity of 64Cu-SAR-bisPSMA. 
All 64Cu-SAR-bisPSMA administrations will be listed with complete information from the 64Cu-
SAR-bisPSMA administration eCRF. 
9.12 
64Cu-SAR-bisPSMA PET/CT Imaging 
64Cu-SAR-bisPSMA PET/CT imaging will be performed on Day 0 and Day 1. The scans will be 
assessed by a local reader and by three central readers. 
For the local reader, the 64Cu-SAR-bisPSMA PET/CT results (at both timepoints), the evidence of 
64Cu-SAR-bisPSMA uptake and number of lesions and any equivocal findings in each 
region/subregion will be summarized in the FAS. 


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All 64Cu-SAR-bisPSMA PET/CT local reader data will be listed.  
All central 64Cu-SAR-bisPSMA PET/CT imaging results, including status and number of 
unequivocal lesions, will be summarized at the region-level, subregion-level, and participant-level 
by central reader.  
All 64Cu-SAR-bisPSMA PET/CT results (at both timepoints) for each central reader per 
participant at the subregion and region level, including lesion number, tumor state, sub-subregion, 
and reader comments on each lesion, will be listed.  
9.13 
Reference Standard 
The reference standard results, as defined in Section 7.7, for the region-level, subregion-level, and 
participant-level will be summarized, including the level of evidence used and details surrounding 
the imaging, histopathology, and confirmation of PSA results that go into the final reference 
standard result. 
All reference standard results for each participant will be listed with information for imaging at the 
region-level, subregion-level, and participant level, histopathology at the region and participant-
level, and confirmation of PSA results at the participant-level.  
9.14 
Efficacy Analyses 
All efficacy endpoints will be assessed using the FAS with supportive analyses performed with the 
PP analysis set for the primary efficacy endpoints and selected secondary endpoints. For 
definitions of 64Cu-SAR-bisPSMA PET/CT positive status criteria see Section 7.7 and for 
definitions of assessment of 64Cu-SAR-bisPSMA results against the Reference Standard results, 
see Section 7.8. Alpha level is set to 0.05 for all p-values but alpha is not controlled, and p-values 
are considered exploratory. 
All analyses that are considered “region-level” will be conducted in 2 ways (unless otherwise 
specified): the analysis will be conducted on all 5 regions as a whole (labeled as “All Regions”) 
and by-region individually, for 6 total calculations. 
9.14.1 Primary Efficacy Analyses 
The co-primary efficacy endpoints are the following: 
• Participant-level CDR at Day 0. 
• Participant-level CDR at Day 1. 
• Region-level PPV at Day 0. 
• Region-level PPV at Day 1. 


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CDR on a participant-level for each central reader is defined as the proportion of TP participants 
out of all scanned participants who had at least 1 evaluable reference standard datapoint collected 
and is calculated as: CDR = TP/(all scanned participants with at least 1 evaluable reference 
datapoint) x 100.  
Participants without a 64Cu-SAR-bisPSMA PET/CT scan at the specific timepoint (Day 0 or Day 
1) will be excluded from the participant-level CDR calculation for that timepoint. Participants 
with non-evaluable participant-level Reference Standard results will be excluded from the CDR 
calculation. 
PPV is measured on a region-level (the primary endpoint will be calculated including all 5 regions 
as a whole) for each central reader and is defined as the proportion of TP regions out of all 
positive regions on the 64Cu-SAR-bisPSMA PET/CT scan with corresponding evaluable 
composite Reference Standard data and will be calculated as: PPV = TP/(TP + FP) x 100, where 
FP = False Positive.  
Regions that are not positive on the 64Cu-SAR-bisPSMA PET/CT scan at a specific timepoint will 
be excluded from the region-level PPV for that timepoint. PET/CT positive regions without 
corresponding evaluable composite Reference Standard results will also be excluded. 
The anatomic regions for the PPV calculation are the following: 
• Region 1 = Prostatic 
• Region 2 = Pelvic lymph nodes 
• Region 3 = Extra pelvic lymph nodes 
• Region 4 = Visceral/soft tissue 
o This region is incorrectly labeled as Region 5 in the raw data and will be recoded 
• Region 5 = Bone 
o This region is incorrectly labeled as Region 4 in the raw data and will be recoded 
CDR and PPV will be summarized by central reader at Day 0 and Day 1 for participants who had 
at least 1 reference datapoint, and 2-sided 95% exact binomial confidence intervals (CI) using the 
Clopper-Pearson method. All primary endpoints will be summarized for the FAS (noting that 
subjects within the FAS without sufficient results to construct the required outcome variable for 
the endpoint [e.g. a participant without and evaluable reference datapoint cannot contribute to the 
determination of CDR] will by nature not be included in the respective endpoint analysis) and will 
be repeated in PP analysis set as supportive analyses. 
Histogram panels will be presented displaying the participant-level CDR and region-level PPV by 
central reader at Day 0 and Day 1 in the FAS analysis set. 


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9.14.1.1 
Sensitivity Analysis for the Primary Endpoints 
The following sensitivity analysis will be conducted on all participants in the FAS  regardless of 
whether there are reference datapoints collected. Missing data will be handled in two different 
ways: 
• Worst-case Imputation: 
o For the participant-level CDR on Day 0 and 1, participants with missing, non-evaluable, 
or inconclusive Reference Standard data will be imputed as non-TP and will be included 
in the denominator. The results will be presented in same way as the primary analysis for 
CDR. 
o For the region-level PPV on Day 0 and 1, PET/CT positive regions with missing, non-
evaluable, or inconclusive Reference Standard data will be imputed as FP. The results will 
be presented in same way as the primary analysis for PPV. 
• Tipping Point Analysis: 
o A tipping point analysis will be performed for both participant-level CDR and region-
level PPV, where participants with missing or non-evaluable Reference Standard data will 
be imputed as TP with probability p ranging from 0 to 1 with an increment of 0.1. 
o p = 0 corresponds to none of the participants in the Reference Standard with missing data 
will be imputed as TP while p = 1 corresponds to all participants in the Reference 
Standard with missing data will be imputed as TP. 
o For each of the 11 values of p (0-1 by 0.1), 20 imputation datasets will be constructed and 
combined, where the value of p is the probability that the imputation will be TP. The 
results will be presented in same way as the primary analysis for CDR and PPV for Day 0 
and 1 without 95% CI. 
o Figures displaying the CDR or PPV curve of point estimates for each value of p will be 
presented. 
 
9.14.2 Secondary Efficacy Analyses 
The following secondary analyses will be performed in a similar manner as the primary analysis, 
and will be summarized by central reader with point estimates and exact Clopper-Pearson 95% CI 
in the FAS and repeated with the PP analysis set: 
• Participant-level PPV at Day 0 and Day 1; 
o PPV = TP/(TP + FP) x 100. 
• Participant-level Detection Rate (DR) at Day 0 and Day 1; 
o DR = (number of participants with positive 64Cu-SAR-bisPSMA PET/CT scan)/(all 
scanned participants with a 64Cu-SAR-bisPSMA PET/CT scan) x 100. 


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• Participant-level False Positive Rate (FPR) on Day 0 and Day 1; 
o FPR = FP/(all scanned participants with a positive 64Cu-SAR-bisPSMA PET/CT scan 
and an evaluable reference standard) x 100. 
• Region-level FPR at Day 0 and Day 1; 
o FPR = FP regions/(all positive regions on the 64Cu-SAR-bisPSMA PET/CT scan and an 
evaluable reference standard) x 100. 
• Participant-level discrepant PET negative rate between Day 0 and Day 1 for reference 
standard positive participants. 
• Discrepant PET negative rate; 
o Discrepant PET negative rate = (number of participants with participant-level 
discrepancy in 64Cu-SAR-bisPSMA results between Day 0 and 1) / (all participants with 
a positive reference standard) x 100. 
• Participant-level True Negative Rate (TNR) on Day 0 and Day 1; 
o TNR = TN/(TN+FP) x 100. 
• Participant-level Apparent Negative Predictive Value (ANPV; referred to as TNR in the 
study protocol) on Day 0 and Day 1;  
o TN/(number of participants with a negative 64Cu-SAR-bisPSMA result) 
• Region-level TNR at Day 0 and Day 1. 
o TNR = TN/(TN+FP) x 100. 
• Region-level Apparent Negative Predictive Value (ANPV; referred to as TNR in protocol) at 
Day 0 and Day 1;  
o TN/(number of regions with a negative 64Cu-SAR-bisPSMA result). 
Note: Discrepant Day 0 and Day 1 64Cu-SAR-bisPSMA PET/CT results (results differ within 
subregion from Day 0 and Day 1 within the same central reader) will also be listed. 
9.14.3 Exploratory Efficacy Analyses  
The following exploratory analyses will be performed on the FAS for each central reader. 
9.14.3.1 
Composite 64Cu-SAR-bisPSMA PET/CT Day 0 and Day 1 Results 
CDR, participant- and region-level PPV, and DR, as described in the primary and secondary 
analyses, will be analyzed separately with the proportions derived using the best outcome from 
both Day 0 and Day 1. 
 
For the composite CDR and PPV a participant or region (if applicable) will be classed as TP if 
they meet one of the following criteria: 
• Classed as TP on Day 0 (regardless of classification on Day 1) 
• Classed as TP on Day 1 (regardless of classification on Day 0) 


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For the composite PPV a participant or region will be classed as FP for the denominator if they 
meet one of the following criteria and are not classed at TP based on the composite PPV TP 
criteria above: 
• Classed as FP on Day 0 and Day 1 
• Classed as FP on Day 0 and classed as either TN, test-negative or non-evaluable on Day 1 
• Classed as FP on Day 1 and classed as either TN, test-negative or non-evaluable Day 0 
For DR a participant will be classed as having a positive composite 64Cu-SAR-bisPSMA PET/CT 
scan if they meet one of the following criteria: 
• A positive 64Cu-SAR-bisPSMA result on both Day 0 and Day 1. 
• A positive 64Cu-SAR-bisPSMA result on Day 0 and negative, missing, or equivocal 64Cu-
SAR-bisPSMA result on Day 1. 
• A negative, missing, or equivocal 64Cu-SAR-bisPSMA result on Day 0 and a positive 
64Cu-SAR-bisPSMA result on Day 1. 
The total number of scanned participants (i.e., the denominator for DR) will be the number of 
participants who underwent a 64Cu-SAR-bisPSMA PET/CT scan on both Day 0 and Day 1. 
The composite CDR, participant- and region-level PPV, and DR will be summarized with 95% 
Exact Clopper-Pearson CIs for each central reader. 
9.14.3.2 
Function of Baseline and Other Variables of Interest 
CDR, participant- and region-level PPV, and DR of both the Day 0 and Day 1 scans will be 
summarized by the following variables: 
• PSA at baseline: <0.5, 0.5 - <1.0, 1.0 - <2.0, 2.0 - <5.0, ≥5.0 ng/mL. 
• PSA doubling time at baseline (PSADT): <3.0, 3.0-8.9, 9.0-14.9, ≥15.0 months. 
• PSA velocity at baseline: 0 to <0.05, 0.05 to <0.10, 0.10 to <0.20, ≥0.20 ng/mL/y. 
• Testosterone at baseline: <230, 230-350, >350 ng/dl. 
• Standardized uptake value (SUV) max: ≤2, 2-<5, 5-<10, ≥10.  
• Initial treatment received (2 categories): radical prostatectomy OR radiation therapy, 
cryotherapy and brachytherapy. 
• Reference Standard Level of Evidence Used: Level 1, Level 2, Level 3 
o Level 1 = histopathology (regardless of imaging results or PSA response being 
available),  
o Level 2 = imaging results (regardless of PSA response being available) but no 
contributing histopathology information,  


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o Level 3 = PSA response only ((i.e., no contribution of histopathology or imaging 
result information (participant-level only)). 
• Size of largest lesion (long axis) identified on 64Cu-SAR-bisPSMA PET/CT central reader 
scan: 0 - <0.5, 0.5 - <1.0, ≥1.0 cm. 
• Time to 64Cu-SAR-bisPSMA PET/CT scan from dosing (Day 0 only): 1 – 2 hours, 2 -4 
hours. 
 
CDR, participant and region-level PPV, and DR will be summarized for each level of the baseline 
categorical variables with CDR, PPV, and DR values in each category by central reader. Region-
level parameters will only be summarized for the “All regions” category and not the individual 
regions. 
 
9.14.3.3 
PET-positivity versus True/False Positivity 
Biodistribution parameters in lesions and organs as percentage of mean and max SUV in all 
lesions, visceral/soft tissue lesions, and bone lesions, lesion-to-background ratio, and lesions size 
will be used to explore the proportion of participants with participant-level TP and FP at Day 0 
and Day 1 by central reader in the Biodistribution Analysis Set. For the summarization of lesions, 
the mean of the lesions within a participant will be used for the definition. 
Biodistribution variables and lesions size will be compared individually between TP vs. FP groups 
using a Wilcoxon rank sum test at a region-level. 
Biodistribution variables will be presented with boxplots for the TP and FP groups. 
9.14.3.4 
Number of Lesions and Number of Positive Regions on Day 0 vs. Day 1 
The total number of, and difference in, the number of lesions detected per participant on the Day 0 
and Day 1 64Cu-SAR-bisPSMA PET/CT scans will be summarized descriptively by central reader. 
The number of lesions on Day 0 and Day 1 will be compared using a Wilcoxon signed rank test, 
with the test p-value and median difference summarized by central reader.  
Additionally, the number of positive regions detected per participant on the Day 0 and Day 1 64Cu-
SAR-bisPSMA PET/CT scans will be summarized descriptively by central reader. The number of 
positive regions on Day 0 and Day 1 will be compared using a chi-square test, with the test p-
value presented by central reader. 
9.14.3.5 
Lesion-level Overall Agreement 
The following scans will be assessed for overall lesion-level agreement rate per scan type (i.e., 
bone scan, CT, MRI, PSMA PET, etc.): 


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• Day 0 vs. Day 1 64Cu-SAR-bisPSMA PET/CT scans 
• Day 0 64Cu-SAR-bisPSMA PET/CT scan vs. SOC Scan for the Day 90 Analysis Visit  
• Day 0 64Cu-SAR-bisPSMA PET/CT scan vs. SOC Scan for the Day 180 Analysis Visit 
• Day 1 64Cu-SAR-bisPSMA PET/CT scan vs. SOC Scan for the Day 90 Analysis Visit  
• Day 1 64Cu-SAR-bisPSMA PET/CT scan vs. SOC Scan for the Day 180 Analysis Visit 
 
Overall agreement rate is defined as the (total number of lesions with matching subregions 
counted from both scans being analyzed across all patients) / (total number of lesions identified 
across both scans being analyzed by either imaging across all patients) x 100. All subregions will 
be used for the agreement rate across all anatomical regions. The overall agreement rate for the 
comparisons above will be presented by central reader. 
If multiple scans of the same type (e.g., bone scans) occur within an analysis window, then the 
later (i.e. most recent) scan’s outcome will be used in the analysis for a given subregion. For 
example, if 2 bone scans occur within the Day 90 Analysis Visit where the first Scan has 
Subregion X with no unequivocal lesions and second Scan (i.e. most recent scan) has Subregion X 
with 1 unequivocal lesion, then the value for the Day 90 Analysis Visit is that Subregion X has 1 
unequivocal lesion (if the subregion in question is evaluable based on the later scan). 
9.14.3.6 
PSA Measures Change from Baseline 
Total PSA, PSA velocity, and PSADT levels will be summarized descriptively at each timepoint 
including a change from baseline. Boxplots showing the mean, median, Q1, Q3, and outliers for 
each PSA measure will be presented for each timepoint to investigate PSA over time.  
Additional summaries of total PSA, PSA velocity, and PSADT levels will be presented for the 
following subgroups: 
• Participants who received salvage focal therapy 
• Participants who were TP for the primary analysis at the participant-level 
• Participants who were FP for the primary analysis at the participant-level 
• Participants who were TN for the primary analysis at the participant-level 
All PSA, PSA velocity, and PSADT levels will be listed. 
9.14.4 Intra and Inter-reader Variability 
9.14.4.1 
Intra-reader Variability 
Sample size calculations were performed to determine the number of Day 0 and Day 1 scans to be 
re-read by the central readers to assess for intra-reader variability. The proportion of 
positive/negative 64Cu-SAR-bisPSMA PET/CT scans for PC was assumed to be the same as for 


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results seen in a similar study of 18F-DCFPyL-PCT/CT (the CONDOR study: 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382991/), where 62% were positive, 38% 
negative, with a Kappa of 0.917 for the intra-reader variability. Using a Kappa for the null 
hypothesis of 0.3, a sample size of 16 re-reads provides 91% power for the intra-reader variability 
analysis for each timepoint (16 re-reads at Day 0 and 16 at Day 1). 
A random subset of 16 participants’ Day 0 or Day 1 64Cu-SAR-bisPSMA PET/CT scans will be 
evaluated twice by each of the central readers in order to assess the reproducibility of the readings 
and consistency among the readers. A total of 16 Day 0 and 16 Day 1 scans will be re-evaluated 
(they may not be the same participants as each timepoint will be randomized separately). The 
results from the second evaluation will only be used for intra-reader variability assessment and in 
no other analyses. 
For each scan evaluated twice, both the original and 2nd evaluation results will be summarized for 
each region and participant-level for 64Cu-SAR-bisPSMA PET/CT positivity and total number of 
positive lesions. The intra-reader variability will be assessed for each reader separately using 
Cohen’s pairwise kappa statistics along with 95% CIs for the dichotomous results (PET-positive 
or not), and the percent agreement (Lin’s concordance correlation coefficient), along with 95% CI, 
for the continuous result (average number of positive lesions) for all participants that have two 
scan interpretations on a participant-level and region-level. The interpretations of Cohen’s kappa 
are presented in Table 4.  
Table 4 
Cohen’s Kappa Levels of Agreement 
Value of Kappa Level of Agreement % of Data that are Reliable 
0–.20 
None 
0–4% 
.21–.39 
Minimal 
4–15% 
.40–.59 
Weak 
15–35% 
.60–.79 
Moderate 
35–63% 
.80–.90 
Strong 
64–81% 
Above .90 
Almost Perfect 
82–100% 
 
The second evaluation of the scans by the central readers will include all of the same data points as 
the first, original evaluation. The following variables will be assessed for intra-reader variability: 
• Participant and region-level 64Cu-SAR-bisPSMA PET/CT positivity described in the 
Primary Endpoint analysis 
• Average number of positive lesions at participant and region-level 
 


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9.14.4.2 
Inter-reader Variability 
For dichotomous results of 64Cu-SAR-bisPSMA PET/CT positivity, the agreement among the 3 
independent readers will be assessed in pairs by calculating the percent pairwise concordance, 
defined as: (# of concordant values across the 2 readers) / (# of concordant values + # of 
discordant values across the 2 readers) with evaluable 64Cu-SAR-bisPSMA PET/CT data. 
Additionally, Fleiss’s overall multi-assessor kappa statistics with 95% CIs will be presented for all 
3 readers together for the same parameter. Day 0 and Day 1 64Cu-SAR-bisPSMA PET/CT scans 
will be analyzed individually. 
For the continuous measures related to the total number of positive lesions for participant-level 
and the 5 regions individually, Pearson interclass correlations (ICC) will be presented with 95% 
CIs. Additionally, Bland-Altman plots will be produced to assess the agreement visually for the 6 
points. This will be done as reader 1 vs. reader 2, reader 1 vs. reader 3, and reader 2 vs. reader 3. 
The following variables will be assessed for inter-reader variability: 
• Participant and region-level 64Cu-SAR-bisPSMA PET/CT positivity 
• Number of positive lesions at participant and region-level  
 
9.14.5 Disease Management 
The impact of the 64Cu-SAR-bisPSMA PET/CT Day 0 or Day 1 scan will be assessed on change 
of intended PC treatment via the Disease Management Form completed at screening (Pre-SAR-
bisPSMA) and at Day 7 (Post-SAR-bisPSMA). These forms will be completed by the treating 
physician to document whether any change in planned disease management was warranted due to 
the 64Cu-SAR-bisPSMA PET/CT findings. 
The proportion of participants with any change in intended PC treatment due to either Day 0, Day 
1, both, and sum of participants who had change due to a 64Cu-SAR-bisPSMA scans will be 
summarized, with binomial Clopper-Pearson 95% CI.  
All disease management data for both timepoints will be listed. 
9.15 
Safety Analyses 
All safety analyses will be conducted on the Safety Analysis Set. Where applicable, Participants 
will be summarized by visit and timepoint.  


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9.15.1 Adverse Events 
AEs will be coded to system organ class and preferred term according to MedDRA, version 25. 
Pretreatment AEs are defined as AEs that have an onset on or after the date the informed consent 
was signed but before the time of the first dose of study drug. Treatment-emergent adverse events 
(TEAEs) are defined as AEs that start or worsen after the first dose of 64Cu-SAR-bisPSMA. 
All AEs with partial or missing dates and times will be considered treatment-emergent unless a 
partial start date and/or time indicates the AE began before the dose of 64Cu-SAR-bisPSMA or a 
stop date indicates the AE ended before the dose of 64Cu-SAR-bisPSMA.  
Summaries will be provided for TEAEs, with the number and percentage of participants reporting 
each type of event presented. If a participant’s reports the same preferred term more than once, it 
is counted only once within that category. Similarly, if a participant has AEs of two or more 
preferred terms under the same system organ class, then that patient only counts once for that 
system organ class. Furthermore, for a given summary, the preferred term will only be counted 
once at its worst severity and strongest relationship to study drug. 
PC symptoms of special interest will be collected and summarized separately by body system. 
The following summaries and listings for AEs will be provided: 
o An overall summary table of AEs summarizing the number and percent of patients, in 
the following categories: any AE, any TEAE, TEAEs by highest severity grade, 
TEAEs by relationship to study drug (related, not related), any serious TEAE, TEAEs 
leading to discontinuation from the study, TEAEs leading to study drug withdrawal, 
any TEAEs with a fatal outcome. 
o Incidence of TEAEs by MedDRA system organ class and preferred terms. 
o Incidence of TEAEs by MedDRA system organ class, preferred terms, and maximum 
severity grade. 
o Incidence of related TEAEs by MedDRA system organ class, preferred terms, and 
maximum severity grade. 
o Incidence of TEAEs grade 3 or higher by MedDRA system organ class and preferred 
term. 
o Incidence of related TEAEs grade 3 or higher by MedDRA system organ class and 
preferred term. 
o Incidence of Serious Adverse Events by MedDRA system organ class and preferred 
term. 


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o Incidence of related Serious Adverse Events by MedDRA system organ class and 
preferred term 
o Listing of all AEs (with non-treatment-emergent events flagged). 
o Listing of all AEs for patients who withdrew from study or study drug due to an AE. 
o Listing of all SAEs. 
9.15.2 Clinical Laboratory Evaluations  
Descriptive statistics for chemistry, hematology, coagulation, urinalysis, eGFR (categorized as 
chemistry), and serum testosterone and the change from baseline will be summarized for the 
Safety Analysis Set at each scheduled time point.  
Laboratory values will be categorized into normal or higher or lower than the normal range. 
Laboratory values will be presented in standard international (SI) units. Number and percent of 
participants with abnormal laboratory values will be summarized by timepoint. Shift tables based 
on CTCAE v5.0 toxicity grading as shown in Appendix 2 will be provided for shifts from baseline 
to the highest and lowest post-baseline grade. Shift tables will be presented for hematology, 
chemistry, coagulation, and urinalysis parameters as applicable.     
Listings will be provided by participant and study visit. Values for all safety laboratory results that 
are outside the laboratory reference ranges will be flagged on the individual patient data listings as 
high or low. Additionally, listings of abnormal laboratory values will be provided. 
9.15.3 Vital Signs 
Systolic and diastolic blood pressures (mmHg), heart rate (bpm), respiratory rate (breaths/minute), 
and temperature (oC), as well as height, weight, and BMI, will be summarized using descriptive 
statistics at all scheduled time points. Descriptive statistics of the change from baseline to each 
post-baseline time point will also be provided.  
9.15.4 Electrocardiogram (ECG) Parameters 
Duplicate 12-lead ECGs will be captured pre-dose and post-dose on Day 0 along with abnormal 
finding and clinical interpretations. The mean of the duplicate ECG values will be calculated, 
presented in listings used for change from baseline calculations. 
The values of the ECG parameters: RR interval, PR interval, QRS interval, QT interval, QTcB, 
and QTcF interval will be summarized using descriptive statistics at all scheduled time points as 
well as changes from baseline. Shift tables will be provided for changes from baseline using the 
categories of normal, abnormal but not clinically significant, and abnormal and clinically 


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significant. For duplicate readings at a single timepoint, the result with the greatest clinical 
significance will be used for the shift table category assignment. 
The number and percentages of participants with QTcF and QTcB values that fall into the 
following categories post-baseline will also be summarized: 
• ≤ 450 msec 
• > 450 and ≤ 480 msec 
• > 480 and ≤ 500 
• > 500 msec 
In addition, the number and percentage of participants with the following post-baseline increases 
in QTcF and QTcB will be summarized: 
• <0 msec 
• 0 - 30 msec 
• > 30-60 msec 
• > 60 msec 
A listing of ECG data will also be provided and will include the overall tracing assessment of 
normal, abnormal and clinically significant status for these measurements. 
9.15.5 Physical Examination 
Physical examination findings will be listed by body system. Abnormal findings will be described. 
9.15.6 Prostate Cancer Symptoms 
PC symptoms will be summarized by body system, symptom, and severity grade for the Safety 
Analysis Set. Locations of symptoms will also be summarized. 
All PC symptom data will be listed. 
9.16 
Biodistribution Analysis 
For the Biodistribution Analysis Set, biodistribution measures for 64Cu-SAR-bisPSMA of mean 
and max SUV, lesion longest diameter, lesion longest perpendicular, lesion-to-background ratios 
(SUVr), and reader confidence levels will be summarized descriptively. Mean and max SUV will 
use the mean of all lesions within a participant to summarize SUV in all lesions, and separately 
will summarize mean and max SUV in lesions in visceral/soft tissues and lesions in bone. 
Similarly, lesion-to-background ratio will use the mean values of the lesions within a participant. 
Boxplots will be provided for the biodistribution measures. 


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Additional summaries the of biodistribution measures above will be provided for the following 
subgroups: 
• Participants who were TP for the primary analysis at the participant-level 
• Participants who were FP for the primary analysis at the participant-level 
All individual, mean and max SUV, and SUVr measurements in organ, all lesions, visceral/soft 
tissue lesions, and bone lesions will be listed for each participant without being combined or 
averaged and will also include the value averaged over all lesions within participant that is used in 
the summaries. Reader confidence levels will also be listed. 
 


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APPENDICES 
Appendix 1 Schedule of Events 
 
Screening1 
64Cu-SAR-bisPSMA PET/CT 
Safety Visit 
Follow-Up  
Study Days 
28 days 
Day 0 
Day 1 
Day 7 (±2 days) Day 90 (±15 days) Day 180 (±15 days) 
Visit  
1 
2 
3 
4 
5 
62 
Timeline 
Pre Dose Post Dose 
24h (±6h) Post 
Dose 
Informed Consent3 
X 
 
 
 
 
 
 
Inclusion/Exclusion  
X 
 
 
 
 
 
 
Demographics and Disease 
Characteristics4 
X 
 
 
 
 
 
 
Medical and Medication History5 
X 
 
 
 
 
 
 
Prior Cancer Treatments 
X 
 
 
 
 
 
 
Prostate Cancer Treatments  
 
 
 
 
X 
X 
X 
Physical Exam6 
 
X 
 
 
X 
 
 
Body Weight 
X 
X 
 
 
X 
 
 
Height 
X 
 
 
 
 
 
 
ECOG Status7 
X 
 
 
 
 
 
 
Vital Signs8 
 
X 
X9 
 
X 
 
 
Duplicate 12-Lead ECG 
 
X 
X10 
 
 
 
 
Hematology11 
X 
 
 
 
X 
 
 
Biochemistry12 
X 
 
 
 
X 
 
 
Coagulation13 
X 
 
 
 
X 
 
 
eGFR (CKD-EPI) in mL/min 
X 
 
 
 
X 
 
 
Serum Testosterone 
X 
 
 
 
 
 
 
Urinalysis14 
 
X 
 
 
X 
 
 
Total PSA15 
X 
 
 
 
 
X 
X 
AEs 
X 
X 
X 
X 
X 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
 
 
64Cu-SAR-bisPSMA Dose 
 
X 
 
 
 
 
64Cu-SAR-bisPSMA PET/CT 
 
 
X16 
X17 
 
 
 
SOC Conventional Scan 
X 
 
 
 
 
 
 
Follow-up Conventional Imaging18 
 
 
 
 
 
X 
X 
Additional Imaging/Histopathology19 
 
 
 
 
X 


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1 Results of SOC tests or examinations performed prior to obtaining informed consent and within 28 days prior to Day 0 may be used; such tests do not need to be repeated for 
Screening. Institutional SOC scan(s) must be performed within 60 days of Day 0. SOC scan(s) performed more than 60 days prior to Day 0 may be repeated as a study screening 
procedure and reviewed by the Investigator prior to Day 0. 
2 Visit 6 is only applicable to participants who were deemed negative or equivocal for PC recurrence based on the Visit 5 follow-up conventional imaging (as per the central expert 
panel’s interpretation). 
3 Informed consent must be documented before any study-specific screening procedure is performed and may be obtained more than 28 days before the 64Cu-SAR-bisPSMA 
administration. 
4 Demographic data include: year of birth, race, ethnicity. Baseline disease characteristics include: initial diagnosis stage (per American Joint Committee on Cancer), initial 
Gleason score, initial diagnosis stage (T, N and M staging), pathology results, date of biochemical recurrence, relevant symptom history including, gastrointestinal, genitourinary 
and musculoskeletal. 
5 Medical history will include evaluation of: relevant past or present diseases or disorders, and relevant surgical history. Medication history within 14 days before signing informed 
consent should be collected. 
6 Physical examination includes assessment of: general appearance, cardiovascular system, respiratory system, and nervous system if vertebral involvement. 
7 ECOG Scale is used by the Investigator to determine the score (0 to 5) that best represents the participants’ activity status. 
8 Vital signs include: body temperature, respiratory rate, heart rate and systolic and diastolic blood pressure. 
9 Post-dose vital signs to be completed prior to the 64Cu-SAR-bisPSMA PET/CT. 
10 Post-dose ECG to be performed at 30 minutes (±10 minutes) post 64Cu-SAR-bisPSMA administration. 
11 Hematology: hemoglobin, hematocrit, red blood cell count, WBC, platelet count, differential WBC (neutrophils, eosinophils, basophils, lymphocytes, and monocytes), absolute 
neutrophil count, and absolute lymphocyte count. 
12 Biochemistry (pre-prandial): albumin, total protein, blood glucose, sodium, potassium, blood urea nitrogen, creatinine, calcium, uric acid, AST, ALT, total bilirubin,  alkaline 
phosphatase. 
13 Coagulation: prothrombin time, activated partial thromboplastin time, D-dimer.  
14 Urinalysis to include determination of protein, glucose and leukocytes (dipstick test). 
15 If radiation or other salvage focal therapy is initiated during the study, PSA levels will be monitored independent of the study visit schedule at every 4 weeks (±2 days) from the 
initiation of the therapy. PSA response (defined as total PSA decline by ≥50% from baseline) must be confirmed by a second value within 4 weeks. 
16 PET/CT scan to be performed at 1 to 4 hours post 64Cu-SAR-bisPSMA administration. If no anatomical imaging (CT or MRI) is 
available within 60 days of Day 0, a diagnostic quality CT must be acquired as part of the Day 0 PET/CT scan.  
17 PET/CT scan to be performed at 24 hours (±6 hours) post 64Cu-SAR-bisPSMA administration. 
18 Follow-up conventional imaging will include MRI or CT (a diagnostic quality CT completed as part of a PET/CT scan is acceptable) and 99mTc-MDP and/or 18F-fluciclovine 
and/or 11C-choline and/or approved PSMA PET (such as 18F-DCFPyL or 68Ga-PSMA-11).  Note: Additional follow-up conventional imaging may be completed at any other 
timepoint, as deemed appropriate by the Investigator. All follow-up scans acquired within 180 days (±15 days) of Day 0 must be transferred to the central reading center. 
Disease Management Form  
X20 
 
 
 
X21 
 
 


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19 Additional follow-up conventional imaging may be performed at the discretion of the Investigator. Where feasible, obtaining histopathology from biopsy or surgery should be 
attempted for as many 64Cu-SAR-bisPSMA PET-positive lesions as possible (based on the local interpretation of the 64Cu-SAR-bisPSMA PET/CT scans). If clinically feasible, the 
Investigator should make every effort to obtain histopathology for at least one 64Cu-SAR-bisPSMA PET-positive lesion per region. All follow-up scans and histopathology 
acquired within 180 days (±15 days) of Day 0 must be transferred to the central reading center. 
20 Pre-SAR-bisPSMA Disease Management Form must be completed by the treating physician to document the initial intended management plan for the participant based on 
available clinical information and conventional imaging results. 
21 Post-SAR-bisPSMA Disease Management Form must be completed by the treating physician for all participants who complete the 64Cu-SAR-bisPSMA PET/CT scan(s). The 
management plan will be based on the result from the local interpretation of the 64Cu-SAR-bisPSMA PET/CT scan(s) to document whether a change to the initial intended 
management plan may be warranted due to the 64Cu-SAR-bisPSMA PET/CT finding(s). 


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Appendix 2 Programmatic CTCAE v5.0 Toxicity Grading 
Laboratory Test/Vital 
Sign 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Chemistry 
(Albumin)  
Hypoalbuminemia 
<LLN – 3 g/dL; 
<LLN – 30 g/L 
<3-2 g/dL; 
<30-20 g/L 
<2 g/dL; 
<20 g/L 
 
Alkaline phosphatase 
increased 
>ULN – 2.5 x ULN if 
baseline was normal;  
 
2.0-2.5 x baseline if 
baseline was abnormal 
>2.5 – 5.0 x ULN if 
baseline was normal;  
 
>2.5-5.0 x baseline if 
baseline was abnormal 
>5.0 – 20.0 x ULN if 
baseline was normal;  
 
>5.0-20.0 x baseline if 
baseline was abnormal 
>20.0 x ULN if baseline 
was normal;  
 
>20.0 x baseline if 
baseline was abnormal 
Alanine 
aminotransferase (ALT) 
increased 
>ULN – 3 x ULN if 
baseline was normal;  
 
1.5-3.0 x baseline  if 
baseline was abnormal 
>3.0 – 5.0 x ULN if 
baseline was normal;  
 
>3.0-5.0 x baseline if 
baseline was abnormal 
>5.0 – 20.0 x ULN if 
baseline was normal;  
 
>5.0-20.0 x baseline if 
baseline was abnormal 
>20.0 x ULN if baseline 
was normal;  
 
>20.0 x baseline if 
baseline was abnormal 
Aspartate 
aminotransferase (AST) 
increased 
>ULN – 3 x ULN if 
baseline was normal;  
 
1.5-3.0 x baseline if 
baseline was abnormal 
>3.0 – 5.0 x ULN if 
baseline was normal;  
 
>3.0-5.0 x baseline if 
baseline was abnormal 
>5.0 – 20.0 x ULN if 
baseline was normal;  
 
>5.0-20.0 x baseline if 
baseline was abnormal 
>20.0 x ULN if baseline 
was normal;  
 
>20.0 x baseline if 
baseline was abnormal 
(Calcium high, 
corrected) 
Hypercalcemia 
>ULN – 11.5 mg/dL; 
>ULN – 2.0 mmol/L 
>11.5 – 12.5 mg/dL; 
>2.9 – 3.1 mmol/L 
>12.5 – 13.5 mg/dL; 
>3.1 – 3.4 mmol/L 
>13.5 mg/dL; 
>3.4 mmol/L;  
(Calcium low, 
corrected) 
Hypocalcemia 
<LLN – 8.0 mg/dL; 
<LLN – 2.0 mmol/L 
<8.0 – 7.0 mg/dL; 
<2.0 – 1.75 mmol/L 
<7.0 – 6.0 mg/dL; 
<1.75 – 1.5 mmol/L 
Hospitalization 
<6.0 mg/dL; 
<1.5 mmol/L 
Life-threatening 


CLARITY PHARMACEUTICALS LTD 
Protocol: CLP06  
Study Drug: 64Cu-SAR-bisPSMA 
 
Statistical Analysis Plan, Version 1.0 
September 4, 2024 
CONFIDENTIAL 
Page 45 of 46 
 
Laboratory Test/Vital 
Sign 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Creatinine Increased 
>ULN – 1.5 ULN 
>1.5 – 3.0 x baseline 
>1.5-3.0 x ULN 
>3.0 x baseline 
>3.0-6.0 x ULN 
>6.0 x ULN 
(eGFR or Creatinine 
Clearance) 
Chronic Kidney Disease 
eGFR or CrCL < LLN 
– 60 ml/min/1.73 m2 
eGFR or CrCl 59 – 30 
ml/min/1.73 m2 
eGFR or CrCl 29 -15 
ml/min/1.73 m2 
eGFR or CrCl < 15 
ml/min/1.73 m2 
(Glucose) 
Hypoglycemia 
<LLN – 55 mg /dL; 
<LLN – 3.0 mmol/L 
<55 – 40 mg/dL; 
<3.0 – 2.2 mmom/L 
<40 – 30 mg/dL; 
<2.2 – 1.7 mmol/L 
<30 mg/dL; 
<1.7 mmol/L; 
Life-threatening 
(Potassium high) 
Hyperkalemia 
>ULN – 5.5 mmol/L 
>5.5 - 6.0 mmol/L; 
intervention initiated 
>6.0-7.0 mmol/L;  
Hospitalization 
>7.0 mmol/L; 
Life-threatening 
(Potassium low) 
Hypokalemia 
 
<LLN – 3.0 mmol/L  
<3.0 – 2.5 mmol/L; 
Hospitalization 
<2.5 mmol/L; 
Life-threatening 
(Sodium high) 
Hypernatremia 
>ULN – 150 mmol/L 
>150-155 mmol/L 
>155-160 mmol/L; 
Hospitalization 
>160 mmol/L; 
Life-threatening 
(Sodium low) 
Hyponatremia 
<LLN – 130 mmol/L 
125-129 mmol/L 
120-124 mmol/L 
<120 mmol/L 
Total bilirubin 
increased 
>ULN – 1.5 x ULN if 
baseline was normal;  
 
1.0-1.5 x baseline if 
baseline was abnormal 
>1.5 – 3.0 x ULN if 
baseline was normal;  
 
 
>1.5-3.0 x baseline if 
baseline was abnormal 
>3.0 – 10.0 x ULN if 
baseline was normal; 
 
 
 >3.0-10.0 x baseline if 
baseline was abnormal 
>10.0 x ULN if baseline 
was normal;  
 
 
>10.0 x baseline if 
baseline was abnormal 
Hematology 
Hemoglobin increased  
Increase in >0-2 g/dL  
Increase in >2-4 g/dL  
Increase in >4 g/dL  
 
(Hemoglobin low) 
<LLN – 10.0 g/dL 
<10.0-8.0 g/dL 
<8.0 g/dL 
 


CLARITY PHARMACEUTICALS LTD 
Protocol: CLP06  
Study Drug: 64Cu-SAR-bisPSMA 
 
Statistical Analysis Plan, Version 1.0 
September 4, 2024 
CONFIDENTIAL 
Page 46 of 46 
 
Laboratory Test/Vital 
Sign 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Anemia 
<LLN – 6.2 mmol/L 
<LLN – 100 g/L 
<6.2-4.9 mmol/L 
<100-80 g/L 
<4.9 mmol/L 
<80 g/L 
Lymphocyte count 
decreased 
<LLN – 800/mm3 
<LLN – 0.8 x 10^9/L 
<800-500/mm3 
<0.8-0.5 x 10^9/L 
<500-200/mm3 
<0.5-0.2 x 10^9/L 
<200/mm3 
<0.2 x 10^9/L 
Lymphocyte count 
increased 
 
>4000/mm3-
20,000/mm3 
>20,000/mm3 
 
Neutrophil count 
decreased 
<LLN – 1500/mm3 
<LLN – 1.5 x 10^9/L 
<1500 - 1000/mm3 
<1.5-1.0 x 10^9/L 
<1000 - 500/mm3 
<1.0-0.5 x 10^9/L 
<500/mm3 
<0.5 x 10^9/L 
Platelet count decreased 
<LLN – 75,000/mm3 
<LLN – 75.0 x 10^9/L 
<75,000 - 50,000/mm3 
<75.0-50.0 x 10^9/L 
<50,000 - 25,000/mm3 
<50.0 – 25.0 x 10^9/L 
<25,000/mm3 
<25.0 x 10^9/L 
WBC Count decreased 
<LLN – 3000/mm3 
<LLN-3.0 x 10^9/L 
<3000-2000/mm3 
<3.0-2.0 x 10^9/L 
<2000-1000/mm3 
<2.0-1.0 x 10^9/L 
<1000/mm3 
<1.0 x 10^9/L 
Coagulation 
aPTT/PTT prolonged 
>ULN – 1.5 x ULN 
>1.5 – 2.5 x ULN 
>2.5 x ULN 
 
Urinalysis 
(Protein high) 
Proteinuria 
1+ proteinuria; 
Urinary protein ≥ULN 
- <1.0 g/24 hrs  
 
2+ and 3+ proteinuria;  
Urinary protein 1.0 - 
<3.5 g/24 hrs;  
 
4+ proteinuria;  
Urinary protein >=3.5 
g/24 hrs;  
 
 
 
 

Prot_000.pdf: 
Investigational Product: 64Cu-SAR-bisPSMA 
 Clarity Pharmaceuticals Ltd 
Protocol: CLP06 
 Version: 3.0, 07Dec2022 
 
 CONFIDENTIAL 
 Page 1 of 70 
Clarity Pharmaceuticals Ltd 
 
 
CLINICAL STUDY PROTOCOL: CLP06 
 
Title: 
64Cu-SAR-bisPSMA Positron Emission Tomography: A 
Phase 1/2 Study of Participants with Biochemical 
Recurrence of Prostate Cancer 
Short Title: 
COBRA (Copper-64 Sar-BisPSMA in Biochemically 
Recurrent prostAte cancer) 
Investigational Product: 
64Cu-SAR-bisPSMA 
Protocol No.: 
CLP06 
Sponsor: 
Clarity Pharmaceuticals Ltd 
National Innovation Centre 
4 Cornwallis St, Eveleigh NSW 2015 
Australia 
Telephone: +61 2 9209 4037 
IND No.: 
NCT Number: 
158388 
NCT05249127 
Phase: 
Phase 1/2 
Medical Monitor: 
Dr Robert M Miller  
+44 203 2913032 
robert.miller@claritypharmaceuticals.com 
Protocol Version (Date): 
3.0 (07-Dec-2022) 
Previous Version(s) of the 
Protocol: 
2.1 (17-Feb-2022) 
Confidentiality Statement 
This document contains information that is confidential and proprietary to Clarity Pharmaceuticals Ltd 
and is provided for the purpose of conducting a clinical trial for Clarity Pharmaceuticals Ltd. The 
contents of this document may be disclosed only to study personnel, the Institutional Review Board, or 
duly authorized representatives of regulatory agencies for this purpose under the condition that they 
maintain confidentiality. The contents of this document may not be used in any other clinical trial, 


Investigational Product: 64Cu-SAR-bisPSMA 
 Clarity Pharmaceuticals Ltd 
Protocol: CLP06 
 Version: 3.0, 07Dec2022 
CONFIDENTIAL 
Page 2 of 70 
disclosed to any other person or entity, or published without prior written permission from Clarity 
Pharmaceuticals Ltd. 


Investigational Product: 64Cu-SAR-bisPSMA 
 Clarity Pharmaceuticals Ltd 
Protocol: CLP06 
 Version: 3.0, 07Dec2022 
CONFIDENTIAL 
Page 3 of 70 
SPONSOR PROTOCOL APPROVAL 
Protocol Title: 
64Cu-SAR-bisPSMA Positron Emission Tomography: A Phase 
1/2 Study of Participants with Biochemical Recurrence of 
Prostate Cancer 
Protocol Number: 
CLP06 
Protocol Version 
(Date): 
3.0 (07-Dec-2022) 
 
This version of the clinical protocol has been approved by Clarity Pharmaceuticals Ltd. 
 
 
 
 
 
 
 
 
Dr Robert M Miller 
Chief Medical Officer 
Clarity Pharmaceuticals Ltd 
 
Date 
 
 


Investigational Product: 64Cu-SAR-bisPSMA 
 Clarity Pharmaceuticals Ltd 
Protocol: CLP06 
 Version: 3.0, 07Dec2022 
CONFIDENTIAL 
Page 4 of 70 
PROTOCOL SYNOPSIS 
Protocol Number 
CLP06 
Investigational 
Product 
64Cu-SAR-bisPSMA 
Protocol Title 
64Cu-SAR-bisPSMA Positron Emission Tomography: A Phase 1/2 Study 
of Participants with Biochemical Recurrence of Prostate Cancer 
Short Title 
COBRA (Copper-64 Sar-BisPSMA in Biochemically Recurrent prostAte 
cancer) 
Phase 
Phase 1/2 
IND Number 
158388 
Study Sponsor 
Clarity Pharmaceuticals Ltd 
Study Centers 
Planned 
Multi-center 
Study Design 
This is a multi-center, single arm, non-randomized, open-label study of 
64Cu-labelled SAR-bisPSMA (64Cu-SAR-bisPSMA) administered to 
participants with biochemical recurrence of prostate cancer (PC) 
following definitive therapy. Participants who provide informed consent 
will undertake a screening visit(s) to determine their eligibility to 
participate in the study. The maximum Screening period for each 
participant is 28 days. After the Screening period, eligible participants will 
receive a single administration of 64Cu-SAR-bisPSMA on Day 0, followed 
by a positron emission tomography (PET)/computed tomography (CT) 
scan at 1 to 4 hours post dose (Day 0 scan) and at 24 hours post dose (Day 
1 scan). Safety of 64Cu-SAR-bisPSMA will be assessed post dose, on Day 
0, Day 1 and Day 7. Participants will then continue into the Follow-Up 
period to verify the 
64Cu-SAR-bisPSMA PET/CT findings by 
histopathology, conventional imaging modalities that are routinely used in 
the diagnosis and staging of PC and prostate-specific antigen (PSA) levels. 
The maximum Follow-up period for each participant is 180 days. 
The 64Cu-SAR-bisPSMA PET/CT scans will be interpreted by an 
appropriately qualified local Investigator and three independent, blinded, 
central readers.  
The 64Cu-SAR-bisPSMA PET/CT findings will be assessed against a 
composite Reference Standard. The composite Reference Standard will be 
determined by an independent, blinded, central expert panel and may 
consist of histopathology, conventional imaging modalities that are 
routinely used in the diagnosis and staging of PC and PSA levels. 
Primary Study Objectives and Endpoints 
Objective 
Endpoint 
To investigate the safety and 
tolerability of 64Cu-SAR-bisPSMA. 
Incidence and severity of treatment-emergent AEs and 
SAEs following the administration of 64Cu-SAR-
bisPSMA. 
To investigate the ability of 64Cu-
SAR-bisPSMA PET/CT to correctly 
detect recurrence of PC. 
• 
Participant-level CDR, defined as the proportion of TP 
participants on the Day 0 scan out of all participants 
with a Day 0 scan. 


Investigational Product: 64Cu-SAR-bisPSMA 
 Clarity Pharmaceuticals Ltd 
Protocol: CLP06 
 Version: 3.0, 07Dec2022 
CONFIDENTIAL 
Page 5 of 70 
• 
Participant-level CDR, defined as the proportion of TP 
participants on the Day 1 scan out of all participants 
with a Day 1 scan. 
• 
Region-level PPV, defined as the proportion of TP 
regions on the Day 0 scan out of all positive regions 
on the Day 0 scan. 
• 
Region-level PPV, defined as the proportion of TP 
regions on the Day 1 scan out of all positive regions 
on the Day 1 scan. 
Abbreviations: AE= adverse event; CDR= correct detection rate; CT= Computed Tomography; PET= Positron 
Emission Tomography; PC= prostate cancer; PPV= positive predictive value; SAE= serious adverse event; 
TP= true positive 
Secondary Study Objectives and Endpoints 
Objective 
Endpoint 
To investigate the biodistribution of 
64Cu-SAR-bisPSMA. 
Biodistribution of 64Cu-SAR-bisPSMA on the Day 0 and 
Day 1 scan:  
• 
Maximum and mean SUVs in lesion(s), visceral/soft 
tissue, bone. 
• 
Lesion-to-background ratio. 
To assess the participant-level PPV 
of 64Cu-SAR-bisPSMA PET/CT.  
• 
Participant-level PPV, defined as the proportion of TP 
participants on the Day 0 scan out of all participants 
with a positive Day 0 scan. 
• 
Participant-level PPV, defined as the proportion of TP 
participants on the Day 1 scan out of all participants 
with a positive Day 1 scan. 
To assess the participant-level DR of 
64Cu-SAR-bisPSMA PET/CT.  
• 
Participant-level DR, defined as the proportion of 
participants with a positive Day 0 scan out of all 
participants with a Day 0 scan. 
• 
Participant-level DR, defined as the proportion of 
participants with a positive Day 1 scan out of all 
participants with a Day 1 scan. 
To assess the FPR 
64Cu-SAR-
bisPSMA PET/CT. 
• 
Participant-level FPR, defined as the proportion of FP 
participants on the Day 0 scan out of all participants 
with a positive Day 0 scan. 
• 
Participant-level FPR, defined as the proportion of FP 
participants on the Day 1 scan out of all participants 
with a positive Day 1 scan. 
• 
Region-level FPR, defined as the proportion of FP 
regions on the Day 0 scan out of all positive regions 
on the Day 0 scan. 
• 
Region-level FPR, defined as the proportion of FP 
regions on the Day 1 scan out of all positive regions 
on the Day 1 scan. 


Investigational Product: 64Cu-SAR-bisPSMA 
 Clarity Pharmaceuticals Ltd 
Protocol: CLP06 
 Version: 3.0, 07Dec2022 
CONFIDENTIAL 
Page 6 of 70 
To assess the discrepant PET 
negativity rate of the 64Cu-SAR-
bisPSMA PET/CT scans. 
Participant-level discrepant PET negativity rate, defined as 
the proportion of participants with contradicting Day 0 and 
Day 1 results for whom the Reference Standard was 
positive. 
To assess the TNR of 64Cu-SAR-
bisPSMA PET/CT. 
• 
Participant-level TNR, defined as the proportion of TN 
participants on the Day 0 scan out of all participants 
with a negative Day 0 scan. 
• 
Participant-level TNR, defined as the proportion of TN 
participants on the Day 1 scan out of all participants 
with a negative Day 1 scan. 
• 
Region-level TNR, defined as the proportion of TN 
regions on the Day 0 scan out of all negative regions 
on the Day 0 scan. 
• 
Region-level TNR, defined as the proportion of TN 
regions on the Day 1 scan out of all negative regions 
on the Day 1 scan. 
Abbreviations: CT= computed tomography; DR= detection rate; FP= false positive; FPR= rate of false positive; 
PET= positron emission tomography; PPV= positive predictive value; SUV= standardized uptake value; TN= 
true negative; TNR= rate of true negative; TP= true positive 
Exploratory Study Objectives and Endpoints 
Objective 
Endpoint 
To evaluate the reproducibility of the 
64Cu-SAR-bisPSMA 
PET/CT 
readings and consistency among 
readers. 
• 
Intra-reader variability per reader. 
• 
Inter-reader variability expressed by kappa statistics. 
To assess the impact of 64Cu-SAR-
bisPSMA 
PET/CT 
on 
disease 
management. 
Proportion of participants with any change in intended PC 
treatment due to either the Day 0 or Day 1 scan. 
Composite performance of the Day 0 
and Day 1 
64Cu-SAR-bisPSMA 
PET/CT scans. 
• 
Composite CDR defined as the proportion of TP 
participants on the Day 0 and/or Day 1 scan out of all 
participants with a Day 0 and/or Day 1 scan. 
• 
Composite participant/region-level PPV defined as the 
proportion of TP participants/regions on the Day 0 
and/or Day 1 scan out of all participants/regions with 
a positive Day 0 and/or Day 1 scan.  
• 
Composite DR defined as the proportion of 
participants with a positive Day 0 and/or Day 1 scan 
out of all participants with a Day 0 and/or Day 1 scan. 
To determine the effect of baseline 
variables on the CDR, PPV and DR 
of 64Cu-SAR-bisPSMA PET/CT. 
CDR, participant- and region-level PPV and DR of the Day 
0 and/or Day 1 scan as a function of baseline variables. 
 To explore the correlation between 
64Cu-SAR-bisPSMA PET-positivity 
and Reference Standard results. 
Relationship between PET-positivity (biodistribution 
measures such as SUVs and lesion-to-background ratio), 
versus true/false positivity and as a function of lesion 
location and size. 


Investigational Product: 64Cu-SAR-bisPSMA 
 Clarity Pharmaceuticals Ltd 
Protocol: CLP06 
 Version: 3.0, 07Dec2022 
CONFIDENTIAL 
Page 7 of 70 
To 
assess 
the 
lesion-level 
performance of 64Cu-SAR-bisPSMA 
PET/CT. 
• 
Difference in the number of lesions detected per 
participant on the Day 0 versus the Day 1 scan. 
• 
Overall agreement rate on the Day 0 and Day 1 scans, 
defined as the number lesions with matching 
subregion divided by the total number of lesions 
identified across all scans by either imaging.  
• 
Overall agreement rate on the Day 0 and reference 
scans, defined as the number lesions with matching 
subregion divided by the total number of lesions 
identified across all scans by either imaging. 
• 
Overall agreement rate on the Day 1 and reference 
scans, defined as the number lesions with matching 
subregion divided by the total number of lesions 
identified across all scans by either imaging. 
Abbreviations: CDR= correct detection rate; CT= computed tomography; DR= detection rate; PC= prostate 
cancer; PET= positron emission tomography; PPV= positive predictive value; TP = true positive 
Number of 
Participants Planned 
50 
Target Population 
The target study population is patients with biochemical recurrence of PC 
and negative or equivocal findings per institutional standard of care (SOC) 
conventional imaging. 
Inclusion Criteria 
Study candidates must meet all the following criteria to be eligible for the 
study: 
1. At least 18 years of age. 
2. Signed informed consent. 
3. Life expectancy ≥ 12 weeks as determined by the Investigator. 
4. Histologically confirmed adenocarcinoma of prostate per original 
diagnosis and completed subsequent definitive therapy. 
5. Suspected recurrence of PC based on rising PSA after definitive 
therapy on the basis of: 
a. Post-radical prostatectomy: Detectable or rising PSA that is ≥ 
0.2 ng/mL with a confirmatory PSA ≥ 0.2 ng/mL (per American 
Urological Association recommendation) or 
b. Post-radiation therapy, cryotherapy, or brachytherapy: 
Increase in PSA level that is elevated by ≥ 2 ng/mL above the 
nadir (per American Society for Therapeutic Radiology and 
Oncology-Phoenix consensus definition). 
6. Negative or equivocal findings for PC on conventional imaging 
performed as part of SOC workup within 60 days prior to Day 0. 
7. The Eastern Cooperative Oncology performance status 0-2.  
8. Adequate recovery from acute toxic effects of any prior therapy.  
9. Estimated Glomerular Filtration Rate of 30 mL/min or higher.  
10. Adequate liver function defined as alanine aminotransferase/ 
aspartate aminotransferase <3 x upper limit of normal (ULN) and 


Investigational Product: 64Cu-SAR-bisPSMA 
 Clarity Pharmaceuticals Ltd 
Protocol: CLP06 
 Version: 3.0, 07Dec2022 
CONFIDENTIAL 
Page 8 of 70 
total bilirubin <1.5 x ULN (except in the case of Gilbert’s 
syndrome). 
11. For participants who have partners of childbearing potential: Partner 
and/or participant must use a method of birth control with adequate 
barrier protection. 
Exclusion Criteria 
Study candidates who meet any of the following criteria are not to be 
enrolled in the study: 
1. Participants who received other investigational agents within 28 days 
prior to Day 0. 
2. Participants administered any high energy (>300 keV) gamma-
emitting radioisotope within 5 physical half-lives prior to Day 0. 
3. Ongoing treatment or treatment within 90 days of Day 0 with any 
systemic therapy (e.g. androgen-deprivation therapy, antiandrogen, 
gonadotropin-releasing hormone, luteinizing hormone-releasing 
hormone agonist or antagonist) for PC. 
4. Known or expected hypersensitivity to 64Cu-SAR-bisPSMA or any 
of its components. 
5. Any serious medical condition or extenuating circumstance which 
the investigator feels may interfere with the procedures or 
evaluations of the study. 
Investigational 
Product, Dose, and 
Regimen 
The investigational product administered in this study 64Cu-SAR-
bisPSMA.  
64Cu-SAR-bisPSMA has three basic components: (a) the radionuclide 
(64Cu) chelated by (b) bisCOSAR (a bifunctional metal chelator) which is 
linked to (c) two urea based small molecule inhibitors of Prostate Specific 
Membrane Antigen.  
200 MBq of 64Cu-SAR-bisPSMA will be administered as a bolus 
intravenous injection at Day 0. 
Statistical Methods 
A Statistical Analysis Plan (SAP) will be written after finalizing the 
protocol and prior to database lock. The SAP will detail the 
implementation of all the planned statistical analysis in accordance with 
the principal features stated in the protocol. 


Investigational Product: 64Cu-SAR-bisPSMA 
 Clarity Pharmaceuticals Ltd 
Protocol: CLP06 
 Version: 3.0, 07Dec2022 
 
 CONFIDENTIAL 
 Page 9 of 70 
TABLE OF CONTENTS 
SPONSOR PROTOCOL APPROVAL............................................................................. 3 
PROTOCOL SYNOPSIS ................................................................................................... 4 
TABLE OF CONTENTS ................................................................................................... 9 
List of Tables ................................................................................................................. 12 
List of Figures ................................................................................................................ 12 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ............................... 13 
AMENDMENT 1 (V2.0, 10-FEB-2022) .......................................................................... 15 
AMENDMENT 1.1 (V2.1, 17-FEB-2022) ....................................................................... 16 
AMENDMENT 2 (V3.0, 07-DEC-2022) .......................................................................... 17 
1 
INVESTIGATIONAL TEAM ................................................................................... 18 
2 
INTRODUCTION ...................................................................................................... 19 
2.1 
Background .......................................................................................................... 19 
2.2 
Imaging of Prostate Cancer .................................................................................. 20 
2.3 
Preclinical Experience ......................................................................................... 21 
2.4 
Clinical Experience .............................................................................................. 22 
2.5 
Rationale for the Study and Study Design ........................................................... 22 
2.5.1 
Imaging Timepoint Selection ........................................................................ 23 
2.5.2 
Dose Selection of 64Cu-SAR-bisPSMA ........................................................ 23 
2.6 
Benefit/Risk Assessment ..................................................................................... 23 
2.7 
Study Objectives and Endpoints .......................................................................... 24 
2.7.1 
Primary Objectives and Endpoints................................................................ 24 
2.7.2 
Secondary Objectives and Endpoints............................................................ 25 
2.7.3 
Exploratory Objectives and Endpoints ......................................................... 26 
3 
STUDY DESIGN ........................................................................................................ 27 
3.1 
Study Overview ................................................................................................... 27 
3.2 
Study Duration, Beginning and End of Study ..................................................... 29 
4 
STUDY ENROLLMENT AND WITHDRAWAL .................................................. 29 
4.1 
Study Population .................................................................................................. 29 
4.1.1 
Inclusion Criteria .......................................................................................... 29 
4.1.2 
Exclusion Criteria ......................................................................................... 30 
4.2 
Enrollment and Method of Assigning Participants to Treatment Groups ............ 30 
4.3 
Study Blinding ..................................................................................................... 30 
4.4 
Participant Withdrawal and Replacement ............................................................ 31 
4.4.1 
Screening Failures and Rescreening ............................................................. 31 
4.4.1.1 
Screen Failures............................................................................................... 31 
4.4.1.2 
Rescreening.................................................................................................... 31 
4.4.2 
Withdrawal of Consent and Discontinuation of Participants from the Study
 
31 
4.4.2.1 
Individual Stopping Rules ............................................................................. 32 


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 Clarity Pharmaceuticals Ltd 
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 Version: 3.0, 07Dec2022 
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4.4.3 
Pregnancy ...................................................................................................... 32 
4.4.3.1 
Acceptable Forms of Contraception .............................................................. 32 
4.4.3.2 
Sperm Donation ............................................................................................. 33 
4.4.4 
Replacement of Participants ......................................................................... 33 
4.5 
Premature Termination or Suspension of Study .................................................. 33 
4.6 
Safety Review Committee ................................................................................... 34 
5 
INVESTIGATIONAL PRODUCT ........................................................................... 34 
5.1 
Dosage and Formulation ...................................................................................... 34 
5.2 
Supply, Packaging and Labeling .......................................................................... 34 
5.3 
Storage and Stability ............................................................................................ 35 
5.4 
Dispensing and Administration ............................................................................ 35 
5.4.1 
Radiation protection ...................................................................................... 35 
5.5 
Compliance and Accountability ........................................................................... 35 
5.5.1 
Storage of Supplies ....................................................................................... 36 
5.5.2 
Control of Supplies ....................................................................................... 36 
5.5.3 
Destruction of Supplies ................................................................................. 36 
5.6 
Investigational Product Administration ............................................................... 36 
5.6.1 
Participant Preparation Prior to Dosing ........................................................ 36 
5.7 
Participant Release and Radioprotection Precautions .......................................... 36 
6 
CONCOMITANT MEDICATIONS ........................................................................ 36 
6.1 
Required Treatments ............................................................................................ 36 
6.2 
Permitted Treatments ........................................................................................... 37 
6.3 
Prohibited Treatments .......................................................................................... 37 
7 
STUDY PROCEDURES AND ASSESSMENTS .................................................... 37 
7.1 
Demographics and Baseline Health Record ........................................................ 40 
7.1.1 
Baseline Demographics and Disease Characteristics ................................... 40 
7.1.2 
Medical and Medication History .................................................................. 40 
7.1.3 
Prior Cancer Treatments ............................................................................... 40 
7.1.4 
Prostate Cancer Treatments .......................................................................... 40 
7.2 
Safety Assessments .............................................................................................. 40 
7.2.1 
Physical Examination.................................................................................... 40 
7.2.2 
Body Weight and Height .............................................................................. 41 
7.2.3 
Eastern Cooperative Oncology Group Performance Status .......................... 41 
7.2.4 
Vital Signs ..................................................................................................... 41 
7.2.5 
Duplicate 12-lead Electrocardiogram ........................................................... 41 
7.2.6 
Clinical Laboratory Assessments .................................................................. 41 
7.2.7 
Total PSA ...................................................................................................... 42 
7.3 
Imaging Assessments ........................................................................................... 43 
7.3.1 
Institutional Standard of Care Conventional Scan ........................................ 43 
7.3.2 
64Cu-SAR-bisPSMA PET/CT ....................................................................... 43 
7.3.2.1 
64Cu-SAR-bisPSMA PET/CT Local Interpretation ....................................... 43 
7.3.2.2 
64Cu-SAR-bisPSMA PET/CT Central Interpretation .................................... 44 
7.3.3 
Follow-up Conventional Imaging ................................................................. 44 
7.4 
Histopathology ..................................................................................................... 44 
7.5 
Diagnostic Efficacy Assessments ........................................................................ 45 
7.5.1 
Assessment of the Composite Reference Standard ....................................... 45 
7.5.2 
Assessment of Reference Standard against the 64Cu-SAR-bisPSMA PET/CT 
Results 46 


Investigational Product: 64Cu-SAR-bisPSMA 
 Clarity Pharmaceuticals Ltd 
Protocol: CLP06 
 Version: 3.0, 07Dec2022 
 CONFIDENTIAL 
 Page 11 of 70 
7.5.3 
Disease Management Plan ............................................................................ 47 
7.6 
Pharmacokinetics ................................................................................................. 47 
7.6.1 
Biodistribution of 64Cu-SAR-bisPSMA ........................................................ 47 
8 
VISIT-SPECIFIC PROCEDURES .......................................................................... 48 
8.1.1 
Screening Period (28 days, Visit 1) .............................................................. 48 
8.1.2 
64Cu-SAR-bisPSMA PET/CT Imaging......................................................... 48 
8.1.2.1 
Day 0 (Visit 2) ............................................................................................... 48 
8.1.2.2 
Day 1 (24 hours ±6 hours Post Dose, Visit 3) ............................................... 49 
8.1.3 
Safety Visit (Day 7 ± 2 days, Visit 4) ........................................................... 49 
8.1.4 
Follow-Up ..................................................................................................... 49 
8.1.4.1 
Day 90 (Day 90 ± 15 days, Visit 5) ............................................................... 49 
8.1.4.2 
Day 180 (Day 180 ± 15 days, Visit 6) ........................................................... 50 
9 
ADVERSE EVENT MONITORING ....................................................................... 50 
9.1 
Adverse Events .................................................................................................... 50 
9.1.1 
Adverse Drug Reaction ................................................................................. 51 
9.1.2 
Unexpected Adverse Drug Reaction ............................................................. 51 
9.1.3 
Assessment of Adverse Events by the Investigator ...................................... 51 
9.1.3.1 
Assessment of Severity .................................................................................. 51 
9.1.3.2 
Causality Assessment .................................................................................... 52 
9.2 
Serious Adverse Event ......................................................................................... 52 
9.3 
Serious Adverse Event Reporting – Procedures for Investigators ....................... 53 
9.3.1 
Initial Reports................................................................................................ 53 
9.3.2 
Follow-Up Reports........................................................................................ 54 
9.4 
Pregnancy ............................................................................................................. 54 
9.5 
Expedited Reporting ............................................................................................ 54 
10 STATISTICAL METHODS ..................................................................................... 54 
10.1 General Considerations ........................................................................................ 54 
10.2 Analysis Sets ........................................................................................................ 55 
10.2.1 Enrolled Analysis Set .................................................................................... 55 
10.2.2 Safety Analysis Set ....................................................................................... 55 
10.2.3 Full Analysis Set ........................................................................................... 55 
10.2.4 Biodistribution Analysis Set ......................................................................... 55 
10.3 Determination of Sample Size ............................................................................. 55 
10.4 Analysis Methods ................................................................................................. 55 
10.4.1 Enrollment and Disposition .......................................................................... 55 
10.4.2 Demographic and Other Baseline Characteristics ........................................ 55 
10.4.3 Prior and Concomitant Medication ............................................................... 56 
10.4.4 Safety Analysis ............................................................................................. 56 
10.4.4.1 
Adverse Event Analysis ................................................................................. 56 
10.4.4.2 
Laboratory Data Analysis .............................................................................. 56 
10.4.4.3 
Vital Sign Analysis ........................................................................................ 56 
10.4.4.4 
Electrocardiogram Analysis ........................................................................... 56 
10.4.5 Efficacy Analysis .......................................................................................... 57 
10.4.5.1 
Primary Efficacy Analyses ............................................................................ 57 
10.4.5.2 
Secondary Efficacy Analyses ........................................................................ 58 
10.4.5.3 
Exploratory Efficacy Analyses ...................................................................... 58 
10.4.6 Intra- and Inter-reader Reliability Assessments ............................................ 59 
10.4.7 Biodistribution Analysis ............................................................................... 60 
10.5 Interim Analysis ................................................................................................... 60 


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10.6 Handling of Missing Data .................................................................................... 60 
11 STUDY ADMINISTRATION AND RESPONSABILITIES ................................. 60 
11.1 General Investigator Responsibilities .................................................................. 60 
11.2 Protocol Compliance ............................................................................................ 61 
11.3 Compliance with Ethical and Regulatory Guidelines .......................................... 61 
11.4 Institutional Review Board .................................................................................. 61 
11.5 Informed Consent Process ................................................................................... 62 
11.6 Confidentiality ..................................................................................................... 62 
11.7 Study Files and Retention of Records and Biological Samples ........................... 63 
11.8 Participant Screening Log .................................................................................... 64 
11.9 Modifications of the Protocol or Informed Consent Documents ......................... 65 
11.10 Case Report Forms ............................................................................................... 65 
11.11 Clinical Monitoring .............................................................................................. 65 
11.12 Inspections ........................................................................................................... 65 
11.13 Data Management ................................................................................................ 66 
11.14 Clinical Study Insurance ...................................................................................... 66 
11.15 Communications with Regulatory Authorities .................................................... 66 
11.16 Publication and Information Disclosure Policy ................................................... 66 
11.17 Study Discontinuation .......................................................................................... 67 
12 REFERENCES ........................................................................................................... 68 
13 INVESTIGATOR AGREEMENT ........................................................................... 70 
 
List of Tables 
Table 1 Primary Study Objectives and Endpoints ............................................................ 25 
Table 2 Secondary Study Objectives and Endpoints ........................................................ 25 
Table 3 Exploratory Study Objectives and Endpoints ...................................................... 26 
Table 4 Investigational Product Administered ................................................................. 34 
Table 5 Schedule of Assessments ..................................................................................... 38 
Table 6 Eastern Cooperative Oncology Group Performance Status Scale ....................... 41 
 
List of Figures 
Figure 1 Overall Study Design ......................................................................................... 29 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
18F-FDG 
18F-fluorodeoxyglucose  
18F-NaF 
18F-Sodium Fluoride  
Cu-SAR-bisPSMA 
copper-labeled bisCOSAR-(Lys-urea-Glu)2 
64Cu-SAR-bisPSMA 
64Cu-labelled SAR-bisPSMA 
99mTc-MDP 
99mTc-methylene diphosphonate  
ADT 
androgen-deprivation therapy 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
CDR 
correct detection rate 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology 
eCRF 
electronic case report form  
EDC 
electronic data capture 
eGFR 
estimated glomerular filtration rate 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
FP 
false positive 
GCP 
Good Clinical Practice 
IA 
injected activity 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council on Harmonisation 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
magnetic resonance imaging 
natCu 
natural stable Cu 
NCI  
National Cancer Institute  
PC 
prostate cancer 
PET 
positron emission tomography 
PPV 
positive predictive value 
ProstaScint® 
111In-labelled-capromab-pendetide 


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Abbreviation 
Definition 
PSA 
prostate-specific antigen 
PSADT 
PSA doubling time 
PSMA 
Prostate Specific Membrane Antigen 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SOC 
standard of care 
SUV 
standardized uptake value 
TEAE 
treatment-emergent adverse event 
TN 
true negative 
TP 
true positive 
ULN 
upper limit of normal 
USA 
United States of America 
WBC 
white blood cell count 
 
 
 


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AMENDMENT 1 (V2.0, 10-FEB-2022) 
Amendment rationale and summary of changes: 
The purpose of this amendment is to address a recommendation provided during health 
authority review and to provide some clarifications on study assessments.  
At the time of implementing this amendment, no participants had been enrolled into the study.  
Summary of Changes  
Section Reference  
Version 2.0, 10-Feb-2022 
Amendment Description 
Throughout the protocol 
Version and date of the document has been updated. 
Section 4.1.1 Inclusion 
Criteria 
Update to Inclusion criterion (#9) to revise the renal function eligibility 
criterion by converting eGFR in mL/min/1.73 m2 to mL/min.  
Table 3 Exploratory Study 
Objectives and Endpoints; 
Section 10.4.6 Intra- and Inter-
reader Reliability Assessments 
Clarification added to the endpoint and section 10.4.6, that Intra- and Inter-
reader Reliability Assessments will be completed on 64Cu-SAR-bisPSMA 
PET/CT scans.  
Table 5 Schedule of 
Assessments; Visit Specific 
Procedures Section 8.1.1; 
Section 8.1.2; Section 8.1.3 
Schedule of Assessments table updated to separate the Body Weight and 
Height assessments.  
Screening period (Visit 1) has been updated to include an assessment of 
body weight and height; Safety visit (Visit 4) has been updated to include 
an assessment of body weight.    
Section 5.3 Storage and 
Stability 
Clarification added that 64Cu-SAR-bisPSMA should be stored at room 
temperature. 
Section 5.4 Dispensing and 
Administration 
The statement regarding flushing the line before and after the end of 
injection has been removed. 
Section 5.4.1 Radiation 
protection 
Additional guidance has been added to confirm that Radiation protection 
precautions must be taken in accordance with national and local 
regulations. 
Table 5 Schedule of 
Assessments; Section 7.2.6 
Clinical Laboratory 
Assessments 
Update to clarify that eGFR should be reported as mL/min (to align with 
inclusion criteria) and guidance on the conversion of mL/min/1.73 m2 to 
mL/min included.  
Section 7.2.7 Total PSA 
Clarification on the PSA results of the 2 previous most recent 
measurements, has been included. 
Abbreviations: eGFR= estimated glomerular filtration rate 
 
 


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AMENDMENT 1.1 (V2.1, 17-FEB-2022) 
Amendment rationale and summary of changes: 
The purpose of this amendment is to address a formatting error that occurred in the final version 
of Protocol V2.0, 10-FEB-2022, in which the Table 5 Schedule of Assessments foot note 21 
was illegible. This minor amendment is administrative and there is no change to the content of 
the protocol.  
At the time of implementing this amendment, no participants had been enrolled into the study. 
Summary of Changes  
Section Reference  
Version 2.1, 17-Feb-2022 
Amendment Description 
Throughout the protocol 
Version and date of the document has been updated. 
Table 5 Schedule of 
Assessments 
Foot note number 21 formatting issue corrected.  
 
 
 


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AMENDMENT 2 (V3.0, 07-DEC-2022) 
Amendment rationale and summary of changes: 
The purpose of this amendment is to address recommendations provided by Investigators, to 
provide clarifications on study assessments, analyses of data and to address minor 
typographical errors.  
Summary of Changes 
Section Reference  
Version 3.0, 07-Dec-2022 
Amendment Description 
Throughout the protocol 
Version and date of the document has been updated. 
Throughout the protocol 
Typographical, formatting corrections, administrative changes, and text 
clarifications. 
Synopsis, Table 2, Section 
7.6.1, Section 10.4.7 
Endpoint for the assessment of biodistribution as “activity in lesion(s) and 
organs as percentage injected activity” has been removed from the study.  
Section 3.1, Section 6.3, Table 
5, Section 7.2.7, Section 7.5.1, 
Section 7.5.2 
List of prohibited treatments amended to allow for any focal salvage therapy. 
PSA response following any focal salvage therapy is to be monitored every 
4 weeks from the initiation of any salvage focal therapy (in the same way as 
after radiation therapy). Histopathological confirmation of PC prior to 
commencement of radiation or other salvage focal therapy is strongly 
encouraged.  
Section 3.1, Section 7.4, Table 
5 
Clarification added regarding histopathology requirements: If clinically 
feasible, the Investigator should make every effort to obtain histopathology 
for at least one 64Cu-SAR-bisPSMA PET-positive lesion per region. 
Section 4.1.1  
Update to Inclusion criterion (#10) to remove reference to “<5 x ULN if 
liver metastases are present” as participants in the study are not expected to 
have liver metastases present at enrollment.  
Section 4.4.4 
Clarification included regarding the participant replacement criteria: 
Participants who do not complete all required study visits (including those 
who receive prohibited treatment and are discontinued early) may be 
replaced if needed to achieve the target sample size. 
Section 6 
Note added: Participants who are known to require prohibited treatment 
(e.g., initiation of ADT due to rapidly rising PSA) before the 64Cu-SAR-
bisPSMA PET/CT results can be verified via histopathology or follow-up 
imaging should not be considered for participation in this study.   
Section 6.3 
Clarification added: Participants who receive prohibited treatment(s) 
should remain in the study until completion of Visit 4. 
Section 7.3.2, Table 5 
Baseline SOC anatomical imaging requirements clarified: If no diagnostic 
quality anatomical imaging (CT or MRI) is available within 60 days of Day 
0, a diagnostic quality CT must be acquired as part of the Day 0 PET/CT 
scan.  
Section 7.2.6 
Removal of the note referencing assessment of triglycerides. Clarification 
added regarding assessment of significance for abnormal PSA values. 
Section 7.3.2, Table 5 
Clarification included regarding the baseline anatomical imaging 
requirements.  
Section 7.3.2.2 
Definition included for equivocal 64Cu-SAR-bisPSMA PET-lesions. 
Section 7.5.1 
Region- and subregion-level requirements for a positive Reference 
Standard status included.  
Section 7.5.1, Section 7.5.2 
Handling of equivocal / unequivocal lesions and non-evaluable and 
inconclusive results in the analyses was clarified. Clarification included 


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Summary of Changes 
Section Reference  
Version 3.0, 07-Dec-2022 
Amendment Description 
regarding the process of matching of the Reference Standard against the 
64Cu-SAR-bisPSMA PET/CT results. 
Section 10.4.5, Section 10.6 
Clarification of the CDR endpoint calculation and requirements for 
reference standard datapoints added. Participants with non-evaluable 
participant-level Reference Standard results will be excluded from the CDR 
calculation. 
Removal of non-evaluable regions from the analysis of region-level PPV 
endpoint. PET/CT positive regions without corresponding evaluable 
composite Reference Standard results will no longer be included in the 
denominator for the region-level PPV calculation. 
Removal of the sensitivity analyses of the participant-level CDR and 
region-level PPV based on participants in the full analysis set who had 
evaluable composite Reference Standard results. 
Section 10.4.5.3 
Assessment of CDR, PPV and DR as a function of anatomic region 
removed.  
Abbreviations: ADT= androgen-deprivation therapy, CDR= correct detection rate, CT= computed tomography, DR= 
detection rate, PET= positron emission tomography, PPV= positive predictive value, PSA= prostate-specific antigen, 
ULN= upper limit of normal 
 
1 INVESTIGATIONAL TEAM 
Refer to the trial specific contact list for details of investigators, sponsor personnel, clinical 
research organization personnel and facilities used in the study. 
 
 


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2 INTRODUCTION 
This study will be conducted in compliance with the protocol, Good Clinical Practice (GCP), 
applicable regulatory requirements, and International Conference on Harmonisation (ICH) 
guidelines. 
2.1 Background 
Prostate cancer (PC) is the second most frequent malignancy in men1. The American Cancer 
Society estimates 248,530 new cases of PC were diagnosed in the United States of America 
(USA) in 2021 accounting for approximately 25% of all new estimated cancer cases in men 
and approximately 13% of all new estimated cancer cases1,2. Incidence correlates with age, 
running between 30% for patients 40-50 years old to 50-80% for patients aged 80 and over3. 
Median age at diagnosis is 67 years and median age at death is 81 years4,5. Although the 
etiology of the disease is unclear, the main risk factors include advanced age, ethnicity, and 
positive family history6. While some patients with PC have indolent disease, where the 
patient’s serum prostate-specific antigen (PSA) values are followed without further treatment, 
the majority of patients will receive some treatment for their PC. Between 20-40% of patients 
with PC will relapse within 10 years of their primary PC treatment, as identified through rising 
PSA levels. At relapse, approximately 25-35% of patients have locally recurrent disease, 20-
25% have metastatic disease, and 45-55% have both local and metastatic disease7. 
Prostate Specific Membrane Antigen (PSMA) is a type II, 750-amino acid transmembrane 
protein (100-120 kDa), anchored in the cell membrane of prostate epithelial cells. Prostate 
Specific Membrane Antigen has two important enzymatic functions; folate hydrolase and N-
acetylated-a-linked acidic dipeptidase, and exhibits an endocytic function, in which it 
spontaneously recycles through endocytic vesicles. Despite its name, PSMA is not specific to 
the prostate gland and is expressed in other tissues, including salivary and lacrimal glands, 
duodenal mucosa, proximal renal tubular cells, and subpopulations of neuroendocrine cells in 
the colonic crypts8. Prostate Specific Membrane Antigen is strongly upregulated in all types of 
PC, and increases with tumor aggressiveness, metastatic disease, and recurrence, making it an 
excellent target for both imaging and therapy of PC9-11. 
The Sponsor is developing a radiolabeled inhibitor of PSMA for the diagnosis and treatment 
of PC. The product is copper-labeled bisCOSAR-(Lys-urea-Glu)2 (Cu-SAR-bisPSMA). Cu-
SAR-bisPSMA uses a radioactive form (radionuclide) of copper, 64Cu to image cancers using 
Positron Emission Tomography (PET) and then 67Cu for therapy by internal beta-radiation.  
The target population for this study is patients with biochemical recurrence of PC following 
initial definitive therapy. Although PSA is the primary biomarker for recurrence, it does not 
reflect the location or the extent of disease recurrence. Despite recent advances in imaging 
techniques, many patients will fail to have their recurrence accurately localized by imaging, 
especially at low PSA levels. Identifying tumor relapses and metastases is challenging for 
conventional imaging modalities such as Computed Tomography (CT) and Magnetic 
Resonance Imaging (MRI) due to limitations in sensitivity and specificity. Early diagnosis of 
recurrence and accurate staging are essential to inform the best treatment strategy. Prostate 
Specific Membrane Antigen-targeting agents have been shown to be well suited for the 
development of radiopharmaceuticals for imaging and therapy of PC. Evolving evidence 
demonstrates superior sensitivity and specificity of these PET agents compared to conventional 
imaging, with frequent identification of sub-centimeter PC lesions. Prostate Specific 
Membrane Antigen-targeting PET scan is effective for imaging disease in the prostate, lymph 
nodes, soft tissue, and bone in a single examination12. 


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Refer to the Investigator’s Brochure (IB) for detailed information on 64Cu-labelled SAR-
bisPSMA (64Cu-SAR-bisPSMA). 
2.2 Imaging of Prostate Cancer 
Conventional imaging modalities such as MRI, CT, and 99mTc-methylene diphosphonate 
(99mTc-MDP) bone scan, suffer from limited sensitivity and specificity, which can result in 
inaccurate disease staging leading to suboptimal treatment. The use of molecular imaging using 
PET has therefore been explored to better identify sites of disease. A number of new PET 
diagnostic radiopharmaceuticals have emerged in the recent years, including agents that 
accumulate on the basis of alterations in cellular metabolism as well as those that bind to 
specific proteins, such as PSMA13.  
Approved diagnostic radiopharmaceuticals that are commonly used to image PC include 99mTc-
MDP bone scan, 18F-fluorodeoxyglucose (18F-FDG), 18F-Sodium Fluoride (18F-NaF), 11C-
choline, 18F-FACBC (or 18F-fluciclovine; registered as Axumin®), and more recently, PSMA-
based PET radiopharmaceuticals, 
68Ga-PSMA-11 and 
18F-DCFPyL (registered as 
PYLARIFY®)13,14.  
Currently, 99mTc-MDP planar whole-body scanning is the imaging standard for detection of 
osseous metastases. 18F-Sodium Fluoride uptake mechanism in the bone is similar to that for 
99mTc-MDP but with better sensitivity and specificity in the detection of bone metastases. 
These scans are both lacking in specificity however, with uptake in areas of bone remodeling 
such as infection and trauma, in addition to osseous metastases. Furthermore, they are limited 
in the detection of soft-tissue malignancies, including the primary tumor, lymph node disease, 
and visceral metastases. 
Although molecular imaging in oncology is most commonly performed with 18F-FDG PET, 
this test has not shown clinical utility in PC imaging15. Prostate cancer cells typically do not 
undergo increased aerobic glycolysis, limiting the use of 18F-FDG. These cells do, however, 
display upregulated de novo lipid synthesis and activity of lipogenic enzymes. This enables 
lipid precursors such as choline to function as radiotracers for PET imaging in PC. 11C-choline 
was approved by the Food and Drug Administration (FDA) in 2012, but choline-based 
radiotracers are not cancer specific, and can be taken up in other tissues or areas of benign 
inflammation. In addition, its use is affected by the short half-life (t1/2=20 minutes). In studies 
comparing 11C-choline to 68Ga-PSMA-11, 68Ga-PSMA-11 showed a higher detection rate than 
11C-choline PET for lymph nodes as well as bone lesions16,17. 18F-FACBC targets multiple 
sodium-dependent and independent channels which are upregulated in PC. 18F-FACBC is a 
synthetic amino acid that is well tolerated and able to detect local and distant PC recurrences 
across a wide range of PSA values18. However, like 11C-choline, 18F-FACBC was shown to be 
inferior to 68Ga-PSMA-11 in prospective imaging trials19.  
Prostate Specific Membrane Antigen has been studied extensively as an imaging target in PC. 
The first commercialized PSMA targeting imaging agent was 111In-labelled-capromab-
pendetide (ProstaScint®), which was approved by the FDA in 1996. However, ProstaScint® 
was only able to bind to the intracellular epitope of PSMA and was therefore not capable of 
visualizing viable PC cells leading to poor clinical performance20. Since then, the class of 
PSMA targeting agents that have been most extensively explored are the urea-based small 
molecule inhibitors of PSMA. Two of these, 68Ga-PSMA-11 and 18F-DCFPyL, have recently 
been approved by the FDA for PET imaging of PSMA positive lesions in men with PC with 
suspected metastasis who are candidates for initial definitive therapy or with suspected 
recurrence based on elevated serum PSA level. The updated National Comprehensive Cancer 
Network Guidelines® for PC (Version 1.2022) specify that 68Ga-PSMA-11 and 18F-DCFPyL 


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or PET/CT can be considered as an alternative to standard imaging of bone and soft tissue for 
initial staging, the detection of biochemically recurrent disease, and as workup for progression 
with bone scan plus CT or MRI for the evaluation of bone, pelvis, and abdomen. Several other 
68Ga- and 18F-based PSMA targeting products are currently in development21.  
Due to the short half-life of 68Ga and 18F-based PSMA products, PET is usually conducted 
around 1 hour post administration. However, most PC lesions present with increased uptake 
and contrast at later imaging timepoints22. Thus, 64Cu with its longer half-life (t1/2=12.7 hours) 
compared to 68Ga (t1/2=68 minutes) and 18F (t1/2=109.7 minutes) has the potential to provide 
advantages over the 68Ga- and 18F-based PET products. Delayed imaging may enable the 
detection of additional or smaller lesions, due to enhanced tumor-to-background ratios 
following biological clearance of the product over time23. A longer half-life also allows for 
large-scale central manufacturing and offers logistical advantages in the manufacture and 
delivery of a finished product to the clinical site, providing superior geographical coverage 
compared to 68Ga and 18F-based products. Thus, 64Cu-SAR-bisPSMA PET/CT has the potential 
to be a useful diagnostic tool to localize PC, including in patients with suspected biochemical 
recurrence of PC with low PSA, where there is a high unmet medical need. 
2.3 Preclinical Experience 
A number of non-clinical studies have been conducted to assess the biodistribution, in vivo 
safety and tolerability, as well as tumor imaging and efficacy of SAR-bisPSMA labeled with 
either natural stable Cu (natCu), 64Cu or 67Cu. 
Preclinical imaging studies with 64Cu-SAR-bisPSMA in a PC xenograft model showed high 
uptake and retention of the product in the tumor over 24 hours (22% Injected Activity[IA]/g at 
1 hour and 26% IA/g at 24 hours post dose)24. These results compare favorably to other PSMA-
targeted products in similar preclinical models.  
A repeat dose toxicology study in mice was conducted to investigate the potential toxicity of 
natCu-labeled SAR-bisPSMA when administered weekly for four administrations by 
intravenous injection. No clinical abnormalities, significant changes in weight or feed intake, 
and no product related effects were observed in hematology, blood biochemistry and urine 
analyses. There were no product related macroscopic, nor microscopic findings in organs by 
histology analysis. The no observed adverse effect level was considered to be 2 mg/kg for 
natCu-SAR-bisPSMA, which corresponds to a safety factor of the chemical entity of the 
product, of 192 times the proposed dose.  
64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA form a true theranostic pair, meaning the 
products behave the same biologically, as they both utilize isotopes of copper, for diagnosis 
and therapy, respectively. Biodistribution studies using either 64Cu-SAR-bisPSMA or 67Cu-
SAR-bisPSMA are therefore applicable to both products. The biodistribution of 67Cu-SAR-
bisPSMA was investigated in healthy male mice. 67Cu-SAR-bisPSMA was utilized to allow 
measurements of the biological clearance of Cu-SAR-bisPSMA out to nine days after injection, 
due to the longer half-life of 67Cu (t1/2= 2.6 days). Effective blood clearance of 67Cu-SAR-
bisPSMA was demonstrated in male mice at one hour (0.7 ± 0.2% IA/g) and at 24 hours, 
activity circulation in the blood had reduced by over 85% of the one hour values. The primary 
excretion pathway for 67Cu-SAR-bisPSMA is via the kidneys into urine. However, the high 
expression of PSMA in murine kidneys resulted in high initial kidney uptake, with the highest 
accumulated activity at 2 hours in male mice (184.1 ± 12.3% IA/g). Over 95% of the 67Cu 
SAR-bisPSMA activity in the kidneys had been cleared at 24 hours. Uptake in the liver and 
intestines suggests there is also some hepatobiliary clearance of 67Cu-SAR-bisPSMA. The 
salivary glands, a PSMA expressing organ, exhibited peak activity at 2 hours however 


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clearance from the salivary glands was rapid with approximately 90% of the activity cleared at 
24 hours.  
Dosimetry calculations from the mouse biodistribution study enabled organ radiation dose 
extrapolations for an adult human male. For 64Cu-SAR-bisPSMA, the largest radiation dose is 
observed in the kidney and urinary bladder, with a value of 0.258 mGy/MBq and 
0.059 mGy/MBq, respectively. The effective whole-body dose was 0.012 mSv/MBq, which 
for an administration of 200 MBq of 64Cu-SAR-bisPSMA would result in an effective whole-
body dose of 2.43 mSv. 
Please refer to the IB for further details on non-clinical studies. 
2.4 Clinical Experience 
The Sponsor is currently conducting two clinical trials using 64Cu-SAR-bisPSMA:  
• 
The CLP05 (“Secure”) clinical trial: Phase I/IIa theranostic study of 64Cu-SAR-
bisPSMA and 67Cu-SAR-bisPSMA for identification and treatment of PSMA-expressing 
metastatic castrate resistant prostate cancer (NCT04868604). This study is currently 
recruiting participants with metastatic castrate resistant PC at a number of clinical sites 
in the USA. In this study, 64Cu-SAR-bisPSMA is used as a diagnostic agent to select 
patients eligible for therapy with 67Cu-SAR-bisPSMA; with the objective of assessing 
safety, dosimetry, biodistribution and the ability of 64Cu-SAR-bisPSMA PET/CT to 
visualize PC, as well as determine the safety and therapeutic efficacy of 67Cu-SAR-
bisPSMA.  
• 
The CLP03 (“Propeller”) clinical trial: Positron Emission Tomography Imaging of 
Participants with Confirmed Prostate Cancer Using 64Cu-SAR-bisPSMA: A Multi-
Centre, Blinded review, Dose Ranging Phase I study (NCT04839367). This study is 
currently recruiting participants at a number of clinical sites in Australia. This is a Phase 
1 safety and dose ranging study of 64Cu-SAR-bisPSMA administered to participants 
with untreated, histopathology confirmed PC, with intermediate- to high-risk features, 
who are planned for radical prostatectomy with lymph node dissection. The aim of the 
study is to assess the safety, image quality and ability of 64Cu-SAR-bisPSMA PET/CT 
to detect PC. 
Based on the preliminary data accrued to date, no significant safety findings have emerged in 
relation to 64Cu-SAR-bisPSMA. 
2.5 Rationale for the Study and Study Design 
The non-clinical data indicate that 64Cu-SAR-bisPSMA binds to PSMA-expressing tumors 
with high affinity, appears to be well-tolerated and has a potential to be used to obtain high 
quality images of PSMA-expressing tumors in human cancers. These findings warrant further 
investigations in clinical studies. 
This is a multi-center, single arm, non-randomized, open-label study of 64Cu-SAR-bisPSMA 
administered to participants with biochemical recurrence of PC following definitive therapy. 
The aim of the study is to evaluate the safety, pharmacokinetics, and preliminary efficacy of 
64Cu-SAR-bisPSMA. The collection of standard safety parameters used in this study such as 
adverse event (AE) reporting, vital signs, electrocardiograms (ECGs), and clinical laboratory 
assessments are considered appropriate for monitoring the health and well-being of participants 
in early phase clinical studies. The biodistribution assessments were selected to characterize 
the pharmacokinetics of 64Cu-SAR-bisPSMA in humans. The diagnostic efficacy assessments 


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used in this study are widely used and considered appropriate for the evaluation of performance 
of diagnostic imaging agents.  
This study will provide the Sponsor with information on the safety, pharmacokinetics and 
preliminary diagnostic efficacy of 64Cu-SAR-bisPSMA in the target population, prior to 
initiating more extensive Phase 2 and Phase 3 studies.  
2.5.1 Imaging Timepoint Selection 
The 64Cu diagnostic radionuclide has a half-life of 12.7 hours which allows for the completion 
of PET scans up to at least 24 hours post administration of the radiopharmaceutical.  
Preclinical PET/CT images captured at 1, 4 and 24 hours post administration of 64Cu-SAR-
bisPSMA showed that the tumor is clearly visible at the 1 hour timepoint. The tumor-to-
background ratio at 4 and 24 hours was much higher than at 1 hour, demonstrating a high 
degree of accumulation and retention.  
For this study, a PET/CT scan completed between 1 and 4 hours post dose of 64Cu-SAR-
bisPSMA (Day 0 scan) is considered to be clinically practical and suitable to assess whether 
64Cu-SAR-bisPSMA is capable of detecting PC in humans. Delayed imaging at 24 hours post 
dose (Day 1 scan) will also be completed as it is hypothesized that delayed imaging may enable 
the detection of smaller lesions due to enhanced tumor-to-background ratios following 
biological clearance of the product over time. 
2.5.2 Dose Selection of 64Cu-SAR-bisPSMA 
64Cu-SAR-bisPSMA will be administered at a fixed administered activity of 200 MBq.  
Preclinical biodistribution studies were used to extrapolate the estimated organ radiation 
dosimetry of 64Cu-SAR-bisPSMA in adult males. These calculations indicate that an 
administration of 200 MBq of 64Cu-SAR-bisPSMA would result in an effective whole-body 
dose of 2.43 mSv (0.012 mSv/MBq). An effective dose of this magnitude is comparable to 
other routinely used imaging agents such as 18F-FDG (8.4 mSv according to the Nuclear 
Medicine Radiation Dose Tool - SNMMI), and the recently approved 68Ga-PSMA-11 and 18F-
DCFPyL at their recommended administered activity (4.4 mSv and 3.9 mSv, respectively, 
according to approved labeling). The preclinical biodistribution study projected that the kidney 
was the organ with the highest absorbed dose. A 200 MBq administered activity of 64Cu-SAR-
bisPSMA will limit the estimated radiation absorbed dose to the kidney to approximately 
50 mGy.  
Based on the data obtained to date in the CLP03 and CLP05 study, the Sponsor believes that 
200 MBq of 64Cu-SAR-bisPSMA is an adequate activity to guarantee sufficient image quality 
for this study across the selected imaging timepoints. 
2.6 Benefit/Risk Assessment 
It is not known if study participants will gain any improvement in their own healthcare 
outcomes as a result of their participation in this study. However, the ability to accurately 
identify and stage PC recurrence would enable more effective treatment decisions and this 
would therefore, be considered a benefit to the participant. A general societal benefit is widely 
considered to accrue from medical scientific knowledge accumulated through the conduct of 
ethical research on participants. 
All study participants will receive a single administration of 64Cu-SAR-bisPSMA. Specific 
foreseeable risks to study participants include:  


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• Radiation dose received by the study participant: Extrapolation of preclinical 
biodistribution studies estimate that an administration of 200 MBq of 64Cu-SAR-
bisPSMA would result in an effective whole-body dose of 2.43 mSv (i.e. 
0.012 mSv/MBq), which is comparable to the whole-body effective doses of other 
routinely used imaging agents at their recommended administered activity. There is a 
potential hazard from the additional radiation burden to study participants. The study 
also involves low dose CT scan(s) performed for attenuation correction of the PET 
scan(s) and for the anatomical correlation to allow more precise delineation of organs. 
Participants without baseline anatomical imaging will undergo a diagnostic quality CT 
(instead of the low dose CT) as part of the Day 0 PET/CT scan. 
• Chemical toxicity of 64Cu-SAR-bisPSMA and other constituents of the injection: The 
constituents (including excipients and stabilizers) of 64Cu-SAR-bisPSMA are at 
concentrations that are known to be safe for human use. 64Cu-SAR-bisPSMA, as 
supplied, will result in a maximum quantity not exceeding 50 μg of peptide mass per 
participant for an administration. The administered peptide mass is therefore at least 
192 times less than the dose of natCu-SAR-bisPSMA that has been demonstrated to be 
without any relevant toxicity in rodent toxicology studies (based on a 60 kg subject). 
The administered dose is well below the limits specified by the FDA for microdosing 
studies. 
• Intravenous administration: Minor pain may occur at the time of venipuncture and 
minor bruising may also result; however, patients are exposed to these same risks 
during routine care. Whilst extravasation of PET radiopharmaceuticals is possible, it is 
unlikely associated with adverse outcomes due to the very small mass of materials 
contained in the injection, and the small amount of radioactivity available for injection. 
Nevertheless, an indwelling canula can be established prior to investigational product 
administration to mitigate this risk. 
• Incidental findings of possible clinical significance: Appropriate diagnostic testing can 
assist in making a correct diagnosis and in providing additional information to guide 
patient management. An incorrect diagnosis (e.g. false negative or false positive results 
of the diagnostic tests) can have important consequences in patient management. An 
incidental finding is an imaging finding of potential health importance concerning the 
study participant, which is discovered while conducting imaging research, but is 
beyond the aims of the study. It is the responsibility of the local site or of the study 
Investigator to arrange for routine clinical review of study scans and clinical follow-up, 
as required. Policies for the communication of the incidental finding to the research 
participant should align with national regulations and customs. As part of the informed 
consent process, research participants will be informed about the possibility that 
incidental imaging findings may be detected, and about the pathway for handling such 
findings.  
2.7 Study Objectives and Endpoints 
2.7.1 Primary Objectives and Endpoints 
The primary study objectives and endpoints to be evaluated in this study are presented in Table 
1. 


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Table 1 Primary Study Objectives and Endpoints 
Objective 
Endpoint 
To investigate the safety and 
tolerability of 64Cu-SAR-bisPSMA. 
Incidence and severity of treatment-emergent AEs and 
SAEs following the administration of 64Cu-SAR-bisPSMA. 
To investigate the ability of 64Cu-
SAR-bisPSMA PET/CT to correctly 
detect recurrence of PC. 
• 
Participant-level CDR, defined as the proportion of TP 
participants on the Day 0 scan out of all participants 
with a Day 0 scan. 
• 
Participant-level CDR, defined as the proportion of TP 
participants on the Day 1 scan out of all participants 
with a Day 1 scan. 
• 
Region-level PPV, defined as the proportion of TP 
regions on the Day 0 scan out of all positive regions on 
the Day 0 scan. 
• 
Region-level PPV, defined as the proportion of TP 
regions on the Day 1 scan out of all positive regions on 
the Day 1 scan. 
Abbreviations: AE= adverse event; CDR= correct detection rate; CT= Computed Tomography; PET= Positron 
Emission Tomography; PC= prostate cancer; PPV= positive predictive value; SAE= serious adverse event; TP= 
true positive 
2.7.2 Secondary Objectives and Endpoints 
The secondary study objectives and endpoints to be evaluated in this study are presented in 
Table 2. 
Table 2 Secondary Study Objectives and Endpoints 
Objective 
Endpoint 
To investigate the biodistribution of 
64Cu-SAR-bisPSMA. 
Biodistribution of 64Cu-SAR-bisPSMA on the Day 0 and 
Day 1 scan:  
• 
Maximum and mean SUVs in lesion(s), visceral/soft 
tissue, bone. 
• 
Lesion-to-background ratio. 
To assess the participant-level PPV 
of 64Cu-SAR-bisPSMA PET/CT.  
• 
Participant-level PPV, defined as the proportion of TP 
participants on the Day 0 scan out of all participants 
with a positive Day 0 scan. 
• 
Participant-level PPV, defined as the proportion of TP 
participants on the Day 1 scan out of all participants 
with a positive Day 1 scan. 
To assess the participant-level DR of 
64Cu-SAR-bisPSMA PET/CT.  
• 
Participant-level DR, defined as the proportion of 
participants with a positive Day 0 scan out of all 
participants with a Day 0 scan. 
• 
Participant-level DR, defined as the proportion of 
participants with a positive Day 1 scan out of all 
participants with a Day 1 scan. 


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To assess the FPR 
64Cu-SAR-
bisPSMA PET/CT. 
• 
Participant-level FPR, defined as the proportion of FP 
participants on the Day 0 scan out of all participants 
with a positive Day 0 scan. 
• 
Participant-level FPR, defined as the proportion of FP 
participants on the Day 1 scan out of all participants 
with a positive Day 1 scan. 
• 
Region-level FPR, defined as the proportion of FP 
regions on the Day 0 scan out of all positive regions on 
the Day 0 scan. 
• 
Region-level FPR, defined as the proportion of FP 
regions on the Day 1 scan out of all positive regions on 
the Day 1 scan. 
To assess the rate of discrepant PET 
negativity rate of the 
64Cu-SAR-
bisPSMA PET/CT scans. 
Participant-level discrepant PET negativity rate, defined as 
the proportion of participants with contradicting Day 0 and 
Day 1 results for whom the Reference Standard was 
positive. 
To assess the TNR of 64Cu-SAR-
bisPSMA PET/CT. 
• 
Participant-level TNR, defined as the proportion of TN 
participants on the Day 0 scan out of all participants 
with a negative Day 0 scan. 
• 
Participant-level TNR, defined as the proportion of TN 
participants on the Day 1 scan out of all participants 
with a negative Day 1 scan. 
• 
Region-level TNR, defined as the proportion of TN 
regions on the Day 0 scan out of all negative regions on 
the Day 0 scan. 
• 
Region-level TNR, defined as the proportion of TN 
regions on the Day 1 scan out of all negative regions on 
the Day 1 scan. 
Abbreviations: CT= computed tomography; DR= detection rate; FP= false positive; FPR= rate of false positive; 
PET= positron emission tomography; PPV= positive predictive value; SUV= standardized uptake value; TN= true 
negative; TNR= rate of true negative; TP= true positive 
2.7.3 Exploratory Objectives and Endpoints 
The exploratory study objectives and endpoints to be evaluated in this study are presented in 
Table 3. 
Table 3 Exploratory Study Objectives and Endpoints 
Objective 
Endpoint 
To evaluate the reproducibility of the 
64Cu-SAR-bisPSMA 
PET/CT 
readings and consistency among 
readers. 
• 
Intra-reader variability per reader. 
• 
Inter-reader variability expressed by kappa statistics. 
To assess the impact of 64Cu-SAR-
bisPSMA 
PET/CT 
on 
disease 
management. 
Proportion of participants with any change in intended PC 
treatment due to either the Day 0 or Day 1 scan. 


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Composite performance of the Day 0 
and 
Day 
1 
64Cu-SAR-bisPSMA 
PET/CT scans. 
• 
Composite CDR defined as the proportion of TP 
participants on the Day 0 and/or Day 1 scan out of all 
participants with a Day 0 and/or Day 1 scan. 
• 
Composite participant/region-level PPV defined as the 
proportion of TP participants/regions on the Day 0 
and/or Day 1 scan out of all participants/regions with a 
positive Day 0 and/or Day 1 scan.  
• 
Composite DR defined as the proportion of participants 
with a positive Day 0 and/or Day 1 scan out of all 
participants with a Day 0 and/or Day 1 scan. 
To determine the effect of baseline 
variables on the CDR, PPV and DR of 
64Cu-SAR-bisPSMA PET/CT. 
CDR, participant- and region-level PPV and DR of the Day 
0 and/or Day 1 scan as a function of baseline variables. 
 To explore the correlation between 
64Cu-SAR-bisPSMA PET-positivity 
and Reference Standard results. 
Relationship 
between 
PET-positivity 
(biodistribution 
measures such as SUVs and lesion-to-background ratio), 
versus true/false positivity and as a function of lesion 
location and size. 
To 
assess 
the 
lesion-level 
performance of 64Cu-SAR-bisPSMA 
PET/CT. 
• 
Difference in the number of lesions detected per 
participant on the Day 0 versus the Day 1 scan. 
• 
Overall agreement rate on the Day 0 and Day 1 scans, 
defined as the number lesions with matching subregion 
divided by the total number of lesions identified across 
all scans by either imaging.  
• 
Overall agreement rate on the Day 0 and reference 
scans, defined as the number lesions with matching 
subregion divided by the total number of lesions 
identified across all scans by either imaging. 
• 
Overall agreement rate on the Day 1 and reference 
scans, defined as the number lesions with matching 
subregion divided by the total number of lesions 
identified across all scans by either imaging. 
Abbreviations: CDR= correct detection rate; CT= computed tomography; DR= detection rate; PC= prostate 
cancer; PET= positron emission tomography; PPV= positive predictive value; TP = true positive 
3 STUDY DESIGN 
3.1 Study Overview 
Approximately 50 participants are planned to be enrolled in this study. This is a multi-center, 
single arm, non-randomized, open-label study of 64Cu-SAR-bisPSMA administered to 
participants with biochemical recurrence of PC following definitive therapy. To be considered 
for inclusion in the study, candidates must demonstrate negative or equivocal findings on 
institutional standard of care (SOC) conventional imaging.  
Participants who provide informed consent will undertake screening visit(s) to determine their 
eligibility to participate in the study. The maximum Screening period for each participant is 28 
days. After the Screening period, eligible participants will receive a single administration of 
64Cu-SAR-bisPSMA on Day 0, followed by a PET/CT scan at 1 to 4 hours post dose (Day 0 
scan) and at 24 hours post dose (Day 1 scan). Safety of 64Cu-SAR-bisPSMA will be assessed 


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post dose on Day 0, Day 1 and Day 7. Participants will then continue into the maximum 180-
day Follow-Up period to verify the 64Cu-SAR-bisPSMA PET/CT findings by:  
• Follow-up conventional imaging: All participants will undergo conventional imaging 
at 90 days ± 15 days post Day 0.  
o Participants who are deemed to be negative or equivocal for PC recurrence 
based on central review of the 90-day conventional imaging will undergo 
further conventional imaging at 180 days ± 15 days post Day 0.  
o Participants who are deemed positive for PC recurrence based on central review 
of the 90-day conventional imaging will require no further study visits. 
However, if additional follow-up imaging per Investigator discretion is acquired 
within 180 days post Day 0, these data must be provided to the central reading 
center.  
• Histopathology: Where feasible, obtaining histopathology from biopsy or surgery 
should be attempted for as many 64Cu-SAR-bisPSMA PET-positive lesions as possible 
(based on the local interpretation of the 64Cu-SAR-bisPSMA PET/CT scans) within 180 
days of Day 0. If clinically feasible, the Investigator should make every effort to obtain 
histopathology for at least one 64Cu-SAR-bisPSMA PET-positive lesion per region. 
• Assessment of PSA levels: PSA will be assessed in all participants at 90 days ± 15 
days and if the participant is returning to the study site for further follow-up imaging, 
at 180 days ± 15 days post Day 0. If radiation therapy or other salvage focal therapy 
(e.g., cryotherapy) is initiated during the study (as long as no concomitant androgen-
deprivation therapy [ADT] is given), PSA levels must be monitored every 4 weeks from 
the initiation of the therapy. Prostate specific antigen response (defined as total PSA 
decline by ≥50% from baseline) must be confirmed by a second value within 4 weeks. 
Central Review of Scans: The 64Cu-SAR-bisPSMA PET/CT scans will be interpreted by an 
appropriately qualified local Investigator and three independent, blinded, central readers. Each 
reader will be required to evaluate the PET/CT scans individually for the presence of 
pathological 64Cu-SAR-bisPSMA uptake in the prostate bed/gland, pelvic lymph nodes, extra 
pelvic lymph nodes, visceral/soft tissue and bone.  
Expert Panel Composite Reference Standard: The 64Cu-SAR-bisPSMA PET/CT findings will 
be assessed against a composite Reference Standard. The composite Reference Standard will 
be determined by an independent, blinded, central expert panel and may consist of 
histopathology, conventional imaging modalities that are routinely used in the diagnosis and 
staging of PC and PSA levels. The Investigator will be required to submit all relevant clinical 
evidence available for the participant to enable the assessment of the Reference Standard. The 
expert panel will determine the composite Reference Standard without knowledge of the 64Cu-
SAR-bisPSMA PET/CT results. 
To assess the impact of 64Cu-SAR-bisPSMA PET/CT on disease management, the treating 
physician will be required to fill out a Pre-SAR-bisPSMA and a Post-SAR-bisPSMA Disease 
Management Form to provide information on the treatment strategy of the participant before 
and after the information from the local read of the 64Cu-SAR-bisPSMA PET/CT scan(s) 
becomes available. 
See Figure 1 for the overall study design schema. Details on study procedures for each visit are 
described in Table 5 and Section 8. 


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Figure 1 Overall Study Design 
  
3.2 Study Duration, Beginning and End of Study 
Participants are considered enrolled in the study once they are appropriately consented and 
screened, with eligibility verified by an Investigator.  
The expected study recruitment period is ~6 months. 
The maximum screening period for each participant is 28 days.  
The maximum on study period for each participant is ~6 months. 
The total trial duration is ~13 months. 
The end of study is defined as the date of the final participant visit/contact.  
In addition, the Sponsor may decide to terminate the study at any time (see Section 4.5). 
4 STUDY ENROLLMENT AND WITHDRAWAL 
4.1 Study Population 
The target study population is patients with biochemical recurrence of PC and negative or 
equivocal findings per institutional SOC conventional imaging. The inclusion and exclusion 
criteria are outlined below.  
4.1.1 Inclusion Criteria  
Study candidates must meet all the following criteria to be eligible for the study: 
1. At least 18 years of age. 
2. Signed informed consent. 
3. Life expectancy ≥ 12 weeks as determined by the Investigator. 
4. Histologically confirmed adenocarcinoma of prostate per original diagnosis and 
completed subsequent definitive therapy. 
5. Suspected recurrence of PC based on rising PSA after definitive therapy on the basis of: 
a. Post-radical prostatectomy: Detectable or rising PSA that is ≥ 0.2 ng/mL with a 
confirmatory PSA ≥ 0.2 ng/mL (per American Urological Association 
recommendation) or 
b. Post-radiation therapy, cryotherapy, or brachytherapy: Increase in PSA level that is 
elevated by ≥ 2 ng/mL above the nadir (per American Society for Therapeutic 
Radiology and Oncology-Phoenix consensus definition). 


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6. Negative or equivocal findings for PC on conventional imaging performed as part of SOC 
workup within 60 days prior to Day 0. 
7. The Eastern Cooperative Oncology (ECOG) performance status 0-2.  
8. Adequate recovery from acute toxic effects of any prior therapy.  
9. Estimated Glomerular Filtration Rate (eGFR) of 30 mL/min or higher.  
10. Adequate liver function defined as alanine aminotransferase (ALT)/ aspartate 
aminotransferase (AST) <3 x upper limit of normal (ULN) and total bilirubin <1.5 x ULN 
(except in the case of Gilbert’s syndrome). 
11. For participants who have partners of childbearing potential: Partner and/or participant 
must use a method of birth control with adequate barrier protection. 
4.1.2 Exclusion Criteria  
Study candidates who meet any of the following criteria are not to be enrolled in the study: 
1. Participants who received other investigational agents within 28 days prior to Day 0. 
2. Participants administered any high energy (>300 keV) gamma-emitting radioisotope 
within 5 physical half-lives prior to Day 0. 
3. Ongoing treatment or treatment within 90 days of Day 0 with any systemic therapy (e.g. 
ADT, antiandrogen, gonadotropin-releasing hormone, luteinizing hormone-releasing 
hormone agonist or antagonist) for PC. 
4. Known or expected hypersensitivity to 64Cu-SAR-bisPSMA or any of its components. 
5. Any serious medical condition or extenuating circumstance which the investigator feels 
may interfere with the procedures or evaluations of the study. 
4.2 Enrollment and Method of Assigning Participants to Treatment 
Groups 
This is a non-randomized, single-arm study. After completing the Screening period, 
participants who meet all inclusion criteria and no exclusion criteria, will be enrolled into the 
study and receive a single administration of 64Cu-SAR-bisPSMA. 
Each participant will be identified in the study by a Participant Number that is assigned when 
the participant is first entered into Screening and is retained as the primary identifier for the 
participant throughout his entire participation in the trial. The Participant Number consists of 
the Center Number (as assigned by the Sponsor to the investigative site) with a sequential 
participant number suffixed to it, so that each participant is numbered uniquely across the entire 
database. Upon signing the informed consent form (ICF), the participant is assigned to the next 
sequential Participant Number available to the Investigator. 
4.3 Study Blinding 
In this study, all participants will receive 64Cu-SAR-bisPSMA and thus blinding of 
investigational product is not applicable.  
However, to allow for a non-biased assessment of the 64Cu-SAR-bisPSMA PET/CT, the scans 
will be assessed by three independent central readers, blinded to the participants-specific 
information (identifiers, medical history, physical exam, laboratory results), the timepoint of 


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the scan, results of evaluations as part of the Reference Standard, results of other imaging 
modalities, final diagnosis / outcome, and details of the protocol. 
To allow for a non-biased assessment of the Reference Standard, an independent central panel 
of experts will be used to assess and determine the composite Reference Standard. The expert 
panel will not include any of the three readers who assess the 64Cu-SAR-bisPSMA PET/CT 
scans. The panel will not have access to the 64Cu-SAR-bisPSMA PET/CT scans or reports from 
the local or central read of the scans. 
4.4 Participant Withdrawal and Replacement  
4.4.1 Screening Failures and Rescreening 
4.4.1.1 Screen Failures 
Screen failures are those participants who do not meet the study eligibility criteria. For 
participants who are considered a screen failure, the reason for screen failure will be entered 
on the screening log. The demographic information, informed consent, and inclusion/exclusion 
pages must also be entered on the electronic Case Report Form (eCRF). If the participant 
experiences a serious adverse event (SAE) during the screening period, this information must 
also be entered (see Section 9.3 for SAE reporting details).  
4.4.1.2 
Rescreening 
Participants who fail screening assessments may be re-screened. Rescreening and specific 
assessments to be repeated is to be discussed on a case-by-case basis with the Medical Monitor.  
Rescreened participants should be assigned the same participant number as for the initial 
screening, which is deemed appropriate and practical from a reporting perspective. Participants 
may only participate in the study once.  
4.4.2 Withdrawal of Consent and Discontinuation of Participants from the Study 
Participants will be informed that they have the right to withdraw consent or discontinue from 
the study at any time for any reason, without prejudice to their medical care.  
Following enrolment into the study, if a participant is discontinued or withdraws consent for 
any reason, whether related to the investigational product or not, the participant will be 
considered an early-discontinued participant. The reason for study discontinuation or 
withdrawal of consent is to be documented in the participants’ source documents and eCRF.  
Refer to Section 4.4.2.1 for individual stopping rules. 
1. Withdraw of Consent to Participate in the Study 
Withdrawal of consent occurs only when a participant (or their substitute decision 
maker/person responsible) does not want to participate in the study any longer, does not want 
any further study related visits or assessments and does not want any further study related 
contact. The Sponsor will continue to retain and use all research data that have already been 
collected for the study evaluation up until the point of withdrawal of consent. All biological 
samples that have already been collected may be retained and analyzed at a later date (or as 
required by local regulations).  
If a participant withdraws consent, the Investigator should make an effort to determine the 
primary reason for this decision (however the patient is not required to provide a reason) and 
record this information along with the withdrawal of consent discussion, which should be 


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documented in the patient notes.  With the participants consent, the Investigator may perform 
some final safety evaluations to ensure that there are no safety risks associated with the 
participants withdrawal. Further attempts to contact the participant for study related discussions 
are not allowed unless safety findings require communication or follow-up. 
2. Investigator Decision to Discontinue the Participant 
The Investigator also has the right to discontinue participants from the study for any of the 
following reasons: 
• Participant non-adherence to protocol requirements; 
• Any other reason based upon the medical judgment of the Investigator.  
The Investigator will make every effort to ensure that early-discontinued participants who have 
received investigational product(s) complete safety follow-up assessments (refer to Schedule 
of Assessments). 
3. Lost to Follow Up 
Reasonable efforts will be made to keep in contact with enrolled study participants. Participants 
who have not responded to at least three such attempts for follow-up may be deemed ‘lost to 
follow-up’. Efforts made to contact study participants must be documented in the participant’s 
file. 
4.4.2.1 
Individual Stopping Rules 
No individual stopping rules apply as only a single 64Cu-SAR-bisPSMA administration is 
delivered in the study. 
4.4.3 Pregnancy 
There is no information about the effects that 64Cu-SAR-bisPSMA could have on the 
development of the fetus in humans. Therefore, it is important that female partners of sexually 
active participants, do not become pregnant during the study and agree to use adequate 
contraception. Participants will be instructed that known or suspected pregnancy occurring 
during the study in female partners, should be confirmed and reported to the Investigator.  
The Investigator should also be notified of a pregnancy of a female partner of the participant 
occurring during the study. In the event that a female partner of a participant is found to be 
pregnant whilst the participant is enrolled in the study, the pregnancy will be followed, and the 
status of mother and child will be reported to the Sponsor (or delegate).  
A Pregnancy Report Form will be completed and submitted for any pregnancy occurring in 
female partners of participants from enrolment until study completion. 
4.4.3.1 Acceptable Forms of Contraception 
Sexually active participants with female partners of childbearing potential are eligible to 
participate if they agree to follow one of the following methods of contraception consistently, 
starting from Screening, during the study and for at least 5 days after the administration of 
64Cu-SAR-bisPSMA: 
• 
Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle 
(abstinent on a long-term and persistent basis) and agree to remain abstinent. 
• 
Are sterilized (with the appropriate post-vasectomy documentation of the absence of 
sperm in the ejaculate); 


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• 
Agree to use a male condom and have their partner use a contraceptive method with a 
failure rate of <1% per year as described below when having penile-vaginal intercourse 
with a woman of childbearing potential who is not currently pregnant, and who agrees 
to the use of a condom by her partner. 
Sexually active male participants with a pregnant or breastfeeding partner must agree to remain 
abstinent from penile‑vaginal intercourse; or use a male condom during each episode of penile 
penetration during the study. 
A highly effective method of contraception/birth control method which result in low failure 
rate (i.e., less than 1% per year when used consistently and correctly) must be used starting 
from the Screening visit, for the duration of the study and for 5 days after the last dose of 64Cu-
SAR-bisPSMA. 
Examples of acceptable contraception include: 
• 
Established use of oral, injected or implanted hormonal methods of contraception; 
• 
Placement of an intrauterine device or intrauterine system; 
Examples of non-acceptable methods of contraception include: 
• 
Condoms alone or double barrier; 
• 
Periodic abstinence (e.g. calendar, ovulation, symptothermal, post ovulation); 
• 
Withdrawal; 
• 
Spermicide. 
4.4.3.2 Sperm Donation 
In addition, participants must refrain from donating sperm starting from Screening, during the 
study and for at least 5 days after the administration of 64Cu-SAR-bisPSMA. 
4.4.4 Replacement of Participants 
Participants who do not complete all required study visits (including those who receive 
prohibited treatment and are discontinued early) may be replaced if needed to achieve the target 
sample size. Participants who withdraw prior to receiving investigational product will be 
replaced.  
4.5 Premature Termination or Suspension of Study 
The study can be temporarily suspended or prematurely terminated at any time for any reason 
by the Sponsor if there is sufficient reasonable cause. Written notification, documenting the 
reason for study suspension or termination, will be provided by the suspending or terminating 
party to the Investigator, and regulatory authorities.  
Should this be necessary, the participants who have received investigational product should be 
seen as soon as possible to perform the Safety Visit. Participants in Follow-up should also be 
contacted for a final visit. The Investigator may be informed of additional procedures to be 
followed in order to ensure that adequate consideration is given to the protection of the 
participant’s interests. 
If the study is prematurely terminated or suspended, the Investigator will be responsible for 
promptly informing the institutional review board (IRB) and will provide the reason(s) for the 
termination or suspension.  


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Circumstances that may warrant termination or suspension include, but are not limited to:  
• Determination of unexpected, significant, or unacceptable risk to participants; 
• Demonstration of efficacy that would warrant stopping; 
• Insufficient compliance to protocol requirements; 
• Data that are not sufficiently complete and/or evaluable; 
• Sponsor terminates the study for administrative, financial, or other reasons. 
4.6 Safety Review Committee 
A Safety Review Committee is not deemed necessary for this study based on what is known 
regarding the safety of 64Cu from other studies. The medical monitor will periodically review 
laboratory and AE data and will review SAE reports in real time. Any clinically important 
findings will be discussed with the Investigators. 
5 INVESTIGATIONAL PRODUCT 
5.1 Dosage and Formulation 
The investigational product administered in this study is 64Cu-SAR-bisPSMA. The Sponsor is 
developing this radiopharmaceutical for the diagnosis (PET imaging) of PSMA-expressing PC.  
64Cu-SAR-bisPSMA has three basic components: (a) the radionuclide (64Cu) chelated by (b) 
bisCOSAR (a bifunctional metal chelator) which is linked to (c) two urea based small molecule 
inhibitors of PSMA. 
64Cu-SAR-bisPSMA will be administered as a bolus intravenous injection. 64Cu-SAR-
bisPSMA will be formulated as a sterile solution for intravenous injection suitable for human 
use. 
64Cu-SAR-bisPSMA is considered an investigational product by the FDA, and as such will be 
under controlled conditions for use in clinical trials. 
Details of the investigational product administration are found in Table 4.  
Table 4 Investigational Product Administered 
Investigational 
Product 
Route of 
administration 
Dose (MBq) 
Dose Frequency 
64Cu-SAR-
bisPSMA 
Intravenous 
Bolus Injection 
200 MBq per Administration 
Single Administration on Day 0 
5.2 Supply, Packaging and Labeling 
64Cu-SAR-bisPSMA will be manufactured, packaged, and labeled on behalf of the Sponsor 
and will be provided with appropriate documentation for human use. 
64Cu-SAR-bisPSMA will be supplied as ready-to-use product according to production and 
quality control methods.  
The release of each final batch of 64Cu-SAR-bisPSMA for human use is subject to the quality 
control measures (product specifications) established by the Sponsor, with quality control 
testing undertaken by the manufacturing facilities or the clinical sites. Available analytical data 


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for each batch will be reviewed by qualified personnel at the facility to ensure suitability for 
human administration. 
5.3 Storage and Stability 
64Cu-SAR-bisPSMA will be stored in a secure location (i.e. limited access area). 
The Investigator (or suitably qualified designee) agrees not to dispense the 64Cu-SAR-
bisPSMA from, nor store them at, any site other than the approved study sites as per local 
regulations. 
Once received at the clinical site, 64Cu-SAR-bisPSMA is stored at room temperature with an 
expiration time designated on the label.  
Refer to the IB for stability information.  
64Cu-SAR-bisPSMA decays to stable (non-radioactive) daughter products. 
5.4 Dispensing and Administration 
64Cu-SAR-bisPSMA should be received, used, and administered only by suitably qualified 
persons at the study center. The receipt, storage, use, transfer, and disposal of 64Cu-SAR-
bisPSMA are subject to the regulations and/or appropriate license of the study center.  
64Cu-SAR-bisPSMA should be handled by the user in a manner which satisfies both radiation 
safety and pharmaceutical quality requirements. Appropriate aseptic precautions should be 
taken. 
64Cu-SAR-bisPSMA will be administered as a bolus intravenous injection under the 
supervision of the study Investigator or medically qualified delegate at a dosage of 200 MBq 
per administration of 64Cu-SAR-bisPSMA.  
The Investigator or medically qualified delegate should ensure that the injected radioactivity is 
within ±10% of the prescribed activity. 
5.4.1 Radiation protection 
64Cu-SAR-bisPSMA is a radiopharmaceutical, therefore it should only be used by personnel 
who are qualified by training and experience in the safe use and handling of radionuclides and 
whose experience and training have been approved by the appropriate governmental agency 
authorized to license the use of radionuclides. 
Radiation protection precautions must be taken in accordance with national and local 
regulations. Full details of restrictions and guidelines to the participant, friends, family, and 
caregivers may be described in the ICF and IB. 
5.5 Compliance and Accountability 
The Investigator (or designee) is responsible for investigational product accountability, 
reconciliation, and record maintenance at the investigational site. In accordance with all 
applicable regulatory requirements, the Investigator or designated site staff must maintain 
investigational product accountability records throughout the course of the study. The amount 
of investigational product received from the Sponsor, and the amount administered to 
participants, and any amount accidentally or deliberately destroyed will be documented.  


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5.5.1 Storage of Supplies 
Study materials will be stored by the study personnel according to the documentation provided 
with the study materials. The Sponsor reserves the right to inspect the investigational product 
storage area before and during the study. 
5.5.2 Control of Supplies 
Dispensing of the investigational products will be carefully recorded on appropriate 
investigational product accountability forms and will be verified by the study monitor during 
monitoring visits. 
The accountability logs should include dates, quantities, batch numbers and any unique pack 
numbers assigned to the investigational product and/or participant. The accountability logs will 
also include general details related to the study including the protocol, Sponsor, and the 
Investigator. 
5.5.3 Destruction of Supplies 
The study monitor will review the investigational product accountability logs which detail the 
destruction of used and unused investigational products by the site.  
5.6 Investigational Product Administration 
5.6.1 Participant Preparation Prior to Dosing 
There is no need for participants to fast before administration of 64Cu-SAR-bisPSMA. 
5.7 Participant Release and Radioprotection Precautions 
Release of participants following administration of 64Cu-SAR-bisPSMA will be in accordance 
with any applicable regulations at the study center. 
6 CONCOMITANT MEDICATIONS 
Any medication or vaccine (including over the counter or prescription medicines, vitamins, 
and/or herbal supplements) that the participant receives during the study (refer to Schedule of 
Assessments) must be recorded on the eCRF along with: 
• Reason for use; 
• Dates of administration including start and end dates; 
• Dosage information including dose and frequency. 
If the use of any concomitant treatment becomes necessary (e.g., for treatment of an AE), the 
treatment and administration details must be recorded in the source documents and the eCRF.  
The Medical Monitor must be notified of all prohibited medications administered to any 
participant, in order to assess the participant’s eligibility to continue in the study.  
Participants who are known to require prohibited treatment (e.g., initiation of ADT due to 
rapidly rising PSA) before the 64Cu-SAR-bisPSMA PET/CT results can be verified via 
histopathology or follow-up imaging should not be considered for participation in this study.   
6.1 Required Treatments 
Nil.  


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6.2 Permitted Treatments 
All SOC treatments are permitted throughout the duration of the participant’s involvement in 
the study with the exception of those treatments outlined in Section 6.3.  
6.3 Prohibited Treatments 
Treatment with investigational agents (that are likely to affect PSA levels or antineoplastic 
agents), 
saw 
palmetto, 
estrogens, 
steroids, 
testosterone 
supplements, 
5ARIs 
(finasteride/dutasteride), and any antineoplastic therapy (with the exception of radiation or 
other salvage focal therapy with no concomitant ADT initiated following completion of Visit 
4) is prohibited throughout the duration of the participant’s involvement in the study.   
Histopathological confirmation of PC prior to commencement of radiation or other 
salvage focal therapy is strongly encouraged.  
Participants who receive prohibited treatment(s) should remain in the study until completion 
of Visit 4 to enable the assessment of safety. 
7 STUDY PROCEDURES AND ASSESSMENTS 
The following sections describe the study procedures and assessments to be performed during 
the study. Unplanned visits not specified by the protocol or unscheduled assessments may be 
performed as clinically indicated at the discretion of the Investigator; the associated data should 
be recorded on the relevant eCRF in support of an AE diagnosis or disease assessments.  
Refer to Table 5 for the Schedule of Assessments. 
 
 


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Table 5 Schedule of Assessments  
 
Screening1 
64Cu-SAR-bisPSMA PET/CT 
Safety Visit 
Follow-Up  
Study Days 
28 days 
Day 0 
Day 1 
Day 7 (±2 days) Day 90 (±15 days) Day 180 (±15 days) 
Visit  
1 
2 
3 
4 
5 
62 
Timeline 
Pre Dose Post Dose 24h (±6h) Post Dose 
Informed Consent3 
X 
 
 
 
 
 
 
Inclusion/Exclusion  
X 
 
 
 
 
 
 
Demographics and Disease 
Characteristics4 
X 
 
 
 
 
 
 
Medical and Medication History5 
X 
 
 
 
 
 
 
Prior Cancer Treatments 
X 
 
 
 
 
 
 
Prostate Cancer Treatments  
 
 
 
 
X 
X 
X 
Physical Exam6 
 
X 
 
 
X 
 
 
Body Weight 
X 
X 
 
 
X 
 
 
Height 
X 
 
 
 
 
 
 
ECOG Status7 
X 
 
 
 
 
 
 
Vital Signs8 
 
X 
X9 
 
X 
 
 
Duplicate 12-Lead ECG 
 
X 
X10 
 
 
 
 
Hematology11 
X 
 
 
 
X 
 
 
Biochemistry12 
X 
 
 
 
X 
 
 
Coagulation13 
X 
 
 
 
X 
 
 
eGFR (CKD-EPI) in mL/min 
X 
 
 
 
X 
 
 
Serum Testosterone 
X 
 
 
 
 
 
 
Urinalysis14  
 
X 
 
 
X 
 
 
Total PSA15 
X 
 
 
 
 
X 
X 
AEs 
X 
X 
X 
X 
X 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
 
 
64Cu-SAR-bisPSMA Dose 
 
X 
 
 
 
 
64Cu-SAR-bisPSMA PET/CT 
 
 
X16 
X17 
 
 
 
SOC Conventional Scan 
X 
 
 
 
 
 
 
Follow-up Conventional Imaging18 
 
 
 
 
 
X 
X 
Additional Imaging/Histopathology19 
 
 
 
 
X 
Disease Management Form  
X20 
 
 
 
X21 
 
 


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Abbreviations: AE= adverse event; CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; CT= computed tomography; ECG= electrocardiogram; ECOG= Eastern 
Cooperative Oncology; eGFR= estimated glomerular filtration rate; PET= positron emission tomography; PSA= prostate-specific antigen; SOC= standard of care
 
1 Results of SOC tests or examinations performed prior to obtaining informed consent and within 28 days prior to Day 0 may be used; such tests do not need to be repeated for Screening. 
Institutional SOC scan(s) must be performed within 60 days of Day 0. SOC scan(s) performed more than 60 days prior to Day 0 may be repeated as a study screening procedure and reviewed by 
the Investigator prior to Day 0. 
2 Visit 6 is only applicable to participants who were deemed negative or equivocal for PC recurrence based on the Visit 5 follow-up conventional imaging (as per the central expert panel’s 
interpretation). 
3 Informed consent must be documented before any study-specific screening procedure is performed and may be obtained more than 28 days before the 64Cu-SAR-bisPSMA administration. 
4 Demographic data include: year of birth, race, ethnicity. Baseline disease characteristics include: initial diagnosis stage (per American Joint Committee on Cancer), initial Gleason score, initial 
diagnosis stage (T, N and M staging), pathology results, date of biochemical recurrence, relevant symptom history including, gastrointestinal, genitourinary and musculoskeletal. 
5 Medical history will include evaluation of: relevant past or present diseases or disorders, and relevant surgical history. Medication history within 14 days before signing informed consent should 
be collected. 
6 Physical examination includes assessment of: general appearance, cardiovascular system, respiratory system, and nervous system if vertebral involvement. 
7 ECOG Scale is used by the Investigator to determine the score (0 to 5) that best represents the participants’ activity status. 
8 Vital signs include: body temperature, respiratory rate, heart rate and systolic and diastolic blood pressure. 
9 Post-dose vital signs to be completed prior to the 64Cu-SAR-bisPSMA PET/CT. 
10 Post-dose ECG to be performed at 30 minutes (±10 minutes) post 64Cu-SAR-bisPSMA administration. 
11 Hematology: hemoglobin, hematocrit, red blood cell count, WBC, platelet count, differential WBC (neutrophils, eosinophils, basophils, lymphocytes, and monocytes), absolute neutrophil count, 
and absolute lymphocyte count. 
12 Biochemistry (pre-prandial): albumin, total protein, blood glucose, sodium, potassium, blood urea nitrogen, creatinine, calcium, uric acid, AST, ALT, total bilirubin,  alkaline phosphatase. 
13 Coagulation: prothrombin time, activated partial thromboplastin time, D-dimer.  
14 Urinalysis to include determination of protein, glucose and leukocytes (dipstick test). 
15 If radiation or other salvage focal therapy is initiated during the study, PSA levels will be monitored independent of the study visit schedule at every 4 weeks (±2 days) from the initiation of the 
therapy. PSA response (defined as total PSA decline by ≥50% from baseline) must be confirmed by a second value within 4 weeks. 
16 PET/CT scan to be performed at 1 to 4 hours post 64Cu-SAR-bisPSMA administration. If no diagnostic quality anatomical imaging (CT or MRI) is available within 60 days of Day 0, a diagnostic 
quality CT must be acquired as part of the Day 0 PET/CT scan.  
17 PET/CT scan to be performed at 24 hours (±6 hours) post 64Cu-SAR-bisPSMA administration. 
18 Follow-up conventional imaging will include MRI or CT (a diagnostic quality CT completed as part of a PET/CT scan is acceptable) and 99mTc-MDP and/or 18F-fluciclovine and/or 11C-choline 
and/or approved PSMA PET (such as 18F-DCFPyL or 68Ga-PSMA-11).  Note: Additional follow-up conventional imaging may be completed at any other timepoint, as deemed appropriate by the 
Investigator. All follow-up scans acquired within 180 days (±15 days) of Day 0 must be transferred to the central reading center. 
19 Additional follow-up conventional imaging may be performed at the discretion of the Investigator. Where feasible, obtaining histopathology from biopsy or surgery should be attempted for as 
many 64Cu-SAR-bisPSMA PET-positive lesions as possible (based on the local interpretation of the 64Cu-SAR-bisPSMA PET/CT scans). If clinically feasible, the Investigator should make every 
effort to obtain histopathology for at least one 64Cu-SAR-bisPSMA PET-positive lesion per region. All follow-up scans and histopathology acquired within 180 days (±15 days) of Day 0 must 
be transferred to the central reading center. 
20 Pre-SAR-bisPSMA Disease Management Form must be completed by the treating physician to document the initial intended management plan for the participant based on available clinical 
information and conventional imaging results. 
21 Post-SAR-bisPSMA Disease Management Form must be completed by the treating physician for all participants who complete the 64Cu-SAR-bisPSMA PET/CT scan(s). The management plan 
will be based on the result from the local interpretation of the 64Cu-SAR-bisPSMA PET/CT scan(s) to document whether a change to the initial intended management plan may be warranted due 
to the 64Cu-SAR-bisPSMA PET/CT finding(s). 


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7.1 Demographics and Baseline Health Record  
7.1.1 Baseline Demographics and Disease Characteristics 
Participant demographics will be recorded, including year of birth, race, ethnicity.  
Baseline disease characteristics will be recorded, including, initial diagnosis stage (per 
American Joint Committee on Cancer), initial Gleason score, initial diagnosis stage (T, N and 
M staging), pathology results, date of biochemical recurrence, relevant symptom history 
including, gastrointestinal, genitourinary and musculoskeletal. 
7.1.2 Medical and Medication History 
Medical history will include evaluation for relevant past or present diseases or disorders, and 
relevant surgical history. 
Medication history includes any medication or vaccine (including over the counter or 
prescription medicines, vitamins, and/or herbal supplements) that the participant has received 
within 14 days before signing informed consent must be recorded on the eCRF along with: 
• Reason for use; 
• Dates of administration including start and end dates; 
• Dosage information including dose and frequency. 
7.1.3 Prior Cancer Treatments 
As part of Screening, review of prior PC treatments received from the time of diagnosis will 
be completed and recorded on the eCRF. This must include type and date of the initial definitive 
treatment modality (e.g., radical prostatectomy, radiation therapy, cryotherapy, or 
brachytherapy). 
7.1.4 Prostate Cancer Treatments 
Any PC treatment that the participant receives during the study must be recorded on the eCRF.  
This includes single agent or combination in order of administration, start and stop dates, 
dose(s), and schedule(s), the disease state in which it was administered (biochemical recurrence 
or M1; for M1 specify if node, visceral/soft tissue or bone), response (resistant or sensitive) on 
the basis of PSA if appropriate; and type of progression (PSA, radiographic [bone, nodal, 
visceral], clinical [e.g., pain escalation]) if applicable. 
For radiation therapy, target region(s), dose (Gy) and number of fractions should be recorded. 
7.2 Safety Assessments 
7.2.1 Physical Examination 
Full physical examinations will be performed by a registered physician (or qualified delegate). 
The full physical examination will include examination of the following: general appearance, 
cardiovascular system, respiratory system, and nervous system if vertebral involvement. 
Any findings made during the physical examination must be noted regardless of if they are part 
of the participant’s medical history. 
Clinically significant observations will be recorded as AEs.  


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Note: Additional symptom directed physical examinations may also be performed at any time 
through the study as clinically indicated. 
7.2.2 Body Weight and Height  
Body weight (in kg) (wearing light clothes, no shoes) and height (in cm) will be measured 
(rounded to one decimal place). 
7.2.3 Eastern Cooperative Oncology Group Performance Status 
The ECOG (Table 6) is used by the Investigator to determine the score (0 to 5) that best 
represents the participants’ activity status. 
Table 6 Eastern Cooperative Oncology Group Performance Status Scale 
Grade 
ECOG Performance Status 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or 
sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about 
more than 50% of waking hours 
3 
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours 
4 
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair 
5 
Dead 
Abbreviations: ECOG=Eastern Cooperative Oncology Group Performance Status 
7.2.4 Vital Signs 
Vital signs measurements will include body temperature, respiratory rate, heart rate and 
systolic and diastolic blood pressure. Wherever possible, vital signs will be recorded after the 
participant has rested comfortably in a seated position with feet on the floor or in a supine 
position for at least 3 minutes (the position must be the same for a particular participant pre 
and post dose) and using consistent methods between participants. 
Clinically significant observations, as deemed by the Investigator, will be recorded as AEs.  
7.2.5 Duplicate 12-lead Electrocardiogram 
Duplicate 12-lead ECGs will be performed after the participant has rested comfortably in the 
supine position for at least 3 minutes. 
The following parameters will be assessed: heart rate, PR, RR, QRS, QT, QTcB (Bazett 
formula), QTcF (Fridericia formula). The Investigator (or a qualified delegate at the 
investigational site) will interpret the ECG using one of the following categories: within normal 
limits, abnormal but not clinically significant, or abnormal and clinically significant. 
Clinically significant observations, as deemed by the Investigator, will be recorded as AEs.  
7.2.6 Clinical Laboratory Assessments 
Clinical laboratory samples will be analyzed by the site’s local laboratory.  
Blood samples will be collected for the following tests: 


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• Hematology: Hemoglobin, hematocrit, red blood cell count, white blood cell count 
(WBC), platelet count, differential WBC (neutrophils, eosinophils, basophils, 
lymphocytes, and monocytes), absolute neutrophil count, and absolute lymphocyte 
count.  
• Biochemistry (pre-prandial): albumin, total protein, blood glucose, sodium, 
potassium, blood urea nitrogen, creatinine, calcium, uric acid, AST, ALT, total 
bilirubin, alkaline phosphatase.  
 
• Coagulation: prothrombin time, activated partial thromboplastin time, D-dimer. Note: 
Coagulation may be assessed at any other timepoint, outside of those specified in the 
Schedule of assessments, in case of an abnormal result, and followed until resolution. 
• eGFR: will be calculated from creatinine using the Chronic Kidney Disease 
Epidemiology Collaboration (CKD-EPI) formula and reported as mL/min. To convert 
mL/min/1.73 m2 to mL/min, multiply by the individual’s Body Surface Area 
(calculated using the Mosteller formula) and divide by 1.73. 
• Biochemical Markers: Serum testosterone. 
Urine samples will be collected for the following tests: 
• Urinalysis: to include determination of protein, glucose and leukocytes (dipstick test). 
In the event of an unexplained, clinically significant abnormal laboratory test result, the test 
should be repeated and followed up until it has returned to the normal range and/or an adequate 
explanation of the abnormality is found.  
During the study, all out of range (abnormal) laboratory values, except for PSA, must be 
evaluated and commented on by the Investigator (or a qualified delegated observer at the 
investigational site) for clinical significance using one of the following categories: within 
normal limits, abnormal but not clinically significant, or abnormal and clinically significant. 
Clinically significant observations will be recorded as AEs unless they are associated with a 
diagnosis that itself has been reported as an AE (e.g., raised white cells and fever associated 
with an infection – in this case the infection is the AE and the lab value and fever are signs and 
symptoms of the AE and should not be reported separately).  
7.2.7 Total PSA 
As part of Screening, baseline PSA will be assessed; additionally, PSA results and dates of 2 
previous most recent measurements (prior measurements are needed to assess PSA 
velocity/doubling time), PSA at initial diagnosis and PSA after initial definitive treatment 
(nadir) must also be recorded on the eCRF. 
Prostate-specific antigen will further be assessed during the Follow-Up as specified in the 
Schedule of assessments. However, if radiation therapy or other salvage focal therapy (e.g., 
cryotherapy) is initiated during the study (as long as no concomitant ADT is given), PSA levels 
must be monitored every 4 weeks from the initiation of the therapy. Prostate-specific antigen 
response (defined as total PSA decline by ≥50% from baseline) must be confirmed by a second 
value within 4 weeks. 


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7.3 Imaging Assessments 
7.3.1 Institutional Standard of Care Conventional Scan 
Institutional SOC conventional scan (e.g., CT, MRI, whole-body 99mTc-MDP, 18F-fluciclovine, 
11C-choline, approved PSMA PET [such as 18F-DCFPyL or 68Ga-PSMA-11]) must be 
performed within 60 days of Day 0.  
For each imaging modality, the date of acquisition and result (as positive, negative or equivocal 
for recurrent PC) must be reported on the eCRF. If equivocal, the site(s) of equivocal disease 
is also to be reported. 
All available scans completed within 60 days of Day 0 will be transferred in DICOM format 
to the central reading center with anonymization of participant specific information as specified 
in the Image Acquisition Manual. 
7.3.2 
64Cu-SAR-bisPSMA PET/CT  
The site will conduct the quantitative PET/CT according to the Image Acquisition Manual, 
which contains details of scan acquisition, processing parameters and quality assurance 
procedures. For a given participant, the same scanner must be used for all scan acquisition 
timepoints. 
Participants will be asked to void prior to imaging. After voiding, a whole-body low dose CT 
and PET scan will be acquired starting from the mid-thigh to the skull vertex. If no diagnostic 
quality anatomical imaging (CT or MRI) is available within 60 days of Day 0, a diagnostic 
quality CT must be acquired as part of the Day 0 PET/CT scan. 
The PET/CT images will be transferred in DICOM format to the central reading center with 
anonymization of participant specific information as specified in the Image Acquisition 
Manual. 
7.3.2.1 
64Cu-SAR-bisPSMA PET/CT Local Interpretation 
The 64Cu-SAR-bisPSMA PET/CT scans will be interpreted locally by an appropriately 
qualified Investigator in a non-blinded fashion.  
The reader will be required to evaluate the PET scans individually for the presence of 
pathological 64Cu-SAR-bisPSMA uptake in the prostate bed/gland, pelvic lymph nodes, extra 
pelvic lymph nodes, visceral/soft tissue and bone. Computed tomography scans from the 
PET/CT will be available to the readers to guide anatomical localization. 
A 64Cu-SAR-bisPSMA PET-positive lesion will be defined as focal uptake that is greater than 
physiologic background uptake in that tissue or greater than adjacent background if no 
physiologic uptake is expected and judged by the reader to be suspicious for disease. The 
number of PET-positive lesion(s) in each anatomical subregion will be documented.  
Any incidental findings on the 64Cu-SAR-bisPSMA PET/CT scan(s) that are of potential 
clinical relevance and are not directly associated with the objectives of the protocol should be 
evaluated and handled by the investigator as per standard medical/clinical judgment. 
The processes for image acquisition, transmittal, and interpretation, including the list of regions 
and subregions to be assessed on the 64Cu-SAR-bisPSMA PET/CT are detailed in the Image 
Acquisition Manual. 


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7.3.2.2 
64Cu-SAR-bisPSMA PET/CT Central Interpretation 
The central reading center will receive and evaluate the 64Cu-SAR-bisPSMA PET/CT scans. 
The scans will be interpreted by three different independent blinded readers in a random order 
at separate reading sessions. Central readers will be blinded as described in Section 4.3. 
Computed tomography scans from the 64Cu-SAR-bisPSMA PET/CT will be available for 
anatomic correlation. 
The readers will be required to evaluate the PET scans individually for the presence of 
pathological 64Cu-SAR-bisPSMA uptake in the prostate bed/gland, pelvic lymph nodes, extra 
pelvic lymph nodes, visceral/soft tissue and bone. The same 64Cu-SAR-bisPSMA PET-positive 
lesion definition will be applied as for the local interpretation. Lesions that do not meet the 
criteria for a positive lesion but are deemed suspicious for PC will be recorded as equivocal. 
The number of lesion(s) in each anatomical subregion will be documented. The size (two axial 
dimensions), location, standardized uptake value (SUV)mean and max, lesion-to-background 
ratio and reader confidence level will be recorded for up to 15 soft tissue lesions and 10 bone 
lesions by the central readers.  
The processes for image acquisition, transmittal, and interpretation are detailed in the Image 
Acquisition Manual and Imaging Review Charter. 
7.3.3 Follow-up Conventional Imaging 
Follow-up conventional imaging must be acquired for all participants as specified in the 
Schedule of assessments, regardless of the 64Cu-SAR-bisPSMA PET/CT findings.  
The follow-up conventional imaging must include the same modality/modalities as the SOC 
conventional imaging performed at baseline to allow for reproducible and accurate 
comparisons and should include anatomical imaging (MRI or CT; a diagnostic quality CT 
completed as part of a PET/CT scan is acceptable) and molecular imaging (e.g., whole body 
99mTc-MDP, 18F-fluciclovine, 11C-choline, approved PSMA PET [such as 18F-DCFPyL or 
68Ga-PSMA-11]). Scan acquisition will be completed according to institutional protocols. 
The imaging modality, date of acquisition and result (including number of lesions suspicious 
for PC within each anatomical subregion) must be recorded on the eCRF. 
All scans will be transferred in DICOM format to the central reading center with anonymization 
of participant specific information as specified in the Image Acquisition Manual. 
Note: Additional follow-up conventional imaging may be completed at any other timepoint, 
outside of those specified in the Schedule of assessments, as deemed appropriate by the 
Investigator. All follow-up scans acquired within 180 days (±15 days) of Day 0 must be 
transferred to the central reading center. 
7.4 Histopathology 
Where clinically feasible, histopathology (from image-guided biopsy or surgery [e.g., salvage 
pelvic lymph node dissection]) should be obtained for as many 64Cu-SAR-bisPSMA PET-
positive lesions as possible based on the local interpretation of the 64Cu-SAR-bisPSMA 
PET/CT scans. If clinically feasible, the Investigator should make every effort to obtain 
histopathology for at least one 64Cu-SAR-bisPSMA PET-positive lesion per region. The 
biopsy or surgery specimens will be processed and analyzed locally. The local pathologist 
evaluating the samples will be blinded to the 64Cu-SAR-bisPSMA PET/CT results. 
The procedure, date of assessment, imaging modality used to guide biopsy (if applicable) and 
local histopathology result will be recorded on the eCRF. 


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For participants undergoing image-guided needle biopsy, the needle biopsy images (e.g., CT, 
transrectal ultrasound-MRI, ultrasound) of the procedure will be sent to central reading center. 
The instruction for capturing biopsy images and directions for submitting the images to the 
central reading center is specified in the Image Acquisition Manual.  
All histopathology results (and any associated images) acquired within 180 days (±15 days) of 
Day 0 must be transferred to the central reading center. 
7.5 Diagnostic Efficacy Assessments 
7.5.1 Assessment of the Composite Reference Standard  
The composite Reference Standard may consist of histopathology, conventional imaging 
modalities that are routinely used in the diagnosis and staging of PC and PSA levels. 64Cu-
SAR-bisPSMA scans will not form part of the Reference Standard. 
The Reference Standard status will be determined by an independent, blinded, central expert 
panel. The expert panel will establish the Reference Standard disease status (on a participant- 
and region-level) for each participant individually, using information provided by the site’s 
Investigator. The experts will be blinded as described in Section 4.3. 
The Investigator will be required to submit all relevant clinical evidence available for the 
participant to enable the assessment of the Reference Standard. Relevant evidence will include: 
• All available histopathology reports related to the participants disease history;  
• All available conventional scans and related local reports collected as part of Screening 
(within 60 days of Day 0) and Follow-up (within 180 days [±15 days] of Day 0); 
• PSA levels recorded as part of Screening and Follow-up; 
• All available PC related symptom and treatment history; 
The composite Reference Standard will be hierarchical in nature, with three levels of evidence 
that will be applied as follows: 
• Level 1: Evaluable histopathology from biopsy or surgery OR in case that 
histopathology is not available, inconclusive or negative: 
• Level 2: Conventional imaging procedures OR if neither histopathology or 
conventional imaging are available or informative: 
• Level 3: Confirmed PSA response following radiation or other salvage focal therapy 
(as long as no concomitant ADT is given), defined as total PSA decline by ≥50% from 
baseline, confirmed by a second value within four weeks as per the Prostate Cancer 
Working Group 3 criteria25. 
The expert panel will use the collective information to determine and record each region with 
histopathology demonstrating PC, the number of lesions suspicious for PC detected on 
conventional imaging in each anatomical subregion and whether the participant achieved 
confirmed PSA response (if applicable).  
Region(s) with no histopathology demonstrating PC or no unequivocal lesion recorded in any 
of the anatomical subregions on conventional imaging will be deemed negative for the region 
level Reference Standard status.  
Region(s) with histopathology demonstrating PC will qualify the region as positive for the 
region level Reference Standard status. A subregion with at least one unequivocal lesion (or 


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cluster of lesions or diffuse sclerotic metastasis) on conventional imaging will qualify the 
subregion as positive for the Reference Standard status.  
If the expert panel judged that the available information is insufficient to provide a reliable 
conclusion, the result will be recorded as non-evaluable (e.g., no follow-up assessments were 
completed) or inconclusive. The reason for selecting a non-evaluable or inconclusive result 
will be documented.  
Further details on the process and interpretation of the conventional imaging will be provided 
in the Imaging Review Charter. 
7.5.2 Assessment of Reference Standard against the 64Cu-SAR-bisPSMA PET/CT 
Results 
For the assessment of the Reference Standard against the 64Cu-SAR-bisPSMA PET/CT, 
region-level matching will be used for histopathology, subregion-level matching for imaging 
and participant-level matching for PSA response to radiation or other salvage focal therapy 
(refer to Section 7.5.1). Matching of the Reference Standard against the 64Cu-SAR-bisPSMA 
PET/CT results will be completed via statistical programming.  
Assessment of region-level Reference Standard against the 64Cu-SAR-bisPSMA PET/CT 
results: 
• Histopathology: A region that is 64Cu-SAR-bisPSMA PET-positive (i.e., includes at 
least one unequivocal PET-positive lesion) and Reference Standard positive, will be 
assigned as true positive (TP) for the region-level status. 
• Imaging: A subregion that is 64Cu-SAR-bisPSMA PET-positive (i.e., includes at least 
one unequivocal PET-positive lesion) and Reference Standard positive (i.e., includes at 
least one unequivocal lesion detected on conventional imaging in that subregion), will 
be assigned as TP. A region that includes at least one TP subregion will be assigned as 
TP for the region-level status.  
• A region that is 64Cu-SAR-bisPSMA PET-positive (i.e., includes at least one 
unequivocal PET-positive lesion) and is Reference Standard negative based on at least 
1 evaluable timepoint, will be assigned as false positive (FP) for the region-level status. 
• A region that is 64Cu-SAR-bisPSMA PET-negative (i.e., no unequivocal PET-positive 
lesion or only equivocal lesion(s) detected within the subregions) and Reference 
Standard negative, will be assigned as true negative (TN) for the region-level status. 
• A region that has either non-evaluable 64Cu-SAR-bisPSMA result for a specific 
timepoint or has a non-evaluable or inconclusive Reference Standard will not be 
assigned for that timepoint. 
Assessment of participant-level Reference Standard against the 64Cu-SAR-bisPSMA PET/CT 
results: 
• A participant with at least one TP region AND/OR at least one unequivocal 64Cu-SAR-
bisPSMA PET-positive lesion and confirmed PSA response to radiation or other 
salvage focal therapy, will be assigned as TP for the participant-level status.  
• A participant with at least one unequivocal 64Cu-SAR-bisPSMA PET-positive lesion 
who does not meet the above criteria to be deemed TP, will be assigned as FP for the 
participant-level status. 


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• A participant with a negative 64Cu-SAR-bisPSMA PET/CT (i.e., no unequivocal PET-
positive lesion or only equivocal lesion(s) detected on the scan) and negative Reference 
Standard, will be assigned as TN for the participant-level status. 
• A participant that has either non-evaluable 64Cu-SAR-bisPSMA result for a specific 
timepoint or has a non-evaluable or inconclusive Reference Standard will not be 
assigned for that timepoint. 
False negative results (on a region- or participant-level) will not be assigned in the study. A 
participant with negative baseline conventional imaging and negative 64Cu-SAR-bisPSMA 
PET/CT imaging, who later demonstrates a positive result at follow-up conventional imaging 
(e.g., during the 90-day follow-up imaging) will not be considered a false negative as there is 
no way to determine whether the disease was initially present, or whether the disease has 
developed since the acquisition of the baseline and 64Cu-SAR-bisPSMA imaging. A positive 
follow-up scan must therefore be interpreted with caution as it may reflect a different disease 
state compared to the one evaluated during the baseline conventional and 64Cu-SAR-bisPSMA 
PET/CT imaging period. 
A positive 64Cu-SAR-bisPSMA PET/CT within the target study population may indicate that 
this new imaging agent is more sensitive in detecting early recurrence than other available 
modalities. The 90- and 180-day follow-up timelines have been selected to allow for further 
development of the disease so the positive 64Cu-SAR-bisPSMA PET/CT findings can be 
validated using conventional, potentially less sensitive reference modalities. The selected 
follow-up timelines therefore enable evaluation of the diagnostic efficacy endpoints that relate 
to positive findings, but do not allow for a reliable assessment of false negative results. 
7.5.3 Disease Management Plan 
The treating physician will be required to fill out a Pre-SAR-bisPSMA and a Post-SAR-
bisPSMA Disease Management Form to provide information on the treatment strategy of the 
participant before and after the information from the local read of the 64Cu-SAR-bisPSMA 
PET/CT scan(s) becomes available. 
The Pre-SAR-bisPSMA Disease Management Form must be completed during Screening by 
the treating physician to document the initial intended management plan for the participant 
based on available clinical information and conventional imaging results. 
The Post-SAR-bisPSMA Disease Management Form must be completed by the treating 
physician for all participants who complete the 64Cu-SAR-bisPSMA PET/CT scan(s). This 
management plan will be based on the result from the local interpretation of the 64Cu-SAR-
bisPSMA PET/CT scan(s) to document whether a change to the initial intended management 
plan may be warranted due to the 64Cu-SAR-bisPSMA PET/CT finding(s). Additionally, the 
operator will be asked to indicate which 64Cu-SAR-bisPSMA PET/CT timepoint has 
influenced the assessment. If both timepoints influenced the assessment (whether for change 
or not) both should be selected. 
7.6 Pharmacokinetics  
7.6.1 Biodistribution of 64Cu-SAR-bisPSMA 
The biodistribution of 64Cu-SAR-bisPSMA utilizing the PET/CT scans will involve the 
calculation of: 
• 
Maximum and mean SUVs in lesion(s), visceral/soft tissue, bone; 


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• 
Lesion-to-background ratio. 
All biodistribution measures will be assessed centrally, according to the study Imaging Review 
Charter to ensure a high and consistent level of quantification across all sites. 
8 VISIT-SPECIFIC PROCEDURES 
8.1.1 Screening Period (28 days, Visit 1) 
The following assessments must be performed/obtained within the 28 days before the 
participant receives the 64Cu-SAR-bisPSMA administration. Informed consent must be 
documented before any study-specific screening procedure is performed and may be obtained 
more than 28 days before the 64Cu-SAR-bisPSMA administration. Results of SOC tests or 
examinations performed prior to obtaining informed consent and within 28 days (within 60 
days for institutional SOC conventional scans) prior to the 64Cu-SAR-bisPSMA administration 
may be used; such tests do not need to be repeated for Screening. 
If the start date for the 64Cu-SAR-bisPSMA administration extends beyond 28 days from the 
start of the Screening assessments (e.g. due to issues related to logistics), the Investigator in 
consultation with the Medical Monitor must determine if any Screening assessments need to 
be repeated. 
Assessments to be completed: 
• 
Informed Consent (Refer to Section 11.5) 
• 
Inclusion/Exclusion (Refer to Section 4.1 
• 
Demographics and Disease Characteristics (Refer to Section 7.1.1) 
• 
Medical and Medication History (Refer to Section 7.1.2) 
• 
Prior Cancer Treatments (Refer to Section 7.1.3) 
• 
Body Weight and Height (Refer to Section 7.2.2) 
• 
ECOG Status (Refer to Section 7.2.3) 
• 
Hematology (Refer to Section 7.2.6) 
• 
Biochemistry (Refer to Section 7.2.6) 
• 
Coagulation (Refer to Section 7.2.6) 
• 
eGFR (CKD-EPI) (Refer to Section 7.2.6) 
• 
Serum Testosterone (Refer to Section 7.2.6) 
• 
Total PSA (Refer to Section 7.2.6) 
• 
Adverse Events (Refer to Section 9.1) 
• 
Concomitant Medications (Refer to Section 6) 
• 
SOC Conventional Scan (Refer to Section 7.3.1) 
• 
Pre-SAR-bisPSMA Disease Management Form (Refer to Section 7.5.3) 
8.1.2 
64Cu-SAR-bisPSMA PET/CT Imaging 
8.1.2.1 Day 0 (Visit 2) 
Enrolled participants who meet all eligibility criteria will receive a single 64Cu-SAR-bisPSMA 
administration followed by a PET/CT scan. Pre-dose assessments will be completed prior to 
the administration of 64Cu-SAR-bisPSMA. Post-dose assessments will be completed as per the 
assessment windows specified below. 
Assessments to be completed: 
• 
Adverse Events (ongoing) 


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• 
Concomitant Medications (ongoing) 
Pre dose 
• 
Body Weight (Refer to Section 7.2.2) 
• 
Physical Exam (Refer to Section 7.2.1) 
• 
Vital Signs (Refer to Section 7.2.4) 
• 
Duplicate 12-Lead ECG (Refer to Section 7.2.5) 
• 
Urinalysis (Refer to Section 7.2.6) 
64Cu-SAR-bisPSMA Dose (Refer to Section 5.4 for dosing and administration details) 
Post dose 
• 
Vital Signs to be completed prior to the 64Cu-SAR-bisPSMA PET/CT (Refer to Section 
7.2.4) 
• 
Duplicate 12-Lead ECG to be performed at 30 min (±10 min) post 64Cu-SAR-bisPSMA 
administration (Refer to Section 7.2.5) 
• 
64Cu-SAR-bisPSMA PET/CT to be performed at 1 to 4 hours post 64Cu-SAR-bisPSMA 
administration (Refer to Section 7.3.2) 
8.1.2.2 Day 1 (24 hours ±6 hours Post Dose, Visit 3) 
This visit is to take place approximately 24 hours after the 64Cu-SAR-bisPSMA administration. 
Assessments to be completed: 
• 
Adverse Events (ongoing) 
• 
Concomitant Medications (ongoing) 
• 
64Cu-SAR-bisPSMA PET/CT (Refer to Section 7.3.2) 
8.1.3 Safety Visit (Day 7 ± 2 days, Visit 4) 
This visit is to take place 7 days (± 2days) after the 64Cu-SAR-bisPSMA administration.  
Assessments to be completed: 
• 
Adverse Events (ongoing) 
• 
Concomitant Medications (ongoing) 
• 
Record Any Prostate Cancer Treatments (Refer to Section 7.1.4) 
• 
Physical Exam (Refer to Section 7.2.1) 
• 
Body Weight (Refer to Section 7.2.2) 
• 
Vital Signs (Refer to Section 7.2.4) 
• 
Hematology (Refer to Section 7.2.6) 
• 
Biochemistry (Refer to Section 7.2.6) 
• 
Coagulation (Refer to Section 7.2.6) 
• 
eGFR (CKD-EPI) (Refer to Section 7.2.6) 
• 
Urinalysis (Refer to Section 7.2.6) 
• 
Additional Imaging/Histopathology (Refer to Section 7.3.3 and 7.4) 
• 
Post-SAR-bisPSMA Disease Management Form (Refer to Section 7.5.3) 
8.1.4 Follow-Up  
8.1.4.1 Day 90 (Day 90 ± 15 days, Visit 5) 
This visit is to take place 90 days (± 15 days) after the 64Cu-SAR-bisPSMA administration. All 
participants must complete this visit, regardless of the 64Cu-SAR-bisPSMA PET/CT results. 


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Participants who based on the central expert panel’s interpretation of the follow-up 
conventional imaging completed during Visit 5 are deemed: 
• negative or equivocal for PC recurrence - must continue to Visit 6.  
• positive for PC recurrence - no further study visits are required. 
Assessments to be completed: 
• 
Record Any Prostate Cancer Treatments (Refer to Section 7.1.4) 
• 
Total PSA (Refer to Section 7.5.3) 
• 
Follow-up Conventional Imaging (Refer to Section 7.3.3)  
• 
Record Any Additional Imaging/Histopathology (Refer to Section 7.3.3 and 7.4) 
8.1.4.2 Day 180 (Day 180 ± 15 days, Visit 6) 
This visit is to take place 180 days (± 15 days) after the 64Cu-SAR-bisPSMA administration.  
Only participants who were deemed negative or equivocal for PC recurrence based on the 
follow-up conventional imaging (as per the central expert panel’s interpretation) completed 
during Visit 5 must complete Visit 6.  
If the participant is not returning to Visit 6, but additional imaging/histopathology was acquired 
within 180 days (± 15 days) of Day 0, the relevant details must be recorded on the eCRF and 
information submitted to the central reading center. 
Assessments to be completed: 
• 
Record Any Prostate Cancer Treatments (Refer to Section 7.1.4) 
• 
Total PSA (Refer to Section 7.5.3) 
• 
Follow-up Conventional Imaging (Refer to Section 7.3.3) 
• 
Record Any Additional Imaging/Histopathology (Refer to Section 7.3.3 and 7.4) 
9 ADVERSE EVENT MONITORING 
9.1 Adverse Events 
An AE is defined as any untoward medical occurrence in a clinical investigation participant 
administered a pharmaceutical product, which does not necessarily have a causal relationship 
with this treatment. An AE can therefore be any unfavorable and/or unintended sign (including 
an abnormal laboratory finding), symptom, or disease temporally associated with the use of an 
investigational product, whether or not related to the investigational product. All AEs, 
including observed or volunteered problems, complaints, or symptoms, are to be recorded on 
the appropriate eCRF. 
Adverse events should be recorded from the time of informed consent until the completion of 
the Safety Visit. Adverse events recorded before the administration of the investigational 
product will be classified as non-treatment emergent AEs. All AEs recorded after the 
investigational product administration will be classified as treatment-emergent AEs (TEAEs). 
Non-related AEs will only be reported and followed up until the Safety Visit. All related AEs 
are to be followed up until resolved or judged to be no longer clinically significant, or until 
they become chronic to the extent that they can be fully characterized. An assessment should 
be made at the last study-related visit for each patient. Certain long-term AEs cannot be 
followed until resolution within the settings of this protocol. In these cases, follow-up will be 
the responsibility of the treating physician. If during AE follow-up the case has progressed to 
the level of SAE, or if a new SAE is observed whose relationship to the study medication 


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cannot be ruled out, the situation must be reported by the Investigator becoming aware of the 
information.  
Participants should be instructed to report any AE that they experience to the Investigator. 
Wherever possible, a specific disease or syndrome rather than individual associated signs and 
symptoms should be identified by the Investigator and recorded on the eCRF. However, if an 
observed or reported sign or symptom is not considered a component of a specific disease or 
syndrome by the Investigator, it should be recorded as a separate AE on the eCRF. 
Additionally, the condition that led to a medical or surgical procedure (e.g., surgery, 
endoscopy, tooth extraction, transfusion) should be recorded as an AE, not the procedure. 
Adverse events should be entered into the eCRF within 5 days of reporting. 
Clinically significant abnormal laboratory or other examination (e.g., ECG) findings that are 
detected during the study should be reported as AEs. The Investigator will exercise his or her 
medical and scientific judgment in deciding whether an abnormal laboratory finding, or other 
abnormal assessment is clinically significant. Clinically significant abnormal laboratory values 
occurring during the clinical study will be followed until repeat tests return to normal, stabilize, 
or are no longer clinically significant. Any abnormal test that is determined to be an error does 
not require reporting as an AE. 
Any event that in the opinion of the Investigator is solely due to the underlying disease should 
not be reported as an AE. 
9.1.1 Adverse Drug Reaction 
All noxious and unintended responses to a medicinal product related to any dose should be 
considered an adverse drug reaction. “Responses” to a medicinal product means that a causal 
relationship between a medicinal product and an AE is at least a reasonable possibility; i.e., the 
relationship cannot be ruled out. 
9.1.2 Unexpected Adverse Drug Reaction 
An unexpected adverse drug reaction is defined as an adverse reaction, the nature or severity 
of which is not consistent with the applicable product information. For 64Cu-SAR-bisPSMA, 
the reference safety information is included in the current IB. The reference safety information 
is reviewed yearly, and the periodicity of the review will be harmonized with the reporting 
period of the Development Safety Update Report. 
9.1.3 Assessment of Adverse Events by the Investigator 
The Investigator will assess the severity (intensity) of each AE according to Common 
Terminology Criteria for Adverse Events (CTCAE) criteria and will also categorize each AE 
as to its potential relationship to investigational product using the categories of related or not 
related. 
9.1.3.1 Assessment of Severity 
Severity of AEs will be graded according to the following definitions: 
The Investigator will make an assessment of severity (intensity) for each AE and SAE reported 
during the study using the National Cancer Institute (NCI) CTCAE V5.0 criteria. The 
assessments will be based on the Investigator’s clinical judgment. The severity of each AE and 
SAE recorded in the eCRF should be assigned to 1 of the following: 


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Mild (Grade 1): 
Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated. 
Moderate (Grade 2): 
Moderate; minimal, local or noninvasive intervention indicated; 
limiting age-appropriate instrumental ADL*. 
Severe (Grade 3): 
Severe or medically significant but not immediately life-
threatening; hospitalization or prolongation of hospitalization 
indicated; disabling; limiting self-care ADL**. 
Life-threatening 
(Grade 4): 
Life-threatening consequences; urgent intervention indicated. 
Fatal (Grade 5): 
Death related to AE. 
Abbreviations: ADL= Activities of Daily Living 
*Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing 
money, etc. 
**Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and 
not being bedridden. 
9.1.3.2 Causality Assessment 
The Investigator is obligated to assess the relationship between investigational product and the 
occurrence of each AE/SAE. The Investigator will use clinical judgment to determine the 
relationship to 64Cu-SAR-bisPSMA. Alternative causes, such as natural history of the 
underlying diseases, concomitant therapy, other risk factors, and the temporal relationship of 
the event to the investigational product will be considered and investigated. 
The causal relationship of the AE to the investigational product or study procedures should be 
assessed by the Investigator (or medically qualified delegate) using the following 
classifications: 
Related: 
An AE that follows a temporal sequence from administration of the 
investigational product, or for which possible involvement of the 
investigational product cannot be ruled out, although factors other than the 
drug, such as underlying diseases, concurrent medical conditions, 
concomitant drugs and concurrent treatments, are also possibly responsible. 
Not related: 
An AE that does not follow a temporal sequence from investigational product 
administration and/or that can reasonably be explained by other factors, such 
as underlying diseases, concurrent medical conditions, concomitant drugs and 
concurrent treatments. 
9.2 Serious Adverse Event 
Any AE, due solely to the underlying disease or disease progression, should not be reported as 
an SAE, unless the study treatment contributed to the AE. 
An AE or adverse reaction is considered serious if, in the view of either the Investigator or 
Sponsor, it results in any of the following outcomes: 
• Death; 


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• Life-threatening AE; 
Note: An AE or adverse reaction is considered “life-threatening” if, in the view of the 
Investigator or Sponsor, its occurrence places the participant at immediate risk of 
death. It does not include an event that, had it occurred in a more severe form, might 
have caused death.) 
• Requires hospitalization or prolongation of existing hospitalization; 
Note: Any hospital admission with at least 1 overnight stay will be considered an 
inpatient hospitalization. An emergency room visit without hospital admission will not 
be recorded as an SAE under this criterion, nor will hospitalization for a procedure 
scheduled or planned before signing of informed consent. However, unexpected 
complications and/or prolongation of hospitalization that occur during elective 
surgery should be recorded as AEs and assessed for seriousness. Admission to the 
hospital for social or situational reasons (eg, no place to stay, live too far away to 
come for hospital visits) or where this is required for a protocolled assessment will 
not be considered inpatient hospitalizations. 
• A persistent or significant disability/incapacity or substantial disruption of the ability 
to conduct normal life functions; 
• A congenital anomaly/birth defect; 
• An important medical event; 
Note: Important medical events that may not result in death, be life-threatening, or 
require hospitalization may be considered an SAE when, based upon appropriate 
medical judgment, they may jeopardize the participant and may require medical or 
surgical intervention to prevent 1 of the outcomes listed above. Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse. 
9.3 Serious Adverse Event Reporting – Procedures for Investigators 
9.3.1 Initial Reports 
All SAEs occurring from the time of consent until the Safety Visit must be reported within 24 
hours of the knowledge of the occurrence (this refers to any AE that meets any of the 
aforementioned serious criteria). All SAEs that the Investigator considers related to 
investigational product occurring until the end of the Safety Visit must be reported to the 
Sponsor. 
To report an SAE, complete the SAE Report Form and email the completed SAE Report Form 
within 24 hours of awareness. An SAE Report Form will be supplied with the study binder. 
In addition to reporting the SAE to Sponsor (or designee), the Investigator must also notify the 
IRB which approved the study according to their requirements. Copies of all correspondence 
relating to reporting of any SAEs should be maintained in the site’s study files and will be 
checked routinely by the study monitor. 
If the Sponsor and the Investigator consider that the SAE is investigational product related (i.e., 
an adverse reaction) and unexpected it will be reported to the appropriate regulatory authorities 
by the Sponsor (or designee) within the pre-defined timelines. 


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9.3.2 Follow-Up Reports 
The Investigator must continue to follow the participant until the SAE has subsided or until the 
condition becomes chronic in nature, stabilizes (in the case of persistent impairment), or the 
participant dies. 
Within 24 hours of receipt of follow-up information, the Investigator must update the SAE 
form and submit any supporting documentation (eg, deidentified participant discharge 
summary, autopsy reports), if requested. 
9.4 Pregnancy 
Pregnancies occurring in a female partner of a participant after the administration of the 
investigational product require immediate reporting. They must be reported within 24 hours 
after the Investigator has become aware of the pregnancy. A pregnancy report will be 
completed and sent within 24 hours of becoming aware of the pregnancy. The Investigator will 
collect follow-up information regarding the outcome of the pregnancy and any postnatal 
sequelae in the infant that must also be reported to the Sponsor or designee. Upon awareness 
of the outcome of the pregnancy, the Investigator must forward a follow-up Pregnancy Report 
with any relevant information.  
If the outcome of the pregnancy meets the criteria for immediate classification of an SAE (e.g., 
spontaneous abortion, stillbirth, neonatal death, or congenital anomaly), the Investigator will 
report the event within 24 hours of being notified of the pregnancy report. 
9.5 Expedited Reporting 
The Sponsor will report all relevant information about suspected unexpected serious adverse 
reactions that are fatal or life-threatening as soon as possible to the FDA and the IRBs, and in 
any case no later than 7 calendar days after knowledge by the Sponsor of such a case, and 
relevant follow-up information will subsequently be communicated within an additional 8 
days.  
All other suspected unexpected serious adverse reactions will be reported to the FDA and the 
IRBs as soon as possible but within a maximum of 15 calendar days of first knowledge by the 
Sponsor.  
The Sponsor will also inform all Investigators as required.  
10 STATISTICAL METHODS 
10.1 General Considerations 
A Statistical Analysis Plan (SAP) will be written after finalizing the protocol and prior to 
database lock. The SAP will detail the implementation of all the planned statistical analysis in 
accordance with the principal features stated in the protocol. Any deviations from the SAP will 
be presented in the final clinical study report. 
Continuous variables will be summarized by the number of subjects, mean, standard deviation, 
standard error of the mean, median, 25th quartile, 75th quartile, minimum, and maximum 
values.  
Categorical variables will be summarized using frequency counts and percentages. 


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10.2 Analysis Sets 
10.2.1 Enrolled Analysis Set 
The Enrolled Analysis Set will include all participants who signed the ICF and were enrolled 
into the study. This analysis set will be used for patient disposition summaries.  
10.2.2 Safety Analysis Set 
The Safety Analysis Set will be used to assess all safety data and will include all participants 
who receive any amount of 64Cu-SAR-bisPSMA. 
10.2.3 Full Analysis Set 
The Full Analysis Set (FAS) will include all participants who receive any amount of 64Cu-
SAR-bisPSMA and have 64Cu-SAR-bisPSMA PET/CT imaging results from at least one 
central reader. The FAS will be used for all efficacy analyses. 
10.2.4 Biodistribution Analysis Set 
The Biodistribution Analysis Set will include all participants in the Safety Analysis Set and 
have at least one biodistribution measure. 
10.3 Determination of Sample Size 
The co-primary endpoints include participant-level correct detection rate (CDR) or true 
positive detection rate and region-level positive predictive value (PPV). 
The assumed participant-level CDR of 64Cu-SAR-bisPSMA PET/CT imaging is 42% in 
participants with biochemical recurrence of PC. A sample size of 40 participants is estimated 
to provide more than 85% power to achieve a lower boundary of a 2-sided 95% exact binomial 
confidence interval (CI) about the estimated CDR that exceeds 20%. Accounting for a 20% 
non-evaluable rate (including lost to follow-up), approximately 50 participants will need to 
undergo 64Cu-SAR-bisPSMA PET/CT in this study. 
For the co-primary efficacy endpoint of region-level PPV, assuming 65% of participants are 
estimated to have 64Cu-SAR-bisPSMA PET/CT positive findings in this target population and 
each participant with positive findings has an average of 1.3 positive regions, then 40 
participants are expected to produce approximately 34 positive regions. The assumed region-
level PPV rate of 64Cu-SAR-bisPSMA PET/CT imaging is approximately 65% in all PET 
positive regions. Therefore, a sample size of 40 participants (i.e., approximately 34 positive 
regions) is estimated to provide more than 80% power to achieve a lower boundary of a 2-sided 
95% exact binomial CI about the estimated region-level PPV that exceeds 40%. 
10.4 Analysis Methods 
10.4.1 Enrollment and Disposition 
Disposition of participants enrolled, treated, and completed the study will be summarized with 
reasons for study discontinuation for the Enrolled Analysis Set. The number and percentage of 
participants in each analysis set will also be presented.  
10.4.2 Demographic and Other Baseline Characteristics 
Baseline characteristics will be summarized for the Safety Analysis Set and the FAS. 
Demographic and baseline data including age, sex, race, ethnicity, ECOG status, weight, height 


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and body mass index at baseline will be listed and summarized. Baseline PC characteristics, 
including but not limited to PC pathology results, PC staging, initial Gleason score, time from 
initial diagnosis, time from last biochemical recurrence, relevant symptom history, PSA level 
at baseline, and prior cancer treatment for PC will be summarized. 
10.4.3 Prior and Concomitant Medication  
Prior and concomitant medications will be coded using the latest version of the World Health 
Organization Drug dictionary and tabulated by the Anatomical Therapeutic Chemical class and 
preferred term for the Safety Analysis Set. Any PC treatment during the study will also be 
summarized in the same manner. 
Prior medications are defined as those medications which stopped prior to the administration 
of the investigational product. Concomitant medication are medications that are taken at least 
once after the start of the administration of the investigational product.    
Prostate cancer treatment received during the study will also be summarized. 
10.4.4 Safety Analysis 
Safety parameters will include AEs, SAEs, laboratory assessments, vital signs, and ECG 
analysis. Safety analyses in general will be descriptive and will be presented in tabular format 
with the appropriate summary statistics.   
All safety analyses will be conducted in the Safety Analysis Set.  
10.4.4.1 Adverse Event Analysis 
Adverse events will be coded using the latest version of Medical Dictionary for Regulatory 
Activities (MedDRA).  
A TEAE is any AE that occurs after the administration of the investigational product. 
TEAEs, TEAEs related to investigational product, TEAEs with grade 3 or higher, TEAEs with 
grade 3 or higher related to investigational product, and treatment-emergent SAEs will be 
tabulated by MedDRA system organ class and preferred term. 
Serious adverse events, AEs leading to study discontinuation and AEs leading to death will be 
listed by participant. 
10.4.4.2 Laboratory Data Analysis 
Safety laboratory parameters and corresponding changes from baseline will be presented as 
descriptive statistics by visit. Shift tables based on the NCI-CTCAE v5.0 toxicity grading will 
be presented for selected laboratory parameter between baseline and the highest/lowest post-
baseline NCI-CTCAE v5.0 toxicity grade. Any clinically significant abnormalities in 
laboratory values will be listed. 
10.4.4.3 Vital Sign Analysis 
Vital signs at each scheduled time point and changes from baseline will be summarized using 
descriptive statistics. 
10.4.4.4 Electrocardiogram Analysis 
For ECGs, all standard parameters (heart rate, RR, PR, QRS, QT, QTcF, and QTcB as 
applicable) at each scheduled time point along with changes from baseline will be summarized 
using descriptive statistics. The incidence of notable ECG changes in maximum absolute QTcF 


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and QTcB intervals (> 450, > 480, and > 500 ms) over all post-treatment evaluations, as well 
as in QTcF and QTcB maximum changes from baseline (> 30 and > 60 ms) over all post-dose 
evaluations will be summarized.  
A listing of ECG data will be provided.  
10.4.5 Efficacy Analysis 
Efficacy endpoints will be assessed using the FAS.  
10.4.5.1 Primary Efficacy Analyses 
The co-primary efficacy endpoints include the following: 
• Participant-level CDR on Day 0 scan;  
• Participant-level CDR on Day 1 scan;   
• Region-level PPV on Day 0 scan; 
• Region-level PPV on Day 1 scan. 
CDR on a participant-level for each central reader is defined as the proportion of TP 
participants out of all scanned participants who had at least 1 evaluable reference standard 
datapoint (as without any follow-up reference data it is not possible to determine if the 
participant is TP or not, which may bias the results) and will be calculated as follows: CDR = 
TP/(all scanned participants with at least 1 evaluable reference datapoints).  
Participants without a 64Cu-SAR-bisPSMA PET/CT scan at a specific timepoint (Day 0 or Day 
1) will be excluded from the participant-level CDR calculation for that timepoint. Participants 
with non-evaluable participant-level Reference Standard results will be excluded from the 
CDR calculation.   
PPV on a region-level for each central reader is defined as the proportion of TP regions out of 
all positive regions on the 64Cu-SAR-bisPSMA PET/CT scan with corresponding evaluable 
composite Reference Standard data and will be calculated as follows: PPV = TP/(TP+FP). 
Regions that are not positive on the 64Cu-SAR-bisPSMA PET/CT scan at a specific timepoint 
(Day 0 or Day 1) will be excluded for the region-level PPV calculation for that timepoint.  
The anatomic regions for lesions include the following: 
Region 
Description of Anatomic Region 
1 
Prostatic 
2 
Pelvic lymph nodes 
3 
Extra pelvic lymph nodes 
4 
Visceral/soft tissue 
5 
Bone 
 
The point estimates of CDR and PPV on Day 0 and on Day 1 will be computed along with the 
2-sided 95% exact binomial CIs using the Clopper-Pearson method. The primary efficacy 
analyses will be performed for each central reader. 
The following sensitivity analyses of the participant-level CDR and region-level PPV will be 
performed: 


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•  
• Based on all participants in the FAS regardless whether there are reference datapoints 
collected. Missing data will be handled as follows: 
o Worst-case imputation: 
o For the participant-level CDR on Day 0 and on Day 1 based on FAS, 
participants with missing/non-evaluable composite Reference Standard data 
will be imputed as non-true positive and included in the denominator. 
o For the region-level PPV calculation on Day 0 and on Day 1 based on FAS, 
PET/CT positive regions with missing/non-evaluable corresponding 
composite Reference Standard data will be imputed as FP and included in 
the denominator. 
o Tipping Point Analysis:  
o In addition, to examine the impact of missing or non-evaluable composite 
Reference Standard data and evaluate the robustness of the results, a tipping 
point analysis will be performed as a sensitivity analysis for participant-
level CDR and region-level PPV based on the FAS, where participants with 
missing or non-evaluable composite Reference Standard data will be 
imputed as TP with probability of p ranging from 0 to 1 with an increment 
of 0.1 (p = 0 corresponds to none of the participants without Reference 
Standard information in a PET positive region will be imputed as true 
positive while p = 1 means all participants without Reference Standard 
information in a PET positive regions will be imputed as TP). 
Details of handling of missing data will be fully described in the SAP. 
10.4.5.2 Secondary Efficacy Analyses 
Secondary efficacy endpoints include the following: 
• Participant-level PPV on Day 0 and on Day 1; 
• Participant-level DR on Day 0 and on Day 1; 
• Participant-level FPR on Day 0 and on Day 1; 
• Region-level FPR on Day 0 and on Day 1; 
• Participant-level discrepant PET negative rate between Day 0 and Day 1; 
• Participant-level TNR on Day 0 and on Day 1; 
• Region-level TNR on Day 0 and on Day 1. 
Secondary efficacy endpoints will be analyzed on the FAS. Point estimates and 2-sided 95% 
exact binomial CIs will be presented for each central reviewer separately. 
10.4.5.3 Exploratory Efficacy Analyses 
The exploratory efficacy endpoints include the following: 
• Proportion of participants with any change in intended PC treatment due to either the 
Day 0 or Day 1 scan; 
• Composite CDR, PPV and DR of the Day 0 and Day 1 scan; 


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• CDR, participant- and region-level PPV and DR of the Day 0 and/or Day 1 scan as a 
function of baseline variables; 
• Relationship between PET-positivity (biodistribution measures such as SUVs and 
lesion-to-background ratio), versus true/false positivity and as a function of lesion 
location and size; 
• Difference in the number of lesions detected per participant on the Day 0 versus the 
Day 1 scan; 
• Lesion-level overall agreement rate on the Day 0 and Day 1 scans, on the Day 0 and 
reference scans, and on the Day 1 and reference scans; 
• PSA over time and change from baseline; 
• PSA velocity and PSA doubling time (PSADT) at the end of the study and at baseline. 
Binary exploratory endpoints will be summarized with points estimates and corresponding 2-
sided 95% exact binomial CIs based on the FAS.  
Difference in the number of lesions detected per participant on the Day 0 versus the Day 1 scan 
will be summarized descriptively and compared using a paired t-test. Other exploratory 
endpoints including PSA value at each scheduled time point and change from baseline, PSA 
velocity, and PSADT will be summarized using descriptive statistics.  
Descriptive statistics, graphical methods, and statistical modeling as appropriate may be used 
to explore the relationship between PET-positivity (biodistribution measures such as SUVs and 
lesion-to-background ratio) and true/false positivity. 
In addition, CDR, PPV and DR will also be assessed as a function of the following baseline 
variables: 
• PSA at baseline prior to the scan (<0.5, 0.5 - <1.0, 1.0 - <2.0, 2.0 - <5.0, ≥5); 
• PSADT; 
• PSA velocity; 
• Testosterone at baseline; 
• SUV mean and max; 
• Lesion-to-background ratio; 
• Initial Treatment Received. 
10.4.6 Intra- and Inter-reader Reliability Assessments 
A subset of each central reader’s 64Cu-SAR-bisPSMA PET/CT scans will be evaluated twice 
to assess the reproducibility of the readings and consistency among readers.   
The intra-reader variability of each reader will be assessed by calculating percent agreement 
(concordance) and Cohen’s pairwise kappa statistics along with the 95% CIs for the 
dichotomous results for all participants with two scan interpretations. 
For inter-reader variability, the agreement among the three independent readers will be 
assessed by calculating percent pairwise concordance and Fleiss’s overall multi-assessor kappa 
statistics and its 95% CIs. 


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10.4.7 Biodistribution Analysis 
Biodistribution measures of 64Cu-SAR-bisPSMA including, maximum and mean SUVs in 
lesions, visceral/soft tissues, bone, and lesion-to-background ratios will be summarized 
descriptively for the Biodistribution Analysis Set. 
10.5 Interim Analysis 
There are no interim analysis planned for this study. 
10.6 Handling of Missing Data 
Exploratory sensitivity analyses of the primary endpoints will be performed using participants 
who had non-evaluable composite Reference Standard data. Additional sensitivity analyses 
based on all participant in the FAS using the worst case imputation method and tipping point 
analysis will also be performed to examine the impact of missing or unevaluable composite 
Reference Standard data. These methods are described in detail in Section 10.4.5.1. 
11 STUDY ADMINISTRATION AND RESPONSABILITIES 
11.1 General Investigator Responsibilities 
The Investigator must ensure that: 
• He or she will personally conduct or supervise the study; 
• His or her staff and all persons who assist in the conduct of the study clearly understand 
their responsibilities and have their names included in the protocol specific Study 
Personnel Responsibility/Signature Log; 
• The study is conducted according to the protocol and all applicable regulations; 
• The protection of each participant’s rights and welfare is maintained; 
• Signed and dated informed consent and, when applicable, permission to use protected 
health information are obtained from each participant before conducting study 
procedures. If a participant withdraws permission to use protected health information, 
the Investigator will obtain a written request from the participant and will ensure that 
no further data will be collected from the participant; 
• The consent process is conducted in compliance with all applicable regulations and 
privacy acts; 
• The IRB complies with applicable regulations and conducts initial and ongoing reviews 
and approvals of the study; 
• Any amendment to the protocol is submitted promptly to the IRB; 
• Any significant protocol deviations are reported to the Medical Monitor, the Sponsor, 
and the IRB according to the guidelines at each study site; 
• Electronic case report form pages are completed within 5 days of each participant’s 
visit (unless required earlier for SAE reporting);  
• All SAEs and pregnancies are reported to the Sponsor or designee within 24 hours of 
knowledge and to the IRB per IRB requirements; 
• All safety reports are submitted promptly to the IRB, as per IRB requirements. 


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11.2 Protocol Compliance 
The Investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol. 
11.3 Compliance with Ethical and Regulatory Guidelines 
The Investigator will ensure that this study is conducted in accordance with International 
Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals 
for Human Use, or with the laws and regulations of the country in which the research is 
conducted, whichever affords the greater protection to the study participant. For studies 
conducted under a USA Investigational New Drug (IND) application, the Investigator will 
ensure adherence to the basic principles of GCP as outlined in 21 Code of Federal Regulations 
(CFR) 312, subpart D, “Responsibilities of Sponsors and Investigators”; 21 CFR, Part 50, 
1998; and 21 CFR, Part 56, 1998. 
This study is also subject to and will be conducted in accordance with 21 CFR, Part 320, 1993, 
“Retention of Bioavailability and Bioequivalence Testing Samples.” 
Because this is a “covered” clinical study, the Investigator will ensure adherence to 21 CFR, 
Part 54, 1998; a covered clinical study is any “study of a drug or device in humans submitted 
in a marketing application or reclassification petition subject to this part that the applicant or 
FDA relies on to establish that the product is effective (including studies that show equivalence 
to an effective product) or that make a significant contribution to the demonstration of safety.” 
This requires that Investigators and all sub-Investigators must provide documentation of their 
financial interest or arrangements with the Sponsor, or proprietary interests in the drug being 
studied. This documentation must be provided before participation of the Investigator and any 
sub Investigator in the study. The Investigator or sub Investigator agrees to notify the Sponsor 
of any change in reportable financial interests during the study and for 1 year following 
completion of the study. Study completion is defined as the date that the last participant has 
completed the protocol-defined activities. 
11.4 Institutional Review Board 
This protocol and any accompanying material to be provided to the participant (such as 
advertisements, participant information sheets, or descriptions of the study used to obtain 
informed consent) will be submitted by the Investigator to an IRB. Approval from the IRB 
must be obtained before starting the study and should be documented in a letter from the IRB 
to the Investigator specifying the protocol number, protocol version, protocol date, documents 
reviewed, and date on which the committee met and granted the approval. A signed protocol 
approval page, a letter confirming IRB approval of the protocol and informed consent, and a 
statement that the IRB is organized and operates according to GCP and the applicable laws and 
regulations must be forwarded to the Sponsor before screening participants for the study. 
Additionally, study sites must forward a signed Form FDA 1572 (Investigator Obligation 
Form) to the Sponsor before screening participants for study enrollment. 
Any modifications or amendments made to the protocol or ICF after receipt of the initial IRB 
approval must also be submitted to the IRB for approval before implementation. Only changes 
necessary to eliminate apparent immediate hazards to the participants may be initiated prior to 
IRB approval. In that event, the Investigator must notify the IRB, the Medical Monitor, and the 
Sponsor in writing within 5 working days after implementation. If a change to the protocol in 
any way increases the risk to the participant or changes the scope of the study, then written 
documentation of IRB approval must be received by the Sponsor before the amendment may 


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take effect. Additionally, under this circumstance, information on the increased risk and/or 
change in scope must be provided to participants already actively participating in the study, 
and they must read, understand, and sign any revised informed consent document confirming 
willingness to remain in the study. 
The Investigator must ensure that all local regulations and reporting requirements to the IRB 
are met. 
11.5 Informed Consent Process 
Note: All references to “participant” in this section refer to the study participant or his legally 
authorized representative. 
The Sponsor (or its designee) will provide Investigators with multicenter ICFs for this study. 
Investigators may adapt the information to suit the needs of their institution, if necessary 
(although it must reflect the required elements of informed consent specified in 21 CFR Part 
50.25). The final ICFs must be accepted by the Sponsor and approved by the IRB. Investigators 
must provide the Sponsor with an unsigned copy of the final ICFs before and after it is approved 
by the IRB. If any new information becomes available that might affect participants’ 
willingness to participate in the study, or if any amendments to the protocol require changes to 
the ICF, the Sponsor will provide Investigators with a revised ICF. 
Prior to participating in any study-related procedure, each participant must sign and date an 
IRB-approved ICF written in a language the participant can understand. The ICF should be as 
nontechnical as practical and understandable to the participant. The ICF must provide the 
participant with all the information necessary to make an informed decision about their 
participation in the study, including the nature and intended purpose of the study, possible 
benefits, possible risks, and disclosures of the participant’s personal information and personal 
health information for purposes of conducting the study. The ICF will include details of the 
requirements of the participant and the fact that he/she is free to withdraw at any time without 
giving a reason and without prejudice to their further medical care. Before informed consent is 
obtained, the participant should be given ample time and opportunity to inquire about the 
details of the study. All questions must be answered to the satisfaction of the participant. 
Once signed, the original ICF will be stored in the Investigator’s site file and made available 
for review by the Sponsor. Documentation of the informed consent discussion must be noted 
in the participant’s case history. All participants will receive a copy of their signed and dated 
ICF. 
If the ICF is revised during the study and requires the participant to be re consented, informed 
consent will be obtained in the same manner as for the original ICF. 
11.6 Confidentiality 
Every effort will be made to maintain the anonymity and confidentiality of all participants 
during this clinical study. However, because of the experimental nature of this investigational 
product, the Investigator agrees to allow the IRB, representatives of the Sponsor and its 
designated agents, and authorized employees of appropriate regulatory agencies to inspect the 
facilities used in this study and, for purposes of verification, allow direct access to the study 
site records of all participants enrolled into this study. This includes providing by fax, e-mail, 
or regular mail de-identified copies of clinical, laboratory, ECG, radiology, pathology, and/or 
other test results when requested by the Sponsor. A statement to this effect will be included in 
the ICF and a permission form authorizing the use of protected health information will also be 
included. 


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In accordance with local and national participant privacy regulations, the Investigator or 
designee must explain to each participant that in order to evaluate study results, the 
participant’s protected health information obtained during the study may be shared with IRBs, 
the Sponsor and its designees, and regulatory agencies. It is the Investigator’s or designee’s 
responsibility to obtain written permission to use protected health information from each 
participant. If a participant withdraws permission to use protected health information, it is the 
Investigator’s responsibility to obtain the withdrawal request in writing from the participant 
and to ensure that no further data will be collected from the participant. Any data collected on 
the participant before withdrawal will be used in the analysis of study results. The Sponsor will 
only use or disclose the participant’s protected health information consistent as defined in the 
ICF. 
The Investigator must assure that each participant’s anonymity will be strictly maintained, and 
that each participant’s identity is protected from unauthorized parties. Only participant initials, 
date of birth, and an identification code (but no participant names) should be recorded on any 
form or biological sample submitted to the IRB, to the Sponsor or its designees (eg, 
laboratories), or to regulatory authorities. However, sufficient information must be retained at 
the study site to permit sample data and data in the database to be connected with the unique 
participant number assigned to each study participant. 
The Investigator agrees that all information received from the Sponsor, including, but not 
limited to, the investigational product, the IB, this protocol, the eCRFs, and any other study 
information remain the sole and exclusive property of the Sponsor during the conduct of the 
study and thereafter. This information is not to be disclosed to any third party (except 
employees or agents directly involved in the conduct of the study or as required by law) without 
prior written consent from the Sponsor. The Investigator further agrees to take all reasonable 
precautions to prevent the disclosure by any employee or agent of the study site to any third 
party or otherwise into the public domain. 
11.7 Study Files and Retention of Records and Biological Samples 
The Investigator must maintain adequate and accurate records to enable the conduct of the 
study to be fully documented and the study data to be subsequently verified by the IRB, 
representatives of the Sponsor and its designated agents, and authorized employees of 
appropriate regulatory agencies. These documents should be classified into at least the 
following 2 categories: Investigator’s study file and participant clinical source documents. 
The Investigator’s study file will contain the protocol/amendments, eCRF and query forms, the 
IRB and governmental approval with correspondence, signed ICF, drug accountability records, 
staff curriculum vitae and authorization forms (eg, Form FDA 1572), and other appropriate 
documents and correspondence pertaining to the conduct of the study. 
The required source data referenced in the monitoring plan for the study should include 
sequential notes containing at least the following information for each participant: 
• Participant identification (name, date of birth, sex, race and ethnicity); 
• Documentation that participant meets each of the eligibility criteria, eg, history, 
physical examination, and confirmation of diagnosis (to support inclusion and 
exclusion criteria); 
• Participation in study (including study number); 
• Study discussed and date of informed consent/re-consent; 


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• Dates of all visits; 
• Documentation that protocol-specific procedures were performed; 
• Results of efficacy parameters, as required by the protocol; 
• Start and end date (including dose regimen) of investigational products (including 
relevant drug dispensing information); 
• Record of all AEs and other safety parameters (including start and end date, causality, 
and severity (intensity)); 
• Concomitant medications (including start and end date and dose if relevant dose 
changes occur); 
• Date of study completion and reason for discontinuation, if applicable. 
All clinical study documents must be retained by the Investigator until at least 2 years after the 
last approval of a marketing application in an ICH region (the United States, Europe, or Japan) 
and until there are no pending or contemplated marketing applications in an ICH region; or, if 
no application is filed or if the application is not approved for such indication, until 2 years 
after the investigation is discontinued and regulatory authorities have been notified or for 15 
years, whichever is longer. Investigators may be required to retain documents longer if required 
by applicable regulatory requirements, by local regulations, or by an agreement with the 
Sponsor. The Investigator must notify the Sponsor and obtain written approval from the 
Sponsor before destroying any clinical study records. The Investigator will promptly notify the 
Sponsor in the event of accidental loss or destruction of any study records. The Sponsor will 
inform the Investigator of the date that study records may be destroyed or returned to the 
Sponsor. 
The Sponsor must be notified in advance and must provide express written approval of any 
change in the maintenance of the foregoing documents if the Investigator wishes to move study 
records to another location or assign responsibility for record retention to another party.  
If the Investigator cannot guarantee this archiving requirement at the study site for any or all 
of the documents, special arrangements must be made between the Investigator and the Sponsor 
to store these in sealed containers outside of the study site so that they can be returned sealed 
to the Investigator in case of a regulatory audit. When source documents are required for the 
continued care of the participant, appropriate copies should be made for storage outside of the 
study site. 
Biological samples retained by the Investigator will be stored and maintained by the 
Investigator until notification is received from the Sponsor that the retained samples and 
records no longer need to be retained. The Investigator must obtain written permission from 
the Sponsor before disposing of any retained samples. The Investigator should promptly notify 
the Sponsor in the event of accidental loss or destruction of any study samples. With the 
permission of the Sponsor, the retained samples may be transferred to an acceptable designee, 
such as another Investigator, another institution, a contract storage site, or to the Sponsor. 
11.8 Participant Screening Log 
The Investigator must keep a record that lists all participants who signed the ICF (including 
those who did not undergo screening assessments). For those participants who declined to 
participate, post signing the ICF or were subsequently excluded from enrollment, the reasons 
for not enrolling in the study must be described. 


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11.9 Modifications of the Protocol or Informed Consent Documents 
Protocol modifications, except those intended to reduce immediate risk to study participants, 
will be made only by the Sponsor. All protocol modifications must be submitted to the IRB in 
accordance with local requirements. Except as noted in Section 11.4, IRB approval must be 
obtained before changes can be implemented. 
The ICF cannot be changed without prior written approval by the Sponsor and the study site’s 
IRB. 
11.10 
Case Report Forms 
Authorized study site personnel will complete eCRFs designed for this study according to the 
completion guidelines that will be provided. An eCRF is required and must be completed for 
each enrolled participant, with all required study data accurately recorded such that the 
information matches the data contained in medical records (eg, physicians’ notes, nurses’ 
notes, study site charts, or other study-specific source documents). The Investigator will ensure 
that the eCRFs are accurate, complete, legible, and completed within 5 days of each 
participant’s visit. The Investigator will ensure that source documents that are required to verify 
the validity and completeness of data transcribed on the eCRFs are never obliterated or 
destroyed. As required by the protocol, eCRFs should also be completed for those participants 
who fail to complete the study (even during the screening period). If a participant withdraws 
from the study, the reason must be noted on the eCRF and thorough efforts should be made to 
clearly document outcome. 
The eCRFs for this study will exist within a web-based electronic data capture (EDC) system. 
After the Investigator or the Investigator’s designees (eg, research coordinators) have been 
appropriately trained, they will be given access to the EDC system and will enter the data 
required by the protocol into the EDC system. Any change of data will be made via the EDC 
system, with all changes tracked by the system to provide an audit trail. 
The eCRF must be completed and signed by the principal Investigator or sub-Investigator (as 
appropriate) within a reasonable time period after data collection. This signature serves to attest 
that the information contained in the eCRF is true. 
11.11 
Clinical Monitoring 
Representatives of the Sponsor or its designee will monitor this study until completion. 
Monitoring will be conducted through personal visits with the Investigator and study site staff 
as well as any appropriate communications by mail, e-mail, or telephone. The monitor is 
responsible for routine review of the eCRFs at regular intervals throughout the study to verify 
adherence to the protocol and the completeness, consistency, and accuracy of the data being 
entered on them. The purpose of monitoring is to ensure compliance with the protocol and the 
quality and integrity of the data. 
In accordance with GCP, the study monitor must have direct access to the Investigator’s source 
documentation in order to verify the data recorded in the eCRFs for consistency. The 
Investigator agrees to cooperate with the monitor to ensure that any problems detected in the 
course of these monitoring visits are resolved. 
11.12 
Inspections 
The source documents for this study must be made available to appropriately qualified 
personnel from the Sponsor or its representatives, to the IRB, and to regulatory authority or 


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health authority inspectors as a part of their responsibility to protect human participants in 
research. The Investigator agrees to provide access to records, facilities, and personnel for the 
effective conduct of any inspection or audit to representatives of the Sponsor and regulatory 
agencies. It is important that the Investigator and relevant institutional personnel are available 
during monitoring visits and possible audits or inspections and that sufficient time is devoted 
to the process. If the Investigator is notified of an inspection by a regulatory authority, the 
Investigator agrees to notify the Sponsor immediately. 
11.13 
Data Management 
Electronic data capture will be used to enter study data eCRFs and to transfer the data into a 
study-specific electronic database. Instances where the eCRF captured data are considered 
source data will be outlined in separate study specific documentation. During the data 
collection process, automated quality assurance programs will be used to identify missing data, 
out-of-range data, and other data inconsistencies. Requests for data clarification or correction 
will be forwarded to the investigative study site for resolution. As appropriate, eCRFs, listings, 
tables, and Statistical Analysis System datasets will be provided to the study sites for review. 
Quality assurance and quality control systems will be implemented and maintained according 
to written standard operating procedures to ensure that the data are generated, recorded, and 
reported in compliance with the protocol, GCP, and applicable regulatory requirements. Data 
collection and storage systems will provide an audit trail, security mechanisms, and electronic 
signature capabilities that meet the requirements of FDA Title 21 of CFR Part 11 regarding 
electronic records and electronic signatures. 
Data security will be controlled through appropriate and specific restriction of access to only 
data and systems required by individual users to accomplish their roles in the data management 
process. Individual login and password protections will be employed at study sites and at the 
Sponsor or its designee. The database will exist on physically secured servers. Data backups 
will be done regularly and will be stored in separate facilities. Printed documents relating to 
the study will be secured when not under review.  
11.14 
Clinical Study Insurance 
The Sponsor will secure clinical study insurance. An insurance certificate will be made 
available to the participating study sites before study initiation. 
11.15 
Communications with Regulatory Authorities 
The Sponsor, working either directly or through designees, will assume responsibility for 
regulatory interactions with relevant regulatory authorities. The Sponsor will maintain an IND 
application for the investigational product in support of the study in the United States and will 
maintain similar regulatory applications with other regulatory authorities as required for 
conduct of the study. In fulfilling this responsibility, the Sponsor (or a designee) will collect, 
assemble, and communicate all required regulatory documents (eg, Form FDA 1572, 
Investigator financial disclosure forms, protocol and protocol amendments, IB, ICFs, annual 
reports) as required by regulation. The Sponsor (or a designee) will also assume responsibility 
for safety reporting to regulatory authorities as described in Section 9.5. 
11.16 
Publication and Information Disclosure Policy 
All information provided by the Sponsor and all data and information generated by the site as 
part of the study (other than a participant’s medical records) are the sole property of Sponsor. 


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For clinical interventional studies in patients, Sponsor will post study results on websites such 
as https://clinicaltrials.gov/ in accordance with FDA reporting rules.  
Any publication or presentation of the results of this study may only be made in compliance 
with the provisions outlined in the executed Clinical Trial Agreement. Publication of scientific 
and clinical data will follow the recommendations of the International Committee of Medical 
Journal Editors, the Consolidated Standards of Reporting Trials group, and Good Publication 
Practice. 
11.17 
Study Discontinuation 
Both the Sponsor and the Investigator reserve the right to terminate the study at any time. 
Should this be necessary, both parties will arrange discontinuation procedures. The Investigator 
will be responsible for notifying the relevant study site’s IRB. The Sponsor will be responsible 
for notifying the appropriate regulatory authorities. In terminating the study, the Sponsor and 
the Investigator will assure that adequate consideration is given to the protection of the 
participants’ interests. As directed by the Sponsor, all study materials must be collected and all 
eCRFs completed to the greatest extent possible. 
 


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Zimmerman ME, Meyer AR, Rowe SP, Gorin MA. Imaging of prostate cancer with 
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Trabulsi EJ, Rumble RB, Jadvar H, et al. Optimum Imaging Strategies for Advanced 
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Alonso O, Dos Santos G, Garcia Fontes M, Balter H, Engler H. (68)Ga-PSMA and 
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Schwenck J, Rempp H, Reischl G, et al. Comparison of (68)Ga-labelled PSMA-11 and 
(11)C-choline in the detection of prostate cancer metastases by PET/CT. Eur J Nucl Med Mol 
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Savir-Baruch B, Zanoni L, Schuster DM. Imaging of Prostate Cancer Using 
Fluciclovine. Urol Clin North Am. Aug 2018;45(3):489-502. doi:10.1016/j.ucl.2018.03.015 


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19. 
Calais J, Ceci F, Eiber M, et al. (18)F-fluciclovine PET-CT and (68)Ga-PSMA-11 PET-
CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-
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Wilkinson S, Chodak G. The role of 111indium-capromab pendetide imaging for 
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Network NCC. National Comprehensive Cancer Network Guidelines® Clinical 
Practice Guidelines in Oncology (NCCN Guidelines®) Prostate Cancer Version 1.2022 — 
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Afshar-Oromieh A, Malcher A, Eder M, et al. PET imaging with a [68Ga]gallium-
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Hicks RJ, Jackson P, Kong G, et al. 64Cu-SARTATE PET imaging of patients with 
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Zia N, Cullinane C, VanZuylekom J, et al. A Bivalent Inhibitor of Prostate Specific 
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Scher HI, Morris MJ, Stadler WM, et al. Trial Design and Objectives for Castration-
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13 INVESTIGATOR AGREEMENT 
 
Protocol Number:  CLP06 
Protocol Title:  
64Cu-SAR-bisPSMA Positron Emission Tomography: A Phase 1/2 
Study of Participants with Biochemical Recurrence of Prostate Cancer 
 
I have carefully read and understand the foregoing protocol and agree that it contains all the 
necessary information for conducting this study safely. I will conduct this study in strict 
accordance with this protocol, ICH guidelines for GCP, the CFR, the Health Insurance 
Portability and Accountability Act, and local regulatory guidelines. I will attempt to complete 
the study within the time designated. I will ensure that the rights, safety, and welfare of 
participants under my care are protected. I will ensure control of the drugs under investigation 
in this study. I will provide copies of the protocol and all other study-related information 
supplied by the Sponsor to all personnel responsible to me who participate in the study. I will 
discuss this information with them to assure that they are adequately informed regarding the 
drug and conduct of the study. I agree to keep records on all participant information (case report 
forms, shipment and drug return forms, and all other information collected during the study) 
and drug disposition in accordance with FDA regulations. I will not enroll any participants into 
this protocol until IRB approval and Sponsor approval are obtained.  
 
 
 
 
 
 
 
 
 
 
Site or Institution Name 
 
 
 
 
 
 
 
 
 
 
Site number 
 
 
 
 
 
 
 
 
 
 
Investigator Name (Print) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Investigator Signature  
 
 
 
 
Date