A Prospective, Phase 3, Multi Center, Single-arm, Imaging Study Investigating the Safety and Diagnostic Performance of rhPSMA 7.3 (18F) PET Ligand in Men With Suspected Prostate Cancer Recurrence Based on Elevated PSA Following Prior Therapy (SPOTLIGHT)
Phase: PHASE3
Conditions: Prostate Cancer
Sponsor: Blue Earth Diagnostics

Study BED-PSMA-302, Protocol Version 4, 23-Oct-2020
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CONFIDENTIAL Blue Earth Diagnostics 
Based on Protocol Template, SOP-MED-002-AD-2, Version 3 
CLINICAL STUDY PROTOCOL 
A prospective, Phase 3, multi-center, single-arm, imaging study investigating the safety 
and diagnostic performance of rhPSMA-7.3 (18F) PET ligand in men with suspected 
prostate cancer recurrence based on elevated PSA following prior therapy 
SPOTLIGHT 
BED-PSMA-302 
Phase: 3 
EudraCT Number: 2019-003382-18 
IND Number: 141,561 
Revision Chronology:  
Protocol Version 1, 31-Oct-2019 
Protocol Version 2, 07-Jan-2020 
Protocol Version 3, 01-Jul-2020 
Protocol Version 4, 23-Oct-2020 
Sponsor: Blue Earth Diagnostics 
Confidentiality Statement 
This document contains confidential information that must not be disclosed to anyone other 
than the Sponsor, the Investigator Team, host organization, and members of the Research 
Ethics Committee, unless authorized to do so. 

Study BED-PSMA-302, Protocol Version 4, 23-Oct-2020
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CONFIDENTIAL Blue Earth Diagnostics  
Based on Protocol Template, SOP-MED-002-AD-2, Version 3 
Blue Earth Diagnostics 
Clinical Study Protocol 
A prospective, Phase 3, multi-center, single-arm, imaging study investigating the safety 
and diagnostic performance of rhPSMA-7.3 (18F) PET ligand in men with suspected 
prostate cancer recurrence based on elevated PSA following prior therapy 
Protocol Number: 
BED-PSMA-302 
Protocol Version / Date: 
Protocol Version 4, 23-Oct-2020 
Investigational Product: 
rhPSMA-7.3 (18F) 
EudraCT Number: 
2019-003382-18 
IND Number: 
141,561 
Development Phase: 
3 
Sponsor: 
Blue Earth Diagnostics  
UK Office: 
The Oxford Science Park, Magdalen Centre, Robert Robinson 
Avenue, Oxford, OX4 4GA, United Kingdom 
Telephone: +44 1865 784186 
IE Office:  
6th Floor, 2 Grand Canal Square, Dublin 2, Ireland. 
Telephone: +353 1 761 7403 
Funding Organization: 
Blue Earth Diagnostics Ltd 
Coordinating Investigator: 
 
 
 
 
Medical Monitor: 
 
 
 
 
Coordinating Center: 
 
 
 
Approval: 
 
 
Sponsor Signature (Name and Title)  
 
Date 
 
This confidential information about an investigational product is provided for the exclusive use of 
investigators of this product and is subject to recall at any time. The information in this document may 
not be disclosed unless federal or state law or regulations require such disclosure. Subject to the 
foregoing, this information may be disclosed only to those persons involved in the study who have a 
need to know, with the obligation not to further disseminate this information. 

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CONFIDENTIAL Blue Earth Diagnostics  
Based on Protocol Template, SOP-MED-002-AD-2, Version 3 
PROTOCOL AGREEMENT 
I have read the protocol specified below. In my formal capacity as Investigator, my duties 
include providing Blue Earth Diagnostics with the information, as outlined in the protocol. It 
is understood that all information pertaining to the study will be held strictly confidential and 
that this confidentiality requirement applies to all study staff at this site. Furthermore, on behalf 
of the study staff and myself, I agree to maintain the procedures required to carry out the study 
in accordance with accepted Good Clinical Practice principles, applicable regulatory 
requirements, and to abide by the terms of this protocol. 
 
Protocol Number: BED-PSMA-302 
 
Protocol Title: A prospective, Phase 3, multi-center, single-arm, imaging study investigating 
the safety and diagnostic performance of rhPSMA-7.3 (18F) PET ligand in men with suspected 
prostate cancer recurrence based on elevated PSA following prior therapy 
 
Protocol Version: 4 
Protocol Date: 23-Oct-2020 
 
 
 
 
 
Investigator Signature  
 
Date 
 
Print Name and Title 
Site # 
 
 
Site Name 
 
Address 
 
 
 
 
 
 
 
Phone Number 
 
 

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CONFIDENTIAL Blue Earth Diagnostics  
Based on Protocol Template, SOP-MED-002-AD-2, Version 3 
CONTENTS 
CONTENTS.............................................................................................................................. 4 
LIST OF TABLES ................................................................................................................... 7 
LIST OF FIGURES ................................................................................................................. 7 
LIST OF ABBREVIATIONS ................................................................................................. 8 
PROTOCOL SYNOPSIS ...................................................................................................... 10 
1. 
BACKGROUND ........................................................................................................... 17 
1.1 
Overview of Non-clinical Studies .................................................................... 17 
1.2 
Overview of Clinical Studies ........................................................................... 18 
2 
STUDY RATIONALE ................................................................................................. 18 
2.1 
Risk-benefit Assessment .................................................................................. 20 
2.1.1 
Benefits ............................................................................................ 20 
2.1.2 
Risks ................................................................................................. 20 
3 
STUDY OBJECTIVES ................................................................................................ 22 
3.1 
Primary Objective ............................................................................................ 22 
3.2 
Secondary Objectives ....................................................................................... 22 
3.3 
Exploratory Objectives ..................................................................................... 22 
4 
STUDY DESIGN .......................................................................................................... 23 
4.1 
Study Overview ................................................................................................ 23 
4.2 
Key Assumptions ............................................................................................. 24 
5 
CRITERIA FOR EVALUATION............................................................................... 24 
5.1 
Primary Efficacy Endpoints ............................................................................. 24 
5.2 
Secondary Endpoints ........................................................................................ 24 
5.3 
Exploratory Efficacy Endpoints ....................................................................... 25 
5.4 
Safety Evaluations ............................................................................................ 25 
6 
PATIENT SELECTION .............................................................................................. 25 
6.1 
Study Population .............................................................................................. 25 
6.2 
Inclusion Criteria .............................................................................................. 25 
6.3 
Exclusion Criteria ............................................................................................. 26 
7 
CONCURRENT MEDICATIONS ............................................................................. 26 
7.1 
Prohibited Medications .................................................................................... 26 
8 
STUDY TREATMENTS ............................................................................................. 27 
8.1 
Method of Assigning Patients to Treatment Groups ........................................ 27 
8.2 
Blinding ............................................................................................................ 27 
8.3 
Formulation of Test and Control Products ....................................................... 27 
8.3.1 
Formulation of Test Product ............................................................ 27 

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8.3.2
Formulation of Control Product.......................................................27
8.3.3 
Packaging and Labeling ................................................................... 27 
8.4 
Supply of IP at the Site ..................................................................................... 28 
8.4.1 
Dispensing ........................................................................................ 28 
8.4.2 
Administration Instructions .............................................................. 28 
8.4.3 
Storage .............................................................................................. 28 
8.5 
IP Accountability .............................................................................................. 29 
8.6 
Measures of Treatment Compliance ................................................................ 29 
8.7 
End of Trial ...................................................................................................... 29 
9 
STUDY PROCEDURES AND GUIDELINES .......................................................... 29 
9.1 
Clinical Assessments ........................................................................................ 29 
9.1.1 
Concomitant Medications ................................................................ 29 
9.1.2 
Demographics .................................................................................. 29 
9.1.3 
Medical History ................................................................................ 29 
9.1.4 
Vital Signs ........................................................................................ 30 
9.1.5 
Conventional Imaging ...................................................................... 30 
9.1.6 
Confirmatory Imaging ...................................................................... 30 
9.1.7 
rhPSMA-7.3 (18F) PET Scan ............................................................ 30 
9.1.8 
Image Interpretation ......................................................................... 31 
9.1.9 
Biopsy/Surgery ................................................................................. 31 
9.2 
SoT 31 
9.2.1 
Step 1: Histological SoT .................................................................. 32 
9.2.2 
Imaging as Standard of Truth (Steps 2 to 4) .................................... 32 
9.2.3 
Post-scan Treatment Options ........................................................... 35 
9.2.4 
Clinical Management ....................................................................... 36 
9.2.5 
Adverse Events ................................................................................. 36 
9.3 
Clinical Laboratory Measurements .................................................................. 36 
10 
EVALUATIONS BY VISIT ........................................................................................ 36 
10.1 
Visit 1 (Screening; Day -28 [Within 28 Days Before IP Administration]) ...... 36 
10.2 
Visit 2 (Day 1; IP Administration) ................................................................... 37 
10.3 
Visit 1 and Visit 2 Combined (Day 1; IP Administration) ............................... 37 
10.4 
Visit 3 (up to 7 Days Post-visit 2; Follow-up Visit) ........................................ 38 
10.5 
Follow-up Procedures (Within 45 Days Following IP Administration) .......... 38 
10.6 
Secondary Follow-up Procedures (46 to 90 Days After IP Administration) ... 38 
10.7 
Early Withdrawal ............................................................................................. 38 
11 
IMAGING PROTOCOL ............................................................................................. 39 
11.1 
PET Scanner ..................................................................................................... 39 
11.2 
rhPSMA-7.3 (18F) Injection Administration .................................................... 39 
11.3 
rhPSMA-7.3 (18F) PET Acquisition ................................................................. 39 
11.4 
Image Transfer ................................................................................................. 39 
11.5 
rhPSMA-7.3 (18F) Image Reads ....................................................................... 39 

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CONFIDENTIAL Blue Earth Diagnostics  
Based on Protocol Template, SOP-MED-002-AD-2, Version 3 
12 
ADVERSE EVENT REPORTING AND DOCUMENTATION ............................. 40 
12.1 
Adverse Events ................................................................................................. 40 
12.1.1 
Severity of Adverse Events .............................................................. 40 
12.1.2 
Relationship of Adverse Events to IP .............................................. 41 
12.2 
Serious Adverse Events (SAEs) ....................................................................... 41 
12.2.1 
Serious Adverse Event Reporting .................................................... 42 
12.3 
Urgent Safety Measures ................................................................................... 42 
12.4 
Medical Monitoring .......................................................................................... 42 
13 
DISCONTINUATION AND REPLACEMENT OF PATIENTS ............................ 42 
13.1 
Discontinuation of IP ....................................................................................... 42 
13.2 
Discontinuation/Withdrawal from the Study ................................................... 42 
13.3 
Replacement of Patients ................................................................................... 43 
13.4 
Lost to Follow-up ............................................................................................. 43 
13.5 
Study Discontinuation or Termination ............................................................. 44 
14 
PROTOCOL DEVIATIONS ....................................................................................... 44 
15 
DATA SAFETY MONITORING ............................................................................... 44 
16 
STATISTICAL METHODS AND CONSIDERATIONS ......................................... 44 
16.1 
Data Sets Analyzed .......................................................................................... 44 
16.2 
Accountability of Patients and Imaging ........................................................... 45 
16.3 
Demographic and Baseline Characteristics ...................................................... 45 
16.4 
Analysis of Primary Endpoints ........................................................................ 45 
16.5 
Analysis of Secondary and Exploratory Endpoints .......................................... 45 
16.6 
Analysis of Safety Endpoint(s) ........................................................................ 46 
16.7 
Planned Interim Analysis ................................................................................. 46 
16.8 
Sample Size and Randomization ...................................................................... 46 
16.8.1 
Assumptions ..................................................................................... 46 
16.8.2 
Sample Size ...................................................................................... 46 
17 
DATA COLLECTION, RETENTION AND MONITORING ................................ 46 
17.1 
Data Collection Instruments ............................................................................. 46 
17.2 
Data Management Procedures .......................................................................... 47 
17.3 
Data Quality Control and Reporting ................................................................ 47 
17.4 
Archive of Data ................................................................................................ 47 
17.5 
Availability and Retention of Investigational Records .................................... 48 
17.6 
Monitoring and Auditing .................................................................................. 48 
17.7 
Patient Confidentiality ...................................................................................... 48 
18 
REGULATORY, ETHICAL AND STUDY OVERSIGHT CONSIDERATIONS 49 
18.1 
Institutional Review Boards and Independent Ethics Committees .................. 49 

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CONFIDENTIAL Blue Earth Diagnostics  
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18.2
Amendments.....................................................................................................49
18.3 
Patient Information and Consent ...................................................................... 49 
18.4 
Post-trial Care ................................................................................................... 51 
18.5 
Publications ...................................................................................................... 51 
19 
REFERENCES ............................................................................................................. 51 
APPENDIX 1: 
STUDY SCHEDULE ............................................................................ 53 
 
LIST OF TABLES 
Table 1: 
Central Reading Plan .............................................................................. 34 
Table 2: 
CTCAE (V5) AE Severity Grading ........................................................ 40 
Table 3: 
AE Severity Grading ............................................................................... 41 
Table 4: 
Relationship of AEs to IP ....................................................................... 41 
 
LIST OF FIGURES 
Figure 1: 
Study Schema ......................................................................................... 15 
Figure 2: 
Structure of rhPSMA-7.3 (18F) ............................................................... 17 
Figure 3: 
Standard of Truth Algorithm (to be Applied for Each PET-positive 
Region) .................................................................................................... 35 
 

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CONFIDENTIAL Blue Earth Diagnostics  
Based on Protocol Template, SOP-MED-002-AD-2, Version 3 
LIST OF ABBREVIATIONS 
ADT 
Androgen deprivation therapy 
AE 
Adverse event 
BCR 
Biochemical recurrence 
CDR 
Correct Detection Rate 
CI 
Confidence interval 
COVID-19 
Corona Virus Disease-19 
CT 
Computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
Cytochrome P450 
eCRF 
Electronic case report form 
EAP 
Efficacy Analysis Population 
EDC 
Electronic data capture 
eTMF 
Electronic trial master file 
EU 
European Union 
18F 
Fluorine-18 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
FP 
False Positive 
FSP 
Full Safety Population 
68G 
Gallium-68 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
HIFU 
High-intensity focused ultrasound 
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
 
ICH 
International Council for Harmonisation 
ICRP 
International Commission on Radiological Protection 
ID 
Identifier 
IEC 
Independent Ethics Committee 
IP 
Investigational product 
IRB 
Institutional Review Board 
IV 
Intravenous 
LHRH 
Luteinizing hormone-releasing hormone 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
Magnetic resonance imaging 
NaF 
Sodium fluoride 
PCa 
Prostate cancer 
PET 
Positron emission tomography 
PP 
Per Protocol 
PPV 
Positive predictive value 

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PSA
Prostate-specific antigen
PSAdt 
PSA doubling time 
PSMA 
Prostate-specific membrane antigen 
rh 
Radiohybrid 
RP 
Radical prostatectomy 
RT 
Radiation therapy 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 
SCID 
Severe combined immunodeficiency 
SOP 
Standard Operating Procedure 
SoT 
Standard of Truth 
99mTc-HDP  
99m Technetium-hydroxydiphosphate  
99mTc-MDP 
99m Technetium-methyldiphosphonate 
TP 
True Positive 
TUM 
Technical University of Munich 
UK 
United Kingdom 
US 
United States 
 

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CONFIDENTIAL Blue Earth Diagnostics  
Based on Protocol Template, SOP-MED-002-AD-2, Version 3 
PROTOCOL SYNOPSIS 
Study Title 
A prospective, Phase 3, multi-center, single-arm, imaging study 
investigating the safety and diagnostic performance of rhPSMA-7.3 (18F) 
PET ligand in men with suspected prostate cancer recurrence based on 
elevated PSA following prior therapy 
Protocol Number 
BED-PSMA-302 
Phase 
3 
Sponsor 
Blue Earth Diagnostics 
Funding 
Organization 
Blue Earth Diagnostics Ltd 
Study Design 
This is a prospective, Phase 3, multi-center, single-arm, single dose study 
designed to evaluate the safety and diagnostic performance of radiohybrid 
prostate-specific membrane antigen (rhPSMA)-7.3 (fluorine-18 [18F])
positron emission tomography (PET) ligand for imaging in men with 
suspected biochemical recurrence (BCR) of prostate cancer (PCa) based on 
elevated prostate-specific antigen (PSA) following prior therapy. 
A number of measures have now been put in place to streamline the study for 
 safety due to the continued impact of the Corona Virus Disease-19 
(COVID-19) pandemic on daily life. 
Patients with a diagnosis of BCR of PCa being worked up for re-staging and 
eligible for potential salvage treatment will be consented and enrolled. After 
enrollment (either before or after conventional imaging if not already 
completed), patients will receive 8 mCi (296 MBq) ± 20% rhPSMA-7.3 (18F), 
delivered as an intravenous (IV) bolus injection, followed by PET imaging. 
If feasible, the patient will undergo image-guided biopsy of a PET-positive 
lesion(s) suspicious for recurrence of PCa within 45 days following
rhPSMA-7.3 (18F) PET imaging. Note: due to the COVID-19 pandemic, this 
may be extended up to 60 days.  
If necessary, confirmatory imaging (for Standard of Truth [SoT]) will be 
performed within 45 days following rhPSMA-7.3 (18F) PET imaging or 
attempted biopsy and, if necessary, additional follow-up confirmatory 
imaging may be performed up to 90 days after rhPSMA-7.3 (18F) PET.
Patients may receive salvage treatment following further consultation with 
their physician (outside of the scope of this study). The salvage treatment 
prescribed will be recorded. If treatment consists of a surgical resection, the 
histology obtained will be correlated with rhPSMA-7.3 (18F) PET imaging
(and will serve as the SoT for PET-positive lesions resected). Follow-up 
confirmatory imaging, as part of the SoT algorithm, should not delay the 
 
Notes: due to the COVID-19 pandemic, biopsy and surgical procedures
performed to obtain SoT histology and initial confirmatory imaging
assessments (in patients not undergoing biopsy/resection) may be delayed up 
to Day 60 to ensure the safety (i.e., decreased potential exposure to severe 
acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) of enrolled 
patients. In patients with multiple PET-positive regions, confirmation of at
least one PET-positive lesion in each region is required either by 
biopsy/surgical resection or confirmatory imaging. 
Safety (adverse events [AEs] and vital signs) will be monitored during the 
study. 

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CONFIDENTIAL Blue Earth Diagnostics  
Based on Protocol Template, SOP-MED-002-AD-2, Version 3 
Study Rationale
The purpose of this study is to assess co-primary endpoints of patient level 
Correct Detection Rate (CDR) and region level positive predictive value 
(PPV) of rhPSMA-7.3 (18F) PET for BCR of PCa using histopathology or 
imaging as a SoT. The CDR is defined as the percentage of all patients 
scanned who have at least one True Positive (TP) lesion (localized 
correspondence between rhPSMA-7.3 (18F) PET imaging and the reference 
standard) regardless of any coexisting False Positive (FP) findings. When 
determining the region level PPV, all rhPSMA-7.3 (18F) PET-positive regions 
will be categorized as TP or FP regions using histopathology or imaging.
Regions will include the prostate bed, pelvic lymph nodes, and other (bone, 
extra-pelvic lymph nodes, viscera and other soft tissues); a region will be 
categorized as a TP region if at least one PET-positive lesion in the region is 
confirmed as a TP. For the primary analysis, pelvic lymph nodes will include 
the right and left external iliac, obturator, hypogastric (internal iliac), 
perirectal and presacral lymph node groups.  
The prostate-specific membrane antigen (PSMA) receptor is over-expressed 
in the majority of PCa. Although not approved in any country or region, 
PSMA PET tracers have been used in many centers around the world to image 
PCa patients. Initial results have demonstrated promising diagnostic 
performance. Most trials investigating diagnostic PSMA ligands have thus far 
focused on patients with prior negative conventional imaging. Going forward 
in routine clinical care, given the low sensitivities of these conventional 
imaging procedures, it is difficult to continue to support subjecting patients 
to two or three non-sensitive imaging procedures before the patient may 
receive a more sensitive one. 
rhPSMA-7.3 (18F) injection is a PET ligand for the detection of PCa. 
rhPSMA-7.3 (18F) has already been administered to patients at the Technical 
University of Munich (TUM). Based on the retrospectively determined high 
sensitivity of PSMA ligands, this study is designed to establish the diagnostic
performance of rhPSMA-7.3 (18F) PET irrespective of the findings of 
conventional imaging in order to support the use of rhPSMA-7.3 (18F) as an 
imaging option during the initial workup of these patients. 
Primary Objective 
and Endpoint 
Objective: 
To assess the patient level CDR and 
region level PPV of rhPSMA-7.3 
(18F) PET for BCR of PCa using 
histopathology or imaging as a SoT.  
Co-primary Endpoints: 
Patient level CDR and region level 
PPV of rhPSMA-7.3 (18F) PET as 
defined above in Study Rationale. 
For details of the null hypothesis, 
see STATISTICS: 
Primary Analysis Plan and Rationale 
for Number of Patients (below). 
Secondary 
Objectives and 
Endpoints 
Objectives: 
1.
To assess the patient level CDR 
and region level PPV of 
rhPSMA-7.3 (18F) PET in the 
subgroup of patients who have 
negative baseline conventional 
imaging. 
Endpoints: 
1.
Patient level CDR and region 
level PPV in patients who have 
negative conventional imaging. 

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Secondary 
Objectives and 
Endpoints (Cont.) 
2.
To assess the patient level CDR 
and region level PPV of 
rhPSMA-7.3 (18F) PET 
separated into subgroups of 
patients with reference standard 
histopathology available and 
unavailable. 
2.
Patient level CDR and region 
level PPV of rhPSMA-7.3 (18F) 
PET for recurrence in those 
patients with and without 
reference standard 
histopathology available. 
 
3.
To assess the patient level CDR 
and region level PPV of 
rhPSMA-7.3 (18F) PET stratified 
by PSA level. 
3.
Patient level CDR and region 
level PPV of rhPSMA-7.3 (18F) 
PET stratified by PSA level. 
 
4.
To assess the CDR of rhPSMA-
7.3 (18F) PET on a region level. 
4.
CDR of rhPSMA-7.3 (18F) PET 
in the following regions: local 
recurrence, pelvic lymph nodes, 
other. 
 
5.
To assess the impact of 
rhPSMA-7.3 (18F) PET imaging 
results on the intended clinical 
management of study 
participants using a clinician 
survey. 
5.
Percentage of patients in whom 
rhPSMA-7.3 (18F) PET imaging 
results changed the intended 
patient management (major and 
other changes). 
 
6.
To assess the inter- and 
intra-reader agreement of 
rhPSMA-7.3 (18F) scan 
interpretation by the blinded 
independent readers. 
6.
Reader kappa statistics of 
rhPSMA-7.3 (18F) scan 
interpretation by the blinded 
independent readers. 
 
7.
To assess the safety of 
rhPSMA-7.3 (18F) injection in 
patients. 
7.
Safety (AEs and vital signs) of 
rhPSMA-7.3 (18F) injection in 
patients. 
Exploratory 
Objectives and 
Endpoints  
Objectives: 
1.
To assess the overall detection 
rate (without SoT confirmation) 
on a patient level and including 
detection rate subgroup analyses 
of patients: a) who have 
negative baseline conventional 
imaging, b) with reference 
standard histopathology 
available and unavailable, and 
also detection rate stratified by 
PSA level and assessed by 
region. 
Endpoints: 
1.
Overall patient level detection 
rate (without SoT confirmation), 
including detection rate 
subgroup analyses of patients: a) 
who have negative baseline 
conventional imaging, b) with 
reference standard 
histopathology available and 
unavailable, and detection rate 
stratified by PSA level and 
assessed by region. 
 
2.
To assess the patient level PPV 
in which a TP patient is defined 
as having at least one TP region, 
regardless of any coexisting FP 
regions. 
2.
Patient level PPV in which a TP 
patient is defined as having at 
least one TP region, regardless 
of any coexisting FP regions. 

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Exploratory 
Objectives and 
Endpoints (Cont.) 
3.
To assess the impact of 
rhPSMA-7.3 (18F) PET on 
upstaging patients with BCR of 
PCa a) post-radical 
prostatectomy (RP) or b) 
post-radiation therapy (RT) 
compared to conventional 
imaging. 
3.
The number of positive 
rhPSMA-7.3 (18F) scans 
compared to conventional 
imaging in defined regions, 
leading to upstaging of the 
patient a) post-RP and b) 
post-RT. 
 
4.
To assess patient and regional 
level detection rates of 
rhPSMA-7.3 (18F) PET. 
4.
Patient and regional level 
detection rates of 
rhPSMA-7.3 (18F) PET. 
 
5.
To assess patient and regional 
level detection rates of 
rhPSMA-7.3 (18F) PET as a 
function of PSA, prior Gleason 
score, and PSA doubling time 
(PSAdt) in a) post-RP or b) 
post-RT patients. 
5.
Patient and regional level 
detection rates of 
rhPSMA-7.3 (18F) PET as a 
function of PSA, prior Gleason 
score and PSAdt in a) post-RP 
and b) post-RT patients. 
Study Sites 
This study will be conducted at up to approximately 35 sites in the United 
States (US) and Europe. 
Investigational 
Product(s), 
Including Control 
Products 
IP: 8 mCi (296 MBq) ± 20% rhPSMA-7.3 (18F), delivered as an IV bolus 
injection with a 10 mL fast 0.9% sodium chloride flush. 
Control: none. 
Study and 
Participant Duration 
Study Duration: The total study duration from first site activation to data 
analysis is estimated to be 18 months. 
Participant Duration: Patients will be screened for inclusion into the study up 
to 28 days before rhPSMA-7.3 (18F) PET imaging (up to 45 days due to the 
COVID-19 pandemic) and remain as a participant until histology or 
confirmatory imaging data has been obtained in order to satisfy the SoT 
assessment. The last visit will be the End of Study assessment which will take 
place within 45 days following administration of rhPSMA-7.3 (18F) for 
patients requiring follow-up procedures (may be extended up to 60 days due 
to the COVID-19 pandemic) or for patients requiring additional confirmatory 
imaging procedure, up to 90 days after rhPSMA-7.3 (18F) PET. 
Planned Interim 
Analyses 
No formal hypothesis testing interim analysis will be performed. 
Once 60% of the planned 190 positive cases have information, the proportion 
of patients with a PSA <1 ng/mL will be assessed. If this proportion exceeds 
60% then investigators will be informed to stop further enrolment of this 
cohort. 
STATISTICS: 
Primary Analysis 
Plan and Rationale 
for Number of 
Patients 
The co-primary endpoints for the study are the patient level CDR and the 
region level PPV of rhPSMA-7.3 (18F) PET. The joint hypothesis is as 
follows: H0
1: CDR >36.5% and PPV 
>62.5%. 
Both primary endpoints will be summarized as a percentage together with a 
two-sided exact 95% confidence interval (CI) for each reader. In addition, a 
one-sided exact binomial test p-value will be provided for each reader for 
each CDR. As this is a by-region endpoint patients may have one to three 
regions that may be included in the PPV assessment. The one-sided test based 
on clustered binary data will be used to evaluate the PPV hypothesis (Zhou, 

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Obuchowski, and McClish (2002), pg. 104) to adjust the variance estimates 
in the analysis based on clustering of regions within a patient. For the study 
to be considered a success, the p-values for both endpoints must be 
statistically significant for at least two out of the three readers (same readers 
for both CDR and PPV).  
In the overall study population, the detection rate of rhPSMA-7.3 (18F) PET 
is expected to be approximately 60%, the overall PPV is estimated to be 
73.5%, and the overall CDR is anticipated to be 49% (point estimates). The 
lower bound of the CI for the region level PPV will be set at 62.5% and the 
overall CDR will have a lower bound of 36.5%. The study will aim to include 
approximately 40% of patients with a PSA level <1 ng/mL and approximately 
60% of patients with a PSA level 
 ng/mL. 
Approximately 316 patients will be enrolled in this study. For the PPV 
endpoint, based on a one-sided 0.025 exact binomial test and assuming a true 
PPV of 73.5%, a sample size of 190 positive cases provides >88% power for 
the evaluation of region level PPV (H0
%). Assuming that 60% of 
all scans have a positive finding, a total of approximately 316 evaluable 
patients would be required to obtain 190 positive rhPSMA-7.3 (18F) PET 
cases. Note that PPV region-based analysis is expected to provide more than 
88% power based upon the number of positive regions per patient being >1, 
even adjusting for the correlation between the regions within a patient. Thus, 
316 patients are planned to be enrolled in order to get at least 190 cases with 
disease detected with rhPSMA-7.3 (18F) and an evaluable result. 
For the patient level CDR endpoint, based on a one-sided 0.025 exact 
binomial test and assuming a true CDR of 49%, a sample size of 316 cases 
provides >99% power for the evaluation of CDR (H0
 
Hence, a sample size of at least 316 patients is adequate based on the region 
level PPV endpoint and is expected to provide at least 90% power for the 
regional PPV analysis. 
Dropouts who fail to complete all study procedures, for reasons other than 
due to adverse reactions/AEs deemed related to IP, will be withdrawn from 
the study and will be replaced. No more than 15% of patients enrolled will be 
replaced. 
Secondary and exploratory endpoints will be summarized descriptively, with 
the exception of consistency of rhPSMA-7.3 (18F) scan interpretation by 
blinded independent readers which will be presented utilizing Kappa 
statistics. Two-sided 95% CIs will be presented, where applicable.  
 

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Figure 1:
Study Schema
ADT=androgen deprivation therapy; AE=adverse event; BCR=biochemical recurrence; COVID-19=Corona Virus Disease-19; 
EBRT=external beam radiation therapy; 18F=fluorine-18; FP=False Positive; HIFU=high-intensity focused ultrasound; 
IP=investigational product; PCa=prostate cancer; PET=positron emission tomography; PPV=positive predictive value; 
PSA=prostate-specific antigen; PSMA=prostate-specific membrane antigen; rh=radiohybrid; RP=radical prostatectomy; 
RRT=radical radiotherapy; RT=radiation therapy; SARS-CoV-2=severe acute respiratory syndrome coronavirus 2; TP=True 
Positive.
a
Patients will be male and aged >18 years, with a history of localized adenocarcinoma of the prostate with prior curative 
intent treatment and experiencing BCR of PCa potentially eligible for salvage therapy with curative intent, following prior
treatment with one or more of the following a) RP, b) RP plus adjuvant RT, c) RP plus adjuvant ADT, d) EBRT or e) focal 
gland therapies (e.g. brachytherapy, HIFU). Note: at least 6 weeks must have elapsed after RP; if previously taking ADT, 
it should have been discontinued at least 16 weeks prior to screening; in the case of focal gland therapies (e.g. HIFU) and 
RT, the treatment will have occurred at least 1 year prior to screening. Patients will have an elevated PSA, clinically 
suspicious for biochemically recurrent disease (following RP: PSA >0.2 ng/mL that increases on serial determination; 
following RT (e.g. RRT or brachytherapy): nadir +2 ng/mL. Patients must be willing to undergo biopsy for histological 
confirmation of rhPSMA-7.3 (18F) PET findings, where safe and feasible.
b
Collect historical conventional imaging. Schedule patient for conventional imaging (to take place following Visit 1 and up 
to 2 weeks after Visit 2 [Optional Visit 2(a)]) if historical conventional imaging took place greater than 90 days before 
Visit 1. Note: conventional imaging that has been performed at non-participating institutions will be accepted provided the 
scans are reviewed by the participating institution. Note: contrast-enhanced CT/MRI and radiopharmaceutical-based 
baseline conventional imaging (performed as per local standard of care) should be performed at least 24 hours apart from
the investigational rhPSMA-7.3 (18F) PET scan.
c
Due to the COVID-19 pandemic, Visit 1 and Visit 2 may be combined (named Visit 1 and Visit 2 combined ) if judged 
by the investigator to be necessary to decrease potential exposure to SARS-CoV-2 for patients. For all patients enrolled 
through the Visit 1 and Visit 2 combined pathway, pre-screening via telephone contact with the patient is required prior to 
Day 1 to review the study eligibility criteria, obtain initial consent (remote consent is acceptable if permitted under local 
regulations and approvals), to promote study visit compliance and to ensure patient understanding of the combined study 
visit and planned IP administration, as well as ask about baseline and historic conventional imaging that may already have 
been performed or needs to be scheduled. Full written informed consent will be taken on Day 1 (Visit 1 and Visit 2 
combined). For sites with on-site manufacturing, the visits may be combined if mutually agreed by the Radiopharmacy 
and investigator even post-COVID-19 pandemic restrictions.
Alternatively, the time from Visit 1 (initial screening) to Visit 2 (rhPSMA-7.3 (18F) PET scan) may be extended up to 
45 days due to the COVID-19 pandemic.
d
Obtain image-guided biopsy of PET-positive lesion(s), if feasible. If surgical resection is planned, record date and make 
arrangements for obtaining histology results. If biopsy is not feasible, obtain confirmatory imaging, if indicated, as per 
algorithm. If necessary, schedule further confirmatory imaging, up to 90 days after rhPSMA-7.3 PET imaging. Record any 
salvage treatment. Record any AEs and change in concomitant medication.
Note: due to the COVID-19 pandemic, biopsy and surgical procedures to obtain SoT histology and initial confirmatory 
imaging assessments (in patients not undergoing biopsy/resection) may be delayed up to Day 60 to ensure the safety (i.e., 
decreased potential exposure to SARS-CoV-2) of enrolled patients.
e
Obtain a second confirmatory image if necessary. Follow-up confirmatory imaging should
treatment. If surgical resection has been performed, correlate with rhPSMA-7.3 (18F) PET imaging. Record any salvage 
treatment since IP administration. Record any AEs and change in concomitant medication.
f
Up to 90 days after rhPSMA-7.3 (18F) PET.
Visit 1c
(Screening from 
Day -28)
Visit 2
(Day 1)c
Visit 3
(Follow-up
up to Day 7)
Follow-up 
Procedures
(up to Day 45)
Patients with BCR of 
PCaa
Consent, screening, 
consent, medical 
history, assessments 
and conventional 
imagingb
Assessments and 
rhPSMA-7.3 
(18F) PET scan
Clinical 
review, AE 
and 
concomitant 
medication 
assessment
Image-guided biopsy, 
schedule resection (if 
planned), 
confirmatory imaging 
(if indicated), record 
salvage therapy, AEs 
and concomitant 
medicationd
Repeat confirmatory 
procedures if 
required, AEs and 
concomitant 
medicatione
Secondary 
Follow-up Procedures
(up to 90 days)f

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Notes: 
* 
In patients with multiple PET-positive regions, confirmation of at least one PET-positive lesion in each region is required 
either by biopsy/surgical resection or confirmatory imaging in order to calculate the region level PPV for the efficacy 
analyses. 
** 
In patients with multiple lesions in a specific region, the presence of one TP lesion determines truth for the region 
regardless of any concurrent FP findings in the same region. Therefore, multiple PET-positive lesions can be evaluated 
in a specific region in order to confirm at least one TP. 
*** Due to the COVID-19 pandemic, investigators should carefully consider the timing of confirmatory imaging procedures 
potential exposure to SARS-CoV-2 by 
combining follow-up visits for multiple confirmatory imaging scans, when feasible. 

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1. 
BACKGROUND 
The investigational product (IP) is fluorine-18 (18F) radiohybrid prostate-specific membrane 
antigen (rhPSMA)-7.3 injection, a positron emission tomography (PET) ligand for the 
detection of prostate cancer (PCa). 
It is designed to target the extracellular epitope of the prostate-specific membrane antigen 
(PSMA) molecule and is administered as a single intravenous (IV) bolus microdose (i.e. the 
mass dose administered is less than 100 µg/patient). 
The molecular structure of the drug substance comprises a PSMA binding motif, a peptide 
spacer, an 18F-radiolabeled silicon fluoride acceptor moiety and a gallium chelator complex 
(Figure 2). 
1.1 
Overview of Non-clinical Studies 
A non-clinical biodistribution and dosimetry study has been performed (Internal report: 
BEDPSMADEV002), in which 100 pmol rhPSMA-7.3 (18F) (N=27) was administered to 
severe combined immunodeficiency (SCID) male mice. Animals were sacrificed at 10, 60, 120, 
180 and 300 minutes post-administration, with urine and blood samples collected immediately 
after sacrifice and tissues harvested and weighed for the measurement of 18F radioactivity. 
Human dosimetry was calculated by extrapolation from the mouse biodistribution data using 
scaling factors to account for the differences between animals and humans. The data 
demonstrated that for rhPSMA-7.3 (18F), the largest accumulation of radioactivity was in the 
kidney, spleen, lung, liver and heart. Clearance from the blood and clearance to the urine was 
rapid for rhPSMA-7.3 (18F), but there was a relatively slow build-up of radioactivity in the 
kidney. Using a 3.5-hour bladder voiding interval, as recommended by the International 
Commission on Radiological Protection (ICRP; ICRP, 1992), the effective dose for humans 
extrapolated from the animal data was 21.7 µSv/MBq for rhPSMA-7.3 (18F). Using a 1.0-hour 
bladder voiding interval, based on the time at which patients will be encouraged to void in the 
clinical setting, the effective dose for humans was 12.8 µSv/MBq. Based on these data, an 
injection of 8 mCi (296 MBq) for a clinical scan would result in a favorable radiation effective 
dose of less than 5 mSv, assuming a 1-hour voiding interval. 
Consistent with the development of a radiodiagnostic agent, rhPSMA-7.3 (18F) is not designed 
to elicit pharmacological activity and an in vitro secondary pharmacology screen has confirmed 

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there is no unintended pharmacological activity in a panel of 44 potential targets. A 
concentration of 5 µg/mL was used in the in vitro pharmacology profiling which compares to 
a maximum concentration in human plasma of 0.04 µg/mL (based on 2500 mL plasma and a 
maximum human dose of 100 µg). In a pivotal single IV bolus dose extended toxicity study in 
rats to determine tolerance and potential target organ toxicity to rhPSMA-7.3 at IV dosages of 
0, 0.1, 1 and 10 mg/kg, the no-observed-adverse-effect-level was the maximum dose 
administered of 10 mg/kg (allometrically scaled human dose equivalent of 1.6 mg/kg). This 
represents a 1000-fold multiple of the maximum clinical microdose of 100 µg based on a 60 
kg human. No target organs of toxicity were identified. Systemic exposure demonstrated rat 
plasma concentrations above the intended maximum human actual dose. In vitro protein 
binding in rat and human indicated moderate binding of 75% and 82% in rat and human, 
respectively, with no concentration dependence. In vitro human cytochrome P450 (CYP) 
reaction phenotyping indicated rhPSMA-7.3 is not metabolized. In vitro rhPSMA-7.3 does not 
inhibit or induce human CYP isoforms and is not a substrate or inhibitor of human drug 
transporters suggesting drug interaction with rhPSMA-7.3 is unlikely. 
Further details of the non-clinical studies performed with rhPSMA-7.3 or rhPSMA-7.3 (18F) 
are provided in the rhPSMA-7.3 (18F) 
. 
1.2 
Overview of Clinical Studies 
Although no PSMA-targeted imaging agents are licensed as radiodiagnostic agents for use in 
either Europe or the United States (US), they are widely used by many imaging centers (Rowe, 
2018). This includes use of rhPSMA-7.3 (18F) at the Technical University of Munich (TUM), 
(exempt from a manufacturing 
authorization as per Section 13, Subsection 2b of the German Medicinal Products Act). In a 
retrospective, non-interventional review of data from patients (N=558) with known or 
suspected PCa who underwent a clinically indicated rhPSMA-7.3 (18F) PET/computed 
tomography (CT) or PET/magnetic resonance imaging (MRI) scans at TUM, diagnostic 
performance, biodistribution and safety data for rhPSMA-7.3 (18F) were analyzed (Study BED-
PSMA-403). Data sources included hospital records and imaging results, as well as routine 
follow-up data. Given the retrospective nature of the data collection, informed consent was not 
obtained from each individual patient; thus, routine clinical data included in the study database 
were totally anonymized and only aggregated anonymized data from chart review were 
available for analysis.  
A total of 558 patients, with known or suspected PCa, underwent a clinically indicated 
rhPSMA-7.3 (18F) PET/CT or PET/MRI scan at TUM between 30 August 2018 and 
15 February 2019. Based on the retrospective chart review, rhPSMA-7.3 (18F) was 
well-tolerated, with no safety concerns identified. A total of 285 consecutive patients with 
biochemical recurrence (BCR) of PCa were analyzed. Overall, 225/285 (79%) had positive 
findings on rhPSMA-7.3 (18F) PET imaging. The detection rates were 58%, 83%, and 97% for 
patients with prostate-specific antigen (PSA) levels of <1 ng/mL, 1 to <2 ng/mL, and 
 ng/mL, respectively.  
Further details of the clinical studies performed or planned for rhPSMA-7.3 (18F) are provided 
in the rhPSMA-7.3 (18F) IB. 
2 
STUDY RATIONALE 
PCa is the most prevalent cancer in men in the developed world and the third leading cause of 
death (Jemal 2011). It is most commonly diagnosed in men aged 65 years and over and 

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diagnosis is often made following the detection of elevated PSA and/or an abnormal digital 
rectal examination, with confirmation of this diagnosis by prostate biopsy. PSA is used as a 
tumor marker and serum levels of PSA positively correlated with the risk of metastatic disease 
or subsequent disease recurrence or progression. 
The PSMA receptor is a 100 kD transmembrane glycoprotein that is over-expressed in the 
majority of PCa (Israeli 1994; Silver 1997; Osborne 2013). Peptidomimetic glu-ureido-based 
PSMA inhibitors, initially described in 2001 (Kozikowski 2001), bind to a carboxypeptidase 
active site on the extracellular motif of the PSMA receptor. In the last 5 years, many centers 
around the world have imaged patients using PSMA PET tracers based on this targeting 
technology (Perera 2016). Whilst these initial results have demonstrated promising diagnostic 
performance, there remains no licensed or approved PSMA PET imaging agent.  
rhPSMA-7.3 (18F) injection, is a PET ligand for the detection of PCa. The rhPSMA-7.3 (18F) 
stereoisomer has already been administered to patients at the TUM (see Section 1.2). Several 
hundred patients with PCa have been imaged clinically, which has informed the design of this 
proposed study. rhPSMA-7.3 (18F) is currently being formally evaluated by Blue Earth 
Diagnostics in a Phase 1, open label, study designed to assess the safety, biodistribution and 
internal radiation dosimetry of rhPSMA-7.3 (18F) injection in healthy volunteers, and to assess 
safety and investigate the imaging characteristics in patients with PCa (Study BED-PSMA-
101; EudraCT No. 2018-004703-39). 
As described in Section 1.2, the detection rate of rhPSMA-7.3 (18F) varies depending on the 
PSA level at scanning. The findings at TUM are consistent with the recently published paper 
(Fendler 2019), describing the use of gallium-68 (68Ga)-PSMA-11 in 635 patients with BCR 
irrespective of the results of other imaging. They reported an overall detection rate of 75%, but 
stratifying for PSA levels, the detection rates were 45%, 84%, 86%, and 97% for patients with 
PSA levels of <1 ng/mL, 1 to <2 ng/mL, 2 to <5 ng/mL and 5 ng/mL, respectively. 
One of the major disadvantages of the (mostly retrospective) studies to date is the lack of 
confirmation of the finding on the PSMA PET scan. Although the detection rates (defined as 
the number of positive scans/all included patients) are reported, it is not known if every positive 
scan is a True Positive (TP) scan. Ideally, both the positive predictive value (PPV) and the 
Correct Detection Rate (CDR) of PET findings should be known. The CDR is defined as the 
percentage of all patients scanned who have at least one TP lesion (localized correspondence 
between rhPSMA-7.3 (18F) PET imaging and the reference standard) regardless of any 
coexisting False Positive (FP) findings. Unfortunately, in the Fendler (2019) study, 
confirmation of the positive scans was only obtained in 217 out of 635 patients. Therefore, the 
PPV and CDR cannot be determined for the entire study population. 
Based on data from the retrospective chart review, data from the Fendler (2019) study, and 
from a comprehensive review of the literature, the influence of the PSA level at the time of 
scanning on detection rate and diagnostic performance cannot be underestimated.  
 ng/mL, detection rates can range from 64% to over 
90% (Perera 2019), with an average of 85%. In this multi-center US study of rhPSMA-7.3 (18F) 
(without the selection bias of many of the studies referenced by Perera [2019]), an estimated 
 ng/mL. Fendler 
(2019) reported PPVs of 92% (composite Standard of Truth [SoT]) and 84% (histopathologic 
SoT) in patients with median PSA levels of 3.5 and 3.9 ng/mL, respectively. It is expected, 
with a composite SoT including both histopathology (when available) and 18F-fluciclovine PET 
imaging (in cases without histopathology) to achieve a PPV of approximately 80% in this 
subpopulation. 

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However, in patients with a PSA level >0.2 to <1 ng/mL, PSMA scans can show detection rates 
between 46% and 63% (Perera 2019), with an average of 56%. A detection rate of 57% was 
reported by Fendler (2019) in patients with a PSA level of 0.5 to <1 ng/mL; this fell to 38% 
for patients with a PSA level <0.5 ng/mL. Therefore, an estimated overall detection rate of 
seen on PSMA PET imaging are TP will be challenging in this subgroup, since these lesions 
may be small, prone to biopsy error, and not yet visible on other diagnostic imaging techniques. 
In patients with PSA levels <1 ng/mL and histopathologic data, the PPV is likely to be well 
below the 92% reported by Fendler (2019) for a group of patients with a median PSA level of 
3.9 ng/mL. Additionally, no patients in this subgroup will have an intact prostate amenable to 
biopsy and we might expect only ~50% concordance between one example imaging reference 
standard test - 18F-fluciclovine - and PSMA PET-positive patients (Calais 2019). Therefore, 
the PPV (using histopathology or conventional/confirmatory imaging as the SoT) is expected 
to be low, at approximately 65%. It is important to note that PSMA PET may be a more 
sensitive way of demonstrating disease in men with recurrent PCa, as compared to conventional 
imaging-based SoT (Perera 2016). Importantly, the overall PPV will also likely be decreased 
by patients with multiple PSMA PET-positive regions given histological confirmation of 
multiple lesions in the same patient is highly unlikely. 
Most trials investigating diagnostic PSMA ligands have thus far focused on those patients with 
prior negative conventional imaging. Going forward in routine clinical care, given the low 
sensitivities of these conventional imaging procedures, it is difficult to continue to support 
subjecting patients to two or three non-sensitive imaging procedures before the patient may 
receive a more sensitive one. Based on the retrospectively determined high sensitivity of PSMA 
ligands (Afshar-Oromieh 2015; Eiber 2015; Afshar-Oromieh 2017), this study is designed to 
establish the performance of rhPSMA-7.3 (18F) PET irrespective of the findings of 
conventional imaging in order to support the use of rhPSMA-7.3 (18F) as an imaging option 
during the initial workup of these patients. This study will do so acknowledging the limitations 
of obtaining proof of true-positivity of the PSMA-positive lesions given the difficulties of 
obtaining histopathology in all patients and the relative insensitivity of other imaging 
modalities. Therefore, CDR and PPV are set at reasonable threshold levels, accounting for the 
limitations of the SoT and consid
performance. 
2.1 
Risk-benefit Assessment 
2.1.1 
Benefits 
The rhPSMA-7.3 (18F) PET scans may provide further clinical information regarding the 
by routine clinical testing. If such 
information arises, this will be reported back to the responsible clinician to help direct the 
 
2.1.2 
Risks 
The risks from the imaging studies to patients mainly relate to the IV injection and the radiation 
emitted by the radiopharmaceutical and the CT transmission scan (when the PET scan is 
acquired on a PET/CT scanner). Intravenous injection carries a small risk of infection and 
hematoma. 
rhPSMA-7.3 (18F) is currently being formally evaluated by Blue Earth Diagnostics Ltd. in a 
Phase 1, open-label study designed to assess the safety, biodistribution, and internal radiation 
dosimetry of rhPSMA-7.3 (18F) injection in healthy volunteers, and to assess safety and 

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investigate the imaging characteristics in patients with PCa (Study BED-PSMA-101; 
EudraCT No. 2018-004703-39). The biodistribution and internal radiation dosimetry of 18F 
following the IV administration of rhPSMA-7.3 (18F) injection have been assessed in a cohort 
of six healthy adult volunteers (three male and three female; aged 25 to 64 years; all White). 
Subjects were scanned at intervals for up to 4 hours post-injection, with radioactivity in blood, 
urine, and organs of interest measured at each timepoint. The mean administered dose of 
radioactivity was 220 MBq. 18F excretion into urine was 7.7% of the administered activity at 
111 minutes post-injection. The three organs or tissues with the highest mean initial uptake of 
18F were liver, heart content, and cortical bone. The critical organs (i.e. those with the highest 
absorbed dose per unit administered activity) were the adrenals (0.1835 mGy/MBq), the 
kidneys (0.1722 mGy/MBq) and the submandibular glands (0.1479 mGy/MBq). The mean 
effective dose per unit administered activity was 13.8 µSv/MBq with a 1-hour voiding interval 
and 14.1 µSv/MBq with a 3.5-hour voiding interval. Based on these data, an injection of 8 mCi 
(296 MBq) would result in a favorable radiation effective dose of less than 5 mSv. 
No serious adverse events (SAEs) were reported and no adverse events (AEs) led to subject 
withdrawal from the study. A total of five AEs were reported in two subjects (gastroenteritis, 
focal liver lesion, headache, and dizziness for one subject and headache for a second subject). 
All events, except one case of headache, were considered unrelated to study treatment and all 
events, except the case of focal liver lesion, resolved or recovered. 
In the current study, the maximum effective dose due to the CT transmission scan on a PET/CT 
scanner will vary from site-to-site, but as a guide a dose of 7 mSv would be expected. The 
effective dose due to the CT acquisition will be in accordance with ALARA (As Low As 
Reasonably Achievable) principles. The estimated total dose of 12 mSv (PET and CT 
transmission scan) is in line with other common nuclear medicine procedures. 
If rhPSMA-7.3 (18F) PET shows one or more sites of recurrence and if clinically feasible, the 
most accessible lesions(s) will be biopsied under radiological guidance. 
A CT-guided biopsy may be required in these patients; mean effective doses of between 4.3 to 
13.9 mSv have been reported (Guberina, 2018) during CT-guided biopsies and is dependent on 
the organ region and CT-scanner generation. A biopsy will cause discomfort and pain and may 
incidentally lead to complications, like prolonged bleeding at the site of the biopsy or infection.  
Confirmatory imaging may include the use of diagnostic CT or PET (see Section 9.1.6). 
Examples of effective doses from such procedures are as follows: abdominal/pelvic CT 6 to 
8 mSv (McCollough, 2015); chest CT 7 mSv (McCollough, 2015); 18F-sodium fluoride (NaF) 
PET 8.9 mSv (Beheshti, 2015); Axumin (18F-Fluciclovine) PET 8 mSv (Axumin USPI; 
Axumin SmPC). 
As with all imaging techniques there is the risk that the PET scan may provide a FP image 
(giving the appearance of cancer) in sites where it is not present, due to other events in the body 
or False Negative (failing to detect a nidus of cancer). Thus, patients should continue to be 
reviewed and may require other investigations, to confirm scan findings. 
As described in Section 1.2, as of 15 February 2019, rhPSMA-7.3 (18F) has been administered 
 men with known or 
suspected PCa, including 285 patients with BCR of PCa after radical prostatectomy (RP) and 
radiation therapy (RT)/brachytherapy. Although 35 out of 146 patients with documents in their 
electronic medical records within 30 days after rhPSMA-7.3 (18F) injection had AEs or SAEs, 
there were no reports of adverse reactions or serious adverse reactions attributed to injection of 
rhPSMA-7.3 (18F) (Study BED-PSMA-403). 

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3 
STUDY OBJECTIVES 
3.1 
Primary Objective 
The primary objective of the study is to assess the patient level CDR and region level PPV of 
rhPSMA-7.3 (18F) PET for BCR of PCa using histopathology or imaging as a SoT. The CDR 
is defined as the percentage of all patients scanned who have at least one TP lesion (localized 
correspondence between rhPSMA-7.3 (18F) PET imaging and the reference standard) 
regardless of any coexisting FP findings. When determining the region level PPV, all 
rhPSMA-7.3 (18F) PET-positive regions will be categorized as TP or FP regions using 
histopathology or imaging. 
3.2 
Secondary Objectives 
The secondary objectives of the study are to: 
1.
Assess the patient level CDR and region level PPV of rhPSMA-7.3 (18F) PET in the 
subgroup of patients who have negative baseline conventional imaging. 
2.
Assess the patient level CDR and region level PPV of rhPSMA-7.3 (18F) PET separated 
into subgroups of patients with reference standard histopathology available and 
unavailable. 
3.
Assess the patient level CDR and region level PPV of rhPSMA-7.3 (18F) PET stratified 
by PSA level. 
4.
Assess the CDR of rhPSMA-7.3 (18F) PET on a region level. 
5.
Assess the impact of rhPSMA-7.3 (18F) results on the intended clinical management of 
study participants using a clinician survey. 
6.
Assess the inter- and intra-reader agreement of rhPSMA-7.3 (18F) scan interpretation by 
the blinded independent readers. 
7.
Assess the safety of rhPSMA-7.3 (18F) injection in patients. 
3.3 
Exploratory Objectives 
The exploratory objectives of the study are to:  
1.
Assess the overall detection rate (without SoT confirmation) on a patient level and 
including detection rate subgroup analyses of patients: a) who have negative baseline 
conventional imaging, b) with reference standard histopathology available and 
unavailable, and also detection rate stratified by PSA level and assessed by region. 
2.
Assess the patient level PPV in which a TP patient is defined as having at least one TP 
region, regardless of any coexisting FP regions. 
3.
Assess the impact of rhPSMA-7.3 (18F) PET on upstaging patients with BCR of PCa 
a) post-RP or b) post-RT compared to conventional imaging. 
4.
Assess patient and regional level detection rates of rhPSMA-7.3 (18F) PET. 
5.
Assess patient and regional level detection rates of rhPSMA-7.3 (18F) PET as a function 
of PSA, prior Gleason score, and PSA doubling time (PSAdt) in a) post-RP or 
b) post-RT patients. 

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4 
STUDY DESIGN 
4.1 
Study Overview 
This is a prospective, Phase 3, multi-center, single-arm, diagnostic imaging study designed to 
evaluate the safety and diagnostic performance of rhPSMA-7.3 (18F) PET ligand for imaging 
in men with suspected BCR of PCa based on elevated PSA following prior therapy. 
Given the different performance of PSMA ligands in patients with PSA levels <1 ng/mL versus 
 ng/mL, the patient population will be weighted to prevent overrepresentation of patients 
with a PSA <1 ng/mL. The proportion of patients with a PSA <1 ng/mL will be maximized at 
approximately 40%, consistent with the study population studied by Fendler (2019). Once 60% 
of the planned 190 positive cases have information, the proportion of patients with a PSA 
<1 ng/mL will be assessed. If this proportion exceeds 60% then investigators will be informed 
to stop further enrolment of this cohort (see Section 16.7).  
Patients with a diagnosis of BCR of PCa being worked up for re-staging and eligible for 
potential salvage treatment will be consented and enrolled. Patients will be screened at Visit 1 
to determine eligibility for the study up to 28 days (up to 45 days due to the Corona Virus 
Disease-19 [COVID-19] pandemic) before rhPSMA-7.3 (18F) PET imaging at Visit 2. Patients 
who meet all of the inclusion criteria and none of the exclusion criteria will be assigned a 
patient identifier (ID) and entered into the study at screening. Participation in this study does 
not replace conventional imaging required for staging as per local guidelines/standard of care. 
If not already completed within 90 days before Visit 1, standard of care conventional imaging 
will be performed following Visit 1 and up to 2 weeks after Visit 2 (Optional Visit 2(a)). 
Conventional imaging that has been performed at non-participating institutions will be 
accepted provided the scans are reviewed by the participating institution. Patients will be asked 
to provide historical imaging if available and if performed as part of their PCa care and 
follow-up. After enrollment (either before or after conventional imaging if not already 
completed), patients will receive an administered activity of 8 mCi (296 MBq) ± 20% 
rhPSMA-7.3 (18F), delivered as an IV bolus injection with a 10 mL fast 0.9% sodium chloride 
flush, followed by PET imaging. 
Note: Due to the COVID-19 pandemic, the screening/eligibility evaluation may take place on 
the day of rhPSMA-7.3 (18F) administration (with pre-screening via telephone), if necessary, 
to ensure the safety of enrolled patients (see Visit 1 and Visit 2 combined; Section 10.3). 
Alternatively, the time from Visit 1 (initial screening) to Visit 2 (rhPSMA-7.3 (18F) PET scan) 
may be extended up to 45 days due to the COVID-19 pandemic. 
If feasible, the patient will undergo image-guided biopsy of a PET-positive lesion(s) suspicious 
for recurrence of PCa within 45 days following rhPSMA-7.3 (18F) PET imaging (see 
Section 9.1.9).  
If necessary, confirmatory imaging (for SoT) will be performed within 45 days following 
rhPSMA-7.3 (18F) PET imaging or attempted biopsy according to the algorithm in Figure 3. If 
necessary, additional confirmatory imaging may be performed up to 90 days after rhPSMA-
7.3 (18F) PET. Note: in patients with multiple PET-positive regions, confirmation of at least 
one PET-positive lesion in each region is required either by biopsy/surgical resection or 
confirmatory imaging. Patients may receive salvage treatment following further consultation 
with their physician (outside the scope of this study). The salvage treatment prescribed will be 
recorded. If treatment consists of a surgical resection, the histology obtained will be correlated 
with rhPSMA-7.3 (18F) PET imaging. Follow-up confirmatory imaging utilized as part of the 
SoT assessment should 
eatment.  

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Note: due to the COVID-19 pandemic, biopsy and surgical procedures performed to obtain 
SoT histology and initial confirmatory imaging assessments (in patients not undergoing 
biopsy/resection) may be delayed up to Day 60 to ensure the safety (i.e., decreased potential 
exposure to severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) of enrolled 
patients. 
Safety (AEs and vital signs) will be monitored during the study. 
An overview of the study is provided in the study schema (Figure 1). 
4.2 
Key Assumptions 
Consistent with the data described in Section 2, the detection rate of rhPSMA-7.3 (18F) PET in 
 ng/mL is expected to be at least 75%. The anticipated PPV in this 
population is expected to be approximately 80%. Therefore, the expected CDR in this 
subpopulation is (75% × 80% =) 60%. 
However, in the subpopulation with a PSA level <1 ng/mL, the detection rate is expected to be 
approximately 45%. The PPV is expected to be lower too (approximately 65%), since it will 
be more difficult to obtain proof of the lesions detected (as outlined in Section 2). Therefore, 
the CDR in this subpopulation is estimated to be low at (45% × 65% =) 29%. 
It is planned to include approximately 40% of patients with a PSA level <1 ng/mL and 
approximately 60% with a PSA level 
 ng/mL. Therefore, it is anticipated that the study will 
demonstrate an overall detection rate of approximately 60%, an overall PPV of at least 73.5% 
(taking into account multiple positive regions is anticipated in a proportion of patients), and, 
hence, an overall CDR of 49% (point estimates). 
5 
CRITERIA FOR EVALUATION 
5.1 
Primary Efficacy Endpoints 
The co-primary endpoints for the study are the (1) patient level CDR defined as the percentage 
of all patients scanned who have at least one TP lesion (localized correspondence between 
rhPSMA-7.3 (18F) PET imaging and the reference standard) regardless of any coexisting FP 
findings and (2) region level PPV (defined as TP/{TP+FP}) of rhPSMA-7.3 (18F) PET. 
Histopathology (preferred method) or imaging will be utilized as the SoT (see Section 9.2). A 
lesion that is deemed positive for PCa based on rhPSMA-7.3 (18F) PET will be assessed using 
the algorithm described in Figure 3.  
5.2 
Secondary Endpoints 
The secondary endpoints for this study will be: 
1.
Patient level CDR and region level PPV of rhPSMA-7.3 (18F) PET in the subgroup of 
patients who have negative baseline conventional imaging. 
2.
Patient level CDR and region level PPV of rhPSMA-7.3 (18F) PET for recurrence in 
those patients with and without reference standard histopathology available. 
3.
Patient level CDR and region level PPV of rhPSMA-7.3 (18F) PET stratified by PSA 
level. 
4.
CDR of rhPSMA-7.3 (18F) PET in the following regions: local recurrence, pelvic lymph 
nodes, other. 

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5.
Percentage of patients in whom rhPSMA-7.3 (18F) PET imaging results changed the 
intended patient management (major and other changes). 
6.
Reader kappa statistics of rhPSMA-7.3 (18F) scan interpretation by the blinded 
independent readers. 
7.
Safety (AEs and vital signs) of rhPSMA-7.3 (18F) injection in patients. 
5.3 
Exploratory Efficacy Endpoints 
The exploratory endpoints for this study will be: 
1.
The overall patient level detection rate (without SoT confirmation), including detection 
rate subgroup analyses of patients: a) who have negative baseline conventional imaging, 
b) with reference standard histopathology available and unavailable, and detection rate 
stratified by PSA level and assessed by region. 
2.
Patient level PPV in which a TP patient is defined as having at least one TP region, 
regardless of any coexisting FP regions. 
3.
The number of positive rhPSMA-7.3 (18F) scans compared to conventional imaging in 
defined regions, leading to upstaging of the patient a) post-RP; b) post-RT. 
4.
Patient and regional level detection rates of rhPSMA-7.3 (18F) PET. 
5.
Patient and regional level detection rates of rhPSMA-7.3 (18F) PET as a function of PSA, 
prior Gleason score and PSAdt in a) post-RP; b) post-RT patients. 
5.4 
Safety Evaluations 
In all patients, safety evaluations will include AE monitoring and reporting from the time of 
informed consent throughout the study. 
Vital sign assessments will also be conducted at screening and pre- and post-IP administration 
on the day of rhPSMA-7.3 (18F) injection. 
6 
PATIENT SELECTION 
6.1 
Study Population 
Patients with BCR of PCa who meet all of the inclusion and none of the exclusion criteria will 
be eligible for participation in this study.  
6.2 
Inclusion Criteria 
1.
Patient willing to provide signed informed consent and willing to comply with all required 
study schedule events, where safe and feasible. 
2.
Patient is male and aged >18 years old. 
3.
Patient with a history of localized adenocarcinoma of the prostate with prior curative intent 
treatment, experiencing BCR of PCa potentially eligible for salvage therapy with curative 
intent, following prior treatment with one or more of the following: a) RP, b) RP plus 
adjuvant RT, c) RP plus adjuvant androgen deprivation therapy (ADT), d) external beam 
radiation therapy or e) focal gland therapies (e.g. brachytherapy, high-intensity focused 
ultrasound [HIFU]). 

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At least 6 weeks must have elapsed after RP.
If previously taking ADT, it should have been discontinued at least 16 weeks prior to 
screening. 
In the case of focal gland therapies (e.g. HIFU) and RT, the treatment will have 
occurred at least 1 year prior to screening. 
4.
An elevated PSA, clinically suspicious for biochemically recurrent disease, that meets one 
of the following conditions: 
Following RP with or without adjuvant or salvage therapy: PSA 0.2 ng/mL followed 
 ng/mL. 
Following RT (e.g. radical radiotherapy or brachytherapy) as the primary treatment: 
nadir +2 ng/mL. 
Following focal gland therapy (e.g. HIFU) as the primary treatment: nadir +2 ng/mL. 
5.
Patient willing to undergo biopsy for histological confirmation of rhPSMA-7.3 (18F) PET 
findings, where safe and feasible. 
6.3 
Exclusion Criteria 
1.
Patients with any medical condition or circumstance (including receiving an IP) that the 
investigator believes may compromise the data collected or lead to a failure to fulfil the 
study requirements. 
2.
Patients who are planned to have an x-ray contrast agent or other PET radiotracer 
<24 hours prior to the PET scan. 
3.
Patients currently receiving ADT (defined as surgical orchidectomy; luteinizing 
hormone-releasing hormone [LHRH] agonist alone [continuous or intermittent]; LHRH 
antagonist alone [continuous or intermittent]; administration or use of a first generation or 
second generation anti-androgen alone or in combination with an LHRH 
agonist/antagonist). 
4.
Patients participating in an interventional clinical trial within 30 days and having received 
an IP within five biological half-lives prior to administration of rhPSMA-7.3 (18F). 
5.
Patients with known hypersensitivity to the active substance or to any of the excipients of 
the IP. 
7 
CONCURRENT MEDICATIONS 
All patients should be maintained on the same medications without change throughout the 
entire study period, as medically feasible. 
Concomitant medications will be recorded at screening and any changes in administration will 
be noted. 
7.1 
Prohibited Medications 
The following medications are prohibited during the study and administration will be 
considered a protocol violation: 
X-ray contrast agent <24 hours prior to the rhPSMA-7.3 (18F) PET scan. 

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Any other PET imaging agent within 24 hours prior to the rhPSMA-7.3 (18F) PET scan.
The initiation of any targeted or systemic therapy should not occur until after definitive 
pathology (if feasible) is obtained satisfying the SoT assessment. 
8 
STUDY TREATMENTS 
As manufacturing and supply of IP will be site-specific, the Study Pharmacy Manual provides 
additional information for the IP (rhPSMA-7.3 [18F] injection).  
8.1 
Method of Assigning Patients to Treatment Groups 
Not applicable. This is a single-arm study. 
8.2 
Blinding 
The local sites will not be blinded and the patients will not be randomized to study treatment. 
All rhPSMA-7.3 (18F) PET images from all study sites will be submitted for a randomized, 
blinded image evaluation. 
The rhPSMA-7.3 (18F) images will be randomized and read by three blinded, independent 
central PET readers who have received specific training on rhPSMA-7.3 (18F) and are also 
blinded to results of conventional imaging. 
8.3 
Formulation of Test and Control Products 
8.3.1 
Formulation of Test Product 
The IP  rhPSMA-7.3 (18F)  is a PET imaging radiopharmaceutical formulated as a solution 
for injection. It is designed to target the extracellular epitope of the PSMA molecule and is 
administered as a single IV bolus microdose (i.e. the mass dose administered is less than 
100 µg/patient). 
The molecular structure of the drug substance comprises a PSMA binding motif, a peptide 
spacer, an 18F-radiolabeled silicon fluoride acceptor moiety and a gallium chelator complex 
(Figure 2, Section 1). 
Company Code: 
rhPSMA-7.3 (18F) 
Chemical Name: 
Gallium 2,2',2''-(10-((3S,7S,12R,26R,34S)-1,3,7,12,26,34-
hexacarboxy-29-((4-(di-tert-
buty-[18F]fluorosilyl)benzamido)methyl)-5,10,17,20,28,31-hexaoxo-
4,6,11,16,21,27,30-heptaazatetratriacontan-34-yl)-1,4,6,10-
tetraazacyclododecane-1,4,7-triyl)triacetate 
Molecular Formula: 
C63H9618FGaN12O25Si 
8.3.2 
Formulation of Control Product 
Not applicable. This is a single-arm study.  
8.3.3 
Packaging and Labeling 
rhPSMA-7.3 (18F) is supplied as a sterile, aqueous solution for IV administration. The product is 
supplied either in a multi-dose vial sealed with a synthetic rubber closure and aluminum overseal 
or in a single unit dose syringe depending on the manufacturing location. The product label will 

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be region-specific and will include the following information: batch number, product expiry 
date/time, total product volume (dispensed), radioactive concentration and/or total radioactivity 
(activity in mCi and/or MBq) and calibration date and time. 
8.4 
Supply of IP at the Site 
Each vial or syringe is transported in a lead or tungsten shield. The quality control analysis of a 
sample of the drug product may be performed in parallel with transportation of the drug product 
to the study site. The investigator (or nominated deputy) will receive release information for the 
drug product. Only product for which confirmation of release has been received shall be used. 
Where the product is transported as a single patient dose, the dose will be measured in a 
radionuclide dose calibrator before administration. Where the product is transported in its 
original container the volume of injection for each patient is calculated and withdrawn into a 
shielded syringe immediately before injection. The calculation is based on the radioactive 
content, the half-life of 18F (109.8 mins), the reference date and time, the prescribed dose and the 
time of injection. 
8.4.1 
Dispensing 
When the study site receives the dose and prior to administration, the activity in the syringe 
will be measured in a dose calibrator. Should the activity be less than 6.4 mCi (236 MBq) or 
the volume required exceed 10 mL (US sites) or 6 mL (European sites) undiluted material or 
the IP be past the expiry date and time, the scan should not be performed. The dose can be 
diluted in the syringe to a maximum volume of 10 mL with 0.9% saline (as required). After 
administration, residual radioactivity in the injection device shall be measured using a 
radionuclide dose calibrator.  
8.4.2 
Administration Instructions 
Patients will receive a dose with an administered activity of 8 mCi (296 MBq) ± 20% of 
rhPSMA-7.3 (18F), delivered as an IV bolus injection with a 10 mL fast 0.9% sodium chloride 
flush, followed by PET imaging. Full details are provided in the Study Imaging Manual. 
8.4.3 
Storage 
The shelf-life of rhPSMA-7.3 (18F) injection is up to 10 hours from the end of synthesis and the 
product must not be used beyond this limit. rhPSMA-7.3 (18F) injection should be stored at room 
temperature in a shielded container. 
All non-radioactive containers (shielding, transport cans) must be returned to the manufacturing 
site. Containers that are radioactive or that contained radioactive products must be disposed of at 
either the study site or another designated facility, with prior approval from the Sponsor, after 
the study and after overall drug accountability has been completed by the Sponsor or its 
representative. 
Waste must be disposed of according to Federal, State and local regulations for radioactive 
material. Imaging sites must comply with all applicable regulations. 
Precautions for the safe handling of radioactive materials should be observed. 

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8.5 
IP Accountability 
An accurate and current accounting of the dispensing and return/disposal of IP for each patient 
will be recorded on the Investigational Drug Accountability Record. The study monitor will 
verify this document throughout the course of the study. 
8.6 
Measures of Treatment Compliance 
Participants will receive the rhPSMA-7.3 (18F) injection under direct supervision of study 
personnel. Each administration volume and total radioactivity injected will be checked. The 
batch number and activity per administration (determined by the radioactivity in the injection 
device before and after administration, with measurement date and time) will be recorded in 
ocument. 
8.7 
End of Trial 
The end of the trial will be when the last blinded image evaluation has been completed and the 
database is locked. The end of patient participation is defined as when the last patient has 
completed all the study procedures and the results of the histology or imaging are available in 
order to satisfy the SoT. 
Any treatment for PCa will be in accordance with local PCa management policy and 
procedures. 
9 
STUDY PROCEDURES AND GUIDELINES 
A Schedule of Events representing the required testing procedures to be performed for the 
duration of the study is summarized in Appendix 1. 
Written informed consent will be obtained prior to conducting any study-related activities (see 
Section 18.3). Patients will provide written informed consent and be assessed for eligibility for 
study participation at screening (performed within 28 days before IP administration [or up to 
45 days due to the COVID-19 pandemic]). 
9.1 
Clinical Assessments 
9.1.1 
Concomitant Medications 
All concomitant medication and concurrent therapies will be documented at screening, with 
any changes in concomitant medication during the study recorded on the eCRF. The dose, 
route, unit frequency of administration, and indication for administration and dates of 
medication will be captured. 
9.1.2 
Demographics 
Demographic information (full/partial date of birth/age, gender, ethnicity/race, sex, height, 
weight, body mass index, as permitted by local regulations) will be recorded at screening. 
Weight will also be recorded pre-rhPSMA-7.3 (18F) PET.  
9.1.3 
Medical History 
Relevant medical history, including history of current disease, concomitant disease record, 
information regarding underlying diseases and family history of cancer will be recorded at 

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screening. A history of localized adenocarcinoma of the prostate with prior curative intent 
treatment must be confirmed at screening. 
9.1.4 
Vital Signs 
Vital signs (body temperature, blood pressure, pulse and respiration rates) will be performed 
after resting for 5 minutes at screening and pre- and post-rhPSMA-7.3 (18F) PET. 
Any clinically significant changes in vital sign measurements should be reported as an AE.  
9.1.5 
Conventional Imaging 
9.1.5.1 
Baseline Conventional Imaging 
Participation in this study does not replace conventional imaging required for staging as per 
local guidelines/standard of care. Conventional imaging may include: planar and/or 
single-photon emission CT bone scan (99mtechnetium-hydroxydiphosphate [99mTc-HDP], 
99mtechnetium-methyldiphosphonate 
[99mTc-MDP] 
per 
institution 
preference), 
abdominal/pelvic CT or MRI, chest CT per institution preference, or PET with (18F-NaF or 
Axumin). Conventional imaging that has been performed within 90 days prior to enrollment at 
non-participating institutions will be accepted provided the scans are reviewed by the 
participating institution. 
If not already completed within 90 days before enrollment, conventional imaging will be 
performed at the study site, between Visit 1 and up to 2 weeks following the rhPSMA-7.3 PET 
scan according to site standard of care. 
Note: contrast-enhanced CT/MRI and radiopharmaceutical-based baseline conventional 
imaging (performed as per local standard of care) should be performed at least 24 hours apart 
from the investigational rhPSMA-7.3 (18F) PET scan. 
9.1.5.2 
Historical Conventional Imaging 
Historical conventional imaging, acquired more than 90 days before Visit 1, if available and if 
PCa staging and treatment in the prior ~24 months, can be 
used to establish SoT where a biopsy cannot be obtained.  
Patients will be asked to provide these pre-existing images, if these were done at another 
institution. If done at the study site, these images will be made available by the study site.  
9.1.6 
Confirmatory Imaging 
In cases where historical conventional imaging is not available or inconclusive for comparison 
to baseline imaging, rhPSMA-7.3 (18F) directed (for confirmation of lesion location only) 
follow-up confirmatory imaging of the site(s), will be acquired at the discretion of the local 
investigator(s), with reference to the Study Imaging Manual. Examples of confirmatory 
imaging modalities include specific body region MRI (including functional or multi-parametric 
MRI), CT, Axumin, NaF, etc (see Sections 9.2.2.2 and 9.2.2.3). 
9.1.7 
rhPSMA-7.3 (18F) PET Scan 
After enrollment (either before or after conventional imaging; see Section 9.1.5), all patients 
will receive an IV bolus of rhPSMA-7.3 (18F) injection and undergo a PET scan as described in 
the Study Imaging Manual.  

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9.1.8 
Image Interpretation 
For biopsy/SoT confirmation guidance: 
Due to logistical and medical liability considerations, results of the image interpretation 
by local site readers must be used when patients are triaged for invasive biopsy 
procedures. rhPSMA-7.3 (18F) PET imaging will be interpreted by on-site readers who 
have received specific training on rhPSMA-7.3 (18F). 
For determination of the primary endpoint: 
rhPSMA-7.3 (18F) PET images will be blinded, randomized, and read by three trained 
independent central PET readers who have received specific training on rhPSMA-7.3 
(18F) scans and are blinded to results of conventional/confirmatory imaging. 
9.1.9 
Biopsy/Surgery 
If rhPSMA-7.3 (18F) PET shows one or more sites of recurrence, the most accessible and 
feasible* (as judged by the local investigator) lesion(s) will be biopsied under radiological 
guidance. In patients with multiple rhPSMA-7.3 PET-positive regions, attempt should be made, 
where safe and medically feasible, to obtain histopathology on the most accessible and feasible 
lesion(s) in each region (prostate bed, pelvic lymph nodes, and other [bone, extra-pelvic lymph 
nodes, viscera and other soft tissues]).  
*Note: in addition to patient safety, assessment of feasibility may include location, but also 
lesion size, where a minimum size may be needed to avoid excessive sampling error on biopsy; 
soft tissue lesions will be preferred over bone lesions due to the higher likelihood of non-
diagnostic bone biopsies (Didolkar 2013; Yang 2010). 
In cases where a patient will undergo a lymph node dissection or other surgical procedure 
(resection of the PET-positive lesion(s)) as part of their standard of care, a biopsy prior to the 
surgical procedure is not required. The histology obtained following surgery will serve as the 
SoT. The removed surgical samples will be carefully correlated to rhPSMA-7.3 (18F) PET and 
the conventional imaging technique(s). 
In cases where a biopsy is not feasible or refused by the patient, then specific imaging may be 
used, to confirm positivity of the finding on rhPSMA-7.3 (18F) PET (see below Steps 2 to 4; 
Sections 9.2.2.1, 9.2.2.2 and 9.2.2.3). Histopathology remains the preferred SoT.  
9.2 
SoT 
One of the following will determine SoT: If a positive lesion on PET is confirmed by one of 
the Steps (1 to 4) listed below, the lesion will be considered TP. When determining the CDR 
on a patient level, a patient will be categorized as a TP if there is at least one TP lesion 
confirmed in one body region (prostate bed, pelvic lymph nodes, or other extra-pelvic sites 
[bone, viscera, lymph nodes and soft tissues]) on rhPSMA-7.3 (18F) PET. For the primary 
analysis, pelvic lymph nodes will include the right and left external iliac, obturator, hypogastric 
(internal iliac), perirectal and presacral lymph node groups.  
Notes:  
a.
In patients with multiple PET-positive regions, confirmation of at least one PET-positive 
lesion in each region is required either by biopsy/surgical resection or confirmatory 
imaging in order to calculate the region level PPV for the efficacy analyses. 
b.
In patients with multiple lesions in a specific region, the presence of one TP lesion 
determines truth for the region regardless of any concurrent FP findings in the same region. 

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Therefore, multiple PET-positive lesions can be evaluated in a specific region in order to 
confirm at least one TP. 
9.2.1 
Step 1: Histological SoT 
Histological confirmation, whenever possible: 
a)
Of PET-positive lesion. 
b)
Of surgically removed sample. 
c)
Re-biopsy (in case of inconclusive histology) or biopsy of a second lesion will be allowed. 
If histology is not available or determined non-diagnostic (and re-biopsy not possible) then 
proceed with imaging confirmation as described below (Steps 2 to 4). If biopsy histology is 
negative, then images acquired during the procedure will be reviewed by local readers to ensure 
the targeted tissue was sampled. If local readers determine the biopsy placement was correct, 
then the biopsy results will stand. If local readers determine the targeted tissue was missed 
during the biopsy procedure, then either a re-biopsy will be performed or the following steps 
will also be undertaken to verify rhPSMA-7.3 (18F) images.  
9.2.2 
Imaging as Standard of Truth (Steps 2 to 4) 
Imaging as SoT should include a longitudinal assessment of all available conventional and 
confirmatory imaging scans. Any change over time at the PET-positive site (upon review of all 
available imaging) suggestive of the presence of cancer is accepted as the SoT. A change 
suggesting the disappearance of disease at the PET-positive site following treatment will also 
be accepted as the SoT (objective criteria defined in the study Independent Review Charter).  
9.2.2.1 
Step 2: Historical and Baseline Conventional Imaging SoT 
If historical conventional imaging (as defined in Section 9.1.5.2) had been acquired prior to 
PCa management, then 
these images can be used along with baseline to establish the SoT.  
Where historical conventional imaging (e.g. CT, MRI, bone scan, PET) is available that could 
be relevant to confirmation of an identified rhPSMA-7.3 (18F) PET-positive lesion then as 
many prior imaging series as practical (from approximately the last 2 years) should be made 
available to the central reviewers. 
In cases where historical imaging and baseline conventional imaging are deemed sufficient (by 
local site reader) for SoT determination, then this will be acceptable, and follow-up 
confirmatory imaging (Steps 3 and 4) will not be needed. 
9.2.2.2 
Step 3: Confirmatory Imaging SoT (up to 45 Days Post-rhPSMA-7.3 (18F) PET) 
In cases where historical conventional imaging is not available or inconclusive for comparison 
to baseline imaging, rhPSMA-7.3 (18F) directed (for confirmation of lesion location only) 
follow-up confirmatory imaging of the site(s), will be acquired. Confirmatory imaging will be 
acquired at the discretion of the local investigator(s), with reference to the Study Imaging 
Manual.  

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9.2.2.3
Step 4: Additional Confirmatory Imaging SoT (up to 90 Days Post-rhPSMA-7.3 
(18F) PET) 
If in the opinion of the local investigator(s) the above imaging Steps 2 or 3 do not allow SoT 
verification, then a final follow-up, rhPSMA-7.3 (18F) PET directed (for confirmation of lesion 
location only) confirmatory imaging scan can be obtained up to 90 days post rhPSMA-7.3 (18F) 
PET.  
Reading of conventional and confirmatory imaging to determine the next steps in the 
confirmation process will be performed locally.  
Both the rhPSMA-7.3 (18F) PET scans and all available conventional and confirmatory imaging 
scans acquired under Steps 2 to 4 above will be read centrally for the primary endpoint 
assessment, according to Table 1 and Figure 3 below. Three central reviewers will review all 
submitted imaging and reach consensus on the nature of the target lesion. Reads of the 
confirmatory imaging as SoT will be directed by rhPSMA-7.3 (18F) PET findings (for 
confirmation of lesion location only). A brief summary of clinical information will be available 
to the readers (e.g. 67-year-old male post-RP with PLND and adjuvant pelvic RT 5 years 
before; PSA rising to 1.2 ng/mL prior to rhPSMA scan; PSAdt 9 months). Readers will be 
blinded to all other information. Further details are given in the study Independent Review 
Charter. 
rhPSMA-7.3 (18F) positive target lesions will be categorized as positive, negative or 
indeterminate by consensus central read of all available imaging when histological 
confirmation is not available. Indeterminate classifications will be categorized as False 
Positives for the primary analysis. Further details are given in the study Independent Review 
Charter. 
If a positive lesion on rhPSMA-7.3 (18F) PET suspicious for PCa recurrence is confirmed by 
SoT, the lesion will be considered a TP. For the primary efficacy analysis, a region will be 
categorized as a TP if there is at least one TP lesion confirmed in that body region (prostate 
bed, pelvic lymph nodes, or other extra-pelvic sites) on rhPSMA-7.3 (18F) PET. For the primary 
analysis, pelvic lymph nodes will include the right and left external iliac, obturator, hypogastric 
(internal iliac), perirectal and presacral lymph node groups.  
If all above SoT techniques fail to positively confirm the PET-positive lesion(s), the rhPSMA-
7.3 (18F) PET lesion will be deemed FP. 

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Table 1: 
Central Reading Plan 
Imaging 
Modalities 
Image Interpretation 
# readers 
Read Criteria 
rhPSMA-7.3 
rhPSMA-7.3 
PET 
Blinded, independent, central 
reads 
3 
Further details are given 
in the Study Independent 
Review Charter  
Conventional 
(Baseline and 
Historical) and 
Confirmatory 
Imaging as SoT 
Conventional: 
Pelvic CT or 
MRI, bone 
scan, chest 
CT, Axumin. 
 
Confirmatory: 
Examples 
include 
specific body 
region MRI 
(including 
functional or 
multi-
parametric 
MRI), CT, 
Axumin, NaF 
PET, etc. 
rhPSMA-7.3 directed image 
re-reads. A brief summary of 
clinical information will be 
available to the readers  
(e.g. 67 year old male post-RP 
with PLND and adjuvant 
pelvic RT 5 years before; 
PSA rising to 1.2 ng/mL prior 
to rhPSMA scan; 
PSAdt 9 months). 
Readers will be blinded to all 
other information. 
3 via 
consensus
Longitudinal assessment 
of all available 
conventional and 
confirmatory imaging 
scans per standard of 
care / society guidelines. 
Further details are given 
in the study Independent 
Review Charter. 
Specifically allowing, 
for example: 
a) sub-cm changes in LN 
size on CT during 
progression/therapy 
response to be indicative 
of cancer or  
b) small bone CT 
scleroses to be indicative 
of cancer 
CT=computed tomography; 18F=fluorine-18; LN=lymph node; MRI=magnetic resonance imaging; NaF=sodium fluoride; 
PET=positron emission tomography; PLND=pelvic lymph node dissection; PSA=prostate-specific antigen; 
PSAdt=prostate-specific antigen doubling time; rhPSMA=radiohybrid prostate-specific membrane antigen; RP=radical 
prostatectomy; RT=radiation therapy. 

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Figure 3:
Standard of Truth Algorithm (to be Applied for Each PET-positive 
Region)
18F=fluorine-18; FP=False Positive; PET=positron emission tomography; PPV=positive predictive value; 
rhPSMA=radiohybrid prostate-specific membrane antigen; TP=True Positive.
Notes: 
a) In patients with multiple PET-positive regions, confirmation of at least one PET-positive lesion in each region is 
required either by biopsy/surgical resection or confirmatory imaging in order to calculate the region level PPV for the 
efficacy analyses. 
b) In patients with multiple lesions in a specific region, the presence of one TP lesion determines truth for the region 
regardless of any concurrent FP findings in the same region. Therefore, multiple PET-positive lesions can be evaluated 
in a specific region in order to confirm at least one TP.
9.2.3
Post-scan Treatment Options
Patients may receive salvage treatment following further consultation with their physician
(outside the scope of this study). The salvage treatment prescribed will be recorded. If treatment 
consists of a surgical resection, the histology obtained will be correlated with rhPSMA-7.3 
(18F) PET imaging. Follow-up confirmatory 
Positive lesion on 
rhPSMA-7.3 (18F) PET 
scan
Histological 
confirmation 
(Step 1)
True Positive or 
False Positive
No histology
Histology not available 
or inconclusive 
Baseline (and if available, 
Historical) conventional 
imaging evaluations 
(Step 2)
True Positive or 
False Positive
True Positive or 
False Positive
Confirmatory imaging 
evaluations 
(Step 3)
Above conventional imaging 
not available or inconclusive
Additional confirmatory 
imaging evaluations 
(Step 4)
Above steps 
inconclusive
True Positive or 
False Positive

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9.2.4 
Clinical Management 
The impact of the rhPSMA-7.3 (18
management will be assessed by means of both a pre-PSMA PET scan (completed prior to 
rhPSMA-7.3 (18F) imaging) and post-PSMA PET scan clinical utility questionnaire, in which 
the investigator will record 
the rhPSMA-7.3 (18F) PET scan. 
9.2.5 
Adverse Events 
AEs will be captured for all patients throughout the study. AEs will be monitored and recorded 
from the time of informed consent until the last study visit. Duration (start and stop dates and 
times), severity/grade, outcome, treatment and relationship to IP will be recorded on the eCRF. 
Patients who experience an SAE or an AE which developed within 3 days of rhPSMA-7.3 (18F) 
PET and that persists at the final visit will be followed until resolution or stabilization of these 
events is recorded.  
9.3 
Clinical Laboratory Measurements 
Not applicable. 
10 
EVALUATIONS BY VISIT 
10.1 
Visit 1 (Screening; Day -28 [Within 28 Days Before IP Administration]) 
1.
Review the study with the patient and obtain written informed consent and Health 
Insurance Portability and Accountability Act (HIPAA) authorization (or equivalent, as 
required), if appropriate. 
2.
Assign the patient a unique screening number. 
3.
Review eligibility criteria and confirm patient suitability for enrollment. 
4.
Record demographics data. 
5.
Record medical history and concomitant disease record, including confirmation of a 
history of localized adenocarcinoma of the prostate with prior curative intent treatment. 
6.
Record concomitant medications. 
7.
Perform and record vital signs (omit if Visit 1 and Visit 2 are combined; see 
Section 10.3). 
8.
Commence AE monitoring.  
9.
Schedule patient for conventional imaging (to take place following Visit 1 and up to 
2 weeks after Visit 2) if historical conventional imaging took place greater than 90 days 
before Visit 1.  
Notes: 
a.
Conventional imaging that has been performed at non-participating institutions will 
be accepted provided the scans are reviewed by the participating institution. 
b.
Contrast-enhanced CT/MRI and radiopharmaceutical-based baseline conventional 
imaging (performed as per local standard of care) should be performed at least 
24 hours apart from the investigational rhPSMA-7.3 (18F) PET scan. 

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10. Schedule patient for Visit 2 within 28 days of consent.
Note: Due to the COVID-19 pandemic, the screening/eligibility evaluation may take place 
on the day of rhPSMA-7.3 (18F) administration (with prior pre-screening via telephone) if 
necessary to ensure the safety of enrolled patients (see Visit 1 and Visit 2 combined; 
Section 10.3). Alternatively, the time from Visit 1 (initial screening) to Visit 2 (rhPSMA-
7.3 (18F) PET scan) may be extended up to 45 days due to the COVID-19 pandemic. 
10.2 
Visit 2 (Day 1; IP Administration) 
1.
Record any changes in concomitant medication since screening (omit if Visit 1 and 
Visit 2 are combined; see Section 10.3). 
2.
Perform and record pre-IP administration vital signs. 
3.
-IP administration. 
4.
Ask about and record any AEs since screening (omit if Visit 1 and Visit 2 are combined; 
see Section 10.3). 
5.
IP administration (IV bolus rhPSMA-7.3 [18F] injection). 
6.
PET scan as described in the Study Imaging Manual. 
7.
Record any AEs occurring during the scan process. 
8.
Perform and record post-IP administration vital signs. 
9.
Schedule patient for Visit 3 within 7 days post-IP administration. 
Optional Visit 2(a): If not already performed, obtain baseline conventional imaging up to 
2 weeks following IP administration. Any conventional imaging performed up to 90 days 
prior to Visit 1 and up to and including Visit 2(a) will be considered baseline conventional 
imaging. 
10.3 
Visit 1 and Visit 2 Combined (Day 1; IP Administration)  
Due to the COVID-19 pandemic, Visit 1 and Visit 2 may be combined (named Visit 1 and 
Visit 2 combined ) if judged by the investigator to be necessary to decrease potential exposure 
to SARS-CoV-2 for patients. 
If Visit 1 and Visit 2 are combined, please complete all the procedures listed under Visit 1 and 
Visit 2 (Sections 10.1 and 10.2, respectively) after obtaining written informed consent. Omit 
those procedures identified as not being required if combining visits.  
Notes: Visit 1 and Visit 2 combined requires pre-screening via telephone contact prior to Day 1 
to review the study eligibility criteria, obtain initial consent (remote consent is acceptable if 
permitted under local regulations and approvals), to promote study visit compliance and to 
ensure patient understanding of the combined study visit and planned IP administration, as well 
as ask about baseline and historic conventional imaging that may already have been performed 
or needs to be scheduled (note above requirement regarding standard of care baseline 
conventional imaging).  
At sites where IP is not manufactured on-site, IP should be ordered prospectively at least 5 days 
in advance in accordance with the IP Supply Manual. 
For sites with on-site manufacturing, the visits may be combined if mutually agreed by the 
Radiopharmacy and investigator even post-COVID-19 pandemic restrictions.  

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Optional Visit 2(a): should still be arranged if required when combining Visit 1 and Visit 2.
Any conventional imaging performed up to 90 days prior to screening and up to and including 
2 weeks post-combined Visit 1 and Visit 2 will be considered baseline conventional imaging. 
10.4 
Visit 3 (up to 7 Days Post-visit 2; Follow-up Visit) 
1.
Perform clinical review (AE collection and discussion of rhPSMA-7.3 [18F] PET imaging 
results). 
2.
Record any AEs and changes in concomitant medication since Visit 2. 
Note: Visit 3 may be performed by an appropriately licensed and credentialed clinician 
and can be conducted by telephone per 
 
10.5 
Follow-up Procedures (Within 45 Days Following IP Administration) 
1.
Obtain image-guided biopsy of PET-positive lesion(s), if feasible. 
2.
If surgical resection is planned, record date and make arrangements for obtaining 
histology results. 
3.
Ensure available Historical and Baseline Conventional Imaging has been performed and 
reviewed by Site Investigator. 
4.
Obtain confirmatory imaging, if indicated, as per algorithm.  
5.
Record treatment 
PCa recurrence. 
6.
Record any AEs and change in concomitant medication. 
Note: due to the COVID-19 pandemic, biopsy and surgical procedures performed to obtain 
SoT histology and initial confirmatory imaging assessments (in patients not undergoing 
biopsy/resection) may be delayed up to Day 60 to ensure the safety (i.e., decreased 
potential exposure to SARS-CoV-2) of enrolled patients. 
10.6 
Secondary Follow-up Procedures (46 to 90 Days After IP Administration) 
1.
Obtain additional confirmatory imaging if necessary, up to 90 days after rhPSMA-7.3 
PET imaging. Follow-up confirmatory imaging should 
 
2.
If surgical resection has been performed, correlate pathology findings with rhPSMA-7.3 
(18F) PET imaging. 
3.
Record any salvage treatment since IP administration. 
4.
Record any AEs and change in concomitant medication. 
Note: due to the COVID-19 pandemic, investigators should carefully consider the timing 
of confirmatory imaging procedures (when histology is not available) and are encouraged 
potential exposure to SARS-CoV-2 by combining follow-up visits 
for multiple confirmatory imaging scans, when feasible. 
10.7 
Early Withdrawal 
Patient participation in the study is entirely voluntary and patients may refuse to participate or 
withdraw from the trial, at any time, without prejudice to their future care. 

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Although patients are not obliged to give a reason(s) for premature withdrawal, the investigator 
rights. 
All withdrawals and dropouts of enrolled patients from the study should be reported and 
explained on the eCRF. 
Dropouts who fail to complete all study procedures, for reasons other than due to adverse 
reactions/AEs deemed related to IP, will be withdrawn from the study and replaced. No more 
than 15% of patients enrolled will be replaced (see Section 13.2). 
11 
IMAGING PROTOCOL 
11.1 
PET Scanner 
A dedicated hybrid PET scanner (e.g. PET/CT) is mandatory. The selected PET scanner must be 
qualified by the study management team. Full details are in the Study Imaging Manual (aka 
Technical Operations Manual). 
11.2 
rhPSMA-7.3 (18F) Injection Administration 
A venous cannula will be inserted and the patient will receive an administered activity of 8 mCi 
(296 MBq) ± 20% rhPSMA-7.3 (18F) injection diluted up to 10 mL. The administration will be 
injected via the cannula with arms down, as an IV bolus injection followed by 10 mL flush with 
normal saline solution. The participant will then be positioned supine in the scanner, with the 
arms above the head (if possible), and will be scanned as described in the Study Imaging Manual. 
The time from the end of injection of rhPSMA-7.3 (18F) to the start of imaging will be between 
50 to 70 minutes.  
Full details are in the Study Imaging Manual. 
11.3 
rhPSMA-7.3 (18F) PET Acquisition 
For the PET acquisition, patients will be imaged for approximately 20 minutes. For the CT 
acquisition (if acquired on a PET/CT scanner), an unenhanced (no IV contrast) CT will be 
employed. Further details on the PET acquisition are given in the Study Imaging Manual. 
11.4 
Image Transfer 
Following the completion of PET imaging at the study site, the scan data will be sent to the 
Invicro Imaging Core Lab (Invicro, LLC) using either the iPACS software or on physical media 
by courier. Full details are in the Study Imaging Manual. 
11.5 
rhPSMA-7.3 (18F) Image Reads 
All local and central readers will undergo training in interpretation of rhPSMA-7.3 (18F) PET 
scans, and will have a training set available for reference. Primary evaluation and reporting of 
the PET scan will be based on the site-based local read (as per standard of care).  

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12 
ADVERSE EVENT REPORTING AND DOCUMENTATION 
12.1 
Adverse Events 
An AE is any untoward medical occurrence in a clinical investigation of a patient administered 
a pharmaceutical product and that does not necessarily have a causal relationship with the 
treatment. An AE is therefore any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom or disease temporally associated with the administration of an 
IP, whether or not related to that IP. An unexpected AE is one of a type not identified in nature, 
severity, or frequency in the current rhPSMA-7.3 (18F) IB or of greater severity or frequency 
than expected based on the information in the rhPSMA-7.3 (18F) IB. 
The investigator will probe, via discussion with the patient, for the occurrence of AEs during 
 AEs will be recorded in 
the patient eCRF. AEs will be described by duration (start and stop dates and times), 
severity/grade, outcome, treatment and relationship to IP, or if unrelated, the cause. 
12.1.1 
Severity of Adverse Events 
Version 5 (2017) will be used to assess and grade event severity, including laboratory 
abnormalities judged to be clinically significant. The severity grading is provided below 
(Table 2).  
Table 2: 
CTCAE (V5) AE Severity Grading 
Severity (Toxicity Grade) 
Description 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated. 
Grade 2 
Moderate; minimal, local or non-invasive intervention indicated; limiting 
age-appropriate instrumental ADL.* 
Grade 3 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
self-care ADL**. 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
Grade 5 
Death related to AE 
ADL=activities of daily living; AE=adverse event; CTCAE=Common Terminology Criteria for Adverse Events. 
* 
Instrumental ADL refer 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 
bedridden.  
If the experience is not covered in the CTCAE criteria, the guidelines shown in Table 3 below 
will be used to grade severity. 
intensity and that a severe event is not necessarily serious. 

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Table 3: 
AE Severity Grading 
Severity (Toxicity Grade) 
Description 
Mild (1) 
Transient or mild discomfort; no limitation in activity; no medical intervention 
or therapy required. The patient may be aware of the sign or symptom but 
tolerates it reasonably well. 
Moderate (2) 
Mild to moderate limitation in activity, no or minimal medical 
intervention/therapy required. 
Severe (3) 
Marked limitation in activity, medical intervention/therapy required, 
hospitalizations possible. 
Life-threatening (4) 
The patient is at risk of death due to the adverse experience as it occurred. This 
does not refer to an experience that hypothetically might have caused death if 
it were more severe. 
Death (5) 
Death related to AE 
AE=adverse event. 
12.1.2 
Relationship of Adverse Events to IP 
The relationship of an AE to IP will be assessed using the guidelines outlined in Table 4. 
Table 4: 
Relationship of AEs to IP 
Relationship to Drug 
Comment 
Definitely 
Previously known toxicity of agent; or an event that follows a reasonable temporal 
sequence from administration of the drug; that follows a known or expected 
response pattern to the suspected drug; that is confirmed by stopping or reducing the 
dosage of the drug; and that is not explained by any other reasonable hypothesis. 
Probably 
An event that follows a reasonable temporal sequence from administration of the 
drug; that follows a known or expected response pattern to the suspected drug; that 
is confirmed by stopping or reducing the dosage of the drug; and that is unlikely to 
be explained by the known characteristics of the patient
interventions. 
Possibly 
An event that follows a reasonable temporal sequence from administration of the 
drug; that follows a known or expected response pattern to that suspected drug; but 
that could readily have been produced by a number of other factors. 
Unrelated 
An event that can be determined with certainty to have no relationship to the IP. 
AE=adverse event; IP=investigational product. 
12.2 
Serious Adverse Events (SAEs) 
An SAE is defined as any AE occurring at any dose that results in any of the following 
outcomes: 
death 
a life-threatening adverse experience 
inpatient hospitalization or prolongation of existing hospitalization 
a persistent or significant disability/incapacity 
a congenital anomaly/birth defect 

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Other important medical events may also be considered an SAE when, based on appropriate 
medical judgment, they jeopardize the patient or require intervention to prevent one of the 
outcomes listed above.  
12.2.1 
Serious Adverse Event Reporting 
Study sites will document all SAEs that occur (whether or not related to IP) on an SAE Report 
Form. The collection period for all SAEs will begin after informed consent is obtained and end 
after procedures for the final study visit have been completed. 
All SAEs must be reported immediately (as soon as possible after the investigator becomes 
aware of the event but no later than 24 hours) by sending the completed SAE Report Form by 
email, to: 
For study sites in the United States: drugsafetyus@blueearthdx.com 
For study sites in Europe: drugsafety@blueearthdx.com  
Additional and further requested information (follow-up or corrections to the original event) 
will be detailed on a new SAE Report Form and emailed to the same address. 
12.3 
Urgent Safety Measures 
An urgent safety measure is an action that the Sponsor and/or investigator may take in order to 
protect study participants against an immediate hazard to their health or safety (e.g. it is 
identified that there is a significant higher incidence of death at one investigator site and as a 
result recruitment is suspended at that site as an urgent safety measure).  
An urgent safety measure taken by the investigator must be immediately notified to the 
Sponsor. For all urgent safety measures, the Institutional Review Board (IRB)/Independent 
Ethics Committee (IEC) and Regulatory Agency/Competent Authority will be notified in 
accordance with International Council for Harmonisation (ICH)-Good Clinical Practice (GCP) 
and applicable regulations. 
Initial notification may be followed by submission of a protocol amendment (see Section 18.2), 
notification of early termination of the trial within 15 days (if applicable) and notification of 
AEs and serious adverse reactions (if applicable). 
12.4 
Medical Monitoring 
Jingke Yang MD, PhD (Parexel) should be contacted directly at the following numbers to 
report medical concerns or questions regarding safety. 
Phone: +1 978 313 3834 or +1 909 317 4177 
13 
DISCONTINUATION AND REPLACEMENT OF PATIENTS 
13.1 
Discontinuation of IP 
Not applicable. rhPSMA-7.3 (18F) is administered as a single IV injection. 
13.2 
Discontinuation/Withdrawal from the Study 
Patients are free to withdraw from participation in the study at any time, for any reason, 
specified or unspecified, and without prejudice. 

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An investigator may discontinue or withdraw a patient for any of the following reasons:
Significant non-compliance/protocol violation requiring discontinuation from the study. 
If any clinical AE, laboratory abnormality, or other medical condition or situation occurs 
such that continued participation in the study would not be in the best interests of the 
patient. 
If the patient meets any of the exclusion criteria (either newly developed or not 
previously recognized) that precludes further study participation. 
Lost to follow-up (see Section 13.4). 
Sponsor request for early termination of study. 
The reason for patient discontinuation or withdrawal from the study will be recorded in the 
patient
 on the eCRF. 
Enrollment will continue until 316 evaluable patients have completed all study procedures; 
therefore, dropouts who fail to complete all study procedures, for reasons other than due to 
adverse reactions/AEs deemed related to IP, will be withdrawn from the study and replaced. 
No more than 15% of patients enrolled will be replaced. A patient is considered to be evaluable 
if he complies with all study procedures, including the SoT algorithm (if the PET scan is 
positive) as provided in Figure 3. 
Note: Any patients who withdraw/are withdrawn due to adverse reactions to rhPSMA-7.3 (18F) 
PET or AEs due to study procedures involved in rhPSMA-7.3 (18F) PET, will not be replaced. 
13.3 
Replacement of Patients 
Patients who sign the informed consent form but do not receive the IP may be replaced. Patients 
who sign the informed consent form and who receive the IP, but subsequently withdraw (or are 
withdrawn or discontinued from the study) before any follow-up procedures are obtained will 
also be replaced except for patients who withdraw/are withdrawn due to adverse reactions to 
rhPSMA-7.3 (18F) PET or AEs due to study procedures involved in rhPSMA-7.3 (18F) PET 
(see Section 13.2). 
13.4 
Lost to Follow-up 
A participant will be considered lost to follow-up if they fail to return for the follow-up 
assessments (histology, imaging) 7 days after their appointment was due and is unable to be 
contacted by the study site staff.  
In order to decrease the extent of missing data for patients completing the rhPSMA-7.3 (18F) 
PET but lacking SoT assessments, the following actions must be taken if a participant fails to 
complete a required study assessment: 
The site will attempt to contact the participant three times to reschedule a missed visit, 
and will counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain if the participant wishes to and/or should continue in the study. 
Before a participant is deemed lost to follow-up, the investigator or designee will make 
every effort to regain contact with the participant (where possible, three telephone calls 
and emails 
address or local equivalent methods). These contact attempts should be documented in 
 

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Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
13.5 
Study Discontinuation or Termination 
Patient enrolment may be temporarily halted or stopped if any of the following occur: 
SAE of severe acute hypersensitivity reaction attributed to the IP. 
SAE of death attributed to the IP. 
A new potential safety signal, e.g. multiple severe AEs which are new to the current 
rhPSMA-7.3 (18F) risk profile. 
Data from other clinical trials which greatly and negatively influence the current 
rhPSMA-7.3 (18F) benefit/risk assessment. 
14 
PROTOCOL DEVIATIONS 
A protocol deviation occurs when the patient, investigator, or Sponsor fails to adhere to 
significant protocol requirements or where there is a significant non-compliance to ICH-GCP, 
affecting patient safety or the scientific value of the trial. 
Any non-compliance with the protocol or GCP which is likely to effect to a significant degree 
the safety or physical or mental integrity of the study patients or the scientific value of the trial 
should be notified to the Sponsor within one working day. 
Protocol deviations for this study include, but are not limited to, the following: 
Failure to meet inclusion/exclusion criteria (see Sections 6.2 and 6.3). 
Use of a prohibited concomitant medication (see Section 7.1). 
IP administration but no subsequent PET scan. 
The Sponsor will determine if a protocol deviation will result in withdrawal of a patient. Major 
protocol deviations will be defined and documented in the Statistical Analysis Plan (SAP) 
which will be written and approved before database lock.  
15 
DATA SAFETY MONITORING 
Not applicable. 
16 
STATISTICAL METHODS AND CONSIDERATIONS 
Prior to the analysis of the final study data, a detailed SAP will be written and approved 
describing all analyses that will be performed. The SAP will contain any modifications to the 
analysis plan described below.  
16.1 
Data Sets Analyzed 
All enrolled patients: all patients who signed the informed consent form. 
Full Analysis Set (FAS): all patients who were scheduled to receive the rhPSMA-7.3 (18F) 
injection by meeting the inclusion/exclusion criteria.  

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Full Safety Population (FSP): all patients who received the rhPSMA-7.3 (18F) injection.
Efficacy Analysis Population (EAP): all patients who received rhPSMA-7.3 (18F) injection 
and with PET scan and sufficient data leading to a clear classification following the SoT 
algorithm. 
Per Protocol Population (PP): All evaluable patients in the EAP population.  
All safety analyses will be performed using the FSP. The primary analysis of CDR and PPV 
will be based on the EAP. 
16.2 
Accountability of Patients and Imaging 
The completion status of all patients will be summarized. Further, availability of results of 
patient disease assessments, completion of visits, and information on image assessments 
performed will be reported. 
16.3 
Demographic and Baseline Characteristics 
The following demographic variables at screening will be summarized: full/partial date of 
birth/age, gender, ethnicity/race, sex ethnicity/race, sex and height. Weight at screening and on 
Day 1 will be summarized. 
Relevant medical history (including history of current disease, concomitant disease record, 
information regarding underlying diseases and family history of cancer) at screening will be 
also be summarized. 
16.4 
Analysis of Primary Endpoints 
The co-primary endpoints for the study are the patient level CDR and the region level PPV of 
rhPSMA-7.3 (18F) PET. The joint hypothesis, based on the assumptions as outlined in 
Section 16.8, is as follows: 
H0
36.5
62.5% versus H1: CDR >36.5% and PPV >62.5% 
Both primary endpoints will be summarized as a percentage together with a two-sided exact 
95% confidence interval (CI) for each reader. In addition, a one-sided exact binomial test 
p-value will be provided for each reader for each CDR. As this is a by-region endpoint, patients 
may have one to three regions that may be included in the PPV assessment. The one-sided test 
based on clustered binary data will be used to evaluate the PPV hypothesis (Zhou, Obuchowski, 
and McClish, (2002), pg 104) to adjust the variance estimates in the analysis based on 
clustering of regions within a patient. For the study to be considered a success, the p-values for 
both endpoints must be statistically significant for at least two out of the three readers (same 
readers for both CDR and PPV).  
16.5 
Analysis of Secondary and Exploratory Endpoints 
Secondary and exploratory endpoints will be summarized descriptively, with the exception of 
consistency of rhPSMA-7.3 (18F) scan interpretation by blinded independent readers which will 
be presented utilizing Kappa statistics. Two-sided 95% CIs will be presented, where applicable.  
Further details will be provided in the SAP. 

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16.6 
Analysis of Safety Endpoint(s) 
Safety data will be summarized descriptively. For AEs and SAEs, the Medical Dictionary for 
Regulatory Activities (MedDRA) System Organ Class and Preferred Terms will be used to 
code the reported events. The number of events, number of patients with one or more event, 
and percentage of patients with one or more event will be provided for all AEs, related AEs, 
SAEs, and all related SAEs. For vital signs results, the change from baseline results will also 
be summarized. 
16.7 
Planned Interim Analysis 
No formal hypothesis testing interim analysis will be performed. 
Once 60% of the planned 190 positive cases have information, the proportion of patients with 
a PSA <1 ng/mL will be assessed. If this proportion exceeds 60% then investigators will be 
informed to stop further enrolment of this cohort. 
16.8 
Sample Size and Randomization 
16.8.1 
Assumptions 
As discussed in Section 4.2, in the overall study population, the detection rate of 
rhPSMA-7.3 (18F) PET is expected to be approximately 60%, the overall PPV is estimated to 
be 73.5% and the overall CDR is anticipated to be 49% (point estimates). The lower bound of 
the CI for the region level PPV will be set at 62.5% and the overall CDR will have a lower 
bound of 36.5%. The study will aim to include approximately 40% of patients with a PSA level 
<1 ng/mL and approximately 60% of patients with a PSA level 
 ng/mL. 
16.8.2 
Sample Size 
Approximately 316 patients will be enrolled in this study. For the PPV endpoint, based on a 
one-sided 0.025 exact binomial test and assuming a true PPV of 73.5%, a sample size of 
190 positive cases provides >88% power for the evaluation of region level PPV (H0: PPV 
316 evaluable patients would be required to obtain 190 positive rhPSMA-7.3 (18F) PET cases. 
Note that the PPV region-based analysis is expected to provide more than 88% power based 
upon the number of positive regions per patient being >1, even adjusting for the correlation 
between the regions within a patient. Thus, 316 patients are planned to be enrolled in order to 
get at least 190 cases with disease detected with rhPSMA-7.3 (18F) and an evaluable result. 
For the patient level CDR endpoint, based on a one-sided 0.025 exact binomial test and 
assuming a true CDR of 49%, a sample size of 316 cases provides >99% power for the 
evaluation of CDR (H0
 
Hence, a sample size of at least 316 patients is adequate based on the region level PPV endpoint 
and is expected to provide at least 90% power for the regional PPV analysis. 
17 
DATA COLLECTION, RETENTION AND MONITORING 
17.1 
Data Collection Instruments 
The investigator will prepare and maintain adequate and accurate study records and source 

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study patients. Particular care should be taken to ensure all data points are recorded in source 
documentation, especially those which are not part of standard practice. Source data should be 
attributable, legible, contemporaneous, original, accurate and complete. Changes to source data 
should be traceable, should not obscure the original entry, and should be explained if necessary.  
Study personnel at each site will enter data from source documents corresponding to a patient
visit into the protocol-specific eCRF when the information corresponding to that visit is 
available.  
Patients will not be identified by name in the study database or on any study documents to be 
collected by the Sponsor (or designee), but will be identified by a site number, patient number 
and initials. Data are pseudo-anonymized as the patient can be identified and as such data 
remains personal data and within the scope of US, European and United Kingdom (UK) law 
(US HIPAA 1996; European Union [EU] General Data Protection Regulation [GDPR] 2018; 
UK Data Protection Act 2018). 
If a correction is required for an eCRF, the time and date stamps track the person entering or 
updating eCRF data and creates an electronic audit trail.  
The investigator is responsible for all information collected on patients enrolled in this study. 
All data collected during the course of this study must be reviewed and verified for 
completeness and accuracy by the investigator. A copy of the eCRF will remain at the 
i
 
17.2 
Data Management Procedures 
The data will be entered into a validated database. The Data Management group at Parexel will 
be responsible for data processing, in accordance with procedural documentation. Database 
lock will occur once quality assurance procedures have been completed. 
All procedures for the handling and analysis of data will be conducted using good computing 
practices meeting the Food and Drug Administration (FDA) guidelines for the handling and 
analysis of data for clinical trials. 
17.3 
Data Quality Control and Reporting 
After data have been entered into the study database, a system of computerized data validation 
checks will be implemented and applied to the database on a regular basis. Queries are entered, 
tracked, and resolved through the electronic data capture (EDC) system directly. The study 
database will be updated in accordance with the resolved queries. All changes to the study 
database will be documented. 
17.4 
Archive of Data 
The database is safeguarded against unauthorized access by established security procedures; 
appropriate backup copies of the database and related software files will be maintained. 
Databases are backed up by the database administrator in conjunction with any updates or 
changes to the database.  
At critical junctures of the protocol (e.g. production of the final report), data for analysis is 
locked and cleaned per established procedures. 
The end of study electronic trial master file (eTMF) will be archived according to Blue Earth 
Diagnostics Standard Operating Procedure (SOP; SOP-GEN-005, Management of Corporate 
and GxP Archive. 

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17.5 
Availability and Retention of Investigational Records 
The investigator/institution should maintain the study documents as specified in Section 8 of 
ICH GCP E6 (R2) and as required by the applicable regulatory requirement(s). The 
investigator/institution should take measures to prevent accidental or premature destruction of 
these documents. 
Upon request of the monitor, auditor, IRB/IEC, or regulatory authority, the 
investigator/institution must make available for direct access all requested study-related 
records. 
Study documents should be retained for a minimum of 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the study intervention. These documents should be 
retained for a longer period, however, if required by local regulations (e.g. 25 years per Clinical 
Trial regulations 536/2014/EC). No records will be destroyed without the written consent of 
the Sponsor, if applicable. It is the responsibility of the Sponsor to inform the investigator when 
these documents no longer need to be retained. 
17.6 
Monitoring and Auditing 
Monitoring visits will be conducted by representatives of the Sponsor according to ICH GCP 
and relevant regulations. By signing this protocol, the investigator grants permission to the 
monitors and auditors, as well as the IRB/IEC and regulatory 
authorities to conduct on-site monitoring and/or auditing and provide direct access to all 
requested study-related records. If on-site monitoring is not permitted due to restrictions 
imposed to maintain social distancing due to the COVID-19 pandemic, then the investigator 
study including review of study-related records. 
17.7 
Patient Confidentiality 
In order to maintain patient confidentiality, only a site number, patient number and, where 
possible, patient initials will identify all study patients on eCRFs and other documentation 
submitted to the Sponsor. Additional patient confidentiality issues (if applicable) are covered 
in the Clinical Study Agreement. 
To maintain confidentiality, all laboratory specimens, evaluation forms, reports and other 
records will be identified by a coded number and initials only. All study records will be retained 
for 25 years 
identification number will be stored separately in another locked file cabinet. 
Clinical information will not be released without written permission of the patient, except as 
necessary for monitoring by Regulatory Authorities. The investigator must also comply with 
all applicable privacy regulations (e.g. US HIPAA 1996; EU GDPR 2018; UK Data Protection 
Act 2018). 

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18 
REGULATORY, ETHICAL AND STUDY OVERSIGHT 
CONSIDERATIONS 
The study will be conducted in accordance with ICH GCP and all applicable regulations. The 
Principal Investigator will assure that no deviation from, or changes to the protocol will take 
place without prior agreement from the Sponsor and documented approval from the relevant 
regulatory authority (if applicable) and IRB/IEC, except where necessary to eliminate an 
immediate hazard(s) to the trial participants. All personnel involved in the conduct of this study 
must have completed ICH GCP training, relevant to their role. 
18.1 
Institutional Review Boards and Independent Ethics Committees 
Any documents that the IRB/IEC may need to fulfil its responsibilities (such as protocol, 
protocol amendments, IB, consent forms, information concerning patient recruitment, payment 
or compensation procedures, or other pertinent information) will be submitted to the IRB/IEC. 
The IRB/IECs written unconditional approval/favorable opinion of the study, and any 
additional local approvals (e.g. hospital management, Administration of Radioactive 
Substances Advisory Committee etc.), must be obtained prior to shipment of IP to the site and 
prior to any patients undergoing study-specific procedures. The investigator will obtain 
assurance of IRB/IEC compliance with regulations. 
Note: Regulatory authority approvals may also be required. 
SOPs and policies will be followed for the submission of SAEs and progress 
reports during the conduct of the study. 
An end of study notification will be submitted as determined by each countries regulatory 
requirements. 
18.2 
Amendments 
Any decision to amend the clinical trial application and/or associated documents (e.g. protocol, 
informed consent form, eCRF, IB etc.) will be made by the Sponsor. 
The relevant regulations will be followed to determine what approvals from regulatory, 
IRB/IEC or local bodies are required. All required approvals will be obtained prior to 
implementation of the amendment, except as necessary to eliminate immediate safety hazards 
to patients (see Section 12.3, Urgent Safety Measures), such as amendments made due to the 
COVID-19 pandemic to ensure patient safety by minimizing potential exposure to SARS-CoV-
2. The Contract Research Organization will notify each participating investigator site when the 
amendment can be implemented. 
All changes to the consent form will be IRB/IEC approved; a determination will be made 
regarding whether a new consent needs to be obtained from patients who provided consent, 
using a previously approved consent form. 
18.3 
Patient Information and Consent 
In obtaining and documenting patient informed consent, the investigator must comply with the 
applicable regulatory requirement(s), ICH GCP and the ethical principles that have their origin 
in the Declaration of Helsinki. 

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Patient information and consent forms, and any other written material provided to the patient,
must be approved by the relevant IRB/IEC (and by any other body as required by national 
regulations) prior to the start of the study at each study site. 
The investigator (or an appropriately qualified designee) will explain the study to the patient 
or, if the patient is unable to provide informed consent, the patient
representative, and answer any questions that arise. A verbal explanation will be provided in 
terms suited to the patient , or patient
representatives, comprehension, of 
the purposes, procedures, and potential risks of the study and the rights of research participants. 
Patients (and the patient
legally acceptable representative) will have the opportunity to 
carefully review the written information and consent form, to discuss the study with their 
family or surrogates, and be given ample time to think about the study and ask questions before 
agreeing to participate. 
Patients (and the patient
legally acceptable representative) must be informed that 
participation is voluntary and that they may withdraw from the study at any time, without 
prejudice. The rights and welfare of the patients will be protected by emphasizing to them that 
the quality of their medical care will not be adversely affected if they decline to participate in 
this study. 
Prior to the patient undergoing any study-specific procedures, the written informed consent 
form must be signed and personally dated by the patient, or their legally acceptable 
representative, and by the person who conducted the informed consent discussion. The 
informed consent process will also be documented in the source document (including the 
date/time consent was obtained). 
If a patient is unable to read or if a legally acceptable representative is unable to read, an 
impartial witness should be present during the entire informed consent discussion. The patient, 
or patient
patient
if the patient, or patient
signing and personally dating the consent form. Once the patient, or patient
representative, has provided consent, the witness should also sign and personally date the 
consent form. By signing the consent form the witness attests that the information sheet/consent 
form/any other written information was accurately explained to, and apparently understood by, 
the patient, or patient
given by the patient, or patient
 
The distribution of the signed information sheet/consent form will be as required by any 
applicable local regulations. Otherwise a copy of the signed informed consent document will 
be given to the patient and the original maintained with the patient
.  
The patient or patient
if new information becomes available that may be relevant to the patient
continue participation in the study. The communication of this information will be documented 
in the source documentation. The written patient information/consent form and any other 
written information provided to the patients should be revised whenever important new 
information becomes available that may be relevant to the patient
 revised 
written patient information and consent form should receive IRB/IEC approval/favorable 
opinion prior to use. The patient, or patient
 sign and 
personally date any revised consent form and receive a copy (or original, if required by 
applicable regulations). 

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18.4 
Post-trial Care 
rhPSMA-7.3 (18F) is a single-use diagnostic agent. Therefore, no additional care for trial 
participants is planned once their participation in the study has ended. All patients will receive 
standard of care treatment in line with their medical condition as determined by their physician. 
18.5 
Publications 
The preparation and submittal for publication of manuscripts containing the study results shall 
be in accordance with a process determined by mutual written agreement among the study 
Sponsor and participating institutions. The publication or presentation of any study results shall 
comply with all applicable privacy laws, including, but not limited to, the US HIPAA 1996 and 
the EU GDPR 2018.  
19 
REFERENCES  
Afshar-Oromieh A, Avtzi E, Giesel FL, et al. The diagnostic value of PET/CT imaging with 
the (68)Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur 
J Nucl Med Mol Imaging 2015;42(2):197-209. 
Afshar-Oromieh A, Holland-Letz T, Giesel FL, et al. Diagnostic performance of 68Ga-PSMA-
11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: evaluation in 1007 patients. 
Eur J Nucl Med Mol Imaging 2017;44(8):1258-68. 
Beheshti M, Mottaghy FM, Paycha F, et al. (18)F-NaF PET/CT: EANM procedure guidelines 
for bone imaging. Eur J Nucl Med Mol Imaging 2015;42(11):1767-77. 
Calais J, Ceci F, Eiber M, et al. 18F-fluciclovine PET-CT and 68Ga-PSMA-11 PET-CT in 
patients with early biochemical recurrence after prostatectomy: a prospective, single-centre, 
single-arm, comparative imaging trial. Lancet Oncol 2019;20(9):1286-94. 
Didolkar MM, Anderson ME, Hochman MG, et al. Image guided core needle biopsy of 
musculoskeletal lesions: are nondiagnostic results clinically useful? Clin Orthop Relat Res 
2013;471(11):3601-9. 
rhPSMA-7.3 (18
2, 13 September 2019. Blue Earth 
Diagnostics. 
Eiber M, Maurer T, Souvatzoglou M, et al. Evaluation of hybrid 68Ga-PSMA ligand PET/CT 
in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med 
2015;56(5): 668-74. 
Fendler WP, Calais J, Eiber M, et al. Assessment of 68Ga-PSMA-11 PET accuracy in 
localizing recurrent prostate cancer: A prospective single-arm clinical trial. JAMA Oncology 
2019;5(6):856-63. 
Guberina N, Forsting M, Ringelstein A, et al. Radiation exposure during CT-guided biopsies: 
recent CT machines provide markedly lower doses. Eur Radiol 2018;28(9):3929-35. 
ICH-GCP E6 (R2). Integrated addendum to ICH E6(R1): guideline for Good Clinical Practice. 
November 
2016. 
Available 
at: 
https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R
2__Step_4_2016_1109.pdf [Accessed 16 August 2019].  
ICRP publication 56, part 2: Age-dependent doses to members of the public from intake of 
radionuclides. Oxford: Pergamon; 1992. 

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Israeli RS, Powell CT, Corr JG, et al. Expression of the prostate-specific membrane antigen. 
Cancer Res 1994;54(7):1807-11. 
Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 
2011;61(2):69-90. 
Kozikowski AP, Nan F, Conti P, et al. Design of remarkably simple, yet potent urea-based 
inhibitors of glutamate carboxypeptidase II (NAALADase). J Med Chem 2001;44(3):298-301. 
McCollough CH, Bushberg JT, Fletcher JG, et al. Answers to common questions about the use 
and safety of CT scans. Mayo Clin Proc 2015;90(10):1380-92. 
Osborne JR, Akhtar NH, Vallabhajosula S, et al. Prostate-specific membrane antigen-based 
imaging. Urol Oncol 2013;31(2):144-54. 
Perera M, Papa N, Christidis D, et al. Sensitivity, specificity, and predictors of positive 
68Ga-prostate-specific membrane antigen positron emission tomography in advanced prostate 
cancer: a systematic review and meta-analysis. Eur Urol 2016;70(6):926-37. 
Perera M, Papa N, Roberts M, et al. Gallium-68 Prostate-specific Membrane Antigen Positron 
Emission Tomography in Advanced Prostate Cancer
Updated Diagnostic Utility, Sensitivity, 
Specificity, and Distribution of Prostate-specific Membrane Antigen-avid Lesions: A 
Systematic Review and Meta-analysis. Eur Urol 2019. pii: S0302-2838(19)30095-8. 
Rowe SP, Pienta KJ, Pomper MG, et al. PSMA-RADS Version 1.0: A step towards 
standardizing the interpretation and reporting of PSMA targeted PET imaging studies. Eur 
Urol 2018; 73(4):485-87. 
Silver DA, Pellicer I, Fair WR, et al. Prostate-specific membrane antigen expression in normal 
and malignant human tissues. Clin Cancer Res 1997;3(1):81-5. 
Study BED-PSMA-403: Study Report. Version 1, 12 September 2019. Blue Earth Diagnostics. 
Yang J, Frassica FJ, Fayad L, et al. Analysis of nondiagnostic results after image-guided needle 
biopsies of musculoskeletal lesions. Clin Orthop Relat Res 2010;468(11):3103-11. 
Zhou XH, Obuchowski NA and McClish, DK. Statistical Methods in Diagnostic Medicine. 
Wiley, New York, 2002 pp 104-6. 
 

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APPENDIX 1: STUDY SCHEDULE 
 
 
 
 
FOLLOW-UP PROCEDURES 
VISIT 1 
SCREENING 
(DAY -28) 
VISIT 2 
(Day 1)* 
VISIT 3 
FOLLOW-UP 
(up to Day 7)** 
UP TO DAY 45*** 
UP TO 90 DAYS 
Informed Consent  
X 
 
 
 
 
Review of Inclusion/Exclusion Criteria 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
Medical History  
Xa 
 
 
 
 
Height (at screening only) 
X 
 
 
 
 
Weight 
X 
X 
 
 
 
Collect Historical Conventional Imagingb 
X 
 
 
 
 
Acquire Conventional Imagingb,  
Between Visit 1 and up to 2 weeks after 
Visit 2 
X (IF NOT YET 
OBTAINED) 
X 
 
 
 
Record Adverse Events 
X 
X 
X 
X 
X 
Concomitant Medication Review 
X 
X 
X 
X 
X 
Vital Signs (blood pressure, pulse, 
respiration rate, temperature) 
X 
Xc 
 
 
 
Administration of IP 
 
X 
 
 
 
Drug Accountability 
 
X 
 
 
 
Post-IP PET Scan 
 
Xd 
 
 
 
Clinical Review 
 
 
X 
 
 
Image-guided Biopsy Reporte 
 
 
 
X 
 
Surgery (with histology report)  
 
 
 
X 
 

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FOLLOW-UP PROCEDURES 
VISIT 1 
SCREENING 
(DAY -28) 
VISIT 2 
(Day 1)* 
VISIT 3 
FOLLOW-UP 
(up to Day 7)** 
UP TO DAY 45*** 
UP TO 90 DAYS 
Record Salvage Therapyf 
 
 
 
X 
 
Follow-up Confirmatory Imagingg 
 
 
 
X 
 
Additional Follow-up Confirmatory 
Imaging h 
 
 
 
 
X 
COVID-19=Corona Virus Disease-19; CT=computed tomography; 18F=fluorine-18; FP=False Positive; IP=investigational product; MRI=magnetic resonance imaging; NaF=sodium fluoride; 
PCa=prostate cancer; PET=positron emission tomography; PPV=positive predictive value; rhPSMA=radiohybrid prostate-specific membrane antigen; SARS-CoV-2=severe acute respiratory 
syndrome 
coronavirus 
2; 
SoT=Standard 
of 
Truth; 
SPECT=single-photon 
emission 
computed 
tomography; 
99mTc-HDP=99mtechnetium-hydroxydiphosphonate; 
99mTc-MDP=99mtechnetium-methyldiphosphonate; TP=True Positive. 
* 
Due to the COVID-19 pandemic, Visit 1 and Visit 2 may be combined (named Visit 1 and Visit 2 combined ) if judged by the investigator to be necessary to decrease potential exposure 
to SARS-CoV-2 for patients. For all patients enrolled through the Visit 1 and Visit 2 combined pathway, pre-screening via telephone contact with the patient is required prior to Day 1 to 
review the study eligibility criteria, obtain initial consent (remote consent is acceptable if permitted under local regulations and approvals), to promote study visit compliance and to ensure 
patient understanding of the combined study visit and planned IP administration, as well as ask about baseline and historic conventional imaging that may already have been performed or 
needs to be scheduled. Full written informed consent will be taken on Day 1 (Visit 1 and Visit 2 combined). For sites with on-site manufacturing, the visits may be combined if mutually 
agreed by the Radiopharmacy and investigator even post-COVID-19 pandemic restrictions. 
Alternatively, the time from Visit 1 (initial screening) to Visit 2 (rhPSMA-7.3 (18F) PET scan) may be extended up to 45 days due to the COVID-19 pandemic. 
** 
Visit 3 Follow-up should be performed within 7 days post-IP administration and may be performed by an appropriately licensed and credentialed clinician and can be conducted by telephone 
 
*** If feasible, the patient will undergo image-guided biopsy of a PET-positive lesion(s) suspicious for recurrence of PCa within 45 days following rhPSMA-7.3 (18F) PET imaging (may be 
extended up to Day 60 due to the COVID-19 pandemic). If biopsy is not feasible, confirmatory imaging should be performed, if indicated, as per algorithm.  
a 
To include medical history and concomitant disease record, including a history of PCa, diagnosis date and prior PCa treatments, as well as confirmation of a history of localized adenocarcinoma 
of the prostate with prior curative intent treatment. 
b 
Conventional imaging may include: planar and/or SPECT bone scan (99mTc-HDP, 99mTc-MDP per institution preference), abdominal/pelvic CT or MRI, chest CT per institution preference, or 
PET with 18F-NaF or Axumin. Conventional imaging that has been performed at non-participating institutions will be accepted provided the scans are reviewed by the participating institution. 
If not already completed up to 90 days before inclusion, conventional imaging will be performed at the study site according to site standard of care (to take place following Visit 1 and up to 2 
weeks after Visit 2). Historical imaging 
 (including approximately the past 2 years) can be used to establish SoT where a biopsy 
cannot be obtained. Patients will be asked to provide these pre-existing images if these were done at another institution. If done at the study site, these images will be made available by the 
study site.  
c 
Vital signs to be recorded at pre-IP administration and post-IP administration. 
d 
For full details see the Study Imaging Manual.  
e 
If feasible, patients will undergo image-guided biopsy of a PET-positive lesion(s) suspicious for recurrence of PCa within 45 days following of rhPSMA-7.3 (18F) PET imaging (may be 
extended up to Day 60 due to the COVID-19 pandemic). 
f 
Patients may receive salvage treatment following further consultation with their physician (outside of the scope of this study). The salvage treatment prescribed will be recorded.  
g 
If biopsy is not feasible, rhPSMA-7.3 (18F) directed (for confirmation of lesion location only) follow-up confirmatory imaging of the site(s), with one or more recommended modalities, will 
be acquired at the discretion of the local investigator(s). Note: this time period may be extended up to Day 60 due to the COVID-19 pandemic. 

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h 
Follow-up confirmatory imaging may be performed, as necessary, up to 90 days after rhPSMA-7.3 PET. 
Notes:  
Due to the COVID-19 pandemic, investigators should carefully consider the timing of confirmatory imaging procedures (when histology is not available) and are encouraged to minimize 
potential exposure to SARS-CoV-2 by combining follow-up visits for multiple confirmatory imaging scans, when feasible. 
In patients with multiple PET-positive regions, confirmation of at least one PET-positive lesion in each region is required either by biopsy/surgical resection or confirmatory imaging in 
order to calculate the region level PPV for the efficacy analyses.  
In patients with multiple lesions in a specific region, the presence of one TP lesion determines truth for the region regardless of any concurrent FP findings in the same region. Therefore, 
multiple PET-positive lesions can be evaluated in a specific region in order to confirm at least one TP.