Clinical trial NCT03739684
Conditions: Prostate Cancer Prostate Adenocarcinoma Prostate Cancer Recurrent Prostate Cancer Metastatic
Keywords: Positron emission tomography biochemical recurrence rising PSA PET/CT Diagnostic Imaging PSMA radical prostatectomy BCR
Sponsor: Progenics Pharmaceuticals, Inc.
Start date: 2018-11-27; Completion date: 2019-08-29
Enrollment: 208 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study evaluates the diagnostic performance and safety of 18F-DCFPyL (PyL) PET/CT imaging in patients with suspected recurrence of prostate cancer who have negative or equivocal findings on conventional imaging.

Detailed description:

Arms: arm 1: 9 mCi (333 MBq) IV injection of 18F-DCFPyL
Interventions: intervention 1: 18F-DCFPyL intervention 2: PET/CT Imaging
Intervention descriptions: intervention 1: A single dose of 9 mCi (333 MBq) IV injection of 18F-DCFPyL intervention 2: PET/CT imaging will be acquired 1-2 hours post-PyL injection

Protocol documents:
Prot_000.pdf: 
Clinical Protocol:  PyL-3301 
18F-DCFPyL 
Original: July 31, 2018 
Confidential 
Page 1 
CLINICAL STUDY PROTOCOL 
Study Number: 
PyL 3301 
Study Title: 
A Phase 3, Multi-Center, Open-Label Study to Assess the DiagNostic 
Performance and Clinical Impact of 18F-DCFPyL PET/CT Imaging 
Results in Men with Suspected Recurrence of PrOstate CanceR 
(CONDOR) 
Product Name: 
18F-DCFPyL (PyL) 
IND Number 
129,952 
Sponsor: 
Progenics Pharmaceuticals, Inc. 
One World Trade Center 
47th Floor, Suite J 
New York, NY 10007   
(646) 975-2500 
Protocol Version 
Original:  July 31, 2018
 
 
 
NCT03739684
 
Confidentiality Statement 
The confidential information in this document is provided to you as an investigator or consultant for review by 
you, your staff, and the applicable Institutional Review Board/Independent Ethics Committee.  Your acceptance 
of this document constitutes agreement that you will not disclose the information contained herein to others 
without prior written authorization from Progenics Pharmaceuticals, Inc. 


 
 
Clinical Protocol:  PyL-3301 
  18F-DCFPyL 
Original: July 31, 2018 
 
Confidential  
Page 2 
INVESTIGATOR’S AGREEMENT 
I acknowledge that I have read the attached protocol and agree that it contains all information 
necessary to conduct the study and agree to conduct the study as outlined within. 
I agree to comply with all stated provisions, including but not limited to regulations/guidelines 
relevant to the conduct of human trials, as set forth in Title 21 of the Code of Federal 
Regulations (CFR), and Good Clinical Practices as set forth by International Conference on 
Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use 
(ICH).   
I will not initiate the study until I have obtained written approval from the appropriate 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC).  I will obtain written 
informed consent from all study participants prior to performing any screening procedures. 
I agree to maintain the confidentiality of all information received or developed in connection 
with this protocol.  I understand and acknowledge that confidential information includes, but is 
not limited to, (i) the study protocol, (ii) the data derived from the study, and (iii) my impressions 
of the progress or results of the study.  I further agree that I will not use such Confidential 
Information for any purpose other than the evaluation or conduct of the clinical investigation.   
I certify that I have not been disqualified by any regulatory authority or otherwise disqualified 
from serving as a principal investigator.  I also agree that in the event I become debarred, I shall 
immediately cease all activities relating to the study. 
I am not presently, nor will I be during the term of the study, a consultant or advisor to any 
division of any financial or securities firm.  
I understand that my signature on a case report form indicates that the data therein have been 
reviewed and are deemed to be complete, accurate, and acceptable to me. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Principal Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Principal Investigator 
 
 
 
 
 
 
 
 
Date 




 
 
Clinical Protocol:  PyL-3301 
  18F-DCFPyL 
Original: July 31, 2018 
 
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PROCEDURES IN CASE OF EMERGENCY 
Table 1: 
Emergency Contact Information 
Role in Study 
Name 
E-mail and Telephone Number 
Clinical Project Manager 
 
 
 
Medical Monitor  
 
  
 


 
 
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  18F-DCFPyL 
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TABLE OF CONTENTS 
INVESTIGATOR’S AGREEMENT ...............................................................................................2 
SPONSOR SIGNATURE PAGE ....................................................................................................3 
PROCEDURES IN CASE OF EMERGENCY ...............................................................................4 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ..................................................9 
1. 
BACKGROUND & RATIONALE ............................................................................11 
1.1. 
Background .................................................................................................................11 
1.1.1. 
Pharmaceutical and Diagnostic Background ..............................................................11 
1.1.2. 
Nonclinical Studies .....................................................................................................12 
1.1.3. 
Previous Human Experience .......................................................................................13 
1.1.4. 
Ongoing Progenics-Sponsored Clinical Trial(s) .........................................................13 
1.2. 
Rationale for the Study ...............................................................................................13 
2. 
TRIAL OBJECTIVES AND PURPOSE ....................................................................15 
2.1. 
Primary Objective .......................................................................................................15 
2.2. 
Secondary Objectives .................................................................................................15 
2.3. 
Exploratory Objectives ...............................................................................................15 
3. 
TRIAL ENDPOINTS .................................................................................................15 
3.1. 
Primary Endpoint ........................................................................................................15 
3.2. 
Secondary Endpoints ..................................................................................................15 
3.2.1. 
Secondary Efficacy Endpoints ....................................................................................15 
3.2.2. 
Safety Endpoints .........................................................................................................15 
3.3. 
Exploratory Endpoints ................................................................................................16 
4. 
INVESTIGATIONAL PLAN .....................................................................................16 
4.1. 
Overall Study Design ..................................................................................................16 
4.2. 
Number of Subjects ....................................................................................................18 
4.3. 
Study Procedures ........................................................................................................18 
4.3.1. 
Screening (Day -30 to 1) .............................................................................................18 
4.3.2. 
18F-DCFPyL – Dosing and PET/CT Imaging (Day 1) ...............................................19 
4.3.3. 
Safety Follow-up (phone call; Day 8 [±3]) .................................................................19 
4.3.4. 
Post-PyL Intended Management Plan (Day 2-60) ......................................................20 
4.3.5. 
Efficacy Follow-up (Performed or Initiated by Day 2-60) .........................................20 
4.3.5.1. 
Verification of PyL-suspected lesion (per local PyL PET/CT finding) .....................20 


 
 
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4.4. 
Study Duration ............................................................................................................21 
4.5. 
Safety Monitoring .......................................................................................................22 
4.6. 
Criteria for Study Termination ...................................................................................22 
5. 
SUBJECT SELECTION AND WITHDRAWAL CRITERIA...................................24 
5.1. 
Subject Inclusion Criteria ...........................................................................................24 
5.2. 
Subject Exclusion Criteria ..........................................................................................24 
5.3. 
Subject Withdrawal Criteria .......................................................................................24 
6. 
TREATMENT OF SUBJECTS ..................................................................................25 
6.1. 
Description of Study Drug ..........................................................................................25 
6.2. 
Concomitant Medications and Procedures .................................................................25 
6.3. 
Treatment Compliance ................................................................................................26 
6.4. 
Randomization and Blinding ......................................................................................26 
7. 
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................26 
7.1. 
Study Drug ..................................................................................................................26 
7.2. 
Restrictions .................................................................................................................26 
7.2.1. 
Food and Fluid Intake .................................................................................................26 
7.2.2. 
Radioactivity ...............................................................................................................26 
7.3. 
Study Drug Packaging and Labeling ..........................................................................26 
7.4. 
Study Drug Storage .....................................................................................................27 
7.5. 
Study Drug Preparation ..............................................................................................27 
7.6. 
Study Drug Administration.........................................................................................27 
7.7. 
Study Drug Accountability .........................................................................................28 
7.8. 
Study Drug Handling and Disposal ............................................................................28 
8. 
ASSESSMENT OF EFFICACY ................................................................................29 
8.1. 
Composite Truth Standard ..........................................................................................29 
8.2. 
Image Acquisition .......................................................................................................29 
8.2.1. 
Follow-up conventional imaging to verify PyL-suspected lesion(s) within 60 
days following 18F-DCFPyL PET/CT ........................................................................29 
8.2.2. 
18F-DCFPyL PET/CT Imaging ...................................................................................29 
8.2.3. 
Imaging at Biopsy (if biopsy is performed) ................................................................30 
8.3. 
Image Interpretation by Central Imaging Core Lab ...................................................30 
8.4. 
Histopathology from Biopsy or Surgery (if performed) of PyL-positive 
lesion(s) within 60 days following 18F-DCFPyL PET/CT .........................................30 


 
 
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8.4.1. 
Image-Guided Biopsy (if feasible) of PyL-positive lesion .........................................30 
8.5. 
PSA (total) Response ..................................................................................................30 
8.6. 
Change in Management Intent ....................................................................................31 
9. 
ASSESSMENT OF SAFETY .....................................................................................31 
9.1. 
Safety Parameters .......................................................................................................31 
9.1.1. 
Demographic Information and Medical History .........................................................31 
9.1.2. 
Vital Signs ..................................................................................................................32 
9.2. 
Adverse and Serious Adverse Events .........................................................................32 
9.2.1. 
Definition of Adverse Events .....................................................................................32 
9.2.1.1. 
Adverse Event (AE) ....................................................................................................32 
9.2.1.2. 
Serious Adverse Event (SAE) ....................................................................................32 
9.2.2. 
Overdose and Underdose ............................................................................................32 
9.3. 
Relationship to Study Drug ........................................................................................32 
9.4. 
Recording Adverse Events .........................................................................................33 
9.5. 
Reporting Serious Adverse Events .............................................................................33 
10. 
STATISTICS ..............................................................................................................34 
10.1. 
Sample Size ................................................................................................................34 
10.2. 
Analysis Populations ..................................................................................................35 
10.2.1. 
Safety Population ........................................................................................................35 
10.2.2. 
Full Analysis Set (FAS) ..............................................................................................35 
10.2.3. 
Per Protocol Set ..........................................................................................................35 
10.3. 
Missing Data ...............................................................................................................35 
10.4. 
Analyses ......................................................................................................................35 
10.4.1. 
Subject Characteristics ................................................................................................35 
10.4.2. 
Efficacy Analyses .......................................................................................................36 
10.4.2.1. 
Primary Endpoint Analysis .........................................................................................36 
10.4.2.2. 
Secondary Endpoints Analyses ...................................................................................37 
10.4.2.3. 
Exploratory Endpoint Analyses ..................................................................................37 
10.4.3. 
Safety Analyses ..........................................................................................................37 
10.4.3.1. 
Exposure .....................................................................................................................37 
10.4.3.2. 
Treatment-Emergent Adverse Events .........................................................................37 
10.4.3.3. 
Vital Signs ..................................................................................................................38 


 
 
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10.4.3.4. 
Concomitant Medications and Procedures .................................................................38 
11. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS.........................................38 
11.1. 
Study Site Monitoring.................................................................................................38 
11.2. 
Audits and Inspections ................................................................................................39 
12. 
ETHICS ......................................................................................................................39 
12.1. 
Good Clinical Practice (GCP), Laws and Regulations ...............................................39 
12.2. 
Institutional Review Board (IRB) or Independent Ethics Committee (IEC) 
Approval .....................................................................................................................40 
12.3. 
Written Informed Consent ..........................................................................................40 
12.4. 
Subject Confidentiality ...............................................................................................40 
12.5. 
Financial Disclosure ...................................................................................................41 
13. 
DATA HANDLING AND RECORDKEEPING .......................................................41 
13.1. 
Case Report Forms and Study Records ......................................................................41 
13.2. 
Inspection of Records .................................................................................................41 
13.3. 
Retention of Records ..................................................................................................41 
14. 
PUBLICATION AND DISCLOSURE POLICY .......................................................41 
15. 
REFERENCES ...........................................................................................................43 
 
LIST OF TABLES 
Table 1: 
Emergency Contact Information ...................................................................................4 
Table 2: 
Abbreviations and Specialist Terms .............................................................................9 
Table 3: 
Schedule of Assessments ............................................................................................23 
Table 4: 
Investigational Product ...............................................................................................25 
 
LIST OF FIGURES 
Figure 1: 
Study Schema .............................................................................................................18 
 


 
 
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  18F-DCFPyL 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 2: 
Abbreviations and Specialist Terms  
Abbreviation or Specialist Term 
Explanation 
AE 
adverse event 
ADT 
androgen deprivation therapy 
AUA 
American Urological Association 
BCR 
biochemical recurrence  
BP 
blood pressure 
CFR 
Code of Federal Regulations 
CLR 
Correct Localization Rate 
CRF/eCRF 
case report form/electronic case report form 
CT 
computed tomography 
DMC 
Data Monitoring Committee 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
18F 
Fluorine-18 
PyL 
18F-DCFPyL  
FDG 
Fluorodeoxyglucose 
68Ga 
Gallium-68 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
hr 
hour(s) 
HR 
heart rate 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IND 
investigational new drug 
IRB 
Institutional Review Board 
IV 
intravenous  
JHU 
Johns Hopkins University 


 
 
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Table 2: 
Abbreviations and Specialist Terms  
Abbreviation or Specialist Term 
Explanation 
KeV 
kiloelectron volt 
kg 
kilogram 
mAbs 
monoclonal antibodies 
MBq 
megaBequerel 
mCi 
milliCurie 
MDP 
methylene diphosphonate bone scan 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
milligram 
mL 
milliliter  
MMQ 
Medical Management Questionnaire 
MRI 
magnetic resonance imaging 
NCCN 
National Comprehensive Cancer Network  
ng 
nanogram 
nM 
nanomol 
NPV 
negative predictive value 
PC 
prostate cancer 
PET 
positron emission tomography 
PI 
Principal Investigator  
PPV 
positive predictive value 
PSA 
prostate specific antigen 
PSADT 
PSA doubling time 
PSMA 
prostate-specific membrane antigen 
PT 
preferred term 
RP 
radical prostatectomy 
RT 
Radiation Therapy 
SAE 
serious adverse event 
SPECT 
single photon emission computed tomography 
SOC 
Standard of Care 
SUV 
Standardized uptake value 
US 
United States/Ultrasound 
 


 
 
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1. 
BACKGROUND & RATIONALE 
1.1. 
Background 
Prostate cancer is the most common cancer among men in the United States (US) with an 
estimated annual incidence of 161,360 cases; it also represents the second most common cause 
of cancer-related death in men.1  The vast majority of men dying of prostate cancer succumb to 
metastatic and/or recurrent disease.2  Conventional imaging modalities such as computed 
tomography (CT), magnetic resonance imaging (MRI), [99mTc] methylene diphosphonate (MDP) 
bone scan, or ultrasound are not able to determine the location of recurrent and/or metastatic 
prostate cancer, particularly at low prostate specific antigen (PSA) levels.3,4,5,6  Thus, imaging 
agents and modalities that will detect and localize the tumor, as well as small metastatic lesions, 
with high sensitivity and specificity are essential to more accurately diagnose and stage the 
disease, detect recurrence and metastases, and potentially monitor therapeutic response. 
A number of new, targeted positron emission tomography (PET) tracers have been introduced for 
imaging prostate cancer.7,8,9,10,11,12  A novel, high specific activity, highly selective, low-
molecular weight prostate-specific membrane antigen (PSMA)-targeted PET radiotracer, 18F-
DCFPyL , has been investigated as an imaging agent for prostate cancer.  Progenics has in-
licensed18F-DCFPyL (PyL) from Johns Hopkins University (JHU) in 2015; and Progenics plans 
to complete the clinical development program of PyL for the detection of recurrent and/or 
metastatic prostate cancer.   
Refer to the Investigator’s Brochure (IB) for detailed information on 18F-DCFPyL Injection.  
1.1.1. 
Pharmaceutical and Diagnostic Background 
18F-DCFPyL (PyL) is a small molecule radiolabeled with the positron-emitting radionuclide 18F 
and binds to the extracellular domain of PSMA with high affinity.  PSMA is a trans-membrane, 
750-amino acid type II glycoprotein primarily expressed in normal human prostate epithelium at 
very low levels, if at all, but is upregulated in prostate cancer, including metastatic disease.  
PSMA is a unique exopeptidase with reactivity toward poly-gamma-glutamated folates that is 
capable of sequentially removing the poly-gamma-glutamyl termini.13,14  Since PSMA is 
expressed by virtually all prostate cancers, it is a very attractive target for developing agents for 
the diagnosis and staging of this disease.15,16,17  In addition to high expression in malignant 
prostatic tissue and being directly related to tumor aggressiveness,18  PSMA has also been 
detected in renal proximal tubules, in cells of the intestinal brush border membrane, in rare cells 
in the colonic crypts, in brain, salivary glands,19,20 and in the neovasculature of nonprostatic solid 
carcinomas (e.g., renal cell, breast, colon, pancreas, melanoma, and lung carcinoma).13,21   
Radiolabeled anti-PSMA monoclonal antibodies (mAbs) have been used to detect prostate 
cancer nodal metastasis and recurrence.  Although the use of radiolabeled anti-PSMA mAbs 
have been met with logistical and clinical limitations as an imaging agent, phase 1 and 2 
therapeutic trials utilizing PSMA as a therapeutic target have shown early promising results.22,23  
Nonetheless, while monoclonal antibodies hold promise for tumor detection and therapy, there 
has been relatively limited clinical success outside of hematological cancers due to their low 
permeability in solid tumors and slow clearance from the circulating blood pool.   


 
 
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  18F-DCFPyL 
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Smaller molecular weight compounds with higher permeability into solid tumors are likely to 
provide a distinct and definitive advantage in achieving higher percent uptake per gram of tumor 
tissue and a high percentage of specific binding.  Small molecules are also expected to have 
improved blood clearance and tissue distribution in normal tissues compared with antibodies, 
thus enhancing the target-to-background ratio and thereby making lesion detection more 
conspicuous.  In the past several years, a number of investigational PSMA-targeted small 
molecules have been synthesized and labeled with various radioisotopes to be tested for use as 
imaging agents for prostate cancer.  A single photon emission computed tomography (SPECT) 
agent, 99mTc-MIP-1404,24, 25, 26  has just completed its phase 3 study enrollment for the detection 
of clinically significant prostate cancer in patients with low grade disease.  PET imaging agents, 
such as 124I-MIP-1095, 18F-DCFCBC, 18F-DCFPyL, 18F-FACBC and 68Ga-HBED-CC, have also 
generated much interest for their potential use in detecting metastatic prostate cancer. Of these, 
68Ga-HBED-CC (68Ga-PSMA) has been more broadly studied at academic centers and mostly 
under retrospective protocols.   
18F-DCFPyL (“PyL”) has been the subject of extensive investigation since its synthesis and 
characterization by investigators at JHU in 2011.27,28   Over the past few years, various versions 
of PyL have been synthesized and used in academic investigator-sponsored studies and on a 
compassionate use basis in the US, Canada, and Europe.  Collectively, published study results 
suggest that 18F-DCFPyL PET/CT provide high image quality and visualize small prostate 
lesions with excellent sensitivity.29,30,31,32,33   Furthermore, F-18 tracers offer important practical 
advantages, including higher production capacity than PET radiopharmaceuticals labeled with 
other radionuclides, such as Ga-68, which would facilitate rapid patient access.  The detection 
rate of 18F-DCFPyL PET/CT compares favorably with that of 68Ga-PSMA PET/CT in patients 
with biochemical recurrence (BCR).34  The results of the Dietlein et al study also showed that 
18F-DCFPyL PET/CT provided high image quality and visualized small prostate lesions with 
excellent sensitivity.  Thus, 18F-DCFPyL PET/CT promises to be a useful diagnostic to localize 
prostate cancer, including in patients with suspected recurrence of prostate cancer where there is 
a high unmet medical need. 
1.1.2. 
Nonclinical Studies 
The nonclinical studies conducted with DCFPyL and 18F-DCFPyL included biochemical activity, 
biodistribution in xenograft mice, small animal PET imaging, and a single dose IV toxicology 
study in rats.  All of these studies were submitted by JHU to FDA under IND 121,064.  Data 
from an enzyme inhibition assay showed that DCFPyL binds competitively to PSMA expressing 
LNCaP cells with a Ki of 1.1 nM.  Studies in PSMA positive tumor bearing nude mice 
demonstrated significant tumor uptake and retention, coupled with a rapid clearance from non-
target organs to provide support for the further development of 18F-DCFPyL as a 
radiopharmaceutical for detection and localization prostate cancer in man.  Results from a 14-day 
single dose rat toxicology studies with DCFPyL resulted in a no observed adverse effect level 
(NOAEL) of 0.5 mg/kg, the highest dose tested.  The maximum human mass dose of DCFPyL is 
expected to be 4 µg; thus, this represents an estimated safety margin of >1200-fold the human 
equivalent dose. 


 
 
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1.1.3. 
Previous Human Experience  
Several investigator-initiated clinical studies with 18F-DCFPyL Injection have been completed at 
JHU under IND 121,064.  Data from two completed clinical studies show that PET imaging with 
18F-DCFPyL Injection is feasible and safe.  Study J1418 was a first-in-human, phase 1/2 study, 
conducted to evaluate the radiation dosimetry, biodistribution, metabolism, and safety of 18F-
DCFPyL Injection with PET/CT imaging in men with metastatic prostate cancer.  Once safety 
was established, the utility of 18FDCFPyL PET/CT imaging to detect local, nodal, and/or 
metastatic prostate cancer was assessed in men with advanced prostate cancer.  Study J1545 was 
a phase 2 single-center, open-label study in men diagnosed with biochemical recurrence of 
prostate cancer.  The study was conducted to evaluate the safety of 18F-DCFPyL Injection, to 
determine the location of putative sites of metastatic disease by 18F-DCFPyL PET/CT, to 
correlate findings on 18F-DCFPyL PET/CT with conventional imaging, and to assess treatment 
response by 18F-DCFPyL PET/CT following six months of standard of care (SOC) therapy. 
Biodistribution following administration of 18F-DCFPyL Injection and an optimal imaging time 
point were determined, and the radiation dose used was within limits for diagnostic radiotracers 
for PET.28,31  Physiologic accumulation of 18F-DCFPyL was found to correspond to the 
distribution of PSMA expressing organs. Accumulation in primary tumor and metastatic lesions 
was very high, suggesting that 18F-DCFPyL Injection can be used to prospectively detect residual 
tumor as well as regional or distance metastases with high sensitivity and specificity.32,33  
Sensitivity and specificity with 18F-DCFPyL PET/CT in patients with at least localized 
intermediate risk prostate cancer who have undergone radical prostatectomy (RP) with 
lymphadenectomy was comparable to published 68Ga-PSMA imaging data. 30,35  
1.1.4. 
Ongoing Progenics-Sponsored Clinical Trial(s) 
An open-label, non-randomized, phase 2/3, multi-center study (PyL 2301) is being conducted in 
the US and Canada to evaluate the safety and diagnostic performance of 18F-DCFPyL PET/CT 
imaging in patients with at least high-risk localized or metastatic prostate cancer.  The study is 
entitled, PrOspective Phase 2/3 Multi-Center Study of 18F-DCFPyL PET/CT Imaging in Patients 
with PRostate Cancer: Examination of Diagnostic AccuracY (OSPREY; NCT02981368).  
Eligible subjects with at least high-risk prostate cancer defined by NCCN v.3.2016 who are 
planned for radical prostatectomy with pelvic lymph node dissection (cohort A), and subjects 
with radiologic evidence of local recurrence or new or progressive metastatic disease (cohort B) 
are enrolled and administered 9 mCi (333 MBq) 18F-DCFPyL Injection followed by PET/CT 
imaging within 1-2 hours post-dosing.  Diagnostic performance characteristics of 18F-DCFPyL 
PET/CT imaging will be evaluated using histopathology as the truth standard. Overall, 18F-
DCFPyL imaging agent has been well-tolerated.   
For study details and current safety findings please refer to the IB for 18F-DCFPyL Injection.  
1.2. 
Rationale for the Study 
One of the most challenging aspects of the clinical management of prostate cancer is the 
development of disease recurrence after prostatectomy, radiotherapy, or other local treatment 
modalities.36, 37, 38   Disease recurrence (rising PSA) after initial definitive therapy, defined as a 
confirmed PSA value of ≥ 0.2 ng/mL after prostatectomy or ≥ 2 ng/mL above nadir after 


 
 
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radiation therapy, is known as biochemical recurrence (BCR) of prostate cancer.39 40  BCR after 
initial therapy may develop in 20-30% of patients.36,37  Although PSA is the primary biomarker 
for recurrence, its values cannot determine the location or the extent of disease burden of 
recurrent and/or metastatic disease.  PSA kinetics, such as PSA velocity as measured by PSA 
doubling time (PSADT), are helpful in early detection of occult disease, however they still 
cannot differentiate between local, regional, or systemic disease to guide further disease 
management.   
The transition to a state of evident metastatic disease (M1) on imaging represents a significant 
clinical event for both the patients and their treating physicians.  Conventional imaging 
modalities all have low sensitivity and are not able to determine the location of recurrent or 
metastatic prostate cancer, particularly at low PSA levels.4,5,6,7   Thus, imaging agents and 
modalities that will detect and localize small metastatic lesions, with high sensitivity and 
specificity, are essential to more accurately diagnose and stage the disease, inform the best 
treatment strategy and potentially monitor therapeutic response.  Early diagnosis of disease 
recurrence is essential as exemplified by analyses of outcomes post salvage radiotherapy, which 
is most effective when initiated at PSA levels < 0.5 ng/ml.41, 42, 43   
A number of radiopharmaceutical PET imaging agents have been explored for the detection of 
prostate cancer, and studied particularly in BCR patients, including 2-deoxy-2-[18F]fluoro-D-
glucose (FDG), 11C-Choline, 18F-FACBC (18F-fluciclovine; Axumin), 68Ga-HBED-CC (68Ga-
PSMA-11), and 18F-DCFPyL.7,11,44 ,45, 46, 47, 48, 49  FDG PET, the clinical standard for a number of 
cancers, has demonstrated mixed results in imaging prostate cancer.7,10   Other tumor 
metabolism-based approaches are the use of radiolabeled choline to take advantage of the 
increased expression of choline kinase (ChKα) in tumor cells, or increased uptake of amino acids 
such as methionine or leucine.8,9  Although 11C choline was approved by FDA in the BCR setting 
in 2012, its sensitivity appears limited for extraprostatic lesions and has low detection rates for 
PSA < 1 ng/mL.50,51,52,53  18F-fluciclovine (synthetic L-leucine analog trans‐1‐amino‐3‐18F‐
fluoro‐cyclobutane carboxylic acid) PET/CT imaging has been studied in recurrent prostate 
cancer as well as suspected recurrent prostate cancer;46 47 5455 it was approved by the FDA in 
2016 in patients with rising PSA after initial definitive therapy.56  However, the detection rate of 
18F-fluciclovine seems to be affected by PSA levels, with higher chance of false positive scans in 
patients with PSA < 1.8 ng/mL.54 56  
The recognition of PSMA as a relatively specific biomarker for prostate cancer has resulted in 
the development of several diagnostic compounds currently under clinical investigation, with the 
promise of better sensitivity to detect early, more likely curable stages of metastatic or recurrent 
prostate cancer.  PSMA is highly expressed in castration-resistant, metastatic prostate cancer.21   
A retrospective evaluation of data from 68Ga-PSMA PET/CT imaging in the BCR setting showed 
58% detection rate, even in patients with low PSA (0.2 to <0.5 ng/ml).48  Studies have also 
compared 68Ga-PSMA PET and 18F-choline PET imaging, and 68Ga-PSMA PET versus 18F-
fluciclovine PET in prostate cancer.57 58,59  Comparison of 68Ga-PSMA PET to both PET-
imaging agents showed significantly higher detection rate and diagnostic accuracy with 68Ga-
PSMA PET in prostate cancer, including patients with recurrent prostate cancer as well as those 
with suspected recurrence (BCR).49,58 


 
 
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Nevertheless, fluorine-18 (F-18) PET tracers offer important advantages over PET tracers 
labeled with other radionuclides, including Ga-68, such as higher production capacity, longer 
half-life, and improved image resolution. Thus, 18F-DCFPyL, a PSMA PET-imaging agent, 
promises to be a useful diagnostic candidate for the detection of metastatic or recurrent prostate 
cancer, including in the BCR setting where there remains a high unmet medical need.  
2. 
TRIAL OBJECTIVES AND PURPOSE 
2.1. 
Primary Objective 
To determine the Correct Localization Rate (CLR) of 18F-DCFPyL PET/CT imaging in the 
detection of recurrent prostate cancer at the subject level  
2.2. 
Secondary Objectives 
1. To assess the impact of 18F-DCFPyL PET/CT disease detection on patient’s clinical 
management plans  
2. To evaluate the safety and tolerability of 18F-DCFPyL 
2.3. 
Exploratory Objectives 
1. To determine detection rates of disease sites with 18F-DCFPyL PET/CT by region 
(prostatic, pelvic, extra-pelvic) and baseline PSA 
2. To determine the Positive Predictive Value (PPV) of 18F-DCFPyL PET/CT imaging in 
the detection of recurrent disease in the prostatic, pelvic, and extra-pelvic regions  
3. 
TRIAL ENDPOINTS 
3.1. 
Primary Endpoint 
The CLR at the subject level, defined as the percentage of subjects for whom there is a one-to-
one correspondence between localization of at least one lesion identified on 18F-DCFPyL 
PET/CT imaging and the composite truth standard (See Section 8.1) 
3.2. 
Secondary Endpoints  
3.2.1. 
Secondary Efficacy Endpoints 
• The percentage of subjects with a change in intended prostate cancer treatment plans due 
to 18F-DCFPyL PET/CT as measured by comparison of intended management 
questionnaires completed Pre- and Post- 18F-DCFPyL PET/CT imaging results 
3.2.2. 
Safety Endpoints 
• Incidence of treatment-emergent adverse events from time of 18F-DCFPyL dosing up to 7 
(±3) days following 18F-DCFPyL dosing  
• Change from Baseline to post 18F-DCFPyL injection vital signs 


 
 
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• Concomitant medications and medical procedures 
3.3. 
 Exploratory Endpoints 
• 
The detection rates of 18F-DCFPyL PET/CT among lesion locations i.e., prostatic, pelvic, 
extra-pelvic  
• 
The PPV of 18F-DCFPyL PET/CT for prostatic, pelvic, extra-pelvic regions from the 
composite truth standard in subjects with positive lesion(s) on 18F-DCFPyL PET/CT 
imaging  
• The percentage of subjects with positive 18F-DCFPyL PET/CT scans who have negative 
findings for prostate cancer based on the composite truth standard  
• The detection rates of 18F-DCFPyL PET/CT imaging as a function of baseline PSA 
groups   
4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design 
This is a phase 3, multi-center, open-label, single-arm, non-randomized study to evaluate the 
diagnostic performance and safety of 18F-DCFPyL (PyL) PET/CT in subjects with suspected 
recurrence of prostate cancer and negative or equivocal findings per institutional standard of care 
conventional imaging. This study is planned to be conducted in approximately 15 sites in the 
United States and Canada, and to be conducted in conformance with Good Clinical Practices 
(GCP). 
Eligible subjects (see Section 5 for Eligibility Criteria) will be enrolled in a non-randomized, 
sequential manner, with competitive enrollment between study sites.  Enrolled subjects will 
receive a single dose of 9 mCi (333 MBq) 18F-DCFPyL Injection followed by a single PET/CT 
scan acquired at 1-2 hours post-dosing.   
Only subjects with positive PyL PET/CT scans (detection of disease at any site) will be followed 
at the Efficacy visit(s) (See Table 3 Schedule of Assessments).  Subjects will undergo Efficacy 
follow-up based on their PyL PET/CT finding(s) per local interpretation and clinical presentation 
for evaluation of the composite truth standard as defined in Section 8.1.    
If biopsy or surgery of a lesion identified on PyL PET/CT is feasible, attempts will be made to 
obtain tissue corresponding to the PyL-suspected lesion(s) within 60 days following PyL 
PET/CT imaging.  If local histopathology results are obtained, they will be recorded in the eCRF 
and if the results are evaluable for prostate cancer, the subject will complete the study.   
If histopathology (from biopsy or surgery) is not evaluable, or biopsy or surgery of the PyL-
suspected lesion was not performed, an attempt will be made to anatomically correlate the PyL-
suspected lesion(s) with conventional imaging modality per the Investigator’s discretion within 
60 days following PyL PET/CT imaging.  The conventional imaging scan will be sent to the 
central imaging core lab for review.  If the scan is deemed evaluable by the central imaging core 
lab, the subject will complete the study.   
 


 
 
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If evaluable histopathology is not available and conventional imaging of the PyL-suspected 
lesion(s) is not informative, those subjects who are planned to receive locoregional RT without 
concomitant androgen deprivation therapy (ADT) within 60 days following PyL PET/CT 
imaging will continue on-study and be followed for PSA changes following RT alone.  PSA 
(total) will be collected every 3 months post-RT alone (until Response is achieved as defined in 
Section 8.1, for a maximum of up to 9 months total duration) and sent to the central lab for 
analysis.  All other subjects not initiated on locoregional RT alone within 60 days post PyL 
PET/CT imaging will be discontinued from the study. 
Subjects who are initiated on any systemic therapy for prostate cancer (PC) will be discontinued 
from the study.  
Once the study reaches the required number of subjects evaluable for calculation of the primary 
endpoint as described in Section 10.4.2 , subject enrollment and follow-up assessments will 
conclude, and the study database will be locked for analysis.  Adverse events (AEs) will be 
assessed following 18F-DCFPyL dosing (Day 1), and again via a safety phone call 7 (±3) days 
post-18F-DCFPyL dosing to capture any late-occurring AEs. 
Medical Management Questionnaires (MMQs) will be completed by the treating investigator at 
two time-points during the study to capture intended changes in the clinical management for all 
subjects who underwent 18F-DCFPyL PET/CT imaging: 
• Prior to 18F-DCFPyL dosing, the treating investigator will complete the Pre-PyL MMQ 
based on baseline clinical information and results from conventional imaging.  
• Post-18F-DCFPyL imaging, the treating investigator will complete the Post-PyL MMQ 
based on the additional result from local interpretation of the 18F-DCFPyL PET/CT scan, 
to assess whether an intended change to the initial medical management plan is warranted 
due to the PyL finding. 
See Figure 1 and Table 3 for the study schema and schedule of study assessments.  Details on 
study procedures for each visit are described in Section 4.3. 


 
 
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Figure 1: Study Schema 
 
4.2. 
Number of Subjects 
Approximately 200 subjects are planned to be enrolled in this study to meet the number of 
subjects required for assessment of the primary endpoint.  The Sponsor will periodically monitor 
the rate of positive 18F-DCFPyL PET/CT scans and the number of evaluable subjects that 
contribute to the efficacy assessment.  If the observed rate of positive 18F-DCFPyL PET/CT 
scans is lower than expected, the sample size may need to be increased.  When the required 
number of subjects are evaluable for calculation of the primary endpoint, subject enrollment and 
follow-up assessments will conclude.   
See Section 5 for eligibility criteria and Section 10.1 for complete sample size assumptions. 
4.3. 
Study Procedures  
See Figure 1 for the study schema and Table 3 Schedule of Assessments for a comprehensive 
summary. 
4.3.1. 
Screening (Day -30 to 1) 
The following screening procedures and assessments must be completed prior to 18F-DCFPyL 
dosing and PET/CT imaging (Day 1):  
• Obtain informed consent 


 
 
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• Demographic information, including date of birth, race, ethnicity, height and weight 
• Clinically relevant medical history  
• Prostate cancer history, including disease history, staging, and treatment(s) 
• Conventional imaging findings per institutional standard of care (SOC) scan(s) (e.g., 
pelvic CT/MRI, whole-body bone scan, NaF, fluciclovine or choline PET) completed 
within 60 days prior to Day 1.  SOC scan(s) performed more than 60 days prior to Day 1 
may be repeated as a study Screening procedure and reviewed by the investigator prior to 
Day 1. 
Subjects who provide signed informed consent and meet all eligibility criteria during Screening 
must also complete the following additional procedures prior to 18F-DCFPyL dosing PET/CT 
imaging (Day 1):  
• Obtain a blood draw for PSA (total) and send to the central lab.  If done on Day 1, the 
blood draw should be collected prior to 18F-DCFPyL dosing. 
• The treating investigator completes the Pre-PyL Medical Management Questionnaire 
(MMQ) to document the initial intended management plan for the subject based on 
available clinical information and local conventional imaging results.  
4.3.2. 
18F-DCFPyL – Dosing and PET/CT Imaging (Day 1) 
Subjects will visit the clinic for 18F-DCFPyL dosing and whole-body PET/CT imaging on Day 1.   
Prior to receiving 18F-DCFPyL Injection, perform the following:  
• Measure vital signs (blood pressure and heart rate); 
• Record current medications and procedures and note changes from Screening. 
All subjects are to receive a prescribed dose of 9 mCi (333 MBq) 18F-DCFPyL Injection.  Dosing 
adjustments of 18F-DCFPyL are not permitted.  See Section 7.6 Study Drug Administration for 
details. 
After dosing of 18F-DCFPyL Injection and within approximately 60-120 minutes post-18F-
DCFPyL dosing, perform the following: 
• Measure vital signs (blood pressure and heart rate); 
• Acquire a single PET/CT scan from mid-thigh to skull (See Imaging Manual for 
guidelines);  
• Record treatment-emergent adverse events (AEs) and any new medications and/or 
procedures since prior to 18F-DCFPyL dosing. 
The site’s local interpretation of 18F-DCFPyL PET/CT results will be recorded in the eCRF.  See 
the Imaging Manual for 18F-DCFPyL PET/CT interpretation guidelines.  
4.3.3. 
Safety Follow-up (phone call; Day 8 [±3]) 
A safety phone call at 7 (±3) days post-18F-DCFPyL dosing is required for all subjects who 
received any dose of 18F-DCFPyL to capture any late-occurring AEs and concomitant 


 
 
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medications and procedures.  If Efficacy follow-up occurs within 7 (±3) days post-18F-DCFPyL 
dosing, the Safety phone call will not be completed, and the late-occurring AEs and concomitant 
medications and procedures will instead be collected at the time of the Efficacy follow-up.  
See Section 9 Assessment of Safety for complete details. 
4.3.4. 
Post-PyL Intended Management Plan (Day 2-60) 
For all subjects who complete the PyL PET/CT scan, the Post-PyL MMQ will be completed by 
the treating investigator based on the additional result from the local PyL PET/CT scan to 
document whether a change to the initial intended management plan may be warranted due to the 
PyL finding.  The Post-PyL MMQ should be completed within 60 days following 18F-DCFPyL 
PET/CT imaging.  
4.3.5. 
Efficacy Follow-up (Performed or Initiated by Day 2-60) 
Only subjects with positive PyL PET/CT scans (detection of disease at any site) per local 
interpretation will continue to be followed for verification of PyL-suspected lesion.  Subjects 
who do not have a positive PyL PET/CT result will have completed the study after completing 
the Safety follow-up. 
4.3.5.1. 
Verification of PyL-suspected lesion (per local PyL PET/CT finding) 
Subjects with at least one positive lesion identified per local PyL PET/CT imaging will undergo 
Efficacy follow-up for the composite truth standard as defined in Section 8.1.  Concomitant 
medications and procedures will be collected at the time of the Efficacy follow-up visit(s).  See 
Table 3 Schedule of Assessments. 
Biopsy or Surgery within 60 days following 18F-DCFPyL PET/CT 
At least 12 hours from time of 18F-DCFPyL dosing and no more than 60 days following PyL 
PET/CT imaging (Day 1) and prior to initiation of any radiation or systemic therapies for 
prostate cancer, an image-guided biopsy or surgery (e.g. salvage pelvic lymph node dissection) 
of a lesion identified by PyL PET/CT scan is encouraged if clinically feasible.   
For subjects undergoing image-guided needle biopsy, the needle biopsy images (e.g., CT, TRUS-
MRI, US) of the procedure will be sent to the central imaging core lab.  
Local histopathology results of tissue(s) obtained will be recorded in the eCRF.  Subjects with an 
evaluable histopathology result for prostate cancer will have completed the study.  If evaluable 
histopathology result is not available, then subjects will undergo conventional imaging follow-up 
within 60 days following 18F-DCFPyL PET/CT imaging.  See Section 8 Assessment of Efficacy.  
Conventional imaging within 60 days following 18F-DCFPyL PET/CT  
If biopsy or surgery is not clinically feasible on a lesion identified by PyL PET/CT scan, 
conventional imaging based on the Investigator’s discretion (e.g., targeted MRI or CT; 
fluciclovine or choline PET) on the PyL-suspected lesion will be performed and sent to the 
central imaging core lab.  The choice of the most appropriate conventional imaging modality will 
be at the discretion of the investigator; use of the most sensitive imaging method is encouraged, 
such as targeted MRI for verification of the PyL-suspected bone lesion(s).   


 
 
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Subjects with informative conventional imaging of the anatomical correlate to the PyL-suspected 
lesion(s) based on central imaging core lab review will have completed the study.  
See Section 8 Assessment of Efficacy. 
Initiation of locoregional radiation therapy (RT) in subjects without evaluable histopathology 
result or informative conventional imaging of the PyL-suspected lesion(s) within 60 days 
following 18F-DCFPyL PET/CT  
If an evaluable histopathology result for prostate cancer is not available and follow-up 
conventional imaging of the PyL-suspected lesion is not informative, subjects initiated on 
locoregional RT alone (no concomitant ADT) within 60 days following PyL PET/CT imaging 
will be followed every 3 months (± 7 days) for up to an additional 9 months to assess PSA 
response to RT alone (without concomitant ADT administered during this time).  To be 
evaluable for PSA response, applicable subjects should undergo RT with fields and target 
volumes adjusted based on presence of PyL-positive prostate bed, pelvic nodal, visceral or 
limited osseous metastases. 
A blood draw for PSA (total) will be obtained and sent to the central lab at each follow-up 
assessment. PSA response is defined by decline of ≥ 50% from baseline PSA and must be 
confirmed within 4 weeks. Subjects will complete follow-up within the 9-month duration once 
PSA response is confirmed per the central lab.   
Concomitant medications and procedures will be collected.  See Section 8 Assessment of 
Efficacy. 
4.4. 
Study Duration 
Subjects will be deemed enrolled once they sign informed consent and meet all inclusion and no 
exclusion criteria and complete all screening assessments.  The study duration of subject 
participation from Screening through 18F-DCFPyL PET/CT imaging and Efficacy visit(s), if 
applicable, will be a maximum duration of approximately 12 months.   At a minimum, all 
subjects who receive a dose of 18F-DCFPyL will be followed from time of informed consent 
until the safety phone call on Day 8 (± 3).   
Only subjects with positive PyL PET/CT scans (detection of disease at any site) will be followed 
at the Efficacy visit(s).  Subjects will undergo Efficacy assessments based on the site’s local PyL 
PET/CT interpretation and clinical presentation.  
• Subjects with any positive PyL PET/CT finding(s) per local interpretation will be 
evaluated as described in Section 4.3.5. 
• Subjects without any positive PyL PET/CT finding per local interpretation will complete 
the study through the safety phone call; no further visits will be required.  
The Sponsor may conclude the study before subjects complete their efficacy follow-up 
assessments (see Section 10.4.2) 


 
 
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4.5. 
Safety Monitoring 
An independent Data Monitoring Committee (DMC) will not be used for this open-label study.  
However, safety monitoring will consist of continuously monitoring adverse events on an 
ongoing basis in accordance with Section 9.  A safety review committee, consisting of Sponsor 
representatives (e.g., Medical Monitor, Clinical, Drug Safety) will also review data on an 
ongoing basis to assess subject safety and eligibility through listings, tables and subject profiles. 
4.6. 
Criteria for Study Termination 
The Sponsor reserves the right to terminate the study at any time. In the event of serious, 
unexpected and related adverse events, the program may be stopped prematurely upon advice 
from the Safety Review Committee, the Sponsor or upon request from the FDA.  In addition, the 
Sponsor or the Institutional Review Board (IRB) or Independent Ethics Committee (IEC) may 
terminate an investigational site for the following (but not limited to) reasons:  
• If any significant safety issues occur; 
• Failure of the Investigator to comply with pertinent International Conference on 
Harmonisation (ICH) E6 guidelines on Good Clinical Practice (GCP) guidelines and 
regulations; 
• If significant protocol violations occur; 
• Submission of knowingly false information from the research facility to the Sponsor, 
Clinical Monitor, or other party involved in the study; 
• Failure of the Investigator to enroll subjects into the study at an acceptable rate as 
agreed-upon with the Sponsor 


 
 
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Table 3: 
Schedule of Assessments 
 
Screening 
18F-DCFPyL Dosing & 
Imaging 
Safety 
Phone call3 
Efficacy follow-up4 
Day 
-30 to 1 
1 
1  
(60-120 min 
post-
dosing) 
8 (±3) 
2 to 
60 
Every 3 months 
following 
initiation of 
locoregional RT, 
up to 9 months7 
Informed Consent & 
Eligibility  
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
Prior Medications and Prior 
Cancer Treatments 
X 
 
 
 
 
 
Vital Signs (blood pressure, 
heart rate) 
 
X (pre-
dosing) 
X 
 
 
 
 
PSA (Total) 
X1 
 
 
 
 
X1,7 
Conventional imaging 
X2  
 
 
 
X6 
 
18F-DCFPyL Administration 
 
X 
 
 
 
 
Whole body PyL PET/CT 
 
 
X 
 
 
 
Surgery or image-guided 
biopsy & histopathology 
 
 
 
 
X5 
 
Locoregional radiation 
therapy per investigator 
discretion 
 
 
 
X7 
 
Treatment-emergent 
Adverse Events 
 
X  
X 
 
 
Concomitant Medications 
and Procedures 
 
X 
X 
X 
 
X 
Medical Management 
Questionnaire  
X8 
 
 
X9 
 
1. 
Total PSA will be collected and sent to central lab for analysis.  If done on Day 1 of Screening, the blood draw should be 
collected prior to 18F-DCFPyL dosing.  
2. 
Applicable conventional imaging performed as part of standard of care workup within 60 days prior to Day 1. 
3. 
A safety phone call will occur 7 (±3) days post-18F-DCFPyL dosing if Efficacy follow-up has not yet occurred. 
4. 
Efficacy follow-up visit(s) are only applicable for subjects with positive 18F-DCFPyL PET/CT finding(s) per local 
interpretation 
5. 
Surgery or biopsy to occur at least 12 hours from time of 18F-DCFPyL dosing but not more than 60 days following 18F-
DCFPyL PET/CT imaging. Imaging used to guide biopsy (e.g., CT, MRI-TRUS, US) will be submitted to the central core 
imaging lab. 
6. 
Follow-up conventional imaging (e.g., targeted MRI/CT, fluciclovine or choline PET) per Investigator’s discretion of the 
anatomical correlate to the lesion(s) identified on 18F-DCFPyL PET/CT is required in subjects whom evaluable 
histopathology for prostate cancer is not available.  The image(s) will be submitted to the central core imaging lab for 
review and determination of evaluability. 
7. 
If evaluable histopathology result for prostate cancer is not available and follow-up conventional imaging of the PyL-
suspected lesion is not informative, subjects initiated on locoregional radiation therapy (RT) alone within 60 days following 
PyL PET/CT (with no concomitant ADT administered during this time) will be followed every 3 months (± 7 days), up to 9 
months post-initiation of RT.  PSA response (decline of ≥50% from baseline PSA) must be confirmed (two consecutive 
levels within 4 weeks) per central lab evaluation. 
8. 
Pre-PyL Medical Management Questionnaire (MMQ) will be completed by the treating investigator for all subjects enrolled 
(who signed informed consent and met all eligibility criteria) in the study prior to Day 1.   
9. 
Post-PyL MMQ will be completed by the treating investigator for all subjects who completed 18F-DCFPyL PET/CT 
imaging.  


 
 
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5. 
SUBJECT SELECTION AND WITHDRAWAL CRITERIA 
5.1. 
Subject Inclusion Criteria 
Subjects must meet all of the following inclusion criteria: 
1. Male ≥ 18 years of age 
2. Histopathologically confirmed prostate adenocarcinoma per original diagnosis, with 
subsequent definitive therapy 
3. Suspected recurrence of prostate cancer based on rising PSA after definitive therapy on 
the basis of: 
a. Post-radical prostatectomy (RP): Detectable or rising PSA that is ≥ 0.2 ng/mL with a 
confirmatory PSA ≥ 0.2 ng/mL (American Urological Association [AUA] 
recommendation)39; or  
b. Post-radiation therapy (RT), cryotherapy, or brachytherapy:  Increase in PSA level 
that is elevated by ≥ 2 ng/mL above the nadir (American Society for Therapeutic 
Radiology and Oncology [ASTRO]-Phoenix consensus definition)40 
4. Negative or equivocal findings for prostate cancer on conventional imaging performed as 
part of standard of care workup within 60 days prior to Day 1 
5. Life expectancy ≥6 months as determined by the investigator 
6. Able and willing to provide informed consent and comply with protocol requirements 
5.2. 
Subject Exclusion Criteria 
Subjects meeting any of the following exclusion criteria are not eligible for this study: 
1. Subjects administered any high energy (>300 KeV) gamma-emitting radioisotope within 
five (5) physical half-lives prior to Day 1 
2. Ongoing treatment with any systemic therapy (e.g., androgen deprivation therapy [ADT], 
antiandrogen, GnRH, LHRH agonist or antagonist) for prostate cancer 
3. Treatment with ADT in the past 3 months of Day 1 
4. Receipt of investigational therapy for prostate cancer within 60 days of Day 1 
5. Subjects with any medical condition or other circumstances that, in the opinion of the 
investigator, compromise the safety or compliance of the subject to produce reliable data 
or completing the study 
5.3. 
Subject Withdrawal Criteria 
A subject may withdraw from the study at any time for any reason without prejudice to his future 
medical care by the physician or at the study site.  Likewise, the Investigator and/or Sponsor 


 
 
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have the right to withdraw patients from the study.  Subjects may be discontinued for any of the 
following reasons: 
• Significant protocol violation or noncompliance  
• Adverse event that precludes further study participation 
• Best medical interest of the patient (Investigator decision) 
• Sponsor terminates the study 
• Subject requests to be withdrawn from the study 
• Subject is lost to follow-up 
• Death 
Should a subject withdraw from the study, all efforts will be made to complete the required study 
procedures as thoroughly as possible prior to withdrawal.   
Data will be collected for all withdrawn subjects up until the time of discontinuation.  The reason 
for discontinuation from the study will be recorded in the subject’s eCRF.   
6. 
TREATMENT OF SUBJECTS 
6.1. 
Description of Study Drug 
A single administration of 18F-DCFPyL Injection will be administered prior to PET/CT imaging 
on Day 1. 
Table 4: 
Investigational Product 
Product Name 
18F-DCFPyL INJECTION  
Dosage Form 
Sterile solution for intravenous injection 
Unit Dose 
9 mCi (333 MBq) at the Time of Administration 
Route of Administration 
Intravenous catheter placed in an antecubital vein or an 
equivalent venous access 
Physical Description 
Colorless, particle-free solution  
6.2. 
Concomitant Medications and Procedures 
All concomitant medications and medical procedures will be recorded in the eCRF from post-
18F-DCFPyL dosing (Day 1) and at all subsequent study visits as shown in Table 3 Schedule of 
Assessments.   
Any new or changed medications, including prostate cancer therapy, from time of 18F-DCFPyL 
injection to each study visit must be recorded in the eCRF.  Subjects who receive concomitant 
systemic or investigational therapy for prostate cancer anytime during participation in the study 
will be discontinued from the study. 


 
 
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6.3. 
Treatment Compliance 
All 18F-DCFPyL injections will be administered under the supervision of the investigator or 
qualified designee.  Details of the study drug injection will be captured in each subject’s source 
documents. 
6.4. 
Randomization and Blinding 
This is an open-label, non-randomized study.   
Independent readers from a central imaging core lab will be given access to 18F-DCFPyL 
PET/CT, biopsy-guided imaging (if performed), and follow-up conventional imaging (if 
performed).  The central readers will be blinded to all other clinical information and 
histopathology results (if available).    
Institutional staff may review all local images in conjunction with available clinical information 
to permit clinical management planning for the subject.   The informed consent form (ICF) must 
include language of potential changes to the medical management plan for the subject.   
7. 
STUDY DRUG MATERIALS AND MANAGEMENT 
7.1. 
Study Drug 
Please reference Section 6.1 for a description of the study drug. 
7.2. 
Restrictions 
7.2.1. 
Food and Fluid Intake 
There are no dietary or food restrictions for this trial.   
Fasting is not required prior to 18F-DCFPyL (PyL) dosing and PET/CT imaging. Increased fluid 
intake should occur before and after image acquisition to maintain proper hydration throughout 
the study period, decrease radiation exposure to the urinary bladder and improve image quality.  
Additionally, subjects should be encouraged to void as frequent as possible.  At a minimum void 
post study drug injection, immediately before imaging, and after imaging. 
Subjects should follow pre-imaging and preoperative guidelines as per institutional practices and 
in accordance with standard of care principles. 
7.2.2. 
Radioactivity  
The radioactivity administered in this study is similar to other diagnostic radiopharmaceuticals 
and should be managed according to institutional policies.   
7.3. 
Study Drug Packaging and Labeling 
The final drug product (18F-DCFPyL) is a clear, particulate-free injectable solution at a strength 
of 1-90 mCi/mL (37-3330 MBq/mL) 18F-DCFPyL at End of Synthesis (EOS).  18F-DCFPyL will 


 
 
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be dispensed and filled into a unit-dose syringe.  The final drug product will be placed into a lead 
shield unit-dose system and delivered to the clinical site.  
Labels will be generated according to local policies and meet minimum requirements for labeling 
radioactive materials in compliance with federal, state, and local pharmacy regulations.  
Progenics minimum requirements for the syringe label will include the following:  subject 
identifier, product name, dispensing lot number, ordered dose, dispense date/time, dispensed 
activity and volume, and beyond use date.  “New Drug—Limited by Federal Law to 
Investigational Use” will be included on the prescription label of the lead shield unit-dose system 
for each unit-dose syringe. 
7.4. 
Study Drug Storage 
The study drug should be maintained at room temperature within the received lead shield unit-
dose system until time of administration.   
7.5. 
Study Drug Preparation 
The final drug product is supplied to each institution on the day of administration in a unit-dose 
syringe (contained in the lead shield unit-dose system) with no additional preparation required. 
Institutional policies and procedures should be followed for receipt and appropriate radiation 
safety handling.   
Before and after each administration, measure the amount of radioactivity in the syringe using an 
appropriate dose calibrator.  Record the exact times of dose calibration and time of injection.  
The decay-corrected administered dose will be calculated in the electronic database management 
system when the dose measurements and times are entered in the eCRF.  Please see the Imaging 
Manual for complete details including pre and post-injection measurement of the 18F-DCFPyL 
Injection dose syringe 
7.6. 
Study Drug Administration 
Administration must occur by the labeled expiration time.  Please see the Imaging Manual for 
complete details including pre and post-injection measurement of the 18F-DCFPyL Injection dose 
syringe.   
• Place an IV catheter in an antecubital vein or an equivalent venous access. 
• Ensure patency of the line with a saline flush. 
• Inject a bolus of the prescribed dose of 18F-DCFPyL (9 mCi or 333 MBq) of into the 
IV line or equivalent venous access by slow push from the appropriately shielded 
syringe according to normal local practices. 
• Administer an intravenous flush (e.g., 5-10 ml sterile Sodium Chloride Injection, 
0.9%), to ensure full delivery of the dose. 
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• Try to aspirate as much extravasated drug as possible through the still-intact catheter.  
Any of the dose remaining should be measured and recorded to permit correction of 
the administered dose for radioactive decay. 
• Imaging should proceed unless contraindicated for safety reasons. 
• Notify the interpreting physician of the extravasation (location and estimated 
amount). 
• Examine the skin area for local toxicity before discharge; instruct subject to contact 
site immediately if local symptoms at injection site do not improve or worsen.  
• Note the extravasation as an Adverse Event in the eCRF. 
7.7. 
Study Drug Accountability 
In accordance with ICH and FDA requirements, the investigator and/or drug dispenser must at 
all times account for all study drug furnished to the institution and prepared for the subject, 
whether used or unused.   
No study agent is to be used outside of this study.  Accurate and adequate accountability records 
must be maintained by the radiopharmacy, hot lab or nuclear medicine department responsible 
for receipt and dispensation of study drug.  Records should include at minimum: 
• Dates of receipt, lot number and quantities received from Sponsor or designee; 
• Dates, subject numbers, and amount dispensed for administration to specific subjects; 
• If applicable, dates, lot numbers, and drug quantities destroyed. 
The investigator is responsible for ensuring that study drug is administered only to subjects 
included in this study in accordance with the study protocol. 
Throughout the study, drug accountability will be performed by appropriate Sponsor 
representative(s) and when appropriate, reconciliation will be performed. 
7.8. 
Study Drug Handling and Disposal 
18F-DCFPyL Injection is a radioactive drug and should be handled by personnel trained in the 
proper use and disposal of radiopharmaceuticals according to institutional policies and applicable 
regulations or guidance.  When handling and administering 18F-DCFPyL Injection, follow 
aseptic procedures and use effective radiation shielding, and appropriate safety measures to 
minimize radiation exposure.   
Empty or unused product should be decayed at the site according to institutional policies and 
applicable state and federal regulations.  Record the use and/or decay of study drug on the Drug 
Accountability record. 


 
 
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8. 
ASSESSMENT OF EFFICACY 
8.1. 
Composite Truth Standard 
Subjects will undergo Efficacy assessments based on their local PyL PET/CT finding(s) and 
clinical presentation for evaluation of the composite truth standard, defined either as: 
1) evaluable local histopathology result for prostate cancer from surgery or biopsy performed 
within 60 days following PyL PET/CT, or  
2) if evaluable histopathology is not available, informative conventional imaging (e.g., targeted 
MRI or CT; fluciclovine or choline PET) finding(s) of the anatomical correlate to the PyL-
suspected lesion(s) within 60 days following PyL PET/CT, before locoregional or systemic 
treatment in started, or  
3) if neither of the above is available or informative, confirmed PSA response (PSA decline by 
≥50% from baseline, confirmed within 4 weeks per central lab evaluation) post-RT (no 
concomitant ADT) that was initiated within 60 days following PyL PET/CT.  PSA will be 
collected every 3 months, up to 9 months until PSA response (if achieved) is confirmed.   
8.2. 
Image Acquisition 
Central imaging core lab readers will independently assess all PyL PET/CT images as well as 
any subsequent conventional images performed following PyL PET/CT. 
8.2.1. 
Follow-up conventional imaging to verify PyL-suspected lesion(s) within 60 days 
following 18F-DCFPyL PET/CT 
Within 60 days following 18F-DCFPyL PET/CT imaging, if a positive lesion(s) is identified on 
18F-DCFPyL PET/CT and tissue acquisition of the PyL-suspected lesion is not feasible, then 
conventional imaging (e.g., targeted MRI or CT, fluciclovine or choline PET) will be performed 
in an attempt to anatomically correlate the PyL-suspected lesion(s).   All follow-up imaging will 
be sent to the central imaging core lab. The choice of the most appropriate conventional imaging 
modality will be at the discretion of the investigator; use of the most sensitive imaging method is 
encouraged, such as targeted MRI for verification of the PyL-suspected bone lesion(s).    
If tissue acquisition (by surgery or biopsy) of the PyL-suspected lesion is feasible, then see 
Section 8.4 Histopathology.   
8.2.2. 
18F-DCFPyL PET/CT Imaging  
Prior to enrollment, all PET/CT scanners to be used in this study must be qualified in accordance 
with the procedures outlined in the Imaging Manual.   
18F-DCFPyL PET/CT imaging will be performed using local PET/CT scanners with low dose CT 
for attenuation correction and anatomic localization as described in the Imaging Manual. 
Subjects will be asked to void prior to imaging.  After voiding, a whole-body CT and PET scan 
will be acquired starting from the mid-thigh through the skull.  Whole body PET/CT scans must 
be obtained within 60-120 minutes following the 18F-DCFPyL dosing.   
All 18F-DCFPyL PET emission data should be acquired and reconstructed in accordance with the 
Imaging Manual.   


 
 
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8.2.3. 
Imaging at Biopsy (if biopsy is performed) 
If a 18F-DCFPyL (PyL) PET-positive lesion is feasible for biopsy, then an image-guided biopsy 
should be performed on the amenable lesion.  The imaging modality (e.g., CT, MRI-TRUS, US) 
used to guide biopsy will be collected in the eCRF.  The image obtained at biopsy will be 
submitted for central review to confirm the anatomical location of interest correlates with the 
lesion identified on the PyL PET/CT.   
The instruction for capturing biopsy images and directions for submitting the images to the 
central imaging core lab is found in the Imaging Manual.  
8.3. 
Image Interpretation by Central Imaging Core Lab 
The central imaging core lab will receive and evaluate all conventional images and PyL PET/CT 
scans, as applicable.  Imaging data will be anonymized at the site upon image submission to the 
central lab and prepared for reading.  PET data will be interpreted by three different independent 
readers in a random order at separate reading sessions. Cross sectional CT imaging from the 
PET/CT scans will be available for anatomic correlation.  Central imaging core lab readers will 
be blinded to all clinical data, including PSA and histopathology (if available).   
The processes for image acquisition, transmittal and interpretation are detailed in the Imaging 
Manual and Imaging Review Charter documents. 
8.4. 
Histopathology from Biopsy or Surgery (if performed) of PyL-
positive lesion(s) within 60 days following 18F-DCFPyL PET/CT 
Within 60 days following PyL PET/CT imaging and prior to initiation of any new systemic or 
radiation PC therapy, if a PyL-positive lesion is identified per the site’s image interpretation, 
tissue acquisition via surgery or image-guided biopsy should be performed if clinically feasible.  
Immediately following biopsy or surgery, the specimens will be sent for local histopathological 
processing and analysis at the site in accordance with the study Pathology Manual.  Procedures 
and results will be recorded in the eCRF.  See Section 8.4 for histopathology processing and 
analysis at the site.  If the subject’s histopathology result is evaluable for prostate cancer, then no 
further visits are required for the subject.  If histopathology is not evaluable, then see Section 
8.2.1 for required conventional imaging follow-up.   
8.4.1. 
  Image-Guided Biopsy (if feasible) of PyL-positive lesion 
Image-guided (e.g., CT, MRI-TRUS, US) needle biopsy of a PyL-positive lesion is highly 
encouraged if clinically feasible.  If tissue acquisition of a PyL-positive lesion is not feasible, see 
Section 8.2.1 for required conventional imaging follow-up.   
See Section 8.2.3 for instructions on image at biopsy and Section 8.3 for submitting the images 
to the central imaging core lab.  
8.5. 
PSA (total) Response 
If evaluable histopathology result for prostate cancer is not available and follow-up conventional 
imaging of the PyL-suspected lesion is not informative, subjects initiated on locoregional RT 


 
 
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alone (no concomitant ADT within 60 days following PyL PET/CT imaging) will be followed 
every 3 months for up to an additional 9 months post initiation of RT to assess PSA response to 
RT alone (without concomitant ADT administered during this time).  A blood draw for PSA 
(total) will be obtained and sent to the central lab at each follow-up assessment. PSA response is 
defined by decline of ≥ 50% from baseline PSA and must be confirmed within 4 weeks. Subjects 
will complete follow-up within the 9-month duration once PSA response is confirmed per the 
central lab.   
To be evaluable for PSA response, applicable subjects should undergo RT with fields and target 
volumes adjusted based on presence of PyL-positive prostate bed, pelvic nodal, visceral or 
limited osseous metastases.   
8.6. 
Change in Management Intent  
The intended clinical management plan for a subject will be entered into the eCRF based on the 
treating investigator’s assessment prior to 18F-DCFPyL PET/CT imaging and within 60 days 
following 18F-DCFPyL PET/CT imaging.   
Medical Management Questionnaires (MMQs) will be completed by the treating investigator at 
two time-points during the study to capture any change in the intended clinical management plan 
for a subject: 
• Prior to 18F-DCFPyL dosing, the treating investigator will complete the Pre-PyL MMQ 
based on baseline clinical information and results from conventional imaging.  
• Post-18F-DCFPyL imaging, the treating investigator will complete the Post-PyL MMQ 
based on the additional result from the 18F-DCFPyL PET/CT scan, to assess whether 
intended change to the initial medical management plan may be warranted due to the PyL 
finding. 
9. 
ASSESSMENT OF SAFETY 
9.1. 
Safety Parameters 
9.1.1. 
Demographic Information and Medical History 
Demographic and baseline information, including date of birth (DOB), race, ethnicity, and height 
and weight will be collected and recorded in the eCRF.   
A complete prostate medical history will be obtained at the first screening visit.  Prostate medical 
history includes review of prostate disease history, prostate cancer staging, biopsy results, and all 
past/present therapies.   
Other clinically relevant medical history will be recorded prior to study drug administration.  
This should include any past and/or current medical conditions that, in the opinion of the 
investigator, are clinically relevant regardless of whether it has resolved. All conditions that 
correspond with the subject’s concomitant medications will be recorded in the eCRF. 


 
 
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9.1.2. 
Vital Signs 
Vital sign measurements will include blood pressure (BP) and heart rate (HR). All measurements 
should be obtained from the subject in the sitting position and measured at two intervals on the 
day of dosing, including pre- and post-PyL dosing.   
9.2. 
Adverse and Serious Adverse Events 
9.2.1. 
Definition of Adverse Events 
9.2.1.1. 
Adverse Event (AE) 
An AE is any untoward medical occurrence in a research subject administered an investigational 
product (IP) at any dose, which does not necessarily have a causal relationship with the IP.  An 
AE can therefore be any unfavorable and unintended sign, symptoms or disease temporally 
associated with the use of the IP, whether or not considered related to the IP.  
All AEs (related and unrelated) will be collected after 18F-DCFPyL dosing on Day 1 and again 
via a safety phone call at 7 (±3) days following 18F-DCFPyL dosing to document possible late-
occurring AEs.  All AEs must be recorded according to Section 9.4.  
9.2.1.2. 
Serious Adverse Event (SAE) 
A serious adverse event is an AE that fulfils one or more of the following: 
• Results in death 
• It is immediately life-threatening 
• It requires in-patient hospitalization or prolongation of existing hospitalization 
• It results in persistent or significant disability or incapacity 
• Results in a congenital abnormality or birth defect of a patient’s child   
• It is an important medical event that may jeopardize the patient or may require 
medical intervention to prevent one of the outcomes listed above. 
9.2.2. 
Overdose and Underdose 
For this study, any administered dose of 18F-DCFPyL differing from the prescribed dose of 9 
mCi (333 MBq) by more than 20% will be considered a dosing deviation.  An overdose is any 
administered dose greater than 10.8 mCi (400 MBq).  Progenics does not recommend specific 
treatments for an overdose.  In the event of an overdose, the subject should be monitored for any 
AEs for the duration of the safety reporting period. Likewise, an underdose is any administered 
dose less than 7.2 mCi (266 MBq). The study site should comply with the reporting requirements 
of their radioactive materials license and 10 CFR Part 35 - Medical Use of Byproduct Material. 
9.3. 
Relationship to Study Drug 
The Principal Investigator or Sub-Investigator must make the determination of relationship to the 
investigational product for each AE (unrelated or related).  The Investigator should decide 


 
 
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whether, in his or her medical judgment, there is a reasonable possibility that the event may have 
been caused by the investigational product.  If there is any valid reason, even if undetermined, 
for suspecting a possible cause-and-effect relationship between the investigational product and 
the occurrence of the AE, then the AE should be considered “related.”  If no valid reason exists 
for suggesting a relationship, then the AE should be classified as “unrelated.”   
9.4. 
Recording Adverse Events 
Adverse events spontaneously reported by the subject and/or in response to an open question 
from the study personnel or revealed by observation will be recorded during the study at the 
investigational site.   
Information about AEs and SAEs will be collected from the first administration of study drug 
until the follow-up safety phone call.  The AE term should be reported in standard medical 
terminology and be the medical diagnosis when possible.  For each AE, the investigator will 
evaluate and report the onset (date and time), resolution (date and time), intensity, causality, 
outcome, and whether or not it caused the patient to discontinue the study. 
Intensity will be assessed according to the NCI CTCAE, version 4.03.  If the CTCAE grading is 
not defined in the NCI CTCAE grading table for a particular AE, severity will be rated according 
to the following definitions 
• Mild (awareness of sign or symptom, but easily tolerated) 
• Moderate (discomfort sufficient to cause interference with normal activities) 
• Severe (incapacitating, with inability to perform normal activities) 
• Life Threatening (immediate risk of death from the event as it occurred) 
• Death (death related to adverse event) 
It is important to distinguish between seriousness and severity of AEs.  Severity is a measure of 
intensity whereas seriousness is defined by the criteria under Section 9.2.1.2.  An AE of severe 
intensity may not be considered serious.  Conversely, a serious AE can be of mild or moderate 
intensity. 
9.5. 
Reporting Serious Adverse Events 
All SAEs (related and unrelated) will be recorded at the same interval defined for AE collection 
as indicated in Section 9.2.1.1.  Any SAEs considered at least possibly related to the 
investigational product and discovered by the Investigator at any time after the protocol-defined 
reporting period, should be reported to the Sponsor or designee within 24 hours of the first 
awareness of the event.  The Investigator must complete, sign and date the SAE form, verify the 
accuracy of the information recorded on the SAE pages with the corresponding source 
documents, and send a copy by email or fax to Sponsor, or designee.   
Additional follow-up information, if required or available, should promptly be emailed or faxed 
to Sponsor, or designee, via a signed and dated follow-up SAE form, within 24 hours of first 
becoming aware of the additional information. 


 
 
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Progenics Pharmaceuticals, Inc. is responsible for notifying the relevant regulatory authorities of 
events that are expedited (unexpected, serious, study drug-related events).  It is the Principal 
Investigator’s responsibility to notify the IRB/IEC of all SAEs that occur at his or her site.  
Investigators will also be notified of all expedited reports that occur at other sites during the 
clinical trial.  Each site is responsible for notifying its IRB/IEC of these additional SAEs. 
10. 
STATISTICS 
10.1. 
Sample Size 
The primary endpoint is the correct localization rate (CLR) at the subject level, in subjects with 
positive PyL PET/CT findings, defined as the percentage of subjects with a one-to-one 
correspondence between localization of at least one lesion identified on 18F-DCFPyL PET/CT 
imaging and the composite truth standard.  The composite truth standard is defined in Section 
8.1.  
The assumed CLR of 18F-DCFPyL PET/CT imaging is 30%.  Based on the variable published 
experience with 68Ga-PSMA PET/CT and a meta-analysis by Perera et al60, approximately 76% 
(95% confidence interval [CI], 66-85%) of PSMA scans are positive in patients with suspected 
recurrence of prostate cancer following initial therapy. Therefore, in subjects with negative or 
equivocal findings for prostate cancer on baseline conventional imaging, 60% of subjects are 
conservatively estimated to have PyL PET/CT positive findings.  In consideration of the extent 
of 68Ga-PSMA PET literature and the present study entry criteria, approximately 30% of PSMA 
PET positive findings may be verified by biopsy/surgery-based histopathology, conventional 
imaging, or PSA follow-up post-RT. 48,58,61,62   It is therefore assumed that 30% of the positive 
PyL results in the study will be confirmed by the composite truth standard.  If 60% of the study 
subjects have positive PyL scans, and 30% of these positive diagnostic scans are confirmed by 
the composite truth standard, the use of the PyL PET/CT will permit the detection/localization of 
recurrent prostate cancer in approximately 18% of the study population, versus at most 5% that 
could be identified by conventional imaging alone. 
The sample size estimates are based on the positive likelihood ratio (PLR) of CLR to prevalence.  
The PLR is estimated as 𝑃𝑃𝑃= (
𝐶𝐶𝐶
1−𝐶𝐶𝐶)/(
𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝
1−𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝) .   
Conservatively assuming the initial prevalence rate as a population parameter to be 5% by 
conventional imaging,42 43  if a CLR of 30% is realized, the positive likelihood ratio is expected 
to be 8.1,implying a considerable increase in the clinical value of PyL PET/CT to identify 
prostate cancer. 
Using a lower bound for the 95% CI for CLR of 20%, the corresponding lower bound for PLR 
would be 4.75 based on a normal approximation to the Binomial. This will thus require a total of 
81 positive PyL scans, which translates to a total of 134 PyL PET/CT scans or evaluable subjects 
needed.  Accounting for a 30% non-evaluable (including loss to follow-up) rate, approximately 
192 subjects will need to undergo PyL PET/CT in the study.  


 
 
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During study enrollment, the rate of positive 18F-DCFPyL PET/CT scans will be calculated 
periodically to confirm the assumption of 60%. If the observed rate is lower than expected, the 
sample size may need to be increased. 
10.2. 
Analysis Populations 
10.2.1. 
Safety Population 
All subjects who receive any amount of 18F-DCFPyL. 
10.2.2. 
Full Analysis Set (FAS) 
All subjects who have received any amount of 18F-DCFPyL and have 18F-DCFPyL PET/CT 
imaging results. 
10.2.3. 
Per Protocol Set 
The per protocol population will consist of the FAS excluding subjects with major protocol 
violations.   
10.3. 
Missing Data 
No imputation of missing data will be applied, with the exception of partial dates for prior 
treatments or medications. 
10.4. 
Analyses 
In general, continuous endpoints will be summarized by visit using summary statistics: N, mean, 
standard deviation, median, minimum, and maximum.  Categorical endpoints will be 
summarized using frequencies and percentages. 
10.4.1. 
Subject Characteristics 
A disposition table will be presented to show the number and percentage of subjects in each 
population set, study completers, and early discontinuations along with reasons for 
discontinuation.  
Baseline characteristics will be summarized for the Safety Population and the Full Analysis Set. 


 
 
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10.4.2. 
Efficacy Analyses 
Efficacy endpoints will be assessed using the FAS.  Continuous monitoring will be performed 
with respect to the number of subjects evaluable for the primary endpoint.  When the required 
number of subjects with positive 18F-DCFPyL PET/CT scans and information for the composite 
truth standard are available for calculation of the CLR, subject enrollment and follow-up 
assessments will conclude, and the study database will be locked for analysis.  Any subjects who 
are undergoing efficacy evaluations who have not contributed endpoint data at the time of 
database lock will be censored and will be treated as unevaluable for efficacy. 
10.4.2.1. Primary Endpoint Analysis 
The primary endpoint of the CLR is evaluated in a subset of FAS subjects with at least one 
positive lesion identified by PyL PET/CT imaging (per local interpretation).  The CLR at the 
subject-level is defined as the percentage of subjects for whom there is a one-to-one 
correspondence between localization of at least one lesion identified on 18F-DCFPyL PET/CT 
imaging and the composite truth standard.   
The composite truth standard is defined in Section 8.1.  
The CLR is computed as 100×TP/(TP+FP); TP = true positives, FP = false positives.  
A true positive (TP) result is defined as a subject with both a positive lesion(s) on 18F-DCFPyL 
PET/CT and a positive result on the composite truth standard:  
• Positive finding for prostate cancer of a PyL-suspected lesion according to local 
histopathology (one confirmed anatomical correlate will suffice to declare the PyL 
PET/CT a true positive), or 
• Positive finding for prostate cancer of a PyL-suspected lesion upon follow-up 
conventional imaging performed following PyL PET/CT (one confirmed anatomical 
correlate will suffice to declare the PyL PET/CT a true positive), or 
• PSA decreases drop by ≥50% from baseline following RT without concomitant ADT up 
to 9 months following initiation of such treatment. 
False positives will be defined as subjects with positive lesion(s) on PyL PET/CT who have the 
following negative findings for prostate cancer according to the composite truth standard: 
• Negative finding for prostate cancer of a PyL-suspected lesion according to local 
histopathology, or 
• Negative finding for all PyL positive lesion(s) upon follow-up conventional imaging 
performed following PyL PET/CT (one confirmed anatomical correlate will suffice to 
declare the PyL PET/CT a true positive), or 
• PSA does not drop by ≥50% from baseline following RT (without concomitant ADT) up 
to 9 months following initiation of such treatment. 
The two-sided 95% CI for the CLR will be computed using the normal approximation to the 
binomial distribution.  This analysis will be performed for each of the central imaging core lab 


 
 
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readers. If the lower bound of the 95% CI is >0.2 for two of the three independent imaging 
reviewers, then the primary endpoint analysis is deemed a success. 
10.4.2.2. Secondary Endpoints Analyses 
The secondary efficacy endpoint will be generated on the FAS for all subjects regardless of 
finding(s) on PyL PET/CT imaging, and be analyzed using a two-sided 95% CI presented for 
each imaging reviewer separately based on a normal approximation to the binomial:  
• The percentage of subjects with a change in intended prostate cancer treatment plan from 
Pre- and Post 18F-DCFPyL PET/CT scan evaluated using a one sample binomial test.   A 
summary of shifts in planned management from Pre- and to Post- 18F-DCFPyL imaging 
evaluations will also be presented. 
10.4.2.3. Exploratory Endpoint Analyses 
Exploratory efficacy endpoints will be generated on the FAS for detection rates on the subset of 
the FAS with at least one positive lesion identified by PyL PET/CT imaging for PPV and false 
positive scan rate endpoints.  
The following endpoints will be analyzed using a two-sided 95% CI presented for each imaging 
reviewer separately based on a normal approximation to the binomial:  
• Detection rates of 18F-DCFPyL PET/CT imaging by lesion locations (i.e., prostatic, 
pelvic, extra-pelvic) 
• The PPV of 18F-DCFPyL PET/CT for (1) prostatic, (2) pelvic, (3) extra-pelvic regions 
from the composite truth standard in subjects with positive lesion(s) on 18F-DCFPyL 
PET/CT imaging  
• The percentage of subjects with positive 18F-DCFPyL PET/CT scans who have negative 
findings for prostate cancer (false positive scans) based on the composite truth standard  
• The percentage of false positive scans is defined as (1-CLR) 
• The detection rates of 18F-DCFPyL PET/CT imaging as a function of baseline PSA 
groups   
10.4.3. 
Safety Analyses 
All Safety parameters will be presented for the Safety Population. 
10.4.3.1. Exposure 
Volume administered of 18F-DCFPyL (mL) and activity administered (mCi) will be summarized 
using the Safety Population. 
10.4.3.2. Treatment-Emergent Adverse Events 
Treatment-emergent adverse events will be those observed from immediately post-dosing of 18F-
DCFPyL on Day 1, through the safety phone call 7 (±3) days post- 18F-DCFPyL dosing for late-
occurring TEAEs.  


 
 
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Adverse event verbatim terms will be coded using the current version of the Medical Dictionary 
for Regulatory Activities (MedDRA) at the start of the study.  This version will be used 
throughout the course of the study.  The frequency and percentage of subjects with an adverse 
event will be summarized by system organ class and preferred term.  Adverse events will also be 
summarized by maximum severity and separately, by highest relationship to treatment.   
Serious adverse events, adverse events leading to study discontinuation and adverse events 
leading to death will be listed.  
10.4.3.3. Vital Signs 
Changes in vital signs relative to 18F-DCFPyL dosing will be computed as the post-dosing values 
(1-2 hours post-18F-DCFPyL dosing) minus the pre-dosing value.  Observed values and changes, 
when computed, will be tabulated for each visit using summary statistics. 
10.4.3.4. Concomitant Medications and Procedures 
Concomitant medications, coded using the current version of the WHO Drug dictionary at the 
start of the study, will be tabulated.  A concomitant medication is a medication administered in 
the period between the day of 18F-DCFPyL dosing through the Follow-up phone call.  Non-
concomitant medications (those administered prior to dosing of 18F-DCFPyL) will also be 
tabulated and considered to be “prior” medications.  Concomitant procedures are all procedures 
performed from the time of 18F-DCFPyL dosing until the follow-up visits are completed. 
Concomitant procedures will be coded using the same version of MedDRA as for medical 
history. 
11. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
Data collected during this study may be used to support the development, registration or 
marketing of 18F-DCFPyL Injection.  All data collected during the study will be controlled by 
Progenics or designee and Progenics will abide by all relevant data protection laws.   
The investigator will grant monitor(s) and auditor(s) from Progenics or its designee and 
regulatory authority(ies) access to the subject’s original medical records for verification of data 
entered into the eCRF and to audit the data collection process.  The subject’s confidentiality will 
be maintained and will not be made publicly available to the extent permitted by the applicable 
laws and regulations. 
11.1. 
Study Site Monitoring 
Before an investigational site can enter a patient into the study, a representative of the Sponsor 
will visit the investigational study site to: 
• Determine the adequacy of the facilities 
• Discuss with the investigator(s) and other personnel their responsibilities with regard 
to protocol adherence, and the responsibilities of Progenics or its representatives.  
This will be documented in a Clinical Study Agreement between Progenics, or 
designee and the investigator. 


 
 
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During the study, a monitor from Progenics or designee will have regular contacts with the 
investigational site, for the following: 
• Provide information and support to the investigator(s) 
• Confirm that facilities remain acceptable 
• Confirm that the investigational team is adhering to the protocol, that data are being 
accurately recorded in the case report forms, and that investigational product 
accountability checks are being performed 
• Perform source data verification.  This includes a comparison of the data in the case 
report forms with the patient’s medical records at the hospital or practice, and other 
records relevant to the study.  This will require direct access to all original records for 
each patient (e.g., clinic charts). 
• Record and report any protocol deviations not previously sent to the Sponsor, or 
designee. 
• Confirm AEs and SAEs have been properly documented on CRFs and confirm any 
SAEs have been forwarded to the Sponsor, or designee, and those SAEs that met 
criteria for reporting have been forwarded to the IRB. 
The monitor will be available between visits if the investigator(s) or other staff needs 
information or advice. 
11.2. 
Audits and Inspections 
Authorized representatives of the Sponsor, a regulatory authority, an IEC or an IRB may visit the 
site to perform audits or inspections, including source data verification.  The purpose of a 
Sponsor audit or inspection is to systematically and independently examine all study-related 
activities and documents to determine whether these activities were conducted, and data were 
recorded, analyzed, and accurately reported according to the protocol, GCP guidelines of the 
International Conference on Harmonization, and any applicable regulatory requirements.   
The investigator should contact Progenics immediately if contacted by a regulatory agency about 
an inspection and will provide Progenics with the results of any such audits and with copies of 
any regulatory documents related to such audits. 
12. 
ETHICS 
This clinical trial will be conducted in accordance with the ethical principles that have their 
origin in the Declaration of Helsinki and that are consistent with GCP and applicable regulatory 
requirement(s).  The rights, safety, and well-being of the trial subjects are the most important 
considerations and should prevail over interests of science and society. 
12.1. 
Good Clinical Practice (GCP), Laws and Regulations 
The investigator must ensure that he/she and all authorized personnel for the study are familiar 
with the principles of GCP and that the study is conducted in full conformity with the current 


 
 
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revision of the Declaration of Helsinki, ICH Guidelines and applicable local laws and 
regulations, with the understanding that local laws and regulations take precedence over 
respective sections in the Declaration of Helsinki and/or the ICH Guidelines. 
12.2. 
Institutional Review Board (IRB) or Independent Ethics Committee 
(IEC) Approval 
The final study protocol, including the final version of the ICF, must be approved or given a 
favorable opinion in writing by an IRB or IEC as appropriate.  The investigator must submit 
documented approval to the Sponsor before he or she can enroll any patient/subject into the 
study. 
The Principal Investigator is responsible for informing the IRB or IEC of any amendment to the 
protocol in accordance with local requirements.  In addition, the IRB or IEC must approve all 
advertising used to recruit patients for the study.  The protocol must be re-approved by the IRB 
or IEC upon receipt of amendments and annually, as local regulations require. 
The Principal Investigator is also responsible for providing the IRB with reports of any 
reportable serious adverse drug reactions from any other study conducted with the investigational 
product.  The Sponsor, or designee, will provide this information to the Principal Investigator. 
Progress reports and notifications of serious adverse drug reactions will be provided to the IRB 
or IEC according to local regulations and guidelines. 
12.3. 
Written Informed Consent 
The Principal Investigator(s) at each center will ensure that the patient is given full and adequate 
oral and written information about the nature, purpose, possible risk and benefit of the study.  
Patients must also be notified that they are free to discontinue from the study at any time.  The 
patient should be given the opportunity to ask questions and allowed time to consider the 
information provided. 
The patient’s signed and dated informed consent must be obtained before conducting any study 
procedures. 
The Principal Investigator(s) must maintain the original, signed ICF.  A copy of the signed ICF 
must be given to the patient. 
12.4. 
Subject Confidentiality 
The Investigator must ensure that the subject’s privacy is maintained.  A subject should only be 
identified by their date of birth and subject number on the case report forms or other documents 
submitted to the Sponsor.  Documents that are not submitted to the Sponsor (e.g., signed ICF) 
should be kept in a strictly confidential section of the study file by the Investigator. 
Written authorization is to be obtained from each subject prior to enrollment into the study in 
accordance with the applicable privacy requirements [e.g., the Health Insurance Portability and 
Accountability Act of 1996 Standards for Privacy of Individually Identifiable Health Information 
(“HIPAA”) and any other state and country privacy requirements]. 


 
 
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12.5. 
Financial Disclosure 
All investigators must provide financial disclosure information in accordance with the U.S. Code 
of Federal Regulations Title 21 CFR 54.2 through 54.6. 
13. 
DATA HANDLING AND RECORDKEEPING 
13.1. 
Case Report Forms and Study Records 
Progenics or designee will provide an electronic case report form (eCRF) and eCRF Completion 
Guidelines for the entry of study data.  eCRFs must be completed for each subject.  All study 
data must be reported accurately on eCRFs from original source data.  Source documents are 
original documents, data and records (e.g., hospital records, office charts, laboratory notes, 
memoranda, evaluation checklists, pharmacy dispensing records, recorded data from automated 
instruments, magnetic media, diagnostic images, subject files).  The investigator will make 
available the source documents for inspection.  This information will be considered as 
confidential. 
The use of eCRFs will encompass electronic data entry, query management and investigator 
approval.  Systems used for electronic data capture will be compliant with FDA regulations 21 
CFR Part 11 and within the constraints of the applicable local regulatory agency guidelines.  
The Investigator or designee will review, sign and date the completed eCRF sections.  This 
signature will indicate a thorough inspection of the data in the eCRF and will certify its content. 
13.2. 
Inspection of Records 
The Sponsor, or designee, will be allowed to conduct site visits to the investigation facilities for 
the purpose of monitoring any aspect of the study.  The Investigator agrees to allow the monitor 
to inspect the drug storage area, study drug stocks, drug accountability records, subject charts 
and study source documents, and other records relative to study conduct.  See Section 11.2. 
13.3. 
Retention of Records 
The Principal Investigator must maintain all documentation relating to the study for a period of 
two (2) years after the last marketing application approval, or if not approved 2 years following 
the discontinuance of the test article for investigation, or per applicable local regulatory 
requirement, whichever is longer.  If it becomes necessary for the Sponsor or the Regulatory 
Authority to review any documentation relating to the study, the Investigator must permit access 
to such records.  No study document should be destroyed without prior written agreement 
between Sponsor and the investigator. 
14. 
PUBLICATION AND DISCLOSURE POLICY 
All unpublished documentation [including the protocol, eCRF and Investigator Brochure (IB)] 
given to the investigator is strictly confidential.  All recipients must agree not to disclose the 


 
 
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Page 42 
information herein contained to any person without the prior written authorization of Progenics.  
The submission of these documents to the IRB is expressly permitted.   
The investigator agrees that Progenics maintains the right to use the results of this study in their 
original form and/or in a global report for submission to governmental and regulatory authorities 
of any country. 
The results of the study may be presented during scientific symposia or published in a scientific 
journal only after review by Progenics in accordance with the guidelines set forth in the 
applicable publication or financial agreement. 
 


 
 
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15. 
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26. Reinfelder J, Kuwert T, Prante1 O, Wullich B, Hennig P, Beck M, Sanders J, Ritt P, 
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PSMA inhibitor for patients with biochemical recurrence of prostate cancer J Nucl Med 
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27. Chen Y, Pullambhatla M, Foss CA, Byun Y, Nimmagadda S, Senthamizhchelvan S, 
Sgouros G, Mease RC, Pomper MG. 2-(3-{1-Carboxy-5-[(6-[18F] fluoro-pyridine-3-
carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid,[ 18F] DCFPyL, a PSMA-based PET 
imaging agent for prostate cancer. Clin Cancer Res. 2011 Dec 15;17(24):7645-53. 
28. Szabo Z et al. Initial Evaluation of [18F]DCFPyL for Prostate-Specific Membrane 
Antigen (PSMA)-Targeted PET Imaging of Prostate Cancer. Mol Imaging Biol. Aug 1, 
2015; 17(4): 565–574. 
29. Li X, Rowe SP, Leal JP et al. Semi-quantitative parameters in PSMA-targeted PET 
imaging with 18F-DCFPyL: Variability in normal organ uptake. J Nucl Med 2017;58(6): 
942-946. 
30. Gorin MA, Rowe SP, Patel HD, Vidal I, Mana-Ay M, Javadi MS, Solnes LB, Ross AE, 
Schaeffer EM, Bivalacqua TJ, Partin AW. PSMA-targeted 18F-DCFPyL PET/CT in the 
Preoperative Staging of Men with High-risk Prostate Cancer: Results of a Prospective 
Phase II Single-Center Study. J Urol 2018; 199(1):126-132. 
31. Wondergem M, van der Zant F, Knol R, Lazarenko S, Pruim J, de Jong IJ. 18F-DCFPyL 
PET/CT in the detection of prostate cancer at 60 and 120 minutes; detection rate, image 
quality, activity kinetics and biodistribution. J Nucl Med 2017 Apr 27:jnumed-117. 
32. Bauman G, Martin P, Thiessen JD et al. [18F]-DCFPyL Positron Emission 
Tomography/Magnetic Resonance Imaging for Localization of Dominant Intraprostatic 
Foci: First Experience. EAU 2016 
33. Rowe SP, Macura KJ, Mena E, et al. PSMA-based [18F]DCFPyL PET/CT is superior to 
conventional imaging for lesion detection in patients with metastatic prostate cancer. Mol 
Imaging Biol 2016; 18:411-419. 
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Dietlein F, Zlatopolskiy BD, Krapf P, Richarz R. Comparison of [18F] DCFPyL and 
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(prostate specific antigen) recurrence probability following radical prostatectomy for 
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37. Amling CL, Blute ML, Bergstralh EJ, Seay TM, Slezak J, Zincke H. Long‐term hazard of 
progression after radical prostatectomy for clinically localized prostate cancer: continued 
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38. Greco C, Cascini GL, Tamburrini O. Is there a role for positron emission tomography 
imaging in the early evaluation of prostate cancer relapse? Prostate Cancer Prostatic Dis. 
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39. Cookson MS, Aus G, Burnett AL, et al.  Variation in the definition of biochemical 
recurrence in patients treated with localized prostate cancer: the American Urological 
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41. Thompson, IM, Valicenti R, Albertsen PC et al. Adjuvant and salvage radiotherapy after 
prostatectomy: ASTRO/AUA guideline 2013. 
42. Pound CR, Partin AW, Eisenberger MA, et al. Natural history of progression after PSA 
elevation following radical prostatectomy. JAMA 1999; 281:1591-1597. 
43. Antonarakis ES et al. The natural history of metastatic progression in men with prostate-
specific antigen recurrence after radical prostatectomy: long-term follow-up. BJU Int. 
2012; 109(1): 32–39. 
44. Rinnab L, Mottaghy FM, Blumstein NM, et al. Evaluation of [11C]choline positron 
emission tomography in patients with increasing prostate-specific antigen levels after 
primary treatment for prostate cancer. BJU Int. 2007;100: 786–793. 
45. Scattoni V, Picchio M, Suardi N, et al. Detection of lymph-node metastases with 
integrated [11C]choline PET/CT in patients with PSA failure after radical retropubic 
prostatectomy: results confirmed by open pelvic-retroperitoneal lymphadenectomy. Eur 
Urol. 2007;52:423–429. 
46. Nanni C, Zanoni L, Pultrone C, et al. 18F-FACBC(anti1-amino-3-18Ffluorocyclobutane-
1-carboxylic acid) versus 11C-choline PET/CT in prostate cancer relapse: results of a 
prospective trial. Eur J Nucl Med Mol Imaging. 2016;43:1601–1610. 
47. Bach-Gansmo T, Nanni C, Nieh PT, et al. Multi-site experience of the safety, detection 
rate and diagnostic performance of FACBC (18F) PET/CT imaging in the staging of 
biochemically recurrent prostate cancer. J Urol. 2017;197:676–683. 
48. Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, Graner FP, Kübler 
H, Haberkorn U, Eisenhut M, Wester HJ. Evaluation of hybrid 68Ga-PSMA ligand 
PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. Journal 
of Nuclear Medicine. 2015 May 1;56(5):668-74. 
49. Bluemel C, Krebs M, Polat B et al. 68Ga-PSMA PET/CT in patients with biochemical 
prostate cancer recurrence and negative 18F-choline PET/CT. Clin Nucl Med 2016. 


 
 
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50. Krause BJ, Souvatzpglou M, Tuncel M, et al. The detection rate of [11C]choline- 
PET/CT depends on the serum PSA-value in patients with biochemical recurrence of 
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51. Castellucci P, Fuccio C, Nanni C, et al. Influence of trigger PSA and PSA kinetics on 
11C-choline PET/CT detection rate in patients with biochemical relapse after radical 
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52. Evangelista L, Briganti A, Fanti S, Joniau S, Reske S, Schiavina R, Stief C, Thalmann 
GN, Picchio M. New Clinical Indications for 18F/11C-choline, New Tracers for Positron 
Emission Tomography and a Promising Hybrid Device for Prostate Cancer Staging: A 
Systematic Review of the Literature. European Urology 2016; 70: 161-175 
53. Treglia G, Ceriani L, Sadeghi R, Giovacchini G, Giovanella L. Relationship between 
prostate-specific antigen kinetics and detection rate of radiolabelled choline PET/CT in 
restaging prostate cancer patients: a meta-analysis. ClinChem Lab Med. 2014 
May;52(5):725–33. 
54. Schuster DM, Nieh PT, Jani AB, et al.  Anti-3-[18F]FACBC positron emission 
tomography-computerized tomography and 111In-Capromab Pendetide Single Photon 
emission computerized tomography-computerized tomography for recurrent prostate 
carcinoma: Results of a prospective clinical trial.  Jour of Urol. 2014; 191:1446-1453.   
55. Odewole OA, Tade FI, Nieh PT, et al.  Recurrent Prostate Cancer Detection with anti-3-
[18F] FACBC PET-CT: Comparison with Computed Tomography. Eur J Nucl Med Mol 
Imaging. 2016; 43(10):1773–1783. 
56. U.S. Food and Drug Administration NDA approval letter (May 27, 2018) accessible at 
https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2016/208054Orig1s000ltr.pdf 
57. Chaussé G,Niazi T, Abikhzer GS, Probst SM. Biopsy-proven diffuse mediastinal prostate 
cancer metastases negative on 18F-fluorocholine, diagnosed on 68Ga-PSMA and 18F-
PSMA PET/CT. Clin Nucl Med 2017;42(10):801-802. 
58. Calais J, Fendler WP, Herrmann K, et al.  Head-to-head comparison of 68Ga-PSMA-11 
and 18F-FACBC PET/CT in a case series of 10 patients with prostate cancer recurrence.  
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59. Pfister D, Porres D, Heidenreich A, Heidegger I, Knuechel R, Steib F, Behrendt FF, 
Verburg FA. Detection of recurrent prostate cancer lesions before salvage 
lymphadenectomy is more accurate with 68Ga-PSMA-HBED-CC than with 18F-
fluoroethylcholine PET/CT. European journal of nuclear medicine and molecular 
imaging. 2016 Jul 1;43(8):1410-1417. 
60. Perra M, Papa N, Christidis et al. Sensitivity, Specificity and Predictors of Positive 68Ga-
Prostate-specific Membrane Antigen Positiron Emission Tomography in Advanced 
Prostate Cancer: A Systematic Review and Meta-Analysis. Eur Urol. 2016; 70:926-937. 
61. Fendler W, et al. Accuracy of 68Ga-PSMA11 PET/CT on recurrent prostate cancer: 
Preliminary results from a phase 2/3 prospective trial. ASCO 2018 


 
 
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62. Yuminaga Y, et al. MP53-14 Evaluation of Gallium-68 PSMA PET/CT for Post-
Prostatectomy biochemical recurrence in comparison to CT abdomen/pelvis and bone 
scan.  The Journal of Urology. 2018 Apr 30;199(4):e709. 

SAP_001.pdf: 
Progenics Pharmaceuticals, Inc. 
Statistical Analysis Plan: Protocol PyL3301 
October 24, 2019 
1 
STATISTICAL ANALYSIS PLAN 
PHASE 3 
VERSION: 2.0 
DATE OF PLAN: 
24-OCT-2019 
BASED ON: 
Protocol Version: Original:  July 31, 2018 
CRF Date: April 18, 2019 
STUDY DRUG: 
18F-DCFPYL (PyL) 
PROTOCOL NUMBER: 
PyL-3301 
STUDY TITLE: 
A Phase 3, Multi-Center, Open-Label Study to Assess the DiagNostic Performance 
and Clinical Impact of 18F-DCFPyL PET/CT Imaging Results in Men with 
Suspected Recurrence of PrOstate CanceR (CONDOR) 
SPONSOR: 
Progenics Pharmaceuticals, Inc. 
One World Trade Center, 47th Floor, Suite J 
New York, NY 10007 
646-975-2500 
This study is being conducted in compliance with good clinical practice, including the archiving 
of essential documents. 
NCT03739684


Progenics Pharmaceuticals, Inc. 
Statistical Analysis Plan: Protocol PyL3301 
October 24, 2019 
2 
SIGNATURE PAGE 
This document has been prepared by: 


Progenics Pharmaceuticals, Inc. 
 
Statistical Analysis Plan: Protocol PyL3301  
 
October 24, 2019 
 
3 
 
 
  
 
TABLE OF CONTENTS 
1. 
LIST OF ABBREVIATIONS.......................................................................................6 
2. 
INTRODUCTION ........................................................................................................8 
3. 
STUDY OBJECTIVES ................................................................................................9 
3.1. 
Primary Objective .........................................................................................................9 
3.2. 
Secondary Objectives ...................................................................................................9 
3.3. 
Exploratory Objectives .................................................................................................9 
4. 
STUDY DESIGN .......................................................................................................10 
5. 
STUDY ENDPOINTS ................................................................................................14 
5.1. 
Efficacy Endpoints ......................................................................................................14 
5.1.1. 
Primary Endpoint ........................................................................................................14 
5.1.2. 
Secondary Endpoints ..................................................................................................18 
5.1.3. 
Tertiary/Exploratory Endpoints ..................................................................................19 
5.2. 
Safety Endpoints .........................................................................................................20 
5.3. 
Pharmacokinetic Endpoints ........................................................................................20 
6. 
ANALYSIS POPULATIONS ....................................................................................21 
6.1. 
Consented Population .................................................................................................21 
6.2. 
Safety Population ........................................................................................................21 
6.3. 
Full Analysis Set (FAS) Population ...........................................................................21 
6.4. 
Per-Protocol (PP) Population ......................................................................................21 
7. 
SAMPLE SIZE ...........................................................................................................22 
7.1. 
Sample Size Justification and Calculation ..................................................................22 
7.2. 
Interim Analyses .........................................................................................................22 
8. 
STATISTICAL ANALYSIS AND DATA CONVENTIONS ...................................23 
8.1. 
Computer Software .....................................................................................................23 
8.2. 
Data Presentation Conventions ...................................................................................23 
8.3. 
Baseline Characteristics ..............................................................................................23 
8.3.1. 
Baseline Definition .....................................................................................................23 
8.3.2. 
Subject Disposition .....................................................................................................23 
8.3.3. 
Demographic and Baseline Characteristics ................................................................23 
8.3.4. 
Medical History ..........................................................................................................23 
8.3.5. 
Prior Prostate Cancer Treatments ...............................................................................23 


Progenics Pharmaceuticals, Inc. 
 
Statistical Analysis Plan: Protocol PyL3301  
 
October 24, 2019 
 
4 
 
 
  
 
8.4. 
Missing Efficacy Endpoints ........................................................................................24 
8.5. 
Efficacy Analysis ........................................................................................................24 
8.5.1. 
General Considerations ...............................................................................................24 
8.5.2. 
Analysis of the Primary Efficacy Endpoint ................................................................24 
8.5.3. 
Analysis of Secondary Efficacy Endpoints ................................................................27 
8.5.4. 
Analysis of Exploratory Efficacy Endpoints ..............................................................28 
8.5.5. 
Other Efficacy Data ....................................................................................................29 
8.5.6. 
Intra- and Inter-reader Reliability Assessments .........................................................29 
8.6. 
Safety Analysis ...........................................................................................................30 
8.6.1. 
Adverse Events ...........................................................................................................30 
8.6.2. 
Study Drug Exposure and Compliance .......................................................................31 
8.6.3. 
Concomitant and Other Medications ..........................................................................31 
8.6.4. 
Laboratory Data ..........................................................................................................32 
8.6.5. 
Vital Signs ..................................................................................................................32 
8.6.6. 
Physical Examination .................................................................................................32 
9. 
DERIVED AND TRANSFORMED DATA ..............................................................33 
9.1.1. 
Baseline Age ...............................................................................................................33 
9.1.2. 
Study Day ...................................................................................................................33 
9.1.3. 
Change from Baseline .................................................................................................33 
9.1.4. 
Visit Windows ............................................................................................................33 
10. 
REFERENCES ...........................................................................................................34 
11. 
APPENDIX.................................................................................................................35 
11.1. 
Table of Contents for Data Displays ..........................................................................35 
 
 


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LIST OF TABLES 
Table 1: 
List of Abbreviations ....................................................................................................6 
Table 2: 
Schedule of Assessments ............................................................................................12 
Table 3: 
Lesion Locations and Anatomic Regions ...................................................................15 
Table 4: 
Primary Endpoint Assessment ....................................................................................16 
Table 5: 
Changes in Planned Therapy ......................................................................................18 
Table 6: 
Shifts in Planned Therapy ...........................................................................................28 
Table 7: 
Visit Windows (Days) ................................................................................................33 
 


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1. 
LIST OF ABBREVIATIONS 
Table 1: 
List of Abbreviations 
Abbreviation 
Term 
ADT 
Androgen Deprivation Therapy 
AE 
Adverse Event 
BCR 
Biochemical Recurrence 
CI 
Confidence Interval 
CLR 
Correct Localization Rate 
CSR 
Clinical Study Report 
CT 
Computerized Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events  
FAS 
Full Analysis Set 
GCP 
Good Clinical Practices 
ICH 
International Council on Harmonisation 
kg 
Kilogram 
LN 
Lymph node(s) 
MAR 
Missing-at-random 
MBq 
megaBequerel 
mCi 
millicurie 
MedDRA 
Medical Dictionary for Regulatory Activities Terminology 
mg 
Milligram 
MI 
Multiple imputation 
mL 
Milliliter 
MMQ 
Medical Management Questionnaire 
MRI 
Magnetic Resonance Imaging 
N 
Total Sample Size 
ng 
Nanogram 
PET 
Positron Emission Tomography 
PP 
Per-Protocol Population 
PPV 
Positive Predictive Value 
PSA 
Prostate-specific Antigen 
PT 
Preferred term 
PyL 
18F-DCFPyL 


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RP 
Radical prostatectomy 
RT 
Radiation therapy 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SOC 
System Organ Class 
SUV 
Standardized uptake value 
WHO 
World Health Organization  
 


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2. 
INTRODUCTION 
The purpose of this statistical analysis plan (SAP) is to describe the planned analyses and data 
displays to be included in the Clinical Study Report (CSR) for Protocol PyL-3301. This SAP was 
developed in accordance with ICH E9 guideline1. All decisions regarding final analysis, as 
defined in this SAP document, will be made prior to database lock unless communicated to the 
governing Regulatory Authority. Further information can be found in the protocol. 
 


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3. 
STUDY OBJECTIVES  
3.1. 
Primary Objective 
To determine the Correct Localization Rate (CLR) of 18F-DCFPyL PET/CT imaging in the 
detection of recurrent prostate cancer at the subject level  
3.2. 
Secondary Objectives 
1. To assess the impact of 18F-DCFPyL PET/CT disease detection on patient’s clinical 
management plans  
2. To evaluate the safety and tolerability of 18F-DCFPyL 
3.3. 
Exploratory Objectives 
1. To determine detection rates of disease sites with 18F-DCFPyL PET/CT by region 
(prostatic, pelvic, extra-pelvic) and baseline PSA 
2. To determine the Positive Predictive Value (PPV) of 18F-DCFPyL PET/CT imaging in the 
detection of recurrent disease in the prostatic, pelvic, and extra-pelvic regions  


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4.
STUDY DESIGN
This is a phase 3, multi-center, open-label, single-arm, non-randomized study to evaluate the 
diagnostic performance and safety of 18F-DCFPyL (PyL) PET/CT in subjects with suspected 
recurrence of prostate cancer and negative or equivocal findings per institutional standard of care 
conventional imaging. This study is planned to be conducted in approximately 15 sites in the 
United States and Canada, and to be conducted in conformance with Good Clinical Practices 
(GCP). 
Eligible subjects will be enrolled in a non-randomized, sequential manner, with competitive 
enrollment between study sites.  Enrolled subjects will receive a single dose of 9 mCi (333 MBq) 
18F-DCFPyL Injection followed by a single PET/CT scan acquired at 1-2 hours post-dosing.   
Only subjects with positive 18F-DCFPyL PET/CT scans per local interpretation (detection of 
disease at any location) will be followed for Efficacy follow-up visit(s) (See Table 1 Schedule of 
Assessments).  18F-DCFPyL PET/CT scans will be evaluated by three independent central 
readers blinded to all clinical and other imaging information.  18F-DCFPyL PET/CT imaging 
results reported by the central readers will be compared to the composite truth standard of 
histopathology where available, imaging follow-up, or treatment response as defined in Section 
5.1.1.    
Once the study reaches the required number of subjects evaluable for calculation of the primary 
endpoint as described in Section 7.1, subject enrollment and follow-up assessments will 
conclude, and the study database will be locked for analysis.  Adverse events (AEs) will be 
assessed following 18F-DCFPyL dosing (Day 1), and again via a safety phone call 7 (±3) days 
post-18F-DCFPyL dosing to capture any late-occurring AEs. 
Medical Management Questionnaires (MMQs) will be completed by the treating investigator at 
two time-points during the study to capture planned changes in the clinical management for all 
subjects who underwent 18F-DCFPyL PET/CT imaging: 
•
Prior to 18F-DCFPyL dosing, the treating investigator will complete the Pre-PyL MMQ
based on baseline clinical information and results from conventional imaging.
•
Post-18F-DCFPyL imaging, the treating investigator will complete the Post-PyL MMQ
based on the additional result from local interpretation of the 18F-DCFPyL PET/CT scan,
to assess whether a planned change to the initial medical management plan is warranted
due to the PyL finding.
The study Schema is in Figure 1 and the Schedule of Assessments is in Table 2 


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Figure 1: 
Study Schema 
 
 


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Table 2: 
Schedule of Assessments 
Screening 
18F-DCFPyL Dosing & 
Imaging 
Safety 
Phone 
call3 
Efficacy follow-up4 
Day 
-30 to 1
1 
1  
(60-120 min 
post-dosing) 
8 (±3) 
2 to 60 
Every 3 months 
following 
initiation of 
locoregional RT, 
up to 9 months7
Informed Consent & Eligibility 
X 
Demographics 
X 
Medical History 
X 
Prior Medications and Prior 
Cancer Treatments 
X 
Vital Signs (blood pressure, 
heart rate) 
X (pre-dosing) 
X 
PSA (Total) 
X1
X1,7 
Conventional imaging 
X2 
X6 
18F-DCFPyL Administration 
X 
Whole body PyL PET/CT 
X 
Surgery or image-guided biopsy 
& histopathology 
X5 
Locoregional radiation therapy 
per investigator discretion 
X7 
Treatment-emergent Adverse 
Events 
X 
X 
Concomitant Medications and 
Procedures 
X 
X 
X 
X 


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Screening 
18F-DCFPyL Dosing & 
Imaging 
Safety 
Phone 
call3 
Efficacy follow-up4 
Day 
-30 to 1
1 
1  
(60-120 min 
post-dosing) 
8 (±3) 
2 to 60 
Every 3 months 
following 
initiation of 
locoregional RT, 
up to 9 months7
Medical Management 
Questionnaire  
X8 
X9
1.
Total PSA will be collected and sent to central lab for analysis.  If done on Day 1 of Screening, the blood draw should be collected prior to 18F-DCFPyL
dosing.
2.
Applicable conventional imaging performed as part of standard of care workup within 60 days prior to Day 1.
3.
A safety phone call will occur 7 (±3) days post-18F-DCFPyL dosing if Efficacy follow-up has not yet occurred.
4.
Efficacy follow-up visit(s) are only applicable for subjects with positive 18F-DCFPyL PET/CT finding(s) per local interpretation
5.
Surgery or biopsy to occur at least 12 hours from time of 18F-DCFPyL dosing but not more than 60 days following 18F-DCFPyL PET/CT imaging. Imaging
used to guide biopsy (e.g., CT, MRI-TRUS, US) will be submitted to the central core imaging lab.
6.
Follow-up conventional imaging (e.g., targeted MRI/CT, fluciclovine or choline PET) per Investigator’s discretion of the anatomical correlate to the
lesion(s) identified on 18F-DCFPyL PET/CT is required in subjects whom evaluable histopathology for prostate cancer is not available.  The image(s) will
be submitted to the central core imaging lab for review and determination of evaluability.
7.
If evaluable histopathology result for prostate cancer is not available and follow-up conventional imaging of the PyL-suspected lesion is not informative,
subjects initiated on locoregional radiation therapy (RT) alone within 60 days following PyL PET/CT (with no concomitant ADT administered during this
time) will be followed every 3 months (± 7 days), up to 9 months post-initiation of RT.  PSA response (decline of ≥50% from baseline PSA) must be
confirmed (two consecutive levels within 4 weeks) per central lab evaluation.
8.
Pre-PyL Medical Management Questionnaire (MMQ) will be completed by the treating investigator for all subjects enrolled (who signed informed consent
and met all eligibility criteria) in the study prior to Day 1.
9.
Post-PyL MMQ will be completed by the treating investigator for all subjects who completed 18F-DCFPyL PET/CT imaging


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5.
STUDY ENDPOINTS
5.1. 
Efficacy Endpoints
Efficacy endpoints that reference 18F-DCFPyL PET/CT imaging findings are based on imaging 
results as reported by central imaging review by three independent, blinded central readers.  The 
primary endpoint of CLR and the exploratory PPV endpoints are also based on the assessments 
made by the Imaging Truth Panel (a consensus of two readers distinct from the independent 
central PyL readers). See the study Imaging Review Charter for read paradigm and details.  The 
change in clinical management endpoint is based on investigator assessment of local 18F-
DCFPyL PET/CT imaging findings.  
5.1.1. 
Primary Endpoint 
The primary endpoint of the CLR is evaluated in a subset of Full Analysis Set (FAS) subjects 
with at least one positive lesion identified by 18F-DCPyL PET/CT imaging by the local reader 
and then evaluated against the composite truth standard by three independent, blinded central 
imaging readers. The CLR at the subject level is defined as the percentage of subjects for whom 
there is a one-to-one correspondence between localization of at least one lesion identified on 18F-
DCFPyL PET/CT imaging (by central review) and the composite truth standard, which is defined 
either as:  
1) evaluable local histopathology result for prostate cancer from surgery or biopsy
performed within 60 days following PyL PET/CT, or
2) if evaluable histopathology is not available, informative conventional imaging (e.g., 18F-
fluciclovine PET (preferred if was not performed at baseline) or choline PET; targeted
MRI or CT; fluciclovine or choline PET) finding(s) of the anatomical correlate to the
PyL-suspected lesion(s) within 60 days following PyL PET/CT, before locoregional or
systemic treatment in is started, or
3) if neither of the above is available or informative, confirmed PSA response (PSA decline
by ≥50% from baseline, confirmed within 4 weeks per central lab evaluation) post-RT
(no concomitant ADT) that was initiated within 60 days following PyL PET/CT.  PSA
will be collected every 3 months, up to 9 months until PSA response (if achieved) is
confirmed.
The CLR in percent is computed as 100×TP/(TP+FP); TP = true positives, FP = false positives. 
A true positive (TP) result is defined as a subject with both a positive lesion(s) on 18F-DCFPyL 
PET/CT evaluated by at least one central reader and a positive result on the composite truth 
standard in the following order of importance:  
•
Positive finding for prostate cancer of a PyL-suspected lesion according to local
histopathology (confirmed by at least one anatomical correlate will suffice to declare the
PyL PET/CT assessed by the central reader defining a true positive), or
•
Positive finding for prostate cancer of a PyL-suspected lesion upon follow-up correlative
imaging by CT, MRI, whole body bone scan, NaF, fluciclovine or choline PET/CT


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performed following PyL PET/CT (one confirmed anatomical correlate will suffice to 
declare the PyL PET/CT assessed by the central reader a true positive), or 
• PSA decreases by ≥50% from baseline following RT (without concomitant ADT) up to 
nine months following initiation of such treatment if the other two truth standards were not 
performed or did not provide evaluable results 
False positives will be defined as subjects with positive lesion(s) on PyL PET/CT from at least 
one central reader who has the following negative findings for prostate cancer according to the 
composite truth standard: 
• Negative finding for prostate cancer of a PyL-suspected lesion according to local 
histopathology, or 
• Negative finding for all PyL positive lesion(s) upon follow-up correlative imaging 
performed following PyL PET/CT, or 
• PSA does not decrease by ≥50% from baseline following RT (without concomitant ADT) 
up to 9 months following initiation of such treatment. 
The CLR lesion location(s) will be matched with the CLR lesion location(s) identified by the 
composite truth standard to determine if colocalization is successful, denoting a true positive 
(TP) assessment.  If a subject has more than one lesion identified by pathology or by correlative 
imaging, then at least one lesion must be successfully colocalized for the subject to be considered 
a TP. The anatomic regions and CLR lesion locations matched by laterality (right or left) where 
applicable are presented in Table 3. The pelvic lymph nodes are grouped together for analysis in 
alignment with the data collected in the PyL-2301 (OSPREY) study. Within the prostatic region 
and extra-pelvic lymph nodes, specific CLR lesion location groupings are further modified 
specific for PET/CT findings based on Prostate Cancer Molecular Imaging Standardized 
Evaluation (PROMISE)2 intended to guide reproducibility, general applicability and clinical 
relevance.  
Table 3: 
Lesion Locations and Anatomic Regions 
Anatomic 
Region 
CLR Lesion Locations 
Prostatic 
Prostate gland or prostate bed (including seminal vesicles) 
Pelvic Lymph 
Nodes 
• Right Pelvic (including Internal Iliac [Hypogastric], External Iliac, Common 
Iliac, Obturator) 
• Left Pelvic (including Internal Iliac [Hypogastric], External Iliac, Common 
Iliac, Obturator) 
• Other pelvic (including Rectal/perirectal and Presacral) 
 
Extra-pelvic 
(Lymph Nodes)  
• Retroperitoneal (including Para/Peri-Aortic R/L and Celiac axis R/L) 
• Supradiaphragmatic (including Supraclavicular R/L, Pre/Paratracheal R/L, 
Posterior Mediastinal R/L, Anterior Mediastinal R/L, Subcarinal, 
Paracardiac R/L, Retrocrural R/L, Thoracic Hilar R/L, Mesenteric R/L, 
Axillary R/L, Cervical R/L) 


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Anatomic 
Region 
CLR Lesion Locations 
• Other extra-pelvic (specify, including Inguinal/Femoral R/L) 
Extra-pelvic 
(Bone) 
• Pelvic bone R/L 
• Skull 
• Clavicle R/L 
• Scapula R/L 
• Sternum 
• Ribcage R/L 
• Spine (including cervical/thoracic/lumbar/sacral) 
• Extremities (including right upper, right lower, left upper, left lower) 
• Other bone lesion 
Extra-pelvic 
(Visceral/soft-
tissue) 
• Lung/pleura 
• Liver 
• Other visceral/soft tissue lesion (including spleen, adrenal, mediastinum, 
pericardium, non-nodal retroperitoneal tissue, and other visceral/soft-tissue) 
Each subject will be evaluated for the primary endpoint using a single truth standard source. If a 
subject has more than one source, e.g., undergoes correlative imaging and needle-guided biopsy, 
the pathology result from the needle biopsy will be evaluated as the truth standard.  If the 
pathology result is unevaluable or the biopsy needle is not in a positive PyL lesion, then the 
results of the correlative imaging will be used as the truth standard. 
Subjects with positive 18F-DCFPyL PET/CT scans per local scan interpretation (detection of 
disease at any location) will be followed at the Efficacy visit(s) based on their 18F-DCFPyL 
PET/CT finding(s) (see Section 4).  If a subject has a negative 18F-DCFPyL scan by the local 
interpretation, then no standard of truth data will be submitted by the study site and no efficacy 
evaluation will be performed by the central Truth Panel readers. If the subject’s 18F-DCFPyL 
PET/CT scan is interpreted as positive by one or more of the central readers and no standard of 
truth data is available for evaluation, then the subject will be considered unevaluable for the 
primary endpoint.  Please see Section 5.1.3 for subjects with positive 18F-DCFPyL scans by local 
interpretation where the central reader(s) identify the scan as negative. 
Subjects with positive 18F-DCFPyL PET/CT scans (by central review) will be classified as TP, 
FP or unevaluable as presented in Table 4. 
Table 4: 
Primary Endpoint Assessment 
Composite Truth 
Standard Source 
Truth Standard 
Location Result 
Central PyL 
Reader Location 
Match 
Subject Outcome 
Surgical pathology 
Positive 
Yes 
TP 
Surgical pathology 
Positive 
No 
FP 
Surgical pathology 
Negative 
Yes or No 
FP 


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Composite Truth 
Standard Source 
Truth Standard 
Location Result 
Central PyL 
Reader Location 
Match 
Subject Outcome 
Surgical pathology 
Unevaluable 
Yes or No 
Unevaluable, evaluate 
with another truth 
standard 
Image guided biopsy, 
needle or tissue 
sampling device in PyL 
positive lesion 
Positive pathology 
in the same 
anatomic region as 
at least one PyL 
positive lesion 
Yes 
TP 
Image guided biopsy, 
needle or tissue 
sampling device in PyL 
positive lesion 
Negative pathology 
in the same 
anatomic region as 
at least one PyL 
positive lesion 
Yes  
FP 
Image guided biopsy, 
needle or tissue 
sampling device not in 
PyL positive lesion 
Positive or negative 
pathology in the 
same anatomic 
region as at least one 
PyL positive lesion 
Yes or No 
Unevaluable, evaluate 
with another truth 
standard 
Image guided biopsy, 
sampling method 
confirmation is not 
applicable or the 
confirmatory image is 
unevaluable 
Positive or negative 
pathology in the 
same anatomic 
region as at least one 
PyL positive lesion 
N/A 
Unevaluable, evaluate 
with another truth 
standard 
Correlative imaging 
(Truth Panel assessment) 
Correlative Imaging 
result positive 
Yes 
TP 
Correlative imaging 
(Truth Panel assessment) 
Correlative Imaging 
result positive 
No 
FP 
Correlative imaging 
(Truth Panel assessment) 
Correlative Imaging 
result negative 
Yes  
FP 
Correlative imaging 
(Truth Panel assessment) 
Correlative Imaging 
unevaluable 
Yes or No 
Unevaluable, evaluate 
with another truth 
standard 
PSA response following 
locoregional RT 
Observed ≥ 50% 
decrease from 
baseline up to 9 
months from start of 
RT, but response not 
confirmed  
N/A 
Unevaluable 
PSA response following 
locoregional RT 
Radiation therapy 
not directed to all 
PyL suspected 
lesions  
N/A 
Unevaluable 


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Composite Truth 
Standard Source 
Truth Standard 
Location Result 
Central PyL 
Reader Location 
Match 
Subject Outcome 
PSA response following 
locoregional RT 
Confirmed ≥ 50% 
decrease from 
baseline at or before 
9 months from start 
of RT 
N/A 
TP 
PSA response following 
locoregional RT 
No observed ≥ 50% 
decrease from 
baseline up to 9 
months from start of 
RT, but PSA results 
are available 
N/A 
FP 
N/A: not applicable 
 
Lesion mismatches are defined as False Positives due to the subject having a positive finding (by 
Central PyL read) on the PyL scan. 
5.1.2. 
Secondary Endpoints 
The percentage of subjects with a change in intended prostate cancer treatment plans due to 18F-
DCFPyL PET/CT as measured by comparison of intended management questionnaires 
completed Pre- and Post- 18F-DCFPyL PET/CT imaging results (based on local reader 
interpretation) (see Section 8.5.3). 
The endpoint is the percentage of subjects with a change in intended prostate cancer treatment 
plan from Pre- and Post 18F-DCFPyL PET/CT scan assessed using the MMQ, based on local 18F-
DCFPyL PET/CT scan read results, as the decision to change the subject’s treatment plan or not 
to change plans is made using this data.  
Any change in planned management, whether from no treatment to any treatment, from one 
treatment to another between treatment categories or within a treatment category will be 
tabulated as a change. Change vs. no change will be analyzed as a binary response. 
The shifts between no planned treatment and the major categories of planned therapy as well as 
between those categories are defined in Table 5.  
Table 5: 
Changes in Planned Therapy 
Pre-18F-DCFPyL PET/CT scan  
Post-18F-DCFPyL PET/CT scan 
No treatment planned  
Any treatment planned 
Any treatment planned 
No treatment planned 
Treatment planned - local therapy 
Treatment planned - systemic therapy 
Treatment planned - systemic therapy 
Treatment planned - local therapy 
Treatment planned - local therapy  
Treatment planned - other therapy 
Treatment planned – systemic therapy  
Treatment planned - other therapy 
Treatment planned – other therapy 
Treatment planned – systemic therapy 
Treatment planned – other therapy 
Treatment planned – local therapy 


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5.1.3. 
Tertiary/Exploratory Endpoints 
• Detection Rates by Anatomic Region 
The detection rate is defined as the percent of positive 18F-DCFPyL PET/CT scans identified 
by the central imaging readers. It is calculated as the number of subjects with positive scans 
divided by the number of subjects who have evaluable scan results reported times 100. For 
this analysis, if a subject has a PyL positive scan in any of the anatomic regions defined in 
Table 3: prostatic, pelvic, extra-pelvic lymph nodes, extra-pelvic bone and extra-pelvic other, 
then the subject will be counted within the respective region.  Another tabulation will assess 
detection rates in the prostatic, pelvic and extra-pelvic regions, where all extra-pelvic regions 
(lymph node, bone and other tissue) will be combined. If a subject has lesions detected in 
more than one anatomic region, then that subject will be counted for all respective regions. 
• PPV by Anatomic Region 
The PPV for subjects with positive 18F-DCFPyL PET/CT scans is defined as the percent of 
subjects with true positive results divided by all subjects with 18F-DCFPyL PET/CT scans or 
TP/(TP+FP)00%.  For this analysis, the subject will be designated as a TP if the 18F-DCFPyL 
PET/CT scan identified by the central imaging readers has at least one lesion and the 
respective truth standard result has a positive finding in the respective regions as defined in 
Table 3: prostatic, pelvic, extra-pelvic lymph nodes, extra-pelvic bone and extra-pelvic other. 
Another tabulation will assess PPV in the prostatic, pelvic and extra-pelvic regions, where all 
extra-pelvic regions (lymph node, bone and other tissue) will be combined. If a subject has 
lesions detected in more than one anatomic region, then that subject’s results will be included 
in all respective regions.  
• False Positive Scan Rates 
Subjects with false positive scans are defined as subjects with positive 18F-DCFPyL PET/CT 
scans identified by a central reader who do not have confirmation of any lesions by a truth 
standard.  The false positive rate is calculated as the number of subjects with positive scans 
defined by the central imaging reader without confirmation by any truth standard, divided by 
the number of subjects who have positive scan results times 100. 
• Detection Rates by Baseline PSA 
In addition to presenting detection rates by anatomic region of the lesions, detection rates of 
any PyL positive lesion at the subject level identified by the central imaging readers will be 
summarized for all subjects grouped by baseline PSA values categorized as: < 0.2 ng/mL, 0.2 
to < 0.5 ng/mL, 0.5 to < 1 ng/mL, 1 to <2 ng/mL, 2 to <5 ng/mL and ≥5 ng/mL.  
• False Negative and True Negative Subjects 
Subjects may have a positive PyL scan by local interpretation and available truth standard 
data, but the central readers identify the scan as negative.  If this situation arises, the 
following rules will apply: 
• 
If the central reader classifies the scan as negative and the truth standard is positive, then 
the subject will be considered a false negative 


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• 
If the central reader classifies the scan as negative and the truth standard is negative, then 
the subject will be considered a true negative 
• 
True Positive Detection Rate 
The overall true positive detection rate (TPR) is the rate of subjects with positive 18F-
DCFPyL PET/CT scans identified by a central reader confirmed to have a positive SOT (ie, a 
true positive [TP] subject) divided by the total number of subjects who had a 18F-DCFPyL 
PET/CT scan interpreted by a central reader times 100.  This represents the total fraction of 
true positive subjects, or TP/ (TP+FP+TN+FN), where the sum of negative PyL scans 
(TN+FN) are reported even if the specific breakdown of TN and FN numbers may be 
unknown. 
5.2. 
Safety Endpoints 
• Incidence of treatment-emergent adverse events from time of 18F-DCFPyL dosing up to 7 
(±3) days following 18F-DCFPyL dosing  
• Change from Baseline to post 18F-DCFPyL injection vital signs 
• Summary of concomitant medications and procedures  
5.3. 
Pharmacokinetic Endpoints 
There are no pharmacokinetic data or endpoints in this study. 


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6. 
ANALYSIS POPULATIONS  
6.1. 
Consented Population 
All subjects who sign an informed consent document will be included in the consented 
population. 
6.2. 
Safety Population 
The safety population includes all subjects who receive any amount of 18F-DCFPyL. 
6.3. 
Full Analysis Set (FAS) Population 
The full analysis set consists of subjects who have received any amount of 18F-DCFPyL and 
have 18F-DCFPyL PET/CT imaging results from at least one central reader. 
6.4. 
Per-Protocol (PP) Population 
The per protocol population consists of the FAS excluding subjects with major protocol 
violations.  Major protocol violations will be defined prior to performing the analysis of the 
study following database lock. The reasons for excluding subjects from the per protocol 
population (PP) will be included in a subject data listing of all protocol deviations.   


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7. 
SAMPLE SIZE  
7.1. 
Sample Size Justification and Calculation 
The primary endpoint is the correct localization rate (CLR) at the subject level, in subjects with 
positive PyL PET/CT findings, defined as the percentage of subjects a one-to-one 
correspondence between localization of at least one lesion identified on 18F-DCFPyL PET/CT 
imaging and the composite truth standard.  The composite truth standard is defined in Section 
5.1.1  
The assumed CLR of 18F-DCFPyL PET/CT imaging is 30%.  Based on the varied published 
experience with 68Ga-PSMA PET/CT and a meta-analysis by Perera et al3, approximately 76% 
(95% confidence interval [CI], 66-85%) of PSMA scans are positive in patients with suspected 
recurrence of prostate cancer following initial therapy. Therefore, in subjects with negative or 
equivocal findings for prostate cancer on baseline conventional imaging, 60% of subjects are 
conservatively estimated to have PyL PET/CT positive findings.  In consideration of the extent 
literature for 68Ga-PSMA PET and the present study entry criteria, approximately 30% of PSMA 
PET/CT positive findings may be verified by biopsy/surgery-based histopathology, conventional 
imaging, or PSA follow-up post-RT.4-7  It is therefore assumed that 30% of the positive PyL 
results in the study will be confirmed by the composite truth standard.  If 60% of the study 
subjects have positive PyL scans, and 30% of these positive diagnostic scans are confirmed by 
the composite truth standard, the use of the PyL PET/CT will permit the detection/localization of 
recurrent prostate cancer in approximately 18% of the underlying target population, versus at 
most 5% that could be identified by conventional imaging alone. 
The sample size estimates are based on the positive likelihood ratio (PLR) of CLR to prevalence.  
The PLR is estimated as 𝑃𝑃𝑃𝑃𝑃𝑃= (
𝐶𝐶𝐶𝐶𝐶𝐶
1−𝐶𝐶𝐶𝐶𝐶𝐶)/(
𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝
1−𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝) .   
Conservatively assuming the initial prevalence rate as a population parameter to be 5% by 
conventional imaging,8,9 4 if a CLR of 30% is realized, the positive likelihood ratio is expected to 
be 8.1, implying a considerable increase in the clinical value of PyL PET/CT to identify prostate 
cancer. 
Using a lower bound for the 95% CI for CLR of 20%, the corresponding lower bound for PLR 
would be 4.75 based on a normal approximation to the Binomial. This will thus require a total of 
81 positive PyL scans, which translates to a total of 134 PyL PET/CT scans or evaluable subjects 
needed.  Accounting for a 30% non-evaluable (including loss to follow-up) rate, approximately 
192 subjects will need to undergo PyL PET/CT in the study.  
During study enrollment, the rate of positive 18F-DCFPyL PET/CT scans will be calculated 
periodically to confirm the assumption of 60%. If the observed rate is lower than expected, the 
sample size may need to be increased. 
7.2. 
Interim Analyses 
There are no interim analyses planned for this study. 


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8. 
STATISTICAL ANALYSIS AND DATA CONVENTIONS 
8.1. 
Computer Software 
All analyses will be performed using SAS® Software, version 9.4 or later. nQuery Advanced and 
Microsoft Excel were used in performing the sample size calculations. Additional software may 
be used if appropriate.  If used, all additional software products will be noted in the Clinical 
Study Report. 
8.2. 
Data Presentation Conventions 
Continuous variables will be presented using descriptive statistics (the number of subjects with 
available data, the mean, standard deviation (SD), median, minimum and maximum values). 
Categorical data will be summarized by the counts and respective percentages. 
8.3. 
Baseline Characteristics 
8.3.1. 
Baseline Definition 
The subjects are required to have a pre-treatment PSA sample submitted to the central 
laboratory.  If more than one sample is included in the CRF, the baseline value is the last value 
obtained prior to study drug administration. The baseline vital signs values will be the last 
measurements obtained prior to dosing. 
Each subject is required to have baseline standard-of-care conventional imaging performed 
within 60 days of study drug administration.  All imaging studies performed prior to 
administration of 18F-DCFPyL will be considered as baseline.  
8.3.2. 
Subject Disposition 
A disposition table will be presented to show the number and percentage of subjects in each 
analysis population. All early discontinuations will be presented with the respective reasons.  All 
subjects who sign informed consent will be accounted in the disposition summary. 
8.3.3. 
Demographic and Baseline Characteristics 
The subjects will undergo a prostate treatment assessment prior to dosing, using the Medical 
Management Questionnaire. The responses to each question on the questionnaire will be 
summarized for all subjects in the safety population. 
8.3.4. 
Medical History  
All relevant medical history other than the subject’s prostate cancer history will be coded using 
the Medical Dictionary for Regulatory Activities (MedDRA version 21.1). Medical history will 
be summarized by the number and percent of subjects in the safety population by system organ 
class (SOC) and unique Preferred Term (PT). 
8.3.5. 
Prior Prostate Cancer Treatments  
The subjects’ prior treatments for prostate cancer will be summarized including surgical 
procedures, prior radiation therapies and systemic therapies (medications). Prior medications will 


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be coded using the World Health Organization drug dictionary (WHO-DDE Sep 2018). Prior 
surgical procedures are categorized as radical prostatectomy (RP), RP with pelvic lymph node 
dissection, pelvic lymph node dissection alone, Trans-urethral resection of prostate (TURP), and 
other procedures. radiation therapy is categorized as external beam radiation, brachytherapy and 
other therapies. The sites of radiation are prostate/prostate bed, pelvic non-prostatic lesions, and 
extra-pelvic lesions. Summaries will be prepared and will present the number and percent of 
subjects in the safety population who have these respective therapies recorded on their case 
report forms. Prior medications will be presented by ATC4 class and preferred term. Prior 
surgical and radiation therapies will be summarized by MedDRA SOC and preferred term. The 
time from original prostate cancer diagnosis to study entry (date of informed consent) in months 
will be summarized, as will the time from each reported prior therapy to study start.  A month is 
defined as (difference in dates /365.25*12.). If partial dates(s) if diagnosis or treatments are 
reported, then a missing day will be set to the 15th of the month and a missing month will be set 
to July. 
8.4. 
Missing Efficacy Endpoints 
Missing values will not be replaced for any endpoint.  There should be no missing primary 
endpoint values for subjects with evaluable PyL scans as assessed by the central readers unless 
no follow-up standard of truth (SOT) was completed.  The subjects will be classified as true 
positive, false positive, or unevaluable. If a subject undergoes PyL imaging and does not have 
any follow-up evaluations or if the follow-up assessments are deemed unevaluable by the central 
readers based on image quality or other reasons, then that subject will be considered as 
unevaluable. 
Exploratory evaluations of the primary endpoint will be performed using multiple imputation 
methods to examine the impact of missing or unevaluable SOTs for subjects with positive PyL 
scans as interpreted by the central readers. These methods are described in detail in section 
8.5.2.2. 
8.5. 
Efficacy Analysis  
8.5.1. 
General Considerations 
8.5.1.1. 
Testing Statistical Assumptions 
The assumption underlying the normal approximation to the binomial distribution, used in the 
computation of the confidence intervals for CLR, PPV and detection rates is that the sample size 
is such that np>5 and n(1-p)>5, where n is the sample size and p is the binomial probability 
within a group.  It is expected that the sample size for each statistic will be sufficient to meet this 
assumption.  If the sample size is not sufficient, Agresti-Coull exact methods will be used.   
8.5.2. 
Analysis of the Primary Efficacy Endpoint 
The FAS will be used to analyze the primary analysis of the primary endpoint.  The per protocol 
set will also be performed as a supplemental analysis of the primary endpoint. 


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8.5.2.1. 
Primary Analysis of Primary Endpoint      
The primary endpoint is the CLR at the subject level, defined as the percentage of subjects with 
positive 18F-DCFPyL PET/CT imaging from the central reads for whom there is a one-to-one 
correspondence between the CLR lesion location of at least one lesion identified on 18F-DCFPyL 
PET/CT imaging and the composite truth standard, computed as 100×TP/(TP+FP).  There are 
three independent central 18F-DCFPyL PET/CT readers who will report whether each subject’s 
PET/CT scan is positive or negative and will indicate the location(s) of the lesion(s) for all 
positive scans.  The location(s) of the lesions will be matched with the standard of truth to 
determine if colocalization is successful, denoting a true positive (TP) assessment. If a subject 
has more than one lesion identified by pathology or by correlative imaging, then at least one 
lesion must be successfully colocalized for the subject to be considered a TP. The lesion 
locations for analysis as well as anatomic regions are defined in Table 3 in section 5.1.1. 
PyL images obtained for subjects will be evaluated by three central readers.  The results for all 
subjects will be summarized for each reader.  The CLR is computed as TP/(TP+FP) *100% for 
each reader across all evaluable subjects. The respective two-sided 95% confidence interval for 
each reader will be computed using the binomial approximation to the normal distribution for 
each central reader. If the lower bound of the 95% CI is >0.2 for at least two of the three 
independent imaging reviewers, then the primary endpoint analysis is considered a success. 
8.5.2.2. 
Sensitivity Analyses of the Primary Endpoint 
The primary endpoint analysis will be repeated for subjects in the per-protocol analysis set, 
which excludes subjects with major protocol deviations.   
There will also be an analysis of the primary endpoint for subjects who have positive 18F-
DCFPyL scans as reported by local interpretation. These subjects will have their endpoint 
evaluated following the same criteria as described in Table 3. The CLR and its corresponding 
95% confidence interval will be calculated in the same manner as for the three independent 
central PyL readers. If there are more subjects with positive PyL scans identified by the central 
readers than those identified by the local readers, then a population of subjects with positive 
scans by local read results may be used. 
There will be an analysis of the primary endpoint in the full analysis set with positive 18F-
DCFPyL PET/CT imaging as assessed by the central imaging readers, where the CLR lesion 
location recorded for pelvic lymph nodes will be grouped according to the PROMISE -
standardized lymph node template2 (internal iliac left, internal iliac right, external iliac left, 
internal iliac right, obturator left, obturator right, common iliac left, common iliac right,  
presacral and other pelvic lymph nodes). All other CLR lesion locations will be assessed, 
including laterality where applicable, as described in Table 3. 
There will be an analysis of the primary endpoint in the full analysis set with positive 18F-
DCFPyL PET/CT imaging as assessed by the central imaging readers, where the specific lesion 
location recorded on the case report form, including laterality where applicable,  is used instead 
of the CLR lesion location as described in Table 3. 
A summary table will present the number and percent of subjects with either false negative or 
true negative outcomes for each central imaging reader. A data listing of subjects in these 
endpoint categories will also be prepared. 


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As noted in section 8.4, pattern mixture model-based multiple imputations (MI) assuming data 
are missing-at-random (MAR) and tipping point analyses will be performed as sensitivity 
analyses to examine the influence of the missing or unevaluable SOTs for subjects who have 18F-
DCFPyL PET/CT results reported by a central reader.10 The locations of lesions as identified by 
the central reader(s) will be imputed as the lesion locations in the multiple imputation scenarios. 
• Subjects with positive 18F-DCFPyL PET/CT findings and missing or unevaluable 
standards of truth (SOTs) will have SOT responses imputed.  Imputations of SOT 
responses will employ a pattern mixture model based multiple imputation method, 
assuming the data are MAR. The subjects with unevaluable SOTs will have responses 
imputed along with those subjects with SOT data within similar baseline PSA groupings 
(< 0.2 ng/mL, 0.2-<0.5 ng/mL, 0.5-< 1 mg/mL, 1-<2 ng/mL, 2-<5 ng/mL and ≥5 ng/mL). 
SAS PROC MI will be used, and 100 imputations will be performed for each of the three 
central readers.   
• A second sensitivity analysis will impute SOT responses for subjects with positive 18F-
DCFPyL scans with missing/unevaluable SOT data by sampling from subjects with SOT 
results by method of SOT, including histopathology, Axumin scan, CT and MRI.  If a 
subject has an unevaluable SOT result, then results from subjects with that same SOT 
will be used as the basis of the imputation pool.  For subjects with no SOT, they will have 
results imputed with results of subjects with biopsy or surgery with histopathology, 
Axumin, CT and MRI scans separately.  
• 
A tipping point analysis11 will be performed to examine the multiple imputation method 
described by baseline PSA grouping.  A group of delta (𝛿𝛿) values 
 (−0.95, −0.90,   … , −0.10, −0.05) will be used. After the imputed datasets are obtained 
from the multiple imputation for each central reader’s result, the predicted responses will 
be estimated within each imputed dataset; applying the delta adjustment to the predicted 
probability of response for those subjects who had missing or unevaluable  SOT results 
by adding 𝛿𝛿 , then generating random variates following a Bernoulli distribution. This 
will create a delta adjusted predicted probability within each imputed dataset. For a given 
delta, the above imputations should produce 100 CLR estimates for each central reader.  
The results for all imputation analyses noted above will be combined using SAS PROC 
MIANALYZE and estimates of CLR and their respective 95% confidence intervals will be 
reported for each central reader. 
8.5.2.3. 
Subgroup Analyses 
The primary endpoint analysis will be performed for the following subgroups: 
• Truth standard category: histopathology, correlative imaging, PSA response following 
locoregional RT 
• Truth standard of each correlative imaging method 
• Age: <65, ≥65 
• Race: White, Black or African American, Other 
• Ethnicity: Not Hispanic or Latino, Hispanic or Latino  


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• Baseline PSA, categorized as < 0.2 ng/mL, 0.2-<0.5 ng/mL, 0.5-<1 ng/mL, 1-<2 ng/mL, 
2-<5 ng/mL, ≥5 ng/mL  and the same PSA categories by historical therapy modality 
(prostatectomy alone, prior radiation  therapy, both prostatectomy and prior radiation 
therapy) 
• Historical initial therapy modality(ies) for prostate cancer at study entry: surgery (radical 
prostatectomy), radiation therapy (to the prostate gland), surgery and radiation therapy, 
prior androgen deprivation therapy (ADT), ADT and radiation therapy 
• Baseline Screening imaging modality, categorized as fluciclovine PET/CT, choline PET, 
NaF PET, Pelvic CT/MRI, Abdomen CT/MRI, Chest CT/MRI, bone scintigraphy  
• Study center: the distribution of treated subjects by center will be created at the end of the 
study. Small centers with five or fewer treated subjects may be combined into one or 
more centers for analysis.  
• Size of largest lesion (long axis) detected on the PyL image by the central imaging 
readers: 0-<0.5 cm, 0.5-<1.0 cm, ≥1.0 cm  
• Maximum standard uptake value (SUVmax) reported for the subject’s lesion(s) on the 
PyL image by the central imaging readers: ≤2, 2-<5, 5-<10, ≥10  
• Time of PyL scan following dosing: < 60 minutes, 60-<90 minutes, 90-≤ 120 minutes, > 
120 minutes 
• Time since discontinuation of ADT until study entry for subjects with prior ADT use 
Subgroup analyses will be performed by tabulating the primary endpoint for each subgroup.  For 
the analysis of the endpoint by SUVmax the tabulations will use the SUVmax value adjusted for 
lesion long axis. This value is the predicted SUVmax from a logistic regression model of CLR 
(0=No,, 1=Yes) for subjects with a positive PyL scan as assessed by the central reader, including 
SUVmax and lesion size (long axis as reported by the central reader). This analysis will be used 
if the lesion size term is significant at an alpha of 0.05. If the lesion size term is not significant 
the unadjusted SUVmax values will be used as reported by the central reader in the tabulations.  
8.5.2.4. 
Multiple Comparisons and Multiplicity 
There will be no correction for multiple comparisons as there is a single primary endpoint based 
on a composite truth standard where each subject is evaluated with only a single truth standard 
source. 
8.5.3. 
Analysis of Secondary Efficacy Endpoints 
The secondary efficacy endpoint, change in planned medical management, will be generated on 
the FAS for all subjects regardless of finding(s) on PyL PET/CT imaging, and be analyzed by 
calculating a two-sided 95% CI for the proportion of subjects with any change in planned 
management as a binary variable. The summary will present the respective proportions and CIs 
calculated using a normal approximation to the binomial distribution if the statistical assumptions 
are met.  
The analysis will present the percentage of subjects with a shift between no planned treatment 
and the major categories of planned therapy as well as between major categories defined in Table 


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5 by the local imaging readers’ results and for all subjects combined. An additional tabulation 
will be presented for the changes in planned therapy between major categories of therapy by the 
results reported by the central PyL readers 
A summary of shifts in planned management from Pre- and to Post- 18F-DCFPyL imaging 
evaluations will also be presented for shifts between the specific categories of treatments within 
local therapies (Table 6). These shifts will also be summarized by the results of the local reader 
of the PyL scan and by the results reported by the three central readers. 
Table 6: 
Shifts in Planned Therapy 
Pre-18F-DCFPyL PET/CT scan  
Post-18F-DCFPyL PET/CT scan 
No treatment planned  
Focal therapy 
Focal therapy 
No treatment planned 
No treatment planned  
Salvage surgery 
Salvage surgery 
No treatment planned 
Another presentation of the change in planned management of the subject’s disease will be a 
tabulation of all post-dose treatments against the pre-dose assessment. 
The shifts within individual categories as well as an all shifts from pre- to post-PyL scan 
assessments will be presented with the number and percent of subjects with the respective 
change in shift tables, by the results reported by the local and central PyL readers.  All pre- and 
post-PyL scan assessments will be presented with the assessment of change in a data listing. 
8.5.4. 
Analysis of Exploratory Efficacy Endpoints 
Exploratory efficacy endpoints will be generated using the FAS to calculate detection rates on the 
subset of the FAS with at least one positive lesion identified by PyL PET/CT imaging for PPV 
and false positive scan rate endpoints.  If a subject has more than one truth standard modality, 
(i.e., an image-guided biopsy and a correlative imaging scan) the information from the 
modality(ies) not used for the primary endpoint will be utilized in the calculation of exploratory 
endpoints.  As there are results reported for three independent readers, these summary tables will 
present the respective endpoints for each reader. 
The following endpoints will be analyzed using a two-sided 95% CI presented for each central 
imaging reviewer and for the local site interpretation separately based on a normal approximation 
to the binomial:  
• Detection rates of 18F-DCFPyL PET/CT imaging by lesions in the following regions: 
prostatic, pelvic, extra-pelvic lymph nodes, extra-pelvic bone and extra-pelvic other 
defined in Table 3 in Section 8.5.2.1 
• Detection rates of 18F-DCFPyL PET/CT imaging by lesions in the following regions: 
prostatic, pelvic, extra-pelvic (lymph nodes, bone and other combined) defined in Table 3 
in Section 8.5.2.1 
• The detection rates of 18F-DCFPyL PET/CT imaging as a function of baseline PSA 
groups categorized as <0.2 ng/mL, 0.2-< 0.5 ng/mL, 0.5-<1 ng/mL, 1-<2 ng/mL, 2-<5 
ng/mL, ≥5 ng/mL 


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• Detection rates of 18F-DCFPyL PET/CT imaging by baseline Screening imaging 
modality, categorized as fluciclovine PET/CT, choline PET, NaF PET, Pelvic CT or MRI, 
Abdomen CT or MRI, Chest CT or MRI, bone scintigraphy  
• The percentage of subjects with positive 18F-DCFPyL PET/CT scans assessed by the 
central reader who have negative findings for prostate cancer (false positive subjects) 
based on the composite truth standard. The percentage of false positive scans is defined as 
(1-CLR). 
• The PPV of 18F-DCFPyL PET/CT for prostatic, pelvic, extra-pelvic lymph nodes, extra-
pelvic bone and extra-pelvic other regions defined in Table 3 in Section 8.5.2.1, based on 
the composite truth standard in subjects with positive lesion(s) on 18F-DCFPyL PET/CT 
imaging  
• The PPV of 18F-DCFPyL PET/CT for prostatic, pelvic and extra-pelvic (lymph nodes, 
bone and other combined) regions defined in Table 3 in Section 8.5.2.1, based on the 
composite truth standard in subjects with positive lesion(s) on 18F-DCFPyL PET/CT 
imaging  
• The overall true positive detection rate (TPR) based on all subjects with a positive 18F-
DCFPyL PET/CT regardless of positive or negative findings as assessed by the central 
reader, as defined in section 5.1.3. This result will be reported on the primary endpoint 
table. 
8.5.5. 
Other Efficacy Data 
Summaries will be created for the following recorded measurements: 
• Pathology results by lesion location and region 
• Imaging results by lesion location and anatomic region for the central imaging readers, 
the imaging truth panel and the local site interpretation 
• Lesion sizes by lesion location as recorded by the central imaging readers (and Imaging 
Truth Panel), excluding lesions indicated as unmeasurable 
• SUVmax, and SUVmean as recorded by the central imaging readers by lesion location 
• The number of lesions detected per subject per CLR lesion location and per region 
(prostatic, pelvic, extra-pelvic) 
8.5.6. 
Intra- and Inter-reader Reliability Assessments 
A subset of each central PyL imaging readers’ scans will be evaluated twice, after a washout 
period of at least four weeks.  The test-retest reliability of each reader will be assessed by 
calculating percent agreement (concordance) and Cohen’s pairwise kappa and its respective 95% 
confidence interval for the dichotomous results (positive or negative) for all subjects with two 
scan interpretations. 
The agreement between the three independent readers will be assessed by calculating percent 
pairwise concordances and Fleiss’s overall multi-assessor kappa and its respective 95% 


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confidence interval will be calculated for the dichotomous result (positive or negative) for each 
scan across all subjects. 
The agreement between the each of three independent readers and the local site reader will be 
assessed by calculating percent concordance and Cohen’s pairwise kappa and its respective 95% 
confidence interval for the dichotomous results (positive or negative) across all subjects. 
8.6. 
Safety Analysis 
8.6.1. 
Adverse Events  
Adverse events are captured from the time of 18F-DCFPyL administration until the scheduled 
safety follow-up telephone call scheduled between 5 and 11 days after dosing.  All adverse 
events are considered treatment-emergent. Adverse events will be coded using MedDRA. The 
severity of each adverse event will be rated using the CTCAE 5-point scale. 
8.6.1.1. 
Summaries of Adverse Event Incidence Rates for All Subjects 
The incidence and percentage of subjects reporting a treatment-emergent AEs (TEAEs) will be 
summarized by MedDRA SOC and Preferred Term. If a subject reports more than one adverse 
event with the same preferred term, the subject will be counted once with the highest severity. 
Subject listings will be prepared for all adverse events, all serious AEs, all AEs leading to study 
discontinuation and for all deaths. 
An overall summary will be prepared that presents: 
• the number and proportion of subjects reporting TEAEs  
• the number and proportion of subjects reporting a treatment-related TEAEs 
• the number and proportion of subjects reporting TEAEs CTCAE grade 3 and above 
• the number and proportion of subjects reporting TEAEs leading to study discontinuation 
• the number and proportion of subjects reporting serious TEAEs, both fatal and non-fatal 
 
Summary tables will be created for:  
• the incidence, presented as the number and percent of subjects, for all TEAEs by 
MedDRA SOC and PT, with all relationships to study drug and severity ratings combined 
• the incidence, presented as the number and percent of subjects, for all TEAEs by 
MedDRA SOC and PT, with all relationships to study drug and severity ratings 
combined, reporting only TEAEs with incidence > 5%. 
• the incidence of all TEAEs by MedDRA SOC and PT for events considered related to 
study drug 
• the incidence of all TEAEs by MedDRA SOC and PT for events by severity as expressed 
by CTCAE grade. 


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8.6.1.2. 
Handling of Missing and Partial AE Onset and Stop Dates 
In this study, the subjects are followed up for approximately one week (±3 days) for the onset of 
adverse events. All efforts will be made to avoid missing start dates. If an adverse event has a 
stop date prior to the safety follow-up telephone call, it is expected to have a complete date. If 
the event is ongoing at the time of the follow-up call, then the stop date will not be recorded. If 
any event has a partial start date or stop date, it will be included in the analysis of adverse events 
and will be considered treatment-emergent. There is no planned imputation to account for 
incomplete dates. 
8.6.1.3. 
Summaries of Adverse Incidence Rates for Serious Adverse Events (SAE), 
Adverse Event Dropouts, and Death 
The incidence of all serious AEs by MedDRA SOC and PT will be summarized by the number 
and percent of subjects. Similarly, the incidence of all AEs leading to study discontinuation and 
all deaths will be presented by MedDRA (SOC) and (PT) as summary tables. 
8.6.2. 
Study Drug Exposure and Compliance 
Each subject will receive a single intravenous injection of 18F-DCFPyL. Exposure to 18F-
DCFPyL will be summarized by administered activity in mCi and volume administered in mL. 
The table will include the number of subjects dosed and descriptive statistics for the injection 
volume administered in mL and activity in mCi.  A listing of drug administration will include 
each subject’s date of administration, volume administered, and activity delivered. 
8.6.3. 
Concomitant and Other Medications 
Concomitant medications are medications taken by the subject after dosing with study drug until 
the end of follow-up for each subject.  Medications that are ongoing at the time of dosing will 
also be included as concomitant medications.  Medications will be coded using the WHO drug 
dictionary.  All recorded medications will be summarized by ATC level 4 category and preferred 
term and presented as number and percentage of subjects in the safety population.  If a subject 
has a specific medication recorded more than once, it will only be counted once. A subject listing 
will present all recorded concomitant medications, dates of administration and timing relative to 
dosing. 
8.6.3.1. 
Handling of Missing and Partial Concomitant and Other Medication Start and 
Stop Dates 
All medications are to be recorded as of the day of dosing and until the end of follow-up for the 
subject.  All new medications are expected to have complete start dates. All medications 
discontinued while the subject is participating in the study should also have complete end dates.  
Any ongoing medications at the end of the subject’s participation will not have a stop date. 
Medications that were ongoing at the time of subject dosing will be allowed incomplete dates if a 
start year is recorded.  These medications will be treated as baseline medications. To calculate 
time since discontinuation of ADT to study entry, the15th of the month will be substituted for 
missing day of the month, July will be substituted for missing month, and July 1 will be 
substituted for missing day and month.  If the entire stop date for prior ADT use is missing, the 
date will be considered missing. 


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8.6.4. 
Laboratory Data 
Only serum PSA will be assessed in this study. No other laboratory parameters are required. PSA 
will be an analyzed by a central laboratory.  The baseline value is required for all subjects in the 
safety population and will be presented as descriptive statistics. For those subjects undergoing 
efficacy follow-up who will undergo radiation therapy, PSA will be evaluated every three 
months until the baseline value decreases by at least 50%, or until the subject is followed for nine 
months.  For those subjects, the PSA values and changes from baseline will be summarized at 
each post-treatment visit.  The number and percent of subjects who achieve the 50% reduction 
from baseline at each 3-month follow-up visit will be presented as an efficacy endpoint. 
8.6.5. 
Vital Signs 
Blood pressure (systolic and diastolic) and heart rate will be measured and recorded prior to 
study drug dosing and following dosing on study day 1. The recorded values and their respective 
changes from the pre-dose values will be summarized using descriptive statistics. A subject 
listing will present the recorded vital signs for each subject. 
8.6.6. 
Physical Examination 
Physical examinations are not required in this study.  Any relevant physical finding noted at the 
screening visit will be included in the subject’s medical history.  Any changes in or new physical 
findings following study drug administration will be recorded as AEs.  


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9. 
DERIVED AND TRANSFORMED DATA 
9.1.1. 
Baseline Age  
The subject’s age in years will be calculated based on date of informed consent using the 
following formula: 
Age (years) = FLOOR((date of informed consent – date of birth)/365.25) 
where the FLOOR function returns the unrounded integer part of the result. 
9.1.2. 
Study Day 
If the date of interest occurs on or after the dosing date, then study day will be calculated as (date 
of interest – date of dosing) + 1. If the date of interest occurs prior to the dosing date, then study 
day will be calculated as (date of interest – dosing date). There is no study day 0. 
9.1.3. 
Change from Baseline 
Change from baseline is calculated as (post-baseline result – baseline result). 
Percent change from baseline is calculated as (change from baseline/baseline result * 100). 
If either the baseline or the post-baseline result is missing, the change from baseline and/or 
percentage change from baseline is set to missing. 
9.1.4. 
Visit Windows 
The visit windows for each study visit are detailed in Table 7. 
Table 7: 
Visit Windows (Days) 
Visit 
Relative Target Day 
Visit Window (Day) 
Screening 
-30 to 1 
-30 to 1 
Study drug dosing and Imaging 
1 
1 
Safety phone call 
8 
5 to 11 
Efficacy follow-up (surgery, 
biopsy or conventional imaging) 
2 to 60 
2 to 60 
PSA month 3 (locoregional RT) 
3 months ±7 days after start of 
RT, which can be on days 2 to 60 
85 to 157 
PSA month 6 (locoregional RT) 
6 months ±7 days after start of 
RT, which can be on days 2 to 60 
115 to 187 
PSA month 9 (locoregional RT) 
9 months ±7 days after start of 
RT, which can be on days 2 to 60 
145 to 217 


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10. 
REFERENCES 
1. ICH E9: Statistical Principles for Clinical Trials 
 
2. Eiber M, Hermann K, Calias J, et al. Prostate Cancer Molecular Imaging Standardized 
Evaluation (PROMISE). Proposed miTNM Classification for the Interpretation of 
PSMA-Ligand PET/CT. J Nuc Med 2018;59(3):470-478. 
 
3. Perera M, Papa N, Christidis 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; 70:926-937. 
4. Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, Graner FP, Kübler 
H, Haberkorn U, Eisenhut M, Wester HJ. Evaluation of hybrid 68Ga-PSMA ligand 
PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. Journal 
of Nuclear Medicine. 2015 May 1;56(5):668-74. 
5. Calais J, Fendler WP, Herrmann K, et al.  Head-to-head comparison of 68Ga-PSMA-11 
and 18F-FACBC PET/CT in a case series of 10 patients with prostate cancer recurrence.  
J Nucl Med 2017; jnumed-117. 
6. Fendler W, et al. Accuracy of 68Ga-PSMA11 PET/CT on recurrent prostate cancer: 
Preliminary results from a phase 2/3 prospective trial. ASCO 2018 
7. Yuminaga Y, et al. MP53-14 Evaluation of Gallium-68 PSMA PET/CT for Post-
Prostatectomy biochemical recurrence in comparison to CT abdomen/pelvis and bone 
scan.  The Journal of Urology. 2018 Apr 30;199(4):e709. 
8. Pound CR, Partin AW, Eisenberger MA, et al. Natural history of progression after PSA 
elevation following radical prostatectomy. JAMA 1999; 281:1591-1597. 
9. Antonarakis ES et al. The natural history of metastatic progression in men with prostate-
specific antigen recurrence after radical prostatectomy: long-term follow-up. BJU Int. 
2012; 109(1): 32–39. 
10. Rubin DB. Multiple Imputation for Nonresponse in Surveys. 1st ed. 1987; New York: 
Wiley. 
11. Liublinska V, Rubin DB. Sensitivity analysis for a partially missing binary outcome in a 
two-arm randomized clinical trial. Stat Med. 2014 Oct 30; 33(24): 4170–4185. 
 
 
 
 


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11. 
APPENDIX 
11.1. 
Table of Contents for Data Displays  
Tables  
Title 
Population 
 
Comments 
Study Population, Disposition and Baseline Characteristics 
14.1.1 
Summary of Subject Enrollment and Disposition  
Consented/Safety 
FAS 
 
14.1.2 
Summary of Demographic and Baseline Characteristics 
Safety/FAS 
 
14.1.3 
Summary of Medical History 
Safety/FAS 
 
14.1.4 
Summary of Prior Treatments for Prostate Cancer 
Safety/FAS 
 
14.1.5 
Summary of Baseline Conventional Imaging 
Safety/FAS 
 
14.2 Efficacy Data Summary  
 
 
 
 
 
14.2.1.1 
Primary Efficacy Endpoint – Correct Localization Rate 
FAS 
 
14.2.1.2.1 
Sensitivity Analysis of Correct Localization Rate with 
Assessment by Local Site Readers 
FAS 
 
14.2.1.2.2 
Sensitivity Analysis of Correct Localization Rate using Lesions 
Grouped using the PROMISE Criteria for All Lymph Nodes  
FAS 
 
14.2.1.2.3 
Sensitivity Analysis of Correct Localization Rate using 
Recorded Lesion Location on CRF 
FAS 
 
14.2.1.2.4 
Sensitivity Analysis of Correct Localization Rate Using Multiple 
Imputations 
FAS 
 
14.2.1.3.1 
Subgroup Analysis of Correct Localization Rate by Size of 
Largest Lesion Size by Imaging Reader  
FAS 
 
14.2.1.4 
Subgroup Analysis of Correct Localization Rate by Maximum 
SUV 
FAS 
 
14.2.1.5 
Subgroup Analysis of Correct Localization Rate by Time of 18F-
DCFPyL PET/CT Scan after Dosing 
FAS 
 
14.2.1.6 
Subgroup Analysis of Correct Localization Rate by Age 
FAS 
 
14.2.1.7 
Subgroup Analysis of Correct Localization Rate by Race 
FAS 
 
14.2.1.8 
Subgroup Analysis of Correct Localization Rate by Ethnicity 
FAS 
 
14.2.1.9 
Subgroup Analysis of Correct Localization Rate by Baseline 
PSA 
FAS 
 
14.2.1.10 
Subgroup Analysis of Correct Localization Rate by Prostate 
Cancer Treatment Modalities Prior to Enrollment 
FAS 
 
14.2.1.11 
Subgroup Analysis of Correct Localization Rate by Study Center 
FAS 
 
14.2.1.12 
Subgroup Analysis of Correct Localization Rate by Standard of 
Truth Method 
FAS 
 
14.2.1.13 
Subgroup Analysis of Correct Localization Rate by 
Baseline/Screening Imaging Modality 
FAS 
 
14.2.1.14 
Subgroup Analysis of Correct Localization Rate by ADT Use at 
Study Entry and Time from Discontinuation of ADT 
FAS 
 
Secondary Endpoint 
 
 
14.2.2.1 
Change in Planned Therapy - Summaries of Changes 
Safety 
 
14.2.2.2 
Shift Table of Changes in Planned Therapy 
Safety 
 
14.2.2.3 
Summary of Treatments in MMQ 
Safety 
 


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Title 
Population 
 
Comments 
Exploratory Endpoints  
 
 
14.2.3.1 
Detection Rates and PPV of 18F-DCFPyL PET/CT Imaging by 
Central Reader Compared to Truth Standard by Anatomic 
Region Groups  
FAS 
 
14.2.3.2 
Detection rates and PPV of 18F-DCFPyL PET/CT imaging for 
prostatic, pelvic and extra-pelvic regions by baseline PSA groups   
FAS 
 
14.2.3.3 
Detection rates and PPV of 18F-DCFPyL PET/CT imaging for 
prostatic, pelvic and extra-pelvic regions 
FAS 
 
14.2.3.4 
Number of Lesions Detected per Subject per Location and 
Anatomic Region 
FAS 
 
14.2.3.5 
Summary of False Negative and True Negative Cases 
FAS 
 
14.2.3.6 
Imaging Results by Lesion Location and Anatomic Region for 
Imaging Readers 
FAS 
 
14.2.7 
Lesion volumes by Lesion Location for Central Imaging Readers 
FAS 
 
14.2.3.8 
Lesion sizes by Lesion Location for Truth Panel Readers 
FAS 
 
14.2.3.9 
Central Imaging SUV Results 
FAS 
 
14.2.3.10 
Pathology Results by Lesion Location and Anatomic Region 
FAS 
 
14.2.3.11 
Summary of Local 18F-DCFPyL PET/CT Imaging Results 
FAS 
 
14.2.3.12 
Intra- and Inter-rater Reliability 
FAS 
 
Efficacy Endpoint – Per-protocol Analysis Set (PP) 
 
 
Primary Endpoint 
 
 
14.2.4.1 
Primary Efficacy Endpoint – Correct Localization Rate 
PP 
 
14.3 Safety Data  
Adverse Events 
 
 
14.3.1 Displays of Adverse Events 
 
 
14.3.1.1 
Overall Summary of Treatment Emergent Adverse Events  
Safety  
 
14.3.1.2 
Most Frequent (>5% Overall) Treatment Emergent Adverse 
Events by SOC and PT  
Safety 
 
14.3.1.3 
Summary of Treatment Emergent Adverse Events by SOC and 
PT 
Safety 
 
14.3.1.4 
Summary of Drug-Related Treatment Emergent Adverse Events 
Safety 
 
14.3.1.5 
Summary of Serious Treatment Emergent Adverse Events 
Safety 
 
14.3.1.6 
CTCAE Grade 3 and Above Treatment Emergent Adverse 
Events  
Safety 
 
14.3.1.7 
Summary of Drug-Related Treatment Emergent Adverse Events 
by Severity Grade 
Safety 
 
 
 
 
 
14.3.2 Listing of Deaths or Other Serious or Significant AEs 
 
 
14.3.2.1 
Listing of Patient Deaths and/or Discontinuations 
Safety 
 
14.3.2.2 
Listing of Serious Treatment Emergent Adverse Events 
Safety 
 
14.3.3 Narratives of Deaths, Other Serious and Certain Other Significant Adverse Events 
14.3.4 Laboratory Data 
 
 
14.3.4.1  
Summary of Values and Changes from Baseline in Serum PSA 
Data and Study Visit 
Safety 
 


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Title 
Population 
 
Comments 
14.3.5 Vital Signs 
 
 
14.3.5.1 
Summary of Values and Change from Baseline in Vital Signs 
from Pre-dosing to Post-dosing  
Safety 
 
14.3.6 Other Safety  
 
 
14.3.6.1 
Summary of Concomitant Medications 
Safety 
 
14.3.6.2 
Summary of Concomitant Procedures 
Safety 
 
14.3.6.3 
Summary of Drug Exposure 
Safety 
 
Listings 
Title 
Population 
Comment 
16.2. 1 Enrollment and Discontinuation 
 
 
16.2.1.1 
Subject Enrollment Information 
Consented 
 
16.2.1.2 
Subject Disposition 
Consented 
 
16.2.2 Protocol Deviations 
 
 
16.2.2.1 
Subjects who did not Satisfy Inclusion/Exclusion Criteria  
Consented 
 
16.2.2.2 
Protocol Deviations 
Safety 
 
16.2.3 Subjects Excluded from Efficacy 
 
 
16.2.3.1 
Subjects Excluded from Efficacy Analysis 
Safety 
 
16.2.4 Demographics and Baseline Characteristics 
 
 
16.2.4.1 
Subject Demographic and Baseline Characteristics 
Safety 
 
16.2.4.2 
Medical History  
Safety 
 
16.2.4.3 
Historical Prostate Cancer Treatments 
Safety 
 
16.2.4.4 
Baseline/Screening Conventional Imaging  
Safety 
 
16.2.5 Compliance and/or Drug Concentration 
 
 
16.2.5.1 
Study Drug Administration  
Safety 
 
16.2.6 Individual Efficacy Response Data 
 
 
16.2.6.1 
Primary Efficacy Results 
FAS 
 
16.2.6.2 
Central Imaging Reader Results 
FAS 
 
16.2.6.3 
Central Imaging Truth Panel Results 
FAS 
 
16.2.6.4 
Local Site Imaging Reader Results 
FAS 
 
16.2.6.5 
Needle-guided Biopsy 
FAS 
 
16.2.6.6 
Surgical Procedures 
FAS 
 
16.2.6.7 
Pathology Results 
FAS 
 
16.2.6.8 
Correlative Imaging and Local Reader Results 
FAS 
 
16.2.6.9 
Locoregional Radiation Therapy 
FAS 
Subset of 
FAS with 
PSA as truth 
standard 
16.2.6.10 
Medical Management Questionnaire Results 
Safety 
 
16.2.7 Adverse Event Listings  
 
 
16.2.7.1 
Adverse Events 
Safety 
 
16.2.8 Listing of Laboratory Results 
 
 
16.2.8.1 
Serum PSA Data 
Safety 
 
16.2.9 Other Safety 
 
 


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Title 
Population 
Comment 
16.2.9.1 
Vital Sign Data  
Safety 
 
16.2.9.2 
Concomitant Medications  
Safety 
 
16.2.9.3 
Concomitant Procedures 
Safety