Clinical trial NCT02981368
Conditions: Prostate Cancer
Keywords: Diagnostic Imaging 2301 PET/CT PyL PSMA radical prostatectomy metastatic prostate cancer recurrent prostate cancer
Sponsor: Progenics Pharmaceuticals, Inc.
Start date: 2016-11-01; Completion date: 2018-07-01
Enrollment: 385 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study evaluates the safety and diagnostic performance of 18F-DCFPyL Injection in patients with at least high risk prostate cancer who are planned for radical prostatectomy with lymphadenectomy (Cohort A) or in patients with locally recurrent or metastatic disease willing to undergo biopsy (Cohort B).

Cohort B is complete and no longer recruiting subjects.

Detailed description:

Arms: arm 1: 9±1 mCi (333±37 MBq) IV injection of 18F-DCFPyL
Interventions: intervention 1: 18F-DCFPyL Injection intervention 2: PET/CT imaging
Intervention descriptions: intervention 1: A single dose of 9±1 mCi (333±37 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-2301 
18F-DCFPyL 
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Page 1 
CLINICAL STUDY PROTOCOL 
Study Number: 
PyL 2301 
Study Title: 
A PrOspective Phase 2/3 Multi-Center Study of 18F-DCFPyL PET/CT 
Imaging in Patients with PRostate Cancer: Examination of Diagnostic 
AccuracY (OSPREY) 
Product Name: 
18F-DCFPyL INJECTION (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 12, 2016 
Amendment 1: September 16, 2016 
Amendment 2: November 6, 2017
NCT02981368 
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. 


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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 




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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 
Clinical Study Leader 
Responsible Physician 


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1.
TABLE OF CONTENTS
2.
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS...............................9 
3.
INTRODUCTION ......................................................................................................12 
3.1. 
Background Information .............................................................................................12 
3.2. 
Rationale for Developing Prostate Cancer Imaging Agents .......................................12 
3.3. 
Targeting PSMA for Prostate Cancer Detection ........................................................13 
3.4. 
18F-DCFPyL ................................................................................................................15 
3.5. 
Rationale for Dose Selection ......................................................................................16 
4.
TRIAL OBJECTIVES AND PURPOSE ....................................................................17 
4.1. 
Primary Objective .......................................................................................................17 
4.2. 
Secondary Objectives .................................................................................................17 
4.3. 
Exploratory Objectives ...............................................................................................17 
5.
TRIAL ENDPOINTS .................................................................................................18 
5.1. 
Primary Endpoints ......................................................................................................18 
5.2. 
Secondary Endpoints ..................................................................................................18 
5.3. 
Exploratory Endpoints ................................................................................................18 
6.
INVESTIGATIONAL PLAN .....................................................................................19 
6.1. 
Overall Study Design ..................................................................................................19 
6.2. 
Number of Subjects ....................................................................................................19 
6.3. 
Treatment Assignment ................................................................................................19 
6.4. 
Dose Adjustment Criteria ...........................................................................................20 
6.5. 
Study Duration ............................................................................................................20 
6.6. 
Safety Monitoring .......................................................................................................20 
6.7. 
Criteria for Study Termination ...................................................................................20 
7.
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................23 
7.1. 
Subject Inclusion Criteria ...........................................................................................23 
7.2. 
Subject Exclusion Criteria ..........................................................................................23 
7.3. 
Subject Withdrawal Criteria .......................................................................................24 
8.
TREATMENT OF SUBJECTS ..................................................................................24 
8.1. 
Description of Study Drug ..........................................................................................24 
8.2. 
Concomitant Medications and Procedures .................................................................25 


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8.3. 
Treatment Compliance ................................................................................................25 
8.4. 
Randomization and Blinding ......................................................................................25 
9.
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................25 
9.1. 
Study Drug ..................................................................................................................25 
9.2. 
Restrictions .................................................................................................................25 
9.2.1. 
Food and Fluid Intake .................................................................................................25 
9.2.2. 
Activity .......................................................................................................................26 
9.3. 
Study Drug Packaging and Labeling ..........................................................................26 
9.4. 
Study Drug Storage .....................................................................................................26 
9.5. 
Study Drug Preparation ..............................................................................................26 
9.6. 
Administration ............................................................................................................26 
9.7. 
Study Drug Accountability .........................................................................................27 
9.8. 
Study Drug Handling and Disposal ............................................................................27 
10.
ASSESSMENT OF EFFICACY ................................................................................28 
10.1. 
Image Acquisition .......................................................................................................28 
10.1.1. 
18F-DCFPyL PET/CT (all cohorts) .............................................................................28 
10.1.2. 
Bone Scan (all cohorts) ...............................................................................................28 
10.1.3. 
CT or MRI (all cohorts) ..............................................................................................28 
10.1.4. 
Biopsy Guided Imaging (cohort B only) ....................................................................28 
10.2. 
Image Interpretation ....................................................................................................28 
10.3. 
Prostatectomy and Lymphadenectomy .......................................................................29 
10.4. 
Interventional Radiology ............................................................................................29 
10.5. 
Biopsy and Surgical Pathology ...................................................................................29 
10.6. 
Pharmacokinetics ........................................................................................................29 
11.
ASSESSMENT OF SAFETY .....................................................................................31 
11.1. 
Safety Parameters .......................................................................................................31 
11.1.1. 
Demographic/Medical History ...................................................................................31 
11.1.2. 
Vital Signs ..................................................................................................................31 
11.1.3. 
Weight and Height ......................................................................................................31 
11.1.4. 
Electrocardiogram (ECG) ...........................................................................................31 
11.1.5. 
Laboratory Assessments .............................................................................................31 
11.1.5.1. 
Hematology, Blood Chemistry, PSA and Testosterone..............................................31 


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11.2. 
Adverse and Serious Adverse Events .........................................................................32 
11.2.1. 
Definition of Adverse Events .....................................................................................32 
11.2.1.1. 
Adverse Event (AE) ....................................................................................................32 
11.2.1.2. 
Serious Adverse Event (SAE) ....................................................................................32 
11.3. 
Relationship to Study Drug ........................................................................................33 
11.4. 
Recording Adverse Events .........................................................................................33 
11.5. 
Reporting Serious Adverse Events .............................................................................34 
12.
STATISTICS ..............................................................................................................34 
12.1. 
Sample Size ................................................................................................................34 
12.2. 
Analysis Populations ..................................................................................................35 
12.2.1. 
Screened Subjects .......................................................................................................35 
12.2.2. 
Safety Set ....................................................................................................................35 
12.2.3. 
Evaluable Set ..............................................................................................................35 
12.2.4. 
Per Protocol Set ..........................................................................................................36 
12.2.5. 
PK Evaluable Set ........................................................................................................36 
12.3. 
Endpoints and Derivations ..........................................................................................36 
12.3.1. 
Sensitivity, Specificity, PPV, and NPV ......................................................................36 
12.3.2. 
Lesions Per Subject .....................................................................................................37 
12.3.3. 
Change from Baseline .................................................................................................37 
12.3.4. 
Pre-Treatment and Concomitant Medications ............................................................37 
12.3.5. 
Treatment-Emergent Adverse Events .........................................................................37 
12.4. 
Missing Data ...............................................................................................................37 
12.5. 
Analyses ......................................................................................................................37 
12.5.1. 
Subject Characteristics ................................................................................................37 
12.5.2. 
Efficacy Analysis ........................................................................................................38 
12.5.2.1. 
Primary Endpoint ........................................................................................................38 
12.5.2.2. 
Secondary Endpoints ..................................................................................................38 
12.5.2.3. 
Exploratory Analyses ..................................................................................................39 
12.5.3. 
Safety ..........................................................................................................................39 
12.5.3.1. 
Exposure .....................................................................................................................39 
12.5.3.2. 
Adverse Events ...........................................................................................................40 
12.5.3.3. 
Clinical Laboratory .....................................................................................................40 


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12.5.3.4. 
ECG ............................................................................................................................40 
12.5.3.5. 
Vital Signs ..................................................................................................................40 
12.5.4. 
Pharmacokinetics ........................................................................................................40 
13.
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS.........................................40 
13.1. 
Study Monitoring ........................................................................................................40 
13.2. 
Audits and Inspections ................................................................................................41 
14.
ETHICS ......................................................................................................................42 
14.1. 
Good Clinical Practice (GCP), Laws and Regulations ...............................................42 
14.2. 
Institutional Review Board (IRB) or Independent Ethics Committee (IEC) 
Approval .....................................................................................................................42 
14.3. 
Written Informed Consent ..........................................................................................42 
14.4. 
Subject Confidentiality ...............................................................................................43 
14.5. 
Financial Disclosure ...................................................................................................43 
15.
DATA HANDLING AND RECORDKEEPING .......................................................43 
15.1. 
Case Report Forms and Study Records ......................................................................43 
15.2. 
Inspection of Records .................................................................................................43 
15.3. 
Retention of Records ..................................................................................................43 
16.
PUBLICATION AND DISCLOSURE POLICY .......................................................44 
17.
REFERENCES ...........................................................................................................45 
LIST OF TABLES 
Table 1: 
Emergency Contact Information ...................................................................................4 
Table 2: 
Abbreviations and Specialist Terms .............................................................................9 
Table 3: 
Schedule of Assessments ............................................................................................21 
Table 4: 
Investigational Product ...............................................................................................24 
Table 5: 
PK Sampling & Imaging Timepoints .........................................................................30 
Table 6: 
Clinical Laboratory Tests ...........................................................................................32 
Table 7: 
Classification of 18F-DCFPyL Imaging Result and Histopathology Result for 
Cohorts A and B Separately .......................................................................................36 
LIST OF FIGURES 
Figure 1: 
Study Schema .............................................................................................................20 


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2.
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 
ALT 
alanine aminotransferase (SGPT) 
AST 
aspartate aminotransferase (SGOT) 
AUC 
area under the time-concentration curve 
BP 
blood pressure 
BUD 
beyond use date 
BUN 
blood urea nitrogen 
CBC 
complete blood count 
CFR 
Code of Federal Regulations 
CL 
total body clearance 
CMP 
comprehensive metabolic panel 
Cmax
maximum (peak) serum concentration 
CRF 
case report form 
CT 
computed tomography 
DMC 
Data Monitoring Committee 
DoB 
date of birth 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EOS 
End of Synthesis 
FDA 
Food and Drug Administration 
18F 
Fluorine-18 
FDG 
Fluorodeoxyglucose 
68Ga 
Gallium-68 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
hr 
Hour(s) 
HR 
Heart Rate 


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Table 2: 
Abbreviations and Specialist Terms 
Abbreviation or Specialist Term 
Explanation 
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 
kg 
Kilogram 
m 
Minute/Meter 
mAb 
Monoclonal Antibody 
MBq 
MegaBequerel 
mCi 
MilliCurie 
MDP 
methylene diphosphonate bone scan 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
mL 
Milliliter 
MRI 
Magnetic Resonance Imaging 
MRT 
Mean Residence Time 
mSv 
millisievert 
N/A 
not applicable 
NCCN 
National Comprehensive Cancer Network 
NCI 
National Cancer Institute 
CTCAE 
Common Terminology Criteria for Adverse Events 
ng 
nanogram 
nM 
nanometer 
NOAEL 
No Observed Adverse Effect Level 
NPV 
negative predictive value 
PET/CT 
positron emission tomography–computed tomography 
PI 
Principal Investigator 
PK 
pharmacokinetics 


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Table 2: 
Abbreviations and Specialist Terms 
Abbreviation or Specialist Term 
Explanation 
PLND 
Pelvic lymph node dissection 
PPV 
Positive Predictive Value 
PSA 
Prostate Specific Antigen 
PSMA 
Prostate-Specific Membrane Antigen 
PT 
Preferred Term 
RBC 
Red Blood Cell count 
RCC 
Renal cell carcinoma 
RP 
radical prostatectomy 
RR 
respiratory rate 
SAE 
Serious Adverse Event 
SAP 
statistical analysis plan 
SD 
Standard deviation 
SoC/SOC 
Standard of Care/System Organ Class 
SOP 
Standard Operating Procedures 
SUVmax 
Maximum Standardized Uptake Value 
SUVpeak 
Peak standardized uptake value 
SUVr 
ratio to reference tissue standardized uptake value 
TIAC 
Time-Integrated Activity coefficients 
US 
United States 
Vss 
Volume of Distribution at Steady State 
WBC 
White Blood Cell count 


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3.
INTRODUCTION
3.1. 
Background Information
Prostate cancer is the most common cancer among men in the United States (US) with an 
estimated number of new cases of 161,360 annually; 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, recurrent disease.  Thus imaging modalities that can detect, monitor, and 
restage residual, recurrent locoregional disease, and metastatic disease are highly desirable.  
Conventional anatomic and functional imaging including contrast-enhanced computed 
tomography (CT), [99mTc] methylene diphosphonate (MDP) bone scan, ultrasound, or magnetic 
resonance imaging (MRI) may not be sufficiently sensitive and specific for detection of prostate 
cancer lesions.2-5 
Tumors typically exhibit abnormally high metabolism and this mechanism has been exploited for 
imaging cancers.  Positron emission tomography (PET) employing 2-deoxy-2-[18F]fluoro-D-
glucose (FDG PET), the clinical standard for a number of cancers, has demonstrated mixed 
results in imaging prostate cancer.6-9  Other tumor metabolism-based approaches tested in 
prostate cancer (and other cancers) are the use of labeled choline to take advantage of the 
increased expression of choline kinase (ChKα) in tumor cells10, or increased uptake of amino 
acids such as methionine or leucine.  11C choline was approved by FDA in 2012; however, the 
sensitivity of 11C choline tends to be limited in extraprostatic lesions.11-14  Most recently, 
synthetic L-leucine analog trans‐1‐amino‐3‐18F‐fluoro‐cyclobutane carboxylic acid (18F‐FACBC; 
Axumin®) was approved for use in men with suspected recurrence of prostate cancer. 
A number of new, targeted PET tracers have been introduced for imaging prostate cancer.15-20  
Proving particularly effective are low-molecular-weight agents that bind to the prostate-specific 
membrane antigen (PSMA), which is highly expressed in castration-resistant, metastatic prostate 
cancer.21,22,23  A novel, high specific activity, highly selective, low-molecular weight PSMA-
targeted PET radiotracer, 18F-DCFPyL, is currently being investigated as an imaging agent for 
prostate cancer at Johns Hopkins University School of Medicine (JHU).  The purpose of the 
current study is to further the clinical development of 18F-DCFPyL to support marketing 
approval. 
3.2. 
Rationale for Developing Prostate Cancer Imaging Agents 
Prostate cancer is a significant public health problem affecting more than 2.3 million men in the 
US and another 4 million in Europe.  Annually, nearly 161,360 new cases of prostate cancer are 
diagnosed in the US, coupled with approximately 400,000 newly diagnosed cases in Europe.1,24  
It is estimated that the disease will affect one in seven men in their lifetimes, leading to 
approximately 293,000 deaths per year in developed countries worldwide.25  The mortality from 
the disease is second only to lung cancer in men.1  An estimated $8 billion is currently spent 
annually in the US on surgery, radiation, drug therapy and minimally invasive treatments.26 
Several imaging modalities are currently employed for the diagnosis, staging and prognosis of 
prostate cancer metastases.  Conventional cross-sectional imaging with CT and MRI rely on 
anatomical changes (lesions >1 cm), often resulting in missed lymph node metastases and low 


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sensitivity.  Nodal enlargement of metastases occurs relatively late in the progression of prostate 
cancer and neither CT nor MRI are effective at detecting the often microscopic lymph node 
metastases at the earliest stages of disease progression.  Additionally, nodal enlargement can also 
be caused by infection or inflammation, thereby reducing the specificity.  Meta-analyses of 24 
published studies revealed that CT and MRI performed equally poorly in the detection of lymph 
node metastases from prostate cancer.  Results of pooled sensitivity and specificity were 42% 
and 82%, respectively, for CT and 39% and 82%, respectively, for MRI.  Thus, the reliance on 
either CT or MRI may misrepresent the patient’s true status regarding nodal metastases, and 
misdirect the therapeutic strategies offered to the patient.27  Radionuclide bone scans are 
commonly used for monitoring bone metastases.  However, as bone scans detect tissue 
remodeling, as opposed to tumor burden, false positives can be caused by inflammation, previous 
bone injuries, and arthritis, especially in older men.28  Therefore, new agents that will detect and 
localize the primary tumor, as well as small metastatic lesions, with high sensitivity and 
specificity are essential to more accurately diagnose and stage the disease, and monitor therapy. 
3.3. 
Targeting PSMA for Prostate Cancer Detection 
Prostate-specific membrane antigen (PSMA), also known as folate hydrolase I (FOLH1) or 
glutamate carboxypeptidase II (GCPII), 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.29,30  Since PSMA is expressed by 
virtually all prostate cancers and its expression is further increased in poorly differentiated, 
metastatic and hormone-refractory prostate carcinomas, it is a very attractive target for 
developing agents for the diagnosis and staging of this disease.31,32,33  In addition to high 
expression in malignant prostatic tissue and being directly related to tumor aggressiveness,34 
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,23,31,35,36 and in the 
neovasculature of nonprostatic solid carcinomas (e.g., renal cell, breast, colon, pancreas, 
melanoma, and lung carcinoma).21 
A radiolabeled anti-PSMA monoclonal antibody (mAb) 7E11, marketed as Indium 111 
ProstaScint® (capromab pendetide) is currently being used to detect prostate cancer nodal 
metastasis and recurrence.  ProstaScint was first approved for marketing by the FDA in 1996, 
and while still available today, it is rarely used in practice due to a number of logistical and 
clinical limitations.  Furthermore, ProstaScint targets the intracellular domain of PSMA and is 
therefore thought to bind mostly necrotic portions of the prostate tumor.32 
More recently, radiolabeled monoclonal antibodies that bind to the extracellular domain of 
PSMA have been developed and have been shown to accumulate in PSMA-positive prostate 
tumors in animals.30  Early promising results in man from various phase 1 and 2 trials have 
utilized PSMA as a therapeutic target.37,38  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.  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 


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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 and thereby making lesion detection more 
conspicuous. 
In the past few 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 SPECT agent, 99mTc-MIP-1404, is currently in phase 3 testing for the 
detection of clinically significant prostate cancer in patients with low grade disease.39,40  PET 
imaging agents, such as 124I-MIP-1095, 18F-DCFCBC, 18F-DCFPyL, and 68Ga-HBED-CC, have 
also generated much interest for their potential use in detecting metastatic prostate cancer.  68Ga-
HBED-CC (68Ga-PSMA) has been broadly studied in the clinical setting at academic centers.  In 
a retrospective analysis of patients with high-risk localized disease prior to radical 
prostatectomy, 68Ga-PSMA PET/CT imaging showed a sensitivity of approximately 93% for 
intraprostatic lesions and 33% for regional lymph node metastases.  Specificity, positive and 
predictive values for lymph nodes were 100%, 100% and 69%, respectively.41  A retrospective 
evaluation of data from 68Ga-PSMA PET/CT imaging in patients with biochemical recurrence of 
prostate cancer showed high detection rates, even in patients with low (0.2 to <0.5 ng/ml) PSA 
(58%).42  Studies have also been conducted to compare 68Ga-PSMA PET/CT and 18F-choline 
PET/CT imaging in prostate cancer.  In patients with recurrent prostate cancer scheduled to 
undergo salvage lymphadenectomy (thus providing histopathology as the truth standard), 68Ga-
PSMA PET/CT showed better performance than 18F-choline PET/CT with a significantly higher 
negative predictive value (NPV) and accuracy for the detection of locoregional recurrent and/or 
metastatic lesions prior to salvage lymphadenectomy, with sensitivity of 71% vs 87%, specificity 
of 87% vs. 93%, and accuracy of 83% vs 92%, respectively.43  In patients with biochemical 
recurrence of prostate cancer with a negative [18F]-choline PET/CT, 68Ga-PSMA-PET/CT 
identified sites of recurrent disease in 43.8% of the patients with negative F-choline PET/CT 
scans.44  Another study was conducted to compare the detection rate of two PSMA-targeted 
PET/CT imaging agents side-by-side (18F-DCFPyL and 68Ga-PSMA) in patients with recurrence 
of prostate cancer.45  The results showed that 18F-DCFPyL PET/CT provided high image quality 
and visualized small prostate lesions with excellent sensitivity.  Furthermore, F-18 tracers in 
general offer important advantages over Ga-68 tracers, including higher production capacity 
from the use of a cyclotron as opposed to depending on the supply from Ga generators, and 
higher image resolution due to the intrinsic physical properties of F-18 (lower positron emission 
energy compared to Ga-68).  Thus, overall, 18F-DCFPyL PET/CT may represent a promising 
alternative to 68Ga-PSMA PET/CT for imaging prostate cancer. 
PyL is a radiolabeled PSMA-targeted small molecule discovered at JHU that was in-licensed by 
Progenics in 2015.  It is currently being studied in phase 1 and phase 2 clinical trials under 
JHU’s IND 121,064 for the detection of primary and metastatic prostate cancer.  In collaboration 
with JHU, Progenics plans to complete the clinical development program of PyL and eventually 
seek FDA approval of PyL for the detection of prostate cancer. 


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3.4. 
18F-DCFPyL 
18F-DCFPyL Injection is a radiolabeled small molecule that binds to the extracellular domain of 
PSMA with high affinity.  PSMA is a transmembrane glycoprotein expressed by virtually all 
prostate cancers, and its expression is further increased in metastatic and hormone-refractory 
prostate carcinomas, which makes it a useful target for developing agents for the diagnosis and 
staging of prostate cancer. 
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.  Data from 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. 
Several investigator-initiated clinical studies with 18F-DCFPyL Injection in prostate cancer, as 
well as non-prostate cancer, are currently ongoing at Johns Hopkins University under IND 
121,064.  As of March 2016, 18F-DCFPyL Injection has been administered to a total of 108 
subjects at doses averaging 9 ± 1 mCi per injection.  Preliminary safety and efficacy data from 
two of these studies (J1418, J1545) are currently available. 
Study J1418 is 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, 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 therapy. 
Data from these clinical studies at JHU demonstrate that PET imaging with 18F-DCFPyL 
Injection is feasible and safe.  Biodistribution following administration of 18F-DCFPyL Injection 
and optimal imaging time point were determined and radiation dose used was within limit for 
diagnostic radiotracers for PET.  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.   


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Safety results from all ongoing studies at JHU to date indicate that 18F-DCFPyL Injection is well 
tolerated, with no reported serious adverse events in any of the studies thus far.  A total of 6 
adverse events have been reported, one of which was attributed as possibly related to study drug 
(Grade 1 Headache). 
Progenics has obtained authorization from JHU to reference, and incorporate by reference, the 
data from the phase 1 and phase 2 studies conducted under the JHU IND.  Based on the 
promising results from these clinical studies, Progenics plans to initiate the current phase 2/3 
study (PyL 2301) under a new, separate IND to investigate the safety and efficacy of PyL 
imaging in patients with prostate cancer.  
3.5. 
Rationale for Dose Selection 
Prior to the first-in-human study with PyL (Study J1418) at JHU, human dosimetry was 
extrapolated from a preclinical biodistribution study in xenograft mice.46  The mouse organ 
activity concentrations in %ID/g were converted to the human %ID/ organ by setting the ratio of 
organ %ID/g to whole-body %ID/g in the mouse equal to that in humans and then solving for the 
human %ID/organ.  The adult male phantom organ masses listed in the OLINDA/EXM 1.0 were 
used for the conversion.  The human source organ time-activity curves were fitted using a 
monoexponential function.  Because the biodistribution data were radioactive decay-corrected, 
only the biological removal constants were obtained from the curve fits, and the physical decay 
constant for F-18 was added in obtaining the time-integrated activity coefficients (TIAC).  The 
source organ TIACs in MBq-h/MBq were entered in the OLINDA/EXM 1.0 for the dose 
calculations.  The dynamic voiding bladder model was used to obtain the TIAC for the urinary 
bladder contents.  The whole-body clearance half-life (obtained as the sum of sampled tissues, 
excluding the tumors) was used as the half-life to describe urinary bladder filling.  All 
radioactivity was assumed to be eliminated via the urine.  A one hour voiding interval was 
assumed. 
The urinary bladder wall was projected to be the organ with the highest absorbed dose.  To limit 
the radiation-absorbed dose to the urinary bladder (≤ 50 mGy), the highest human dose is 
estimated to be 8.95 mCi.  As a result, the first-in-human dose used at JHU for obtaining basic 
information regarding the metabolism (including kinetics, distribution, and localization) was 
determined to be ≤9 mCi.  The 9 mCi administered dose of 18F-DCFPyL Injection results in a 
comparable radiation dose to that of other radiotracers used in oncology such as [18F]-FDG. 


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4.
TRIAL OBJECTIVES AND PURPOSE
4.1. 
Primary Objective
The primary objective of the study is to assess the diagnostic performance of 18F-DCFPyL 
PET/CT imaging to determine the presence or absence of metastatic disease in pre-prostatectomy 
patients with high risk prostate cancer (cohort A)   
4.2. 
Secondary Objectives 
1. To evaluate the safety and tolerability of 18F-DCFPyL
2. To assess the diagnostic performance of 18F-DCFPyL PET/CT imaging to determine the
presence or absence of prostate cancer within sites of metastasis or local recurrence
(cohort B)
3. To determine detection rates of 18F-DCFPyL PET/CT and conventional imaging among
lesion locations (e.g., bone, lymph nodes, soft tissue, prostate gland)
4. To determine positive and negative predictive value (PPV and NPV) of 18F-DCFPyL
PET/CT imaging
5. To determine the pharmacokinetics, biodistribution, and excretion of 18F-DCFPyL
4.3. 
Exploratory Objectives 
1. To assess 18F-DCFPyL uptake among lesion locations (e.g., bone, lymph nodes, soft
tissue, prostate gland)
2. To assess the relationship between 18F-DCFPyL uptake in prostatic and extraprostatic
lesions with baseline PSA and testosterone levels, and Gleason Score at time of radical
prostatectomy
3. To assess the diagnostic performance of 18F-DCFPyL PET/CT imaging to detect prostate
cancer within the prostate gland (cohort A)
4. To assess the  impact of 18F-DCFPyL PET/CT imaging on clinical management plans
5. To determine the PPV of 18F-DCFPyL PET/CT imaging for lesions detected by PET that
are outside the planned surgical template or biopsy site


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5.
TRIAL ENDPOINTS
5.1. 
Primary Endpoints
1. Specificity of 18F-DCFPyL PET/CT imaging to determine the absence of metastatic
prostate cancer within the pelvic lymph nodes relative to histopathology (cohort A)
2. Sensitivity of 18F-DCFPyL PET/CT imaging to determine the presence of metastatic
prostate cancer within the pelvic lymph nodes relative to histopathology (cohort A)
5.2. 
Secondary Endpoints 
1. Safety and tolerability (Cohorts A and B combined):
a.
Treatment-emergent adverse events
b. Pre- and post-18F-DCFPyL PET/CT lab values, ECGs and vital signs
2. Sensitivity of 18F-DCFPyL PET/CT imaging to detect prostate cancer within sites of
metastasis or local recurrence relative to histopathology (Cohorts B)
3. Comparison of detection rates (Cohorts A and B combined) for lesion counts overall and
by  location (i.e., bone, lymph nodes, soft tissue, prostate gland) between 18F-DCFPyL
and conventional imaging
4. PPV and NPV of 18F-DCFPyL PET/CT imaging (Cohort A) to predict prostate cancer
within the prostate gland and lymph nodes
5. PPV of 18F-DCFPyL PET/CT imaging to predict prostate cancer within sites of local
recurrence and other metastatic lesions (cohort B)
6. Pharmacokinetic parameters [e.g., Cmax, area under the curve (AUC), total clearance
(CL), steady-state volume of distribution (Vss) and mean residence time (MRT)] (subset
of Cohorts A and B combined)
5.3. 
Exploratory Endpoints 
1.
18F-DCFPyL uptake in different lesion locations (i.e., bone, lymph nodes, soft tissue,
prostate gland) as defined by SUVpeak, SUVmax, SUVr results derived from central
readers, compared to histopathology (cohorts A and B)
2. To assess the relationship between SUVpeak, SUVmax and SUVr in prostatic and
extraprostatic lesions with each of the following: baseline PSA, baseline testosterone
level, and Gleason Score at time of radical prostatectomy
3. Sensitivity and specificity of 18F-DCFPyL PET/CT imaging to detect prostate cancer
within the prostate gland relative to histopathology (cohort A)
4. Changes to clinical management plan based on a review of clinical and radiographic
subject data before and after 18F-DCFPyL PET/CT imaging by a central panel of disease
experts using a structured questionnaire


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5. PPV of 18F-DCFPyL PET/CT imaging in subjects with corresponding histopathology that
is outside the planned protocol surgical template or biopsy site
6.
INVESTIGATIONAL PLAN
6.1. 
Overall Study Design
This is an open-label, non-randomized, Phase 2/3, multi-center study designed to evaluate the 
safety and diagnostic performance of 18F-DCFPyL PET/CT imaging to determine the presence or 
absence of metastatic prostate cancer in subjects with at least high risk prostate cancer who are 
planned for radical prostatectomy [RP] with pelvic lymph node dissection [PLND]) (cohort A), 
and subjects with radiologic evidence of local recurrence or new or progressive metastatic 
disease (cohort B). 
Eligible subjects (see Section 7.1 for Inclusion Criteria) will be enrolled in a non-randomized, 
sequential manner, with competitive enrollment between study sites.   
Diagnostic performance characteristics of 18F-DCFPyL PET/CT imaging will be evaluated using 
histopathology as the truth standard.  See Section 8.4 for details on blinding.  
The study will explore changes to clinical management plans based on data before and after 18F-
DCFPyL PET/CT imaging.  
This study is planned to be performed in approximately 10 sites in the United States and Canada. 
See Figure 1 and Table 3 for the study schema and schedule of assessments.  
6.2. 
Number of Subjects 
Approximately 377 subjects are planned to be dosed in this study: 
•
Approximately 262 subjects will be dosed in Cohort A.
•
Approximately 115 subjects will be dosed in Cohort B.
See Section 7 for complete eligibility details and Section 12.1 for complete sample size 
assumptions. 
6.3. 
Treatment Assignment 
All subjects will be administered 9 ± 1 mCi (333 ± 37 MBq) 18F-DCFPyL Injection followed by 
PET/CT imaging as illustrated in the schema below.  See Section 9.6 Study Drug Administration 
and Table 3 Schedule of Assessments for complete details.   


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Figure 1: 
Study Schema 
6.4. 
Dose Adjustment Criteria 
Dosing adjustments of 18F-DCFPyL Injection are not permitted.   
6.5. 
Study Duration 
The duration of subject participation will be from informed consent through 18F-DCFPyL 
PET/CT scanning and follow-up visit, a total maximum duration of 58 days.   
6.6. 
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 11.  A Safety Review Committee, consisting of 
Sponsor representatives (e.g., Medical Monitor, Clinical Operations designee, Biometrics 
designee) and at least one active Principal Investigator will also review data on an ongoing basis 
to assess subject safety, eligibility and baseline characteristics through listings, tables and subject 
profiles. 
6.7. 
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 Ethics Committee (EC) may terminate an 
investigational site for the following (but not limited to) reasons:  
•
If any 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 serious protocol violations occur;


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•
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
Table 3: Schedule of Assessments 
Screening
/ Baseline 
18F-
DCFPyL 
Dosing 
18F-
DCFPyL 
Imaging 
Pre-
Surgery/Biopsy 
Follow-Up 
Day-30 to 
Day 1 
Day 1 
1-2 Hours
Post
Dosing
Within 28 Days 
Post Dosing 
Cohorts A and B 
Informed Consent & Eligibility 
X 
Demographics (date of birth, race, 
ethnicity, height, weight, BMI) 
X 
Medical History (see Section 11.1.1)  
X 
Prior Cancer Medications & 
Treatments 
X 
Clinical Labs (Hematology, 
Chemistry) see Table 6  
X1 
X 
PSA (Total) & Testosterone 
X1 
Vital Signs (Blood Pressure, Heart 
Rate, Temperature, Respiratory Rate) 
X 
X 
(pre-
dosing) 
X 
(pre-
imaging) 
X 
12-Lead Electrocardiogram (ECG)
(see Section 11.1.4)
X 
(pre-
dosing) 
X 
(pre-
imaging) 
18F-DCFPyL Administration (see 
Section 9) 
X 
Whole Body PET/CT (see 
Section 10.1) 
X 
Adverse Events (see 
Section 11.2.1.1)  
X 
X5 
Concomitant Medications (see 
Section 8.2) 
X 
X 
X 
Conventional Imaging (CT or MRI, 
Bone Scan) (see Section 10.1)  
X2 
Surgery or Image-Guided Biopsy 
X3,6 


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Table 3: Schedule of Assessments 
Screening
/ Baseline 
18F-
DCFPyL 
Dosing 
18F-
DCFPyL 
Imaging 
Pre-
Surgery/Biopsy 
Follow-Up 
Day-30 to 
Day 1 
Day 1 
1-2 Hours
Post
Dosing
Within 28 Days 
Post Dosing 
Subset of Cohort A or B at Johns Hopkins University only for Pharmacokinetic (PK) 
Analysis 
Blood Collection  
X (9 
collections)4 
Urine Collection 
X (3 
collections)4 
Whole Body PET/CT 
X (3 
scans)4 
1 To be collected prior to dosing, if collected on day of dosing.  If PSA and testosterone have not been tested within 30 
days of study drug injection, a blood draw will be collected prior to dosing. 
2 If not obtained as standard of care ≤ 6 weeks (Cohort A) or ≤ 4 weeks (Cohort B) prior to Day 1. Na-18F-PET bone 
scans conducted at screening must be at least 10 hours prior to dosing (see Section 7.2).   
3 Surgery or biopsy to occur at least 12 hours from time of 18F-DCFPyL dosing but not more than 28 days from 
dosing.  In Cohort B, imaging used to guide biopsy (i.e., CT, MRI) will be submitted to a central core imaging lab.  
4 See Section 10.6  for complete details. Analysis should occur immediately following last sample collected. 
5 A safety phone call will also occur 7(±3) days post-dosing [if surgery (Cohort A) or biopsy (Cohort B) has not yet 
occurred] and 21(±7) days post biopsy (Cohort B).  See Section 11.2.1.1 for complete details. 
6  If a subject’s planned procedure (RP or biopsy) for prostate cancer changes following 18F-DCFPyL imaging, the 
alternate or additional prostate cancer procedure and corresponding histopathology data will be recorded in the 
electronic case report form (eCRF).


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7.
SELECTION AND WITHDRAWAL OF SUBJECTS
7.1. 
Subject Inclusion Criteria
Subjects must meet all of the following inclusion criteria: 
All Cohorts: 
1. Adults ≥18 years of age.
2. Subjects provide signed informed consent and confirm that they are able and willing to
comply with all protocol requirements.
3. Histologically confirmed adenocarcinoma of the prostate.
Cohort A Only: 
4. At least high risk prostate cancer defined by NCCN Guidelines Version 3.2016 (clinical
stage ≥T3a or PSA >20 ng/mL or Gleason score ≥8).47
5. Scheduled or will be scheduled to undergo radical prostatectomy with PLND.
Cohort B Only: 
6. Radiologic evidence of local recurrence or new or progressive metastatic disease
demonstrated on anatomical imaging (CT, MRI, or ultrasound), whole-body bone scan
(99mTc-MDP or Na18F) within 4 weeks of Day 1.
7. If prior treatment with radiation or ablative therapy, evidence of recurrence outside the
confines of prior treated site(s).
8. Scheduled or will be scheduled for percutaneous biopsy of at least one amenable lesion.
7.2. 
Subject Exclusion Criteria 
Subjects meeting any of the following exclusion criteria are not eligible for this study: 
All Cohorts: 
9. Subjects administered any high energy (>300 KeV) gamma-emitting radioisotope within
five physical half-lives, or any IV iodinated contrast medium within 24 hours, or any high
density oral contrast medium (oral water contrast is acceptable) within 5 days, prior to
study drug injection.
10. Subjects with any medical condition or other circumstances that, in the opinion of the
investigator, compromise obtaining reliable data, achieving study objectives, or
completion.
Cohort A Only: 
11. Patients with prior androgen deprivation therapy or any investigational neoadjuvant agent
or intervention


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Cohort B Only: 
12. Prior radiation or ablative therapy to intended site of biopsy, if within the prostate bed.
13. Initiation of new systemic therapy for recurrent and/or progressive metastatic disease
since radiographic documentation of recurrence/progression.
7.3. 
Subject Withdrawal Criteria 
A patient may withdraw from the study at any time for any reason without prejudice to his/her 
future medical care by the physician or at the study site.  Likewise, the Investigator and/or 
Sponsor have the right to withdraw patients from the study.  Subjects may be discontinued for 
any of the following reasons: 
•
Significant protocol violation or noncompliance (e.g., initiation of treatments
forbidden per Section 7.2)
•
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, all efforts will be made to complete the required study procedures as 
thoroughly as possible.   
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.   
8.
TREATMENT OF SUBJECTS
8.1. 
Description of Study Drug
A single administration of 18F-DCFPyL Injection (PyL) will be administered 1-2 hours prior to 
PET/CT imaging on Day 1. 
Table 4: Investigational Product 
Investigational Product 
Product Name 
18F-DCFPyL INJECTION (PyL) 
Dosage Form 
Sterile solution for intravenous injection 
Unit Dose 
9 ± 1 mCi (333 ± 37 MBq) 
Route of Administration 
Intravenous catheter placed in an antecubital vein or an equivalent 
venous access 
Physical Description 
Colorless, particle-free solution 


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8.2. 
Concomitant Medications and Procedures 
All concomitant medications and medical procedures that occur within 7 days of consent will be 
recorded.  
Any new prostate cancer therapy is strictly prohibited from time of dosing (Day 1) to surgery 
(Cohort A), or from time of radiographic documentation of disease progression to biopsy (Cohort 
B).  If a subject reports having received a new prostate cancer therapy (e.g., hormone, drug, 
biologic, radiologic, or chemotherapy) or alternate medical procedure(s) for prostate cancer, 
during these time periods, the subject should be discontinued from the study.   
Medical procedure(s) and histopathology data for subjects who do not receive the planned 
protocol procedure but who received alternate or additional medical procedure(s) for prostate 
cancer will be recorded in the eCRF. 
8.3. 
Treatment Compliance 
All 18F-DCFPyL drug injected 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. 
8.4. 
Randomization and Blinding 
This is an open-label, non-randomized study.  Three independent readers from a central imaging 
core lab will be given access to 18F-DCFPyL PET/CT imaging, conventional imaging, and 
biopsy-guided imaging.  The central readers will be blinded to all other clinical information and 
radiology assessments.  Likewise, the Investigator is responsible for ensuring that local 
pathologists who generate the histopathology results for the primary endpoint remain blinded to 
all imaging results.   
9.
STUDY DRUG MATERIALS AND MANAGEMENT
9.1. 
Study Drug
Please reference Section 8.1 for a description of the study drug. 
9.2. 
Restrictions 
9.2.1. 
Food and Fluid Intake 
There are no dietary or food restrictions for this trial. 
Increased fluid intake should occur before and after image acquisition to maintain proper 
hydration throughout the study period and decrease radiation exposure to the urinary bladder.  To 
enhance imaging, subjects should be encouraged to void post study drug injection and prior to 
imaging. 
Subjects should follow pre-imaging and preoperative guidelines as per institutional practices and 
in accordance with standard of care principles. 


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9.2.2. 
Activity 
The radioactivity administered in this study is similar to other diagnostic radiopharmaceuticals 
and should be managed according to institutional policies.   
9.3. 
Study Drug Packaging and Labeling 
The final drug product (18F-DCFPyL) is a clear, colorless injectable solution at a strength of 5-
75 mCi/mL (185-2775 MBq/mL) 18F-DCFPyL at End of Synthesis (EOS).  18F-DCFPyL will be 
dispensed and filled into a unit-dose syringe.  The final drug product will be placed into a lead 
pig and delivered to the clinical site in shipping containers with lead shielding.  
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 (BUD).  An auxiliary sticker reading “New Drug—
Limited by Federal Law to Investigational Use” shall be affixed to the unit-dose container. 
9.4. 
Study Drug Storage 
The study drug should be maintained at room temperature within the received lead shield unit-
dose system until time of administration.   
9.5. 
Study Drug Preparation 
The final drug product is supplied to each institution on the day of administration in a unit-dose 
syringe with no additional preparation required. Institutional policies and standard operating 
procedures (SOPs) 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. Apply decay correction if necessary and calculate the administered 
dose accordingly. 
9.6. 
Administration 
Please see the Imaging Manual for complete details including pre-and post-injection 
measurement of the 18F-DCPyL Injection dose syringe.  Administration must occur by the 
labeled expiration time. 
1. Place an intravenous catheter in an antecubital vein or an equivalent venous access.
2. Ensure patency of the line with a saline flush.
3. Inject a bolus of 9±1 mCi (333±37 MBq) of 18F-DCPyL into the IV line or equivalent
venous access by slow push from the appropriately shielded syringe according to normal
local practices.
4. 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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If dose extravasation is noticed during or after completion of the drug administration: 
1. Try to aspirate as much extravasated drug as possible through the still-intact catheter.
2. Imaging should proceed unless contraindicated for safety reasons.
3. Examine the skin area for local toxicity before discharge, and instruct subject to contact
site immediately if local symptoms at injection site do not improve or worsen.
4. Note the event as an Adverse Event in the CRF and notify the Sponsor within 24 hours.
9.7. 
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 patient, 
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 agents are 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 personnel 
and when appropriate, reconciliation will be performed. 
9.8. 
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 agent on the Drug 
Accountability record.   


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10.
ASSESSMENT OF EFFICACY
10.1. 
Image Acquisition 
10.1.1. 
18F-DCFPyL PET/CT (all cohorts) 
18F-DCFPyL PET imaging will be performed on local PET/CT scanners with CT for correction 
of physical effects (e.g., attenuation, scatter) and anatomic localization.   
At 1-2 hours post 18F-DCFPyL injection, the subject will be asked to void, and a whole body CT 
and PET scan will be acquired from the mid-thigh through the vertex of the skull.  Parameters for 
PET/CT scanning can be found in the Imaging Manual.   
10.1.2. 
Bone Scan (all cohorts) 
A radionuclide bone scan (either 99mTc-MDP or 18F-NaF PET/CT, depending upon the site’s 
standard of care) will be obtained at Screening if one has not been obtained within six weeks 
(Cohort A) or four weeks (Cohort B) prior to study drug injection.  If conducted as part of 
Screening, 18F-NaF PET bone scans must be done at least five physical half-lives (10 hours) 
prior to 18F-DCFPyL injection.  Bone scan images will be submitted to the independent central 
imaging core lab per instruction in the Imaging Manual for assessment. 
10.1.3. 
CT or MRI (all cohorts) 
A contrast-enhanced CT of the chest, abdomen and pelvis (or non-contrast CT chest with 
Gadolinium-enhanced MRI of the abdomen and pelvis for subjects who have a medical 
contraindication to iodinated contrast) will be obtained at Screening if not already obtained 
within 6 weeks (Cohort A) or 4 weeks (Cohort B) prior to study drug injection.  If CT is 
conducted at Screening, IV iodinated contrast medium cannot be administered within 24 hours of 
study drug injection.  High density oral contrast medium (oral water contrast is acceptable) 
cannot be administered within 5 days prior to study drug injection.  Copies of baseline CT or MR 
images will be submitted to the independent central imaging core lab per instruction in the 
Imaging Manual for assessment. 
10.1.4. 
Biopsy Guided Imaging (cohort B only) 
In Cohort B, imaging used to guide biopsy (i.e., CT/MRI) will be collected and reviewed 
centrally to confirm the biopsy location in the area of interest.  The instruction for capturing 
biopsy images and directions for submitting the images to the independent central imaging core 
lab will be found in the Image Guided Biopsy Manual. 
10.2. 
Image Interpretation 
An independent imaging core lab will receive and evaluate 18F-DCFPyL PET/CT baseline, 
conventional images, and imaging used to guide biopsy (i.e., CT, MRI).  The processes for 
image acquisition, transmittal and interpretation are detailed in the Imaging Manual and Imaging 
Review Charter documents.   


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10.3. 
Prostatectomy and Lymphadenectomy 
Within 28 days post-study drug injection, all subjects in Cohort A will undergo standard of care 
RP with PLND as detailed in the Surgical Manual.  Extent of PLND will be captured in the 
eCRF. 
Surgical staff will label all specimens removed during surgery to correlate with the specific 
anatomic location of removal, in accordance with the Surgical Manual.   
Should a subject receive alternate or additional procedure(s) for prostate cancer after dosing, the 
procedure and corresponding histopathology data will be recorded in the eCRF.   
10.4. 
Interventional Radiology 
Up to two lesions (one bone and one soft-tissue lesion, wherever feasible) may be biopsied in 
cohort B, within 28 days following 18F-DCFPyL imaging.  If more than one lesion is obtained, 
the interventional radiologist will identify the specimen to be evaluated for diagnostic assessment 
and statistical analysis.  The lesions most preferred for biopsy will be those that are suspicious on 
all or most imaging modalities and are in the investigators judgement safe for biopsy.  The final 
biopsy site will be decided in consultation with the Interventional Radiology service for 
feasibility.  Details regarding the collection of imaging used to guide biopsy (e.g., X-ray, CT, 
MRI) and transmittal to the central imaging lab can be found in the Image Guided Biopsy 
Manual.  Images will be reviewed centrally to confirm uptake of 18F-DCFPyL in the area of 
interest. 
Should a subject receive alternate or additional procedure(s) for prostate cancer after dosing, the 
procedure and corresponding histopathology data will be recorded in the eCRF.  
10.5. 
Biopsy and Surgical Pathology 
Immediately following biopsy or surgery, the specimens will be sent for histopathological 
processing and analysis at the site in accordance with the study Pathology Manual.   
Gross handling of the prostate gland and lymphadenectomy specimens, if applicable, will include 
whole gland assessment and sectioning of the entire prostate gland, overall measurement of 
specimen size, lesion location, dissection and description (including location) of identified lymph 
nodes, and submission of lymph nodes in their entirety plus all remaining fibroadipose tissue for 
each harvested regional packet.  Histopathology results of the prostate gland and pelvic lymph 
nodes (Cohort A) or biopsy location (Cohort B) will be recorded in the eCRF.  
Should a Cohort A subject forego RP surgery and undergo alternative procedure for prostate 
cancer (e.g., biopsy), the procedure and corresponding histopathology data will be recorded in 
the eCRF.  Likewise, should a Cohort B subject receive additional procedure for prostate cancer, 
the procedure and corresponding histopathology data will be recorded in the eCRF.  
10.6. 
Pharmacokinetics 
A total of 10 subjects from either cohort at the JHU site will complete the pharmacokinetics (PK) 
portion of the study.  For detailed instructions on sample collection, processing, and analysis, 
please refer to the PK Manual. 


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A 4.5 mL blood sample will be collected at the following nine time points:  pre-dose, 5±2 m, 
15±2 m, 30±5 m, 1±0.25 hr, 2±0.25 hr, 4±0.25 hr, 6±0.25 hr, and 8±0.25 hr post-dose.   
Urine samples will be collected over the following intervals: 0-2 hr, 2-4 hr and 4-8 hr post dose. 
Whole body PET/CT scans will be collected at three time points:  up to 17 minutes after PyL 
injection and prior to voiding, 1± 0.25 hr and 4± 0.25 hr post dose. 
Table 5: PK Sampling & Imaging Timepoints 
Procedure 
Pre- 
dose 
0 
hr 
5±2 
m 
15± 
2 m 
30± 
5 m 
1± 
0.25 
hr 
2± 
0.25 
hr 
3± 
0.25 
hr 
4± 
0.25 
hr 
6± 
0.25 
hr 
8± 
0.25 
hr 
18F-DCFPyL 
Administration 
X 
Blood & Plasma 
Collection 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine 
Collection 
<-----------X-----------> 
<-----X-----> 
<------X------> 
18F-DCFPyL 
PET/CT 
Imaging 
X 
X 
X 
Analysis will be generated as described below and in Section 12.5.4.  Aliquots of blood, plasma 
and urine samples will be batch counted in an automated gamma counter immediately following 
the sample collection period.  Resulting raw radioactivity counts will be converted into 
radioactivity concentrations using an aliquot of the dosing formulation as a reference standard.   
Blood concentration-time data will be computed by non-compartmental analysis and 
pharmacokinetic parameters, e.g., Cmax, AUC, CL, Vss, and MRT will be generated.  Ratios of 
blood to plasma radioactivity at each time point will be calculated. 
The total amount of excreted radioactivity per urine collection interval will be calculated as a 
product of urine radioactivity concentration and volume, and then expressed as a percent of 
administered dose.  
Metabolic profiles in urine will be determined using radio-chromatographic methods.  The areas 
under the radio-chromatographic peaks corresponding to the parent compounds and putative 
metabolites, if applicable, will be used in the qualitative assessment of metabolic profiles in 
urine. 
Whole-body PET/CT images acquired immediately after PyL injection and at 1 hr and 4 hr post-
dose will be used to obtain volumes and activity concentrations for selected tissues/organs.  
Based on these data, time-integrated activity coefficients will be derived and may be used for 
subsequent calculation of radiation absorbed doses using the OLINDA/EXM software.  This 
analysis will be described in a dosimetry report for 18F-DCFPyL. 


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11.
ASSESSMENT OF SAFETY
11.1. 
Safety Parameters 
11.1.1. 
Demographic/Medical History 
Demographic and baseline information, including date of birth, race, and ethnicity, will be 
collected.   
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, PSA results, biopsy 
results, and all past/present therapies.   
Other clinically relevant medical history will be collected 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. Special attention should 
be paid to prior malignancies other than prostate cancer or concurrent or past conditions that can 
change pelvic anatomy or cause lymphadenopathies (e.g., viral, bacterial or parasitic infections). 
11.1.2. 
Vital Signs 
Vital sign measurements will include temperature, respiratory rate, blood pressure, and heart 
rate.  All measurements should be obtained from the subject in the sitting position and measured 
at two intervals on the day of dosing, including pre-dosing and pre-imaging. 
11.1.3. 
Weight and Height 
Height, weight, and BMI at screening will be captured. 
11.1.4. 
Electrocardiogram (ECG) 
A 12-lead electrocardiogram (ECG) will be taken at two intervals on the day of dosing, including 
prior to dosing and prior to imaging.  Please refer to the ECG Procedure Manual for acquisition 
and transmittal details.  The onsite Investigator has the responsibility to evaluate the ECG for the 
assessment of subject safety.  Adverse events will be reported in the CRF.   
11.1.5. 
Laboratory Assessments 
11.1.5.1. Hematology, Blood Chemistry, PSA and Testosterone 
A blood draw will be collected at the screening and follow-up visits as stated in Table 6.  
Clinical hematology and blood chemistry will be evaluated for safety monitoring.  If PSA and 
testosterone have not been tested within 30 days of study drug injection, a blood draw will be 
collected prior to dosing. 


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Table 6: Clinical Laboratory Tests 
Category 
Analytes 
Frequency1 
Hematology 
CBC:  WBC differential (neutrophils, 
lymphocytes, monocytes, eosinophils, basophils), 
WBC count, RBC count, Hematocrit, 
Hemoglobin, Platelets 
Screening, Follow-Up 
Chemistry 
CMP:  Sodium, Potassium, Calcium, Chloride, 
Glucose, BUN, Creatinine, Total Bilirubin,  ALT, 
AST, Alkaline Phosphatase, Albumin, Total 
Protein 
Screening, Follow-Up 
PSA 
Total 
Screening 
Testosterone 
Total 
Screening 
CBC=complete blood count; WBC=white blood cell; RBC=red blood cell; CMP=comprehensive metabolic panel; 
BUN=blood urea nitrogen; ALT=alanine aminotransferase; AST=aspartate aminotransferase; PSA=prostate-specific 
antigen 
1 Blood draws and laboratory testing will be conducted according to local standard practices.  PSA and testosterone 
resulted within 30 days of Day 1 does not need to be re-tested. 
11.2. 
Adverse and Serious Adverse Events 
11.2.1. 
Definition of Adverse Events 
11.2.1.1. Adverse Event (AE) 
An AE is the development of an undesirable medical occurrence or the deterioration of a pre-
existing condition following or during exposure to a pharmaceutical product, whether or not 
considered related to the product.   
All AEs (related and unrelated) will be collected on the day of, after 18F-DCFPyL dosing and at 
time of follow-up visit (pre-surgery/biopsy).  Adverse events will also be assessed via a safety 
phone call at the following timepoints, if applicable:  1) 7 (±3) days post study drug injection (if 
surgery or biopsy has not yet occurred), and 2) 21 (±7) days post biopsy.   
All AEs, whether or not they are related to study drug, must be recorded on the study case report 
forms.  
11.2.1.2. 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


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•
Results in a congenital abnormality or birth defect of a subject’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.
All SAEs that occur after any patient/subject has been dosed until study completion, whether or 
not related to the study, must be recorded on forms provided by the Sponsor, or designee. 
11.3. 
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 
whether, in his or her medical judgment, there is a reasonable possibility that the event may have 
been caused by the investigational product.  If no valid reason exists for suggesting a 
relationship, then the AE should be classified as “unrelated.”  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.” 
11.4. 
Recording Adverse Events 
Adverse events spontaneously reported by the patient/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.   
The investigator should assess all clinical laboratory results for clinical significance and record 
the assessment in source documents.  The investigator should evaluate any laboratory result 
change from pre- and post-study drug administration to determine if the change meets the 
definition of an AE or SAE.  Record any clinically significant lab results determined to meet the 
definition of an AE and SAE on the AE eCRF and SAE Report Form, respectively. 
Information about AEs and SAEs will be collected from the first administration of study drug 
until the pre-surgery/biopsy follow-up visit.  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, 
action taken, serious outcome (if applicable), 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)


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It is important to distinguish between serious and severe AEs.  Severity is a measure of intensity 
whereas seriousness is defined by the criteria under Section 11.2.1.2.  An AE of severe intensity 
may not be considered serious. 
Should a pregnancy occur, it must be reported and recorded on the Sponsor’s pregnancy form.  
Pregnancy in itself is not regarded as an AE. 
The outcome of all pregnancies (spontaneous miscarriage, elective termination, normal birth or 
congenital abnormality) must be followed up and documented even if the patient was 
discontinued from the study. 
All reports of congenital abnormalities/birth defects are SAEs.  Spontaneous miscarriages should 
also be reported and handled as SAEs.  Elective abortions without complications should not be 
handled as AEs. 
11.5. 
Reporting Serious Adverse Events 
All SAEs (related and unrelated) will be recorded at the same interval defined for AE collection 
as indicated in Section 11.2.1.1 .  Any SAEs considered possibly or probably related to the 
investigational product and discovered by the Investigator at any time after the study should be 
reported.  All SAEs must be reported to Progenics or designee within 24 hours of the first 
awareness of the event.  The Investigator must complete, sign and date the SAE pages, 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 follow-up SAE form and placed with the original SAE information 
and kept with the appropriate section of the CRF and/or study file. 
Progenics Pharmaceuticals, Inc. is responsible for notifying the relevant regulatory authorities of 
certain events.  It is the Principal Investigator’s responsibility to notify the IRB or IEC of all 
SAEs that occur at his or her site.  Investigators will also be notified of all unexpected, serious, 
drug-related events (7/15 Day Safety Reports) that occur during the clinical trial.  Each site is 
responsible for notifying its IRB or IEC of these additional SAEs. 
12.
STATISTICS
12.1. 
Sample Size 
Approximately 262 subjects will be dosed in cohort A.   No formal power calculations will be 
performed for cohort B; reliable estimates should be achievable from approximately 115 dosed.  
This results in a total sample size of approximately 377 subjects dosed in the study.   
The primary analysis in Cohort A will test the co-primary endpoints of sensitivity and specificity 
of 18F-DCFPyL PET imaging relative to histopathology for metastatic disease in pre-
prostatectomy patients.  For each co-primary endpoint there will be three independent imaging 
readers.  At least two of the three readers must reject the null hypothesis for specificity to be 
deemed a success.  If specificity is a success, then the same two readers need to reject the null 


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hypothesis for sensitivity to reach overall success of the primary endpoint.  The null hypotheses 
will be tested in the following order: 
1. Specificity of 18F-DCFPyL PET/CT imaging relative to histopathology in cohort A
H0: πSp = 0.80 versus H1: πSp ≠ 0.80,
2. Sensitivity of 18F-DCFPyL PET/CT imaging relative to histopathology in cohort A
H0: πSe = 0.40 versus H1: πSe ≠ 0.40
where πSe is the true sensitivity and πSp is the true specificity of 18F-DCFPyL PET imaging. 
A total of approximately 262 subjects from Cohort A will provide 80% power to reject the null 
hypothesis about sensitivity at the 5% significance level if the true sensitivity is at least 60% and 
at least 80% power to reject the null hypothesis about specificity at the 5% significance level if 
the true specificity is at least 87.8%.  These calculations are based on the following assumptions:    
•
the probability of a positive histopathology sample in Cohort A is 20%,
The sample size is based on the normal approximation to the binomial distribution without a 
continuity correction48:  
𝑛≥൝
𝑧𝛼/2ඥ𝑃0(1 −𝑃0) + 𝑧𝛽ඥ𝑃1(1 −𝑃1)
𝑃1 −𝑃0
ൡ
2
P0 are P1 are values of sensitivity under the null and alternative hypotheses, respectively.  
After adjusting sensitivity and specificity separately by their corresponding prevalence values, a 
total in 236 evaluable subjects are needed in cohort A.  Assuming 10% drop out or non-evaluable 
rate increases the required number of subjects in cohort A to approximately 262.  
The type I error rate of 5% will be preserved by requiring that both null hypotheses be rejected in 
order to draw the conclusion that 18F-DCFPyL is efficacious for imaging. The second primary 
endpoint is only tested if the first primary endpoint is rejected at 5% per a fixed sequential 
method.  If the first hypothesis fails to be rejected, no further testing will be conducted.  
12.2. 
Analysis Populations 
12.2.1. 
Screened Subjects 
All subjects who sign an informed consent document will be included in the screened subject 
population. 
12.2.2. 
Safety Set 
All subjects who receive any amount of 18F-DCFPyL will be included in the safety set. 
12.2.3. 
Evaluable Set 
Evaluable subjects in Cohort A are those who provide a 18F-DCFPyL PET image result (positive 
or negative) and a corresponding RP histopathology result (positive or negative).   
Evaluable subjects in Cohort B are those who provide a 18F-DCFPyL PET image result (positive 
or negative) and a corresponding biopsy histopathology result (positive or negative for each 


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subject), along with a conventional image that confirms the location of the histopathology 
sample. 
12.2.4. 
Per Protocol Set 
The per protocol set is the evaluable set, excluding subjects with major protocol deviations 
impacting efficacy endpoint(s). 
12.2.5. 
PK Evaluable Set 
Subjects who provide at least six of the nine scheduled blood samples will be evaluable for PK 
analysis of blood samples.  Subjects with at least two of the three scheduled urines will be 
evaluable for PK analysis of urine samples. 
12.3. 
Endpoints and Derivations 
12.3.1. 
Sensitivity, Specificity, PPV, and NPV 
Table 7 will be used to classify the combined pelvic lymph node packets (left or right) from 
Cohort A and biopsy from Cohort B according to its 18F-DCFPyL image result (positive or 
negative) generated from central imaging review and its histopathology result (positive or 
negative for prostate cancer) generated by the sites’ pathology review.    Nodes identified on 18F-
DCFPyL PET/CT images in areas that were not removed in surgery for Cohort A will not be 
tabulated due to absence of histopathology. 
Table 7: Classification of 18F-DCFPyL Imaging Result and Histopathology Result for 
Cohorts A and B Separately 
Histopathology Result 
18F-DCFPyL Image 
Positive* 
Negative 
Positive 
TP 
FP 
I(p) 
Negative 
FN 
TN 
I(n) 
R(p) 
R(n) 
N1 
TP=true positive; FP=false positive; FN=false negative; TN=true negative.   
R(p) and R(n) denote the subjects with a positive or negative lobe or biopsy, respectively, based on histopathology. 
I(p) and I(n) denote the subjects with a positive and negative lesion, respectively, based on the 18F-DCFPyL image. 
N1 indicates the number of subjects with evaluable pelvic lymph node packets from Cohort A or the number of 
subjects with evaluable biopsies from Cohort B. 
*Positive histopathology should be for prostate cancer only.
The following statistics will be computed: 
•
Sensitivity = TP/R(p),
•
Specificity = TN/R(n),
•
Positive predictive value (PPV) = TP/I(p),
•
Negative predictive value (NPV) = TN/I(n).


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For Cohort A, a true positive or true negative must be determined from imaging and 
histopathology aligning on outcome overall. 
12.3.2. 
Lesions Per Subject 
The number of lesions detected on the 18F-DCFPyL PET/CT image in each of bone, lymph 
nodes, soft tissue, and prostate gland will be determined by each of the three central imaging 
core lab independent readers.  The number of lesions per subject per region will be computed for 
each subject based on each reader’s lesion count. 
12.3.3. 
Change from Baseline 
For laboratory data, baseline will be the screening/baseline value.  Change from baseline will be 
computed as the pre-surgery/biopsy follow-up value minus the baseline value +1. 
For ECG data, baseline will be the pre-dose value.  Change from baseline will be computed as 
the post-dose value minus the pre-dose value +1. 
For vital signs, baseline will be the pre-dose value.  Change from baseline will be computed as 
the post-dose value minus the pre-dose value +1 and the pre-surgery/biopsy value minus the 
baseline value +1. 
12.3.4. 
Pre-Treatment and Concomitant Medications 
Pre-treatment medications are those administered prior to 18F-DCFPyL administration; 
concomitant medications are those administered from 18F-DCFPyL administration through last 
study visit.   
12.3.5. 
Treatment-Emergent Adverse Events 
Treatment-emergent adverse events will be those observed from the day of 18F-DCFPyL 
administration until 7 (±3) days post study drug injection [if surgery (Cohort A) or biopsy 
(Cohort B) has not yet occurred] and 21 (±7) days post biopsy in Cohort B.   
12.4. 
Missing Data 
No imputation of missing data will be applied. 
12.5. 
Analyses 
In general, continuous endpoints will be summarized by visit using summary statistics: sample 
size, mean, standard deviation, median, minimum, and maximum.  Categorical endpoints will be 
summarized by visit using frequencies and percentages. 
12.5.1. 
Subject Characteristics 
A disposition table will be presented to show how many subjects were screened, the number and 
percentage of subjects in each population set, study completers, and early discontinuations along 
with reasons for discontinuation.  
Baseline characteristics (age in years, categorical age [<65 years, ≥65 years], race, gender, 
ethnicity, height [cm], weight [kg], BMI [kg/m2]) will be summarized for all analysis population 


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sets.  Medical history verbatim terms will be coded using Medical Dictionary for Regulatory 
Activities (MedDRA).  Subject frequencies and percentages will be tabulated by system organ 
class (SOC) and preferred term (PT) for all analysis population sets.  Prior prostate cancer 
medical history will be summarized for all analysis populations.  Type of CT, MRI or bone scans 
will be summarized along with days each occurred prior to study drug administration by all 
analysis populations. 
Medications will be coded using the WHO Drug Dictionary.   Pre-treatment medications will 
each be summarized by ATC4 class and generic name for all analysis population sets.   
12.5.2. 
Efficacy Analysis 
12.5.2.1. Primary Endpoint 
Cohort A 
The primary analysis in Cohort A will be addressed by computing point estimates and 95% two-
sided confidence intervals (CIs) for specificity first and if the null hypothesis is rejected for 
specificity then sensitivity will be tested next.  Both outcomes are on the subject level (one 
overall outcome per subject) in the evaluable set.  If the per protocol population exists then this 
analysis will be performed on the per protocol population as a supplemental analysis.   The 
normal approximation to the binomial distribution will be used.  Sensitivity and specificity will 
be computed for each of three central imaging core lab independent readers. 
The null hypothesis for specificity will be rejected if the lower limit of the 95% CI exceeds 0.80 
for at least two readers.  If statistical significance is achieved for specificity where the null 
hypothesis is rejected, then sensitivity will be tested where the null hypothesis will be rejected if 
the lower limit of 95% CI exceeds 0.40 for the same two readers who rejected the null hypothesis 
for specificity.  
A sensitivity analysis will be performed to allow any 2 of the 3 central readers to reject the null 
hypothesis for sensitivity only after specificity has been deemed a success. This analysis will not 
require the same 2 central readers to reject the null hypothesis for specificity and sensitivity. This 
analysis will be performed for the evaluable and per protocol populations. 
12.5.2.2. Secondary Endpoints 
The following secondary efficacy endpoint analyses will be generated on the evaluable set.  
Point estimates and two-sided 95% CIs will be presented for the following secondary endpoints:   
•
PPV and NPV will be computed for the pelvic lymph node packets (one observation
per subject for cohort A).
•
Sensitivity of 18F-DCFPyL PET/CT imaging within sites of metastasis or local
recurrence relative to histopathology (cohort B)
•
PPV will be computed for the biopsies (one observation per subject for cohort B).
The normal approximation to the binomial distribution will be used for endpoints having one 
observation per subject.  The null hypothesis will be rejected for each if the lower limit of the 


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95% CI exceeds 0.50 for at least 2 of the 3 central readers. Statistics will be computed for each 
of the three central imaging core lab independent readers. 
Lesions per subject, as detected by 18F-DCFPyL PET/CT and conventional images will be 
summarized for each tissue type (bone, lymph nodes, soft tissue, and prostate gland) and each of 
the three central imaging core lab independent readers using evaluable subjects from both 
cohorts.   
12.5.2.3. Exploratory Analyses 
Analyses will be generated on the evaluable set for the following exploratory endpoints: 
•
The number of lesions per subject will be plotted against baseline PSA and baseline
testosterone for each of the three central imaging core lab independent readers using
evaluable subjects from both cohorts.
•
SUVmax, SUVpeak and SUVr will be summarized for each tissue type (e.g., bone, lymph
nodes, soft tissue, and prostate gland) and each of the three central imaging core lab
independent readers using evaluable subjects from both cohorts.  The relationship
between SUVr in prostatic lesions and baseline PSA and testosterone levels, and Gleason
score at time of radical prostatectomy will be evaluated.
•
Sensitivity, SUVmax, SUVpeak, and SUVr will be computed for the following subgroups in
Cohort A:
-
Previous radiation therapy (yes/no)
-
Previous hormonal therapy (yes/no)
-
Previous chemotherapy (yes/no)
•
SUVmax, SUVpeak, and SUVr will be summarized with positive and negative
histopathology.  Each will be summarized by Gleason score for the single or dominant
prostate tumor nodule.
•
The clinical management plans before and after review of 18F-DCFPyL PET/CT scans
will be summarized.
An exploratory analysis of PPV of 18F-DCFPyL PET/CT imaging in subjects who are excluded 
from the evaluable set but have corresponding histopathology outside the planned protocol 
procedure will be performed on the safety set. 
12.5.3. 
Safety 
All safety parameters will be presented for the safety set. 
12.5.3.1. Exposure 
Volume administered (mL) and activity administered (mCi) will be summarized using the Safety 
Set and the Evaluable Set. 


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12.5.3.2. Adverse Events 
Adverse event verbatim terms will be coded using MedDRA.  The frequency and percentage of 
subjects with an adverse event and the number of events will be summarized by SOC and PT.  
Adverse events will also be summarized by severity and, separately, by relationship to treatment.  
Serious adverse events, adverse events leading to study discontinuation and adverse events 
leading to death will be listed. 
12.5.3.3. Clinical Laboratory 
Observed values and changes will be tabulated using summary statistics in the safety set. 
12.5.3.4. ECG 
Observed values and changes will be tabulated for each visit using summary statistics.  Shift 
tables comparing pre- to post-dosing categorical ECG values will be presented using the safety 
set. 
12.5.3.5. Vital Signs 
Observed values and changes will be tabulated using summary statistics in the safety set. 
12.5.4. 
Pharmacokinetics 
Mean (±SD) and individual activity-time plots will be presented for blood (mCi/mL), urine (% 
injected dose excreted per collection interval) and selected organs/tissues, including “whole 
body” (% injected dose at each scanning time-point).  Summary statistics (sample size [N], 
arithmetic mean, geometric mean, median, SD, minimum, and maximum) will be presented by 
timepoint for each of blood, urine and selected organs/tissues, including “whole body”.   
Summary statistics will be presented for Cmax, area under the curve (AUC), total clearance (CL), 
steady-state volume of distribution (Vss), and mean residence time (MRT) for the subset of 
subjects (PK evaluable set). 
13.
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS
Data collected during this study may be used to support the development, registration or 
marketing of 18F-DCFPyL.  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. 
13.1. 
Study Monitoring 
Before an investigational site can enter a patient into the study, a representative of Sponsor will 
visit the investigational study site to: 


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•
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.
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.
•
Confirm serious/unexpected/related SAE notification letter(s) from the Sponsor have
been acknowledged and returned to the Sponsor.
The monitor will be available between visits if the investigator(s) or other staff needs 
information or advice. 
13.2. 
Audits and Inspections 
Authorized representatives of the Sponsor, a regulatory authority, an Independent Ethics 
Committee or an Institutional Review Board 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, Good Clinical Practice 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. 


Clinical Protocol:  PyL-2301 
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Amendment 2: 06 Nov 2017 
Page 42 
14.
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. 
14.1. 
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 Good Clinical Practice (GCP) and that the study is conducted in full 
conformity with the current 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. 
14.2. 
Institutional Review Board (IRB) or Independent Ethics Committee 
(IEC) Approval 
The final study protocol, including the final version of the Informed Consent Form, 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. 
14.3. 
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 Informed Consent Form.  A copy 
of the signed Informed Consent Form must be given to the patient. 


Clinical Protocol:  PyL-2301 
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Amendment 2: 06 Nov 2017 
Page 43 
14.4. 
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 
informed consent form) 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]. 
14.5. 
Financial Disclosure 
All investigators must provide financial disclosure information in accordance with the US Code 
of Federal Regulations Title 21 CFR 54.2 through 54.6. 
15.
DATA HANDLING AND RECORDKEEPING
15.1. 
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. 
15.2. 
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 13.2. 
15.3. 
Retention of Records 
The Principal Investigator must maintain all documentation relating to the study for a period of 2 
years after the last marketing application approval, or if not approved 2 years following the 


Clinical Protocol:  PyL-2301 
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Amendment 2: 06 Nov 2017 
Page 44 
discontinuance of the test article for investigation.  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. 
16.
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 
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. 


Clinical Protocol:  PyL-2301 
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Amendment 2: 06 Nov 2017 
Page 45 
17.
REFERENCES
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3. Hricak H, Dooms GC, Jeffrey RB, et al. Prostatic carcinoma: staging by clinical
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4. Scheidler J, Hricak H, Vigneron DB, et al. Prostate cancer: localization with three-
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5. Blomqvist L, Carlsson S, Gjertsson P, et al. Limited evidence for the use of imaging to
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6. Turlakow A, Yeung HW, Pui J, et al. Fludeoxyglucose positron emission tomography in
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7. Hofer C, Laubenbacher C, Block T. Fluorine-18-fluorodeoxyglucose positron emission
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Eur Urol. 1999;36:31–35.
8. Nunez R, Macapinlac HA, Yeung HW, et al. Combined 18F-FDG and 11C-methionine
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9. Shreve PD, Grossman HB, Gross MD, Wahl RL. Metastatic prostate cancer: initial
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10. Ramírez de Molina A, Rodriguez-Gonzalez A, Gutierrez R, et al. Overexpression of
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11. 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
prostate cancer. Eur J Nucl Med Mol Imaging. 2008;35:18–23.
12. Rinnab L, Mottaghy FM, Blumstein NM, et al. Evaluation of [11C]choline positron
emission tomography in patients with increasing prostate-specific antigen levels after
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13. Giovacchini G, Picchio M, Coradesschi E, et al. 11C-choline uptake with PET/CT for the
initial diagnosis of prostate cancer: relation to PSA levels, tumor stage and anti-
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14. Castellucci P, Fuccio C, Nanni C, et al. Influence of trigger PSA and PSA kinetics on
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15. Hricak H, Choyke PL, Eberhardt SC, et al. Imaging prostate cancer: a multidisciplinary
perspective. Radiology. 2007;243:28–53.
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molecular imaging of the prostate: an update. BJU Int. 2006;97:923–931.
17. de Jong IJ, Pruim J, Elsinga PH, et al. 11C-choline positron emission tomography for the
evaluation after treatment of localized prostate cancer. Eur Urol. 2003;44:32–38.
18. Picchio M, Messa C, Landoni C, et al. Value of [11C]choline-positron emission
tomography for re-staging prostate cancer: a comparison with [18F]fluorodeoxyglucose-
positron emission tomography. J Urol. 2003;169:1337–1340.
19. 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
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20. 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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21. Chang SS. Overview of prostate-specific membrane antigen. Rev Urol. 2004;6(Suppl
10):S13–S18.
22. Wright GL, Jr, Grob BM, Haley C, et al. Upregulation of prostate-specific membrane
antigen after androgen-deprivation therapy. Urology. 1996;48:326–334.
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membrane antigen expression in normal and malignant human tissues. Clin Cancer Res.
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24. Wong MC, Goggins WB, Wang HH, Fung FD, Leung C, Wong SY, Ng CF, Sung JJ.
Global Incidence and Mortality for Prostate Cancer: Analysis of Temporal Patterns and
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25. Dy GW, Gore JL, Forouzanfar MH, Naghavi M, Fitzmaurice C. Global Burden of
Urologic Cancers, 1990-2013. Eur Urol. 2017 71(3):437-446..
26. Racioppi M, Palermo G, D’Addessi A, Pinto F, Sacco E, D’Agostino D, Vittori M, Bassi
PF. Hot topics in urological health economics. A mini review. Archivio Italiano di
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27. Hövels AM, Heesakkers RA, Adang EM, Jager GJ, Strum S, Hoogeveen YL, Severens
JL, Barentsz JO. The diagnostic accuracy of CT and MRI in the staging of pelvic lymph
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28. Hillier SM, Maresca KP, Femia FJ, Marquis JC, Foss CA, Nguyen N, Zimmerman CN,
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glutamate-urea-lysine analogues that target prostate-specific membrane antigen as
molecular imaging pharmaceuticals for prostate cancer. Cancer research. 2009 Sep
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29. Pinto JT, Suffoletto BP, Berzin TM, Qiao CH, Lin S, Tong WP, May F, Mukherjee B,
Heston WD. Prostate-specific membrane antigen: a novel folate hydrolase in human
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30. Smith-Jones PM, Vallabahajosula S, Goldsmith SJ, Navarro V, Hunter CJ, Bastidas D,
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31. Kinoshita Y, Kuratsukuri K, Landas S, Imaida K, Rovito Jr PM, Wang CY, Haas GP.
Expression of prostate-specific membrane antigen in normal and malignant human
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tissue localization and diagnostic utility of prostate specific membrane antigen. Cancer.
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brain N-acetylated α-linked acidic dipeptidase (NAALADase). Journal of Pharmacology
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SAP_001.pdf: 
Progenics Pharmaceuticals, Inc. 
Statistical Analysis Plan – Protocol PyL-2301 
September 5, 2018
1 
STATISTICAL ANALYSIS PLAN 
PHASE II-III 
VERSION: 
2.0 
STUDY DRUG: 
18F-DCFPyL Injection (PyL) 
PROTOCOL 
NUMBER: PyL-2301 
NCT02981368
STUDY TITLE: 
A PrOspective Phase 2/3 Multi-Center Study of 18F-DCFPyL PET/CT Imaging in Subjects with 
PRostate Cancer:  Examination of Diagnostic AccuracY (OSPREY) 
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. 


Progenics Pharmaceuticals, Inc. 
Statistical Analysis Plan – Protocol PyL-2301 
            September 5, 2018 
2 
SIGNATURE PAGE 


Progenics Pharmaceuticals, Inc. 
Statistical Analysis Plan – Protocol PyL-2301 
            September 5, 2018 
 
3 
 
 
 
 
TABLE OF CONTENTS 
1. 
LIST OF ABBREVIATIONS.......................................................................................8 
2. 
INTRODUCTION ......................................................................................................11 
3. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................12 
3.1. 
Study Objectives .........................................................................................................12 
3.1.1. 
Primary Objective .......................................................................................................12 
3.1.2. 
Secondary Objectives .................................................................................................12 
3.1.3. 
Exploratory Objectives ...............................................................................................12 
3.2. 
Efficacy Endpoints ......................................................................................................12 
3.2.1. 
Primary Efficacy Endpoints ........................................................................................12 
3.2.2 
Secondary Efficacy Endpoints ....................................................................................13 
3.2.3 
Exploratory Efficacy Endpoints .................................................................................13 
3.3. 
Safety Endpoints .........................................................................................................13 
4. 
STUDY DESIGN .......................................................................................................14 
4.1. 
Summary of Study Design ..........................................................................................14 
4.2. 
Definition of Study Drugs and Treatment Follow-up .................................................14 
4.3. 
Sample Size ................................................................................................................15 
4.4. 
Randomization ............................................................................................................16 
4.5. 
Clinical Assessments ..................................................................................................16 
4.6. 
Interim Analyses .........................................................................................................17 
4.7. 
Final Analyses ............................................................................................................17 
5. 
GENERAL CONSIDERATIONS FOR DATA ANALYSES AND 
HANDLING ...............................................................................................................18 
5.1. 
General Summary Table and Individual Subject Data Listing Considerations ..........18 
5.2. 
General Post Text Summary Table and Individual Subject Data Listing 
Format Considerations ................................................................................................18 
5.3. 
Data Presentation Conventions ...................................................................................18 
5.4. 
Analysis Populations ..................................................................................................18 
5.4.1. 
Consented Set .............................................................................................................18 
5.4.2. 
Safety Set ....................................................................................................................18 
5.4.3. 
Evaluable Set ..............................................................................................................19 
5.4.4. 
Change in Planned Protocol Procedure Set ................................................................19 
5.4.5. 
Per Protocol Set ..........................................................................................................19 


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Statistical Analysis Plan – Protocol PyL-2301 
            September 5, 2018 
 
4 
 
 
 
 
5.4.6. 
PK Blood Set ..............................................................................................................19 
5.4.7. 
PK Urine Set ...............................................................................................................19 
5.5. 
Derived and Transformed Data ..................................................................................19 
5.5.1. 
Baseline Definition .....................................................................................................19 
5.5.2. 
Baseline Age ...............................................................................................................19 
5.5.3. 
Study Day ...................................................................................................................19 
5.5.4. 
Change and Percent Change from Baseline ................................................................19 
5.5.5. 
Prior and Concomitant Medications ...........................................................................20 
5.5.6. 
Treatment-Emergent Adverse Events .........................................................................20 
5.5.7. 
Sensitivity, Specificity, PPV, and NPV ......................................................................20 
5.5.8. 
Lesions Per Subject .....................................................................................................24 
5.5.9. 
Visit Windows ............................................................................................................25 
5.5.10. 
Decay Corrected Dose at Time of Administration .....................................................25 
5.5.11. 
Lesion location defined from SUV values..................................................................25 
5.5.12. 
Change in Clinical Management Plan from Questionnaire ........................................26 
5.5.13. 
PSA groups .................................................................................................................26 
5.5.14. 
Gleason Scores ............................................................................................................26 
5.5.15. 
Prior Prostate Cancer History and Therapies ..............................................................27 
5.5.16. 
Estimate GFR ..............................................................................................................27 
5.5.17. 
Renal impairment ........................................................................................................27 
5.5.18. 
Laboratory Parameter Unit Conversions ....................................................................28 
5.6. 
Handling of Missing Data ...........................................................................................29 
5.6.1. 
Missing Efficacy Endpoints ........................................................................................29 
5.6.2. 
Missing Start and Stop Dates for Concomitant Medication .......................................29 
6. 
STUDY POPULATION .............................................................................................31 
6.1. 
Disposition ..................................................................................................................31 
6.2. 
Protocol Deviations ....................................................................................................31 
6.3. 
Demographic and Baseline Characteristics ................................................................31 
6.4. 
Medical History, including Prostate Cancer History ..................................................31 
6.5. 
Prior Prostate Cancer Therapies and Surgeries ..........................................................31 
6.6. 
Prior Medication History and Medications Present at Entry ......................................32 
6.7. 
Conventional Imaging at Baseline ..............................................................................32 
7. 
EFFICACY .................................................................................................................32 


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Statistical Analysis Plan – Protocol PyL-2301 
            September 5, 2018 
 
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7.1. 
General Considerations ...............................................................................................32 
7.2. 
Testing Statistical Assumptions Including Comparability at Baseline .......................32 
7.2.1. 
Test of Proportions .....................................................................................................32 
7.2.2. 
Test of means ..............................................................................................................32 
7.3. 
Statement of the Null and Alternate Hypotheses ........................................................33 
7.4. 
Subgroup Analyses .....................................................................................................33 
7.5. 
Multiple Comparisons and Multiplicity......................................................................33 
7.6. 
Analysis of the Primary Efficacy Endpoint ................................................................33 
7.6.1. 
Primary Efficacy Analysis of Primary Endpoints ......................................................33 
7.6.2. 
Sensitivity Analyses of the Primary Endpoints ..........................................................33 
7.7. 
Analysis of Secondary Efficacy Endpoints ................................................................34 
7.7.1. 
NPV and PPV in Cohort A .........................................................................................34 
7.7.2. 
PPV and Sensitivity in Cohort B ................................................................................34 
7.7.3. 
Detection Rates for Lesion Counts in both Cohorts Combined .................................34 
7.7.4. 
PK ...............................................................................................................................34 
7.8. 
Analysis of Exploratory Endpoints .............................................................................35 
7.9. 
Reader Reliability .......................................................................................................36 
7.9.1. 
Intra-Reader Reliability ..............................................................................................36 
7.9.2. 
Inter-Reader Reliability ..............................................................................................36 
8. 
SAFETY AND TOLERABILITY ..............................................................................37 
8.1. 
Adverse Event Preferred Term and System Organ Class Summary Tables ...............37 
8.1.1. 
Summaries of Adverse Event Incidence Rates for All Subjects.................................37 
8.1.2. 
Summaries of Adverse Incidence Rates for Serious Adverse Events (SAE), 
Adverse Event Discontinuations, and Death ..............................................................38 
8.2. 
Exposure to Study Drug ..............................................................................................38 
8.3. 
Concomitant and Other Medications ..........................................................................38 
8.4. 
Routine Laboratory Data ............................................................................................38 
8.5. 
Vital Signs ..................................................................................................................38 
8.6. 
ECG ............................................................................................................................39 
8.7. 
Physical Examination .................................................................................................39 
9. 
PHARMACOKINETICS ...........................................................................................39 
9.1. 
Derived Data ...............................................................................................................39 


Progenics Pharmaceuticals, Inc. 
Statistical Analysis Plan – Protocol PyL-2301 
            September 5, 2018 
 
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10. 
PLANNED TREATMENT SAP CHANGES THAT DIFFER FROM THE 
PROTOCOL ...............................................................................................................41 
11. 
REFERENCES ...........................................................................................................41 
12. 
APPENDIX.................................................................................................................43 
12.1. 
Table of Contents for Data Display Specifications ....................................................43 
 
 


Progenics Pharmaceuticals, Inc. 
Statistical Analysis Plan – Protocol PyL-2301 
            September 5, 2018 
 
7 
 
 
 
 
LIST OF TABLES 
Table 1: 
List of Abbreviations ....................................................................................................8 
Table 2: 
Schedule of Assessments ............................................................................................16 
Table 3: 
Classification of 18F-DCFPyL Imaging Result and Histopathology Result ...............20 
Table 4: 
List of Tables, Listings and Figures ...........................................................................43 
LIST OF FIGURES 
Figure 1:  Study Schema ................................................................................................................15 
 
 


Progenics Pharmaceuticals, Inc. 
Statistical Analysis Plan – Protocol PyL-2301 
            September 5, 2018 
 
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1. 
LIST OF ABBREVIATIONS 
Table 1: 
List of Abbreviations 
Abbreviation 
Term 
18F 
fluorine 18 
ADT 
androgen deprivation therapy 
AE 
adverse event 
ATC 
anatomical therapeutic classification 
AUC 
area under the curve 
BN 
bone 
BP 
blood pressure 
CI 
confidence interval 
Cmax 
maximum observed concentration 
CL 
clearance 
cm 
centimeter 
CPM 
counts per minute 
CT 
computed tomography 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
eGFR 
estimated Glomerular filtration rate 
ePLND 
Extended lymph node dissection in prostate cancer 
FN 
false negative 
FP 
false positive 
HR 
heart rate 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
I(p) 
total positive imaging 
I(n) 
total negative imaging  
Kg/m2 
kilograms per metered squared 
LLN 
lower limit of normal 
LN 
lymph node 
MBq 
Megabecquerel 
mCi 
millicurie 
MDRD 
Modification of diet in renal disease study 


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Table 1: 
List of Abbreviations 
Abbreviation 
Term 
MedDRA 
Medical Dictionary for Regulatory Activities 
mL 
milliliter 
MRI 
magnetic resonance imaging 
MRT 
mean residence time 
NC 
North Carolina 
ng/mL 
nanogram/milliliter 
NPV 
negative predictive value 
PET/CT 
positron emission tomography/computed tomography 
PK 
pharmacokinetics 
PPV 
positive predictive value 
PSA 
prostate specific antigen 
PSMA 
Prostate specific membrane antigen 
PT 
preferred term 
R(n) 
total negative histopathology 
R(p) 
total positive histopathology 
RP 
radical prostatectomy 
RR 
respiratory rate 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SCr  
serum creatinine 
SD 
standard deviation 
SOC 
system organ class 
ST 
Soft tissue 
SUVmax 
maximum standardized uptake value 
SUVmean 
Mean standardized update value 
SUVpeak 
peak standardized uptake value 
SUVr 
ratio to reference tissue standardized uptake value 
TEAE 
treatment-emergent adverse event 
T1/2 
half life 
T1/2alpha 
alpha phase distributive half life 
T1/2beta 
beta phase elimination help life 


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Table 1: 
List of Abbreviations 
Abbreviation 
Term 
T1/2elim 
elimination half life 
Tmax 
time to maximum concentration 
TN 
true negative 
TOA 
time of administration 
TP 
true positive 
ULN 
Upper limit of normal 
USA 
United States of America 
Vss 
steady state volume of distribution 
WHODD 
World Health Organization Drug Dictionary 
 


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2. 
INTRODUCTION 
The statistical analysis plan (SAP) is based on:  
 Protocol amendment 2 dated November 6, 2017, 
 ICH guidelines E61 and E92. 
The purpose of this document is to provide details about study populations, how variables will be 
derived, how missing data will be handled as well as details about statistical methods to be used 
to analyze the safety and efficacy data from Study PyL-2301. 
The list of tables, listings and their shells are guidelines which may be refined to facilitate 
programming.  Such changes will not be documented in an amendment to this document.  
However, any changes to populations, endpoints or analysis methods will be documented in a 
SAP amendment and will be noted in the clinical study report, as relevant. 


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3. 
STUDY OBJECTIVES AND ENDPOINTS 
3.1. 
Study Objectives 
3.1.1. 
Primary Objective 
The primary objective of the study is to assess the diagnostic performance of 18F-DCFPyL 
PET/CT imaging to determine the presence or absence of metastatic disease in pre-prostatectomy 
subjects with high risk prostate cancer (cohort A). 
3.1.2. 
Secondary Objectives 
1. To evaluate the safety and tolerability of 18F-DCFPyL 
2. To assess the diagnostic performance of 18F-DCFPyL PET/CT imaging to determine the 
presence or absence of prostate cancer within sites of metastasis or local recurrence 
(cohort B). 
3. To determine detection rates of 18F-DCFPyL PET/CT and conventional imaging among 
lesion locations (e.g., bone, lymph nodes, soft tissue, prostate gland) 
4. To determine positive and negative predictive value (PPV and NPV) of 18F-DCFPyL 
PET/CT imaging 
5. To determine the pharmacokinetics, bio-distribution and excretion of 18F-DCFPyL 
3.1.3. 
Exploratory Objectives 
1. To assess 18F-DCFPyL uptake among lesion locations (e.g., bone, lymph nodes, soft 
tissue, prostate gland) 
2. To assess the relationship between 18F-DCFPyL uptake in prostatic and extra-prostatic 
lesions with baseline PSA and testosterone levels and Gleason Score at time of radical 
prostatectomy 
3. To assess the diagnostic performance of 18F-DCFPyL PET/CT imaging to detect prostate 
cancer within the prostate gland (Cohort A) 
4. To assess the impact of 18F-DCFPyL PET/CT imaging on clinical management plan  
5. To determine PPV of 18F-DCFPyL PET/CT imaging for lesions detected by PET that are 
outside the planned surgical template or biopsy site 
3.2. 
Efficacy Endpoints 
3.2.1. 
Primary Efficacy Endpoints 
1. Specificity of 18F-DCFPyL PET/CT imaging to determine the absence of metastatic 
prostate cancer within the pelvic lymph nodes relative to histopathology in Cohort A 
2. Sensitivity of 18F-DCFPyL PET/CT imaging to determine the presence of metastatic 
prostate cancer within the pelvic lymph nodes relative to histopathology in Cohort A 


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3.2.2 Secondary Efficacy Endpoints  
1. Sensitivity of 18F-DCFPyL PET/CT imaging to detect prostate cancer within sites of 
metastasis or local recurrence relative to histopathology in Cohorts B 
2. Comparison of detection rates for lesion counts overall and by location (i.e., bone, lymph 
nodes, soft tissue, prostate gland) between 18F-DCFPyL PET/CT and conventional 
imaging in Cohorts A and B combined 
3. PPV of 18F-DCFPyL PET/CT imaging to predict prostate cancer within the prostate gland 
and lymph nodes in Cohort A 
4. NPV of 18F-DCFPyL PET/CT imaging to predict the absence of prostate cancer within 
the prostate gland and lymph nodes in Cohort A 
5. PPV of 18F-DCFPyL PET/CT imaging to predict prostate cancer within sites of local 
recurrence and other metastatic lesions in Cohort B 
6. Pharmacokinetic parameters derived from blood samples [e.g., Cmax, area under the curve 
(AUC), total clearance (CL), steady-state volume of distribution (Vss), and mean 
residence time (MRT)] (subset of Cohorts A and B combined) 
3.2.3 Exploratory Efficacy Endpoints 
1. 18F-DCFPyL uptake in different lesion locations as defined by SUVpeak, SUVmax, and 
SUVr results derived from central readers for cohorts A and B combined and compared 
between histology outcomes 
2. To assess the relationship between SUVpeak, SUVmax, volume, and SUVr and Gleason 
Score at time of radical prostatectomy, baseline PSA, and testosterone levels for both 
cohorts 
3. Sensitivity of 18F-DCFPyL PET/CT imaging within the prostate gland relative to 
histopathology in Cohort A  
4. Specificity of 18F-DCFPyL PET/CT imaging within the prostate gland relative to 
histopathology in Cohort A  
5. Changes to clinical management based on a review of clinical and radiographic subject 
data before and after 18F-DCFPyL PET/CT imaging by a central panel of disease experts 
using a structured questionnaire (Cohort A only) 
6. PPV of 18F-DCFPyL PET/CT imaging in subjects with corresponding histopathology for 
subjects who had a change in the planned protocol procedure (Both Cohorts combined) 
3.3. 
Safety Endpoints 
1. Treatment-emergent adverse events (TEAEs) and SAEs 
2. Change from baseline in clinical laboratory parameters   
3. Change from baseline in ECGs  
4. Change from baseline in vital signs 
5. Concomitant medication use 


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4. 
STUDY DESIGN 
4.1. 
Summary of Study Design 
This is an open-label, non-randomized, Phase 2/3, multi-center study designed to evaluate the 
safety and diagnostic performance of 18F-DCFPyL PET/CT imaging to determine the presence or 
absence of metastatic prostate cancer in subjects with high risk prostate cancer who were 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) who 
were biopsied if a positive lesion was found on the 18F-DCFPyL PET/CT scan.  The physician 
has the option to change the planned protocol specified procedure (i.e., RP ePLND for Cohort A 
subjects and Biopsy for Cohort B subjects) for the subjects based on the 18F-DCFPyL PET/CT 
scan.  The details of these changes will be collected on the CRF, and these subjects obviating the 
planned procedure will not be included in any of the primary or secondary endpoints. 
Eligible subjects will be enrolled in a non-randomized, sequential manner, with competitive 
enrollment between study sites.  Ten (10) study sites will be used in the U.S. and Canada. 
Diagnostic performance characteristics of 18F-DCFPyL PET/CT imaging will be evaluated using 
histopathology as the truth standard.  Three independent readers from a central imaging core lab 
will be given access to 18F-DCFPyL PET/CT imaging, conventional imaging, and biopsy-guided 
imaging. The central readers will be blinded to all other clinical information (i.e. pathology data) 
and radiology assessments. Likewise, local pathologists who generate the histopathology results 
for the primary endpoint are blinded to all imaging results. 
A change in clinical management questionnaire will be filled out by an independent urologist 
who is not otherwise a participant of the study.  To maintain the blind for imaging, a statistician 
who is independent from the PyL study team will generate subject listings.  A combination of 
imaging and clinical data will then be posted to a share point site where the independent 
urologist will review these data and fill out the questionnaire based on the results he sees prior to 
PyL imaging and then again after PyL imaging.  To keep things simple, only imaging data from 
reviewer 1 will be presented for this assessment to be performed.   
   
4.2. 
Definition of Study Drugs and Treatment Follow-up 
All subjects will be administered 9 ± 1 mCi (333 ± 37 MBq) 18F-DCFPyL injection followed by 
PET/CT imaging and either a biopsy or prostatectomy and lymphadenectomy as illustrated in the 
white boxes in Figure 1.  These are the protocol’s planned procedures.  If a Physician decides to 
change these planned procedures after PET/CT imaging is obtained, subjects in Cohort A would 
not have surgery and subjects in Cohort B would not have a conventional imaging guided biopsy.  
These changes in planned protocol procedures are listed in the shaded boxes below.  This should 
be a small number of subjects who will not be included in the primary analysis of the primary 
endpoint or any of the secondary endpoints. 


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Figure 1:  Study Schema 
 If the subject did not want to go through with this planned procedure or withdrew from the 
study then this would not constitute a change in planned protocol procedure. If the planned 
procedure was intended but could not be completed, then this is also not a change in planned 
procedure. 
4.3. 
Sample Size 
The primary analysis in Cohort A will test the co-primary endpoints of sensitivity and specificity 
of 18F-DCFPyL PET imaging relative to histopathology for the evaluable set of subjects in 
Cohort A with metastatic disease.  For each co-primary endpoint, there will be three independent 
imaging readers.  At least two of the three readers must reject the null hypothesis for specificity 
to be deemed a success.  If specificity is a success, then the same two readers need to reject the 
null hypothesis for sensitivity leading to overall success of the primary endpoint.  The null 
hypotheses will be tested in the following order: 
1.
Specificity of 18F-DCFPyL PET imaging relative to histopathology in Cohort A
H0: πSp = 0.80 versus H1: πSp ≠ 0.80
2. Sensitivity of 18F-DCFPyL PET/CT imaging relative to histopathology in Cohort A
H01: πSe = 0.40 versus H11: πSe ≠ 0.40
where πSe is the true sensitivity and πSp is the true specificity of 18F-DCFPyL PET imaging. 
A total of 262 subjects from Cohort A will provide 80% power to reject the null hypothesis about 
sensitivity at the 5% significance level if the true sensitivity is at least 60% and at least 80% 
power to reject the null hypothesis about specificity at the 5% significance level if the true 
specificity is at least 87.8%.  These calculations are based on the following assumptions: 

the probability of a positive histopathology sample in Cohort A is 20%,
The sample size is based on the normal approximation to the binomial distribution without a 
continuity correction3. 
Cohort A
High Risk PC
N=262
Screening
18F-DCFPyL Injection 
PET/CT Imaging
Radical Prostatectomy and ePLND
Radiation
Systemic Therapy 
Biopsy
Cryoablation hormonal 
therpay/ADT
Cohort B
Recurrent or 
Metastatic PC
N=115
Screening
18F-DCFPyL Injection
PET/CT Imaging
Conventional Imaging guided Biopsy
Prostatectomy
Chemotherapy
lymphadenectomy (lymph node removal)
ADT


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𝑛≥൝
𝑧ఈ/ଶඥ𝑃଴(1 −𝑃଴) + 𝑧ఉඥ𝑃ଵ(1 −𝑃ଵ)
𝑃ଵ−𝑃଴
ൡ
ଶ
 
 
 
where P0 are P1 are values of sensitivity under the null and alternative hypotheses, respectively.    
After adjusting sensitivity and specificity separately by their corresponding prevalence values, a 
total in 236 subjects are needed.  Assuming a 10% drop out or non-evaluable rate increases the 
required number of subjects in Cohort A to 262.  
The type I error rate will be preserved at 5% by requiring that both null hypotheses be rejected to 
draw the conclusion that 18F-DCFPyL is efficacious for imaging. The second primary endpoint is 
only tested if the first primary endpoint is rejected at the 0.05 level of significance per a fixed 
sequential method. If the first hypothesis fails to be rejected, no further testing will be conducted. 
No formal power calculations will be performed for Cohort B since it is not a primary endpoint.  
Approximately 115 subjects will be dosed in this cohort. 
4.4. 
Randomization 
This study is not randomized.  One treatment will be administered. 
4.5. 
Clinical Assessments 
See Table 2 for the schedule of study assessments. 
Table 2: 
Schedule of Assessments 
 
Screening/ 
Baseline 
18F-DCFPyL 
Dosing 
18F-DCFPyL 
Imaging 
Pre-Surgery/ 
Biopsy 
Follow-Up 
 
Day -30 to 
Day 1 
Day 1 
1-2 Hours 
Post-Dosing 
Within 28 
Days Post-
Dosing 
Cohorts A and B 
Informed Consent & Eligibility 
X 
 
 
 
Demographics (date of birth, race, ethnicity, height, 
weight) 
X 
 
 
 
Medical History 
X 
 
 
 
Prior Cancer Medications & Treatments 
X 
 
 
 
Clinical Labs (hematology, chemistry) 
X1 
 
 
X 
PSA (total) & Testosterone 
X1 
 
 
 
Vital Signs (blood pressure, heart rate, temperature, 
respiratory rate) 
X 
X 
(pre-dosing) 
X 
(pre-imaging) 
X 
12-Lead ECG 
 
X 
(pre-dosing) 
X 
(pre-imaging) 
 
18F-DCFPyL Administration 
 
X 
 
 
Whole Body PET/CT 
 
 
X 
 


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Table 2: 
Schedule of Assessments 
 
Screening/ 
Baseline 
18F-DCFPyL 
Dosing 
18F-DCFPyL 
Imaging 
Pre-Surgery/ 
Biopsy 
Follow-Up 
 
Day -30 to 
Day 1 
Day 1 
1-2 Hours 
Post-Dosing 
Within 28 
Days Post-
Dosing 
Adverse Events 
 
X 
X5 
Concomitant Medications 
X 
X 
X 
Conventional Imaging (CT or MRI, bone scan) 
X2 
 
 
 
Surgery or Image-Guided Biopsy 
 
 
 
X3,6 
Subset of Cohort A or B at Johns Hopkins University only for PK Analysis 
Blood Collection 
 
X4 
(9 collections) 
 
 
Urine Collection 
 
X4 
(3 collections) 
 
 
Whole Body PET/CT 
 
 
X4 (3 scans) 
 
1 To be collected prior to dosing, if collected on day of dosing. If PSA and testosterone have not been tested within 
30 days of study drug injection, a blood draw will be collected prior to dosing. 
2 If not obtained as standard of care ≤6 weeks (Cohort A) or ≤ 4 weeks (Cohort B) prior to Day 1.  If Na-18F-PET 
bone scans conducted at screening must be at least 10 hours prior to dosing.   
3 Surgery or biopsy to occur at least 12 hours from time of 18F-DCFPyL dosing but not more than 28 days from 
dosing. In Cohort B, imaging used to guide biopsy (i.e., CT, MRI) will be submitted to a central core imaging lab. 
4 Analysis should occur immediately following last sample collected. 
5 A safety phone call will also occur 7(±3) days post dosing [if surgery, biopsy or a change in planned protocol 
procedure has not yet occurred] and 21(±7) days post biopsy for just the subjects who had a conventional image 
guided biopsy in Cohort B.  
6 If a subject’s planned procedure (RP or biopsy) for prostate cancer changes following 18F-DCFPyL imaging, the 
alternate or additional prostate cancer procedure and corresponding histopathology data will be recorded in the 
electronic case report form (eCRF). 
4.6. 
Interim Analyses 
No interim analysis is planned for this study. 
4.7. 
Final Analyses 
The final analysis will be conducted after the database is locked. 


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5. 
GENERAL CONSIDERATIONS FOR DATA ANALYSES AND 
HANDLING 
5.1. 
General Summary Table and Individual Subject Data Listing 
Considerations 
Adverse event and medical history verbatim terms will be coded using the Medical Dictionary 
for Regulatory Activities (MedDRA), version 4.0.  Medications will be coded using the World 
Health Organization Drug Dictionary (WHODDE) from December 2016. 
Summary tables and listings will include the following information:  dataset(s) used in table 
production, date of data extract, date of output generation, the SAS program name and location 
(directory path), page x of y numbering.  Adverse event and medical history summaries will 
indicate the MedDRA version; prior and concomitant medication summaries will indicate the 
WHODD version. 
Summary tables for demographics and baseline characteristics, medical history, exposure, 
concomitant medications, and safety will include the following columns: Cohort A, Cohort B, 
overall (Cohorts A and B combined).  Efficacy tables will be produced by cohort.   
5.2. 
General Post Text Summary Table and Individual Subject Data 
Listing Format Considerations 
Statistical analyses will be performed, and datasets and tables will be generated using SAS 
version 9.4 (SAS Institute, Inc., Cary, NC, USA). 
5.3. 
Data Presentation Conventions 
Continuous data will be summarized using descriptive statistics [i.e., N, arithmetic mean, 
standard deviation (SD), median, minimum, and maximum].  The minimum and maximum will 
be displayed to the same level of precision as collected data; mean and median will be displayed 
to one level of precision greater than the data collected; SD will be displayed to two levels of 
precision greater than the data collected.  Categorical data will be described using frequencies 
and percentages.  A row for missing values will be included, when applicable.  P-values will be 
presented at four decimal places.       
Dates will be presented in DDMMMYY format and times will be presented as HH:MM using a 
24-hour clock. 
In tables and listings, columns of data will be decimal aligned. 
5.4. 
Analysis Populations  
5.4.1. 
Consented Set 
All subjects who sign an informed consent document will be included in the consented set. 
5.4.2. 
Safety Set 
All subjects who receive any amount of 18F-DCFPyL will be included in the safety set.   


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5.4.3. 
Evaluable Set 
Evaluable subjects in Cohort A are those who were dosed, had a prostatectomy or 
lymphadenectomy, and provided a 18F-DCFPyL PET image result (positive or negative) and a 
corresponding histopathology result (positive or negative).   
Evaluable subjects in Cohort B are those who were dosed, received a conventional image guided 
biopsy, and provided a 18F-DCFPyL PET image result (positive or negative) and a corresponding 
histopathology result (positive for prostate cancer or negative), along with a conventional image 
that confirms the location of the histopathology sample. 
5.4.4. 
Change in Planned Protocol Procedure Set 
The change in planned protocol procedure set includes dosed subjects in Cohort A who did not 
have a prostatectomy and lymphadenectomy due to change of planned management, and subjects 
in Cohort B who did not have conventional guided biopsy due to change of planned 
management. See figure 1 above for definition of change in planned management. 
5.4.5. 
Per Protocol Set 
The Per-protocol set is defined as subjects in the Evaluable set without any major protocol 
deviations.  Major protocol deviations will be identified prior to database lock and analysis. 
5.4.6. 
PK Blood Set 
Subjects who provide at least six of the nine scheduled blood samples. 
5.4.7. 
PK Urine Set 
Subjects who provided at least two of the three scheduled urine samples.  
5.5. 
Derived and Transformed Data 
5.5.1. 
Baseline Definition 
Baseline will be the latest pre-dose value.   
5.5.2. 
Baseline Age  
Age is computed in the database as the number of full year increments from date of birth to 
informed consent date. 
5.5.3. 
Study Day 
Study day will be computed as the date of assessment minus the Dosing date (plus one if the 
assessment date is on or after the dose date).   
5.5.4. 
Change and Percent Change from Baseline 
Change from baseline will be computed as any post baseline follow-up value minus the baseline 
value. 


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Percent change from baseline will be computed as 100 times the (post-baseline value minus the 
baseline value) divided by the baseline value.  If the baseline value or the post-baseline value is 
missing, change from baseline and percent change from baseline will be missing. 
5.5.5. 
Prior and Concomitant Medications 
Prior medications are those administered prior to 18F-DCFPyL administration date; concomitant 
medications are those administered from 18F-DCFPyL administration through last study visit.  If 
the concomitant medication does not have a full date then the algorithm in Section 5.6.2 will be 
used to determine if it is a pre- or post-dose medication. 
5.5.6. 
Treatment-Emergent Adverse Events 
Treatment emergent AEs are defined for all subjects as AEs occurring from the day of, but after 
18F-DCFPyL administration through the date prior to prostatectomy, lymphadenectomy, or 
change in planned procedure for subjects who underwent a procedure. For subjects who did not 
receive a procedure, TEAEs are collected up to10 days after drug administration.  For subjects in 
Cohort B who had a conventional imaging guided biopsy only, treatment emergent is defined as 
AEs occurring from the day of 18F-DCFPyL administration through 28 days post biopsy.   
5.5.7. 
Sensitivity, Specificity, PPV, and NPV 
Sensitivity, specificity, PPV and NPV will be defined based on a 18F-DCFPyL image result 
(positive or negative) and a histopathology result (positive or negative).  
  
Table 3: Classification of 18F-DCFPyL Imaging Result and Histopathology Result   
 
Histopathology Result 
 
18F-DCFPyL Image 
Positive* 
Negative 
 
Positive 
TP 
FP 
I(p) 
Negative 
FN 
TN 
I(n) 
 
R(p) 
R(n) 
N 
TP=true positive; FP=false positive; FN=false negative; TN=true negative.   
R(p) and R(n) denote the number of subjects with positive and negative histopathology results, respectively. 
I(p) and I(n) denote the number of subjects with positive and negative 18F-DCFPyL images, respectively. 
N indicates the number of subjects  
*positive histology should be for prostate cancer only
The following statistics will be computed: 
 Sensitivity = TP/R(p), 
 Specificity = TN/R(n), 
 Positive predictive value (PPV) = TP/I(p), 
 Negative predictive value (NPV) = TN/I(n).   


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5.5.7.1. 
Primary Endpoints and Pelvic Lymph Nodes  
The primary endpoints of sensitivity and specificity are defined from lymph node imaging results 
and corresponding pelvic lymph node histology.  For an imaging result to be deemed positive for 
this endpoint, the tissue must have first been removed from that corresponding area. This ensures 
that an imaging result has the ability to align with the results achieved from pathology.  This will 
be applied to Cohort A subjects only.  
PPV and NPV will also be calculated as secondary endpoints from the pelvic lymph nodes.  The 
same definitions used below will apply. 
Criteria for Positive PyL Imaging Result 
Criteria for Lymph Node Dissection and 
Positive Histology 
If Right or Left Pelvic Lymph Nodes 
Minimum Template = Positive and  
 Tissue was removed from left template 
and total left nodes removed ≥1 and 
Template Left Pelvic LN Lesion Count 
≥1 or  
 Tissue was removed from right template 
and total right nodes removed ≥1 and 
Template Right Pelvic LN Lesion Count 
≥1  
or  
Tissue was removed from Pre-sacral nodes and 
total pre-sacral nodes removed ≥1 and Pre-
Sacral Pelvic LN Lesion Count ≥ 1  
or  
 Tissue was removed from Other lymph 
 nodes and Total nodes removed >=1 and Other 
Pelvic LN Lesion Count ≥ 1 or
≥1 positive lymph node on right template if 
Template Right Pelvic LN Lesion Count 
from imaging is ≥0 or 
≥1 positive lymph nodes on left template if 
Template Left Pelvic LN Lesion Count from 
imaging is ≥0 or 
≥1 positive lymph nodes on pre-sacral nodes 
if Pre-Sacral Pelvic LN Lesion Count from 
imaging is ≥0 or  
≥1positive lymph nodes on other pelvic 
lymph nodes if Other Pelvic Lymph Node 
Count from imaging is ≥0 


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If tissue was removed from right template and 
total right nodes removed ≥1 and resection 
included tissue along the external iliac artery 
and Right pelvic lymph node external iliac 
artery= positive or  
If tissue was removed from left template and 
total left nodes removed ≥1 and resection 
included tissue along the external iliac artery 
and left pelvic lymph node external iliac 
artery= positive or 
If tissue was removed from right template and 
total right nodes removed ≥1 and resection 
included tissue along the common iliac vein 
and Right pelvic lymph node common iliac 
vein= positive or  
If tissue was removed from left template and 
total left nodes removed ≥1 and resection 
included tissue along the common iliac vein 
and left pelvic lymph node common iliac vein= 
positive or 
If tissue was removed from right template and 
total right nodes removed ≥1 and resection 
included tissue along the common iliac artery 
and Right pelvic lymph node common iliac 
artery= positive or  
If tissue was removed from left template and 
total left nodes removed ≥1and resection 
included tissue along the common iliac artery 
and left pelvic lymph node common iliac 
artery= positive   
If Template Right Pelvic LN Lesion Count 
from imaging is ≥0 and Total number of 
positive lymph nodes from Right Template 
≥1 or 
If Template Left Pelvic LN Lesion Count 
from imaging is ≥0 and Total number of 
positive lymph nodes from Left Template ≥1 
If any of the above criteria are met for imaging then PyL Imaging Result=Positive.  If Cohort =A 
and lymphadenectomy was performed, and lesion counts from imaging results are available for 
at least one location (right, left, pre-sacral or other) but the above criteria are not met for 
imaging, then PyL Imaging Results = Negative. 
If the above criteria for histology are met then Histology is positive.  If all available positive 
lymph nodes=0 where the corresponding lesion count from imaging≥0 then Histology is 
negative. 
If the lesion counts from all 4 locations (right, left, pre-sacral, and other lymph nodes) are not 
evaluable on imaging or tissue is not removed from all 4 locations then this endpoint will be 
missing.  


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5.5.7.2. 
Biopsy  
Sensitivity and PPV are defined from imaging results in subjects undergoing a biopsy confirmed 
by conventional imaging and histology obtained from this biopsy. This will be performed for 
Cohort B only. 
Criteria for Positive PyL Imaging Result 
Criteria for Biopsy and Positive Histology 
Biopsied Lesion consistent with PSMA Positive 
uptake on the 18F-DCFPyL PET/CT = yes  
Pathology result=Positive for prostate 
cancer  
If Cohort =B, imaging and histology are obtained for the biopsy, and the above criteria are not 
met (Biopsied Lesion consistent with PSMA Positive uptake on the 18F-DCFPyL PET/CT = no 
or pathology result = negative) then results = Negative for each respective endpoint. 
5.5.7.3. 
Prostate Gland  
Sensitivity, specificity, PPV and NPV will be calculated from imaging and histology results from 
the prostate gland. This will be performed for subjects in Cohort A only. 
Criteria for Positive PyL Imaging Result 
Criteria for Positive Histology 
For category = PYL and Prostate gland right 
lesion count ≥ 1 or Prostate gland left lesion 
count ≥ 1 
If Prostate gland right lesion count ≥0 from 
imaging and Adenocarcinoma is present at 
right side of prostate or 
Prostate gland left lesion count ≥0 from 
imaging and Adenocarcinoma is present at 
left side of prostate 
If Cohort =A and Adenocarcinoma results are not missing for the right or left side of the prostate 
and the above criteria is not met, then result = Negative. 
 
If imaging results are both not evaluable or the presence of adenocarcinoma is missing from both 
the left and right side of the prostate then this endpoint is missing. 
5.5.7.4. 
PPV for Changes in Planned Treatment 
PPV will be calculated from imaging and histology results for the subset of subjects who had a 
change in the planned protocol procedure.  Only a subset of these subjects may have tissue 
available for PPV. 
Criteria for Positive PyL Imaging Result 
Criteria for Procedure and Positive 
Histology 


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If subject in Cohort A and category=PYL and Is 
the 18F-DCFPyL PET/CT scan consistent with 
PSMA Positive cancer uptake = yes and 
Location of lesion count from imaging = 
location of lesion from histology and Lesion 
count for location >=1 from imaging 
If Cohort A and prostatectomy and 
lymphadenectomy performed=no and 
Reason= Other, unscheduled Biopsy=’Yes’ 
and Pathology result=Positive for prostate 
cancer 
If Cohort B and category = PYL and Prostate 
gland right lesion count ≥ 1 or Prostate gland left 
lesion count ≥ 1  
If Cohort B and Biopsy performed =no and 
Adenocarcinoma present at right or left 
side of prostate = yes  
If Cohort B and category = PYL and positive 
imaging criteria from Section 5.5.7.1 is met. 
If cohort B and biopsy performed = no and 
≥1 positive lymph node on right or left 
template, pre-sacral nodes, or other pelvic 
lymph nodes 
The denominator of the above subset is the subset of subjects who had a change in the planned 
protocol procedure defined in Figure 1 and who had both imaging and histology results.   
If imaging results are not evaluable then this endpoint is missing. 
5.5.8. 
Lesions Per Subject 
The number of lesions detected on imaging categorized as bone, lymph nodes, soft tissue, and 
the prostate gland will be determined by each of the central imaging core lab independent 
readers.  The sum of lesions per subject per tissue type and overall will be computed for each 
subject based on each reader’s lesion count.  This will be calculated from the 18F-DCFPyL 
PET/CT scan results as well as the conventional imaging results.   
Bone 
Soft Tissue 
Lymph nodes 
Prostate Gland 
BN Skull 
ST Brain 
LN Cervical  
ST Prostate Gland Left 
BN Thorax
ST Neck 
LN Supraclavicular
ST Prostate Gland Right
BN Spine
ST Lungs
LN Axillary
BN Pelvis
ST Esophageal
LN Mediastinal
BN Extremities
ST Liver
LN Hilar
ST Gall Bladder
LN Mesenteric
ST Spleen
LN Elbow
ST Pancreas
LN Popliteal
ST Adrenal
LN Peri-aortic/para-aortic
ST Kidney
LN Other, Non-Pelvic
ST Bladder
PLN Template Right
ST Prostate Bed
PLN Template Left
ST Seminal Vesicle
PLN Pre-Sacral
ST Skin
PLN Other, Pelvic
ST Muscle
ST Other


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5.5.9. 
Visit Windows 
Data will be analyzed according to the nominal time points. Visit windows will not be used. 
5.5.10. 
Decay Corrected Dose at Time of Administration 
The calculations in this section will need to be performed for the pre- and post- injection values 
for 18F-DCFPyL administration as well as pre- and post- injection from the Syringe to the flask 
for reference values.  
If a decay correction was performed for the pre-or post- dose values then Correction Factor =1. 
Otherwise: 
Correction Factor = 𝑒
(୪୬(ଶ)∗(௣௥௘ ௢௥ ௣௢௦௧ ௜௡௝௘௖௧௜௢௡ ௧௜௠௘(௠௜௡)ି௜௡௝௘௖௧௜௢௡ ௧௜௠௘ (௠௜௡)))
ଵଵ଴ ௠௜௡
ൗ
 
where the above formula will be calculated for each of the following pre and post injection 
times:  
 
 
 
pre-dose 
  
 
 
 
 
 
post dose 
syringe prior to flask 
syringe post flask 
start of measurement times with each PK period 
  
 
Convert all pre- and post- injection amounts to mCi:  37MBq = 1mCi 
 
If there was no post decay correction then: 
Decay Corrected Dose at time of Administration = (pre injection amount 
(mCi)*Correction Factor Pre Dose)- 
௉௢௦௧ ௜௡௝௘௖௧௜௢௡ ௔௠௢௨௡௧ (௠஼௜)
஼௢௥௥௘௖௧௜௢௡ ி௔௖௧௢௥ ௉௢௦௧ ஽௢௦௘ 
If there was a post decay correction then: 
Decay Corrected Dose at time of Administration(mCi) = (pre injection amount(mCi) – 
post injection amount(mCi)) 
Calculate decay corrected doses at time of administration in both mCi for all subjects and MBq 
for all subjects.  
 
The Decay corrected pre-injection Reference Standard of syringe prior to injection into flask = 
amount (µCi) in syringe prior to injection into flask*Correction Factor of syringe prior to flask. 
 
The Decay corrected post-injection Reference Standard of syringe after injection into flask = 
amount (µCi) in syringe after injection into flask*Correction Factor of syringe after flask. 
 
The decay corrected reference standards are only needed in µCi. 
 
5.5.11. 
Lesion location defined from SUV values  
There are three SUV values collected:  SUVmax, SUVpeak and SUVmean.  There are four locations 
that each of these SUV values could be present in: Bone, Soft tissue, prostate, and lymph nodes 
(‘prostate gland right’ and ‘prostate gland left’ were defined as a separate location from soft 


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tissue) as defined in Section 5.5.8.  There are three reference values per subject at the following 
locations:  Aorta, Liver and Muscle.  For each tumor location that is not a reference location, 
SUVR will be calculated against each reference as follows: 
SUVR= 
ference
MEAN
Tumor
MAX
SUV
SUV
Re
_
_
 
Some subjects may have multiple SUV values within each location.  These results will be 
averaged to derive one result per location and since there results should be similar per reviewer, 
only results for reviewer 1 will be used in any analyses.  Subjects in Cohort B may have both a 
biopsied lesion and a tissue lesion within the same location. These SUV values should be 
summarized separately. 
5.5.12. 
Change in Clinical Management Plan from Questionnaire 
A change in the Clinical Management plan from the pre-PyL scan assessment to the post-PyL 
scan assessment will be defined from any of the following questions: 
 If there is a change in planned diagnostic biopsy from pre-PyL to post-PyL 
 If there is a change in planned surgery from pre-PyL to post-PyL 
 If type of surgery planned pre-PyL does not match post-PyL 
 If type of planned chemotherapy changes from pre-PyL to post-PyL 
 If there is a change in planned other immunotherapy/investigational therapy from pre-
PyL to post-PyL 
 If planned radiation therapy changed from pre-PyL to post-PyL 
 If chemotherapy plan changed from pre-PyL to post-PyL 
 If hormonal/ADT plan changed from pre-PyL to post-PyL 
 If there is a change in other therapy/intervention from pre-PyL to post-PyL 
An overall change score will be calculated as well as a change in each of the above criteria alone.  
5.5.13. 
PSA groups 
PSA will be categorized into the following groups: 
<0.2 ng/mL 
0.2 to <4.0 ng/mL
4 to <20.0 ng/mL
20.0 to <50.0 
ng/mL
≥50 ng/mL
5.5.14. 
Gleason Scores  
The Gleason score will be derived by concatenating the primary Gleason grade to the secondary 
Gleason grade, separated by a plus sign (e.g., 3+4).  The total Gleason score will be computed as 
the sum of the primary and secondary Gleason grades (7 in the example of 3+4 provided here). 


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Gleason Score from prostatectomy will be categorized into the following groups as shown in the 
table based on the sum of primary and secondary Gleason Grades: 
Primary Gleason Grade
Secondary Gleason Grade 
Total 
3
3
≤ 6
3
4
7
4
3
7
4
4
8
4
5
9
5 
5 
10 
5.5.15. 
Prior Prostate Cancer History and Therapies 
If any of the follow variables have partial dates where only month and year are present, then 
months will be calculated as ((dose year - parameter year) x12) + ((dose month-parameter 
month) +1). Otherwise, with full dates, the calculation would be as follows: 
Months since last prostate cancer staging = (Dose date – prior prostate cancer staging date)/30.4. 
Months from Prior Therapy to Dose = (𝐷𝑜𝑠𝑒 𝐷𝑎𝑡𝑒−𝑃𝑟𝑖𝑜𝑟 𝑝𝑟𝑜𝑠𝑡𝑎𝑡𝑒 𝑇ℎ𝑒𝑟𝑎𝑝𝑦 𝑠𝑡𝑜𝑝 𝑑𝑎𝑡𝑒)/
30.4 
Months from Prior Radiation to Dose= (𝐷𝑜𝑠𝑒 𝐷𝑎𝑡𝑒−
𝑃𝑟𝑖𝑜𝑟 𝑟𝑎𝑑𝑖𝑎𝑡𝑖𝑜𝑛 𝑇ℎ𝑒𝑟𝑎𝑝𝑦 𝑠𝑡𝑜𝑝 𝑑𝑎𝑡𝑒)/30.4 
Months from Prior Surgery to Dose = (𝐷𝑜𝑠𝑒 𝐷𝑎𝑡𝑒−𝑃𝑟𝑖𝑜𝑟 𝑝𝑟𝑜𝑠𝑡𝑎𝑡𝑒 𝑠𝑢𝑟𝑔𝑒𝑟𝑦 𝑑𝑎𝑡𝑒)/30.4 
Months from Staging to Dose= (Dose Date – Primary tumor staging date)/30.4 
Months since last Prior Therapy to Dose = (Dose Date – Prior therapy date)/30.4. 
Full dates must be present for duration variables below: 
Duration of Prior Therapy (days) = (Prior Prostate Therapy stop date – Prior prostate therapy 
start date) +1. 
Duration of Prior Radiation Therapy (days) = (Prior Radiation Therapy stop date – Prior 
Radiation therapy start date) +1 
5.5.16. 
Estimate GFR 
Estimate GFR (eGFR) will be calculated using the Modification of Diet in Renal Disease 
(MDRD) Equation4: 
eGFR (mL/min/1.73 m2) = 175 × (Scr)-1.154 × (Age in years)-0.203 × (0.742 if female) × (1.212 if 
African American) 
Where Scr= Serum creatinine (mg/dL) 
5.5.17. 
 Renal impairment 
If Estimated GFR ≥90 then Normal (no impairment), otherwise if 0≤eGFR<90 then Abnormal.   


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5.5.18. 
Laboratory Parameter Unit Conversions 
 
Lab Parameter 
Original 
Unit 
Conversion 
Factor (multiply) 
Final SI 
Unit 
ALT, Alkaline Phosphatase 
U/L 
0.0167 
Ukat/L 
Albumin, Total Protein, hemoglobin 
g/dL 
10 
g/L 
BUN 
mg/dL 
0.357 
mmol/L 
Calcium 
mg/dL 
0.25 
mmol/L 
Chloride, Potassium, Sodium 
mEq/L 
1 
mmol/L 
Creatinine 
mg/dL 
88.4 
umol/L 
Glucose 
mg/dL 
0.0555 
mmol/L 
Total Bilirubin 
mg/dL 
17.104 
umol/L 
Total Testosterone 
ng/dL 
0.0347 
nmol/L 
Total Testosterone 
ng/mL 
3.4672 
nmol/L 
Triglycerides 
mg/dL 
0.0113 
mmol/L 
Hematocrit 
% 
0.01 
L/L 
Basophils, Eosinophils, lymphocytes, 
monocytes, neutrophils, platelets, 
WBC count 
k/cumm 
1 
109/L 
Basophils, Eosinophils, lymphocytes, 
monocytes, neutrophils, platelets, 
WBC count 
k/L 
1 
109/L 
Basophils, Eosinophils, lymphocytes, 
monocytes, neutrophils, platelets, 
WBC count 
103/L 
1
109/L
Basophils, Eosinophils, lymphocytes, 
monocytes, neutrophils, platelets, 
WBC count 
109/L
1
109/L


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Basophils, Eosinophils, lymphocytes, 
monocytes, neutrophils, platelets, 
WBC count 
k/mcl 
1 
109/L 
RBC Count 
m/mcl 
1 
1012/L 
RBC Count 
m/L 
1 
1012/L 
RBC Count 
mil/cumm 
1 
1012/L 
RBC Count 
1012/L 
1 
1012/L 
RBC Count 
1012/L 
1 
1012/L 
RBC Count 
106/L 
1 
1012/L 
PSA 
ng/mL 
1 
ug/L 
5.6. 
Handling of Missing Data 
5.6.1. 
Missing Efficacy Endpoints 
No imputation methods will be employed. 
5.6.2. 
Missing Start and Stop Dates for Concomitant Medication 
Partial or missing medication start, and end dates will be categorized as occurring prior to or 
after dose using the following logic.  If a medication categorized as post-dose had a start date< 
dose date or a start year <dose year or a start year=dose year and start month<dose month then it 
will be summarized as both a pre- and post- medication.  


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Start Date 
Stop Date 
Category 
< dose date or Year< dose 
year or year= dose year and 
month< dose month or 
year=dose year or 
date=missing
date< dose date or year<dose 
year or year=dose year and 
month<dose month 
Pre-dose 
< dose date or Year< dose 
year or year= dose year and 
month< dose month  
Missing or date< dose date or 
year<dose year or year=dose 
year and month<dose month or 
year=dose year
Pre-Dose 
Year = dose year and month 
= dose month and day is 
missing
Year = dose year and month < 
dose month  
Pre-dose 
>dose date or year=dose year 
and month≥ dose month 
missing 
Post Dose 
>dose date or year=dose year 
and month> dose month
 
Post Dose 
 
≥ dose date or year>dose year 
or year=dose year and month ≥ 
dose month 
 Post Dose 
Date<dose date or year ≤ 
dose year and month≤dose 
month
Year=dose year and 
month=dose month 
Post Dose 
Missing
missing
Post Dose
< dose date or Year< dose 
year or year= dose year and 
month< dose month
≥ dose date or year>dose year 
or year=dose year and month ≥ 
dose month 
Pre and Post Dose 


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6. 
STUDY POPULATION 
6.1. 
Disposition 
Subject disposition will display the number of consented subjects and the percentage of them 
who failed screening.  The number of subjects in the safety analysis set as well as the number 
and percentage of subjects in the evaluable set, per-protocol set, change in planned protocol 
procedure set, and PK sets will also be summarized.  The number and percentage of subjects who 
completed or discontinued from the study with the reason for discontinuation, will be tabulated.  
All percentages for discontinuation reasons will be based on the number of subjects in the safety 
population.  
6.2. 
Protocol Deviations 
Protocol deviations will be summarized in the clinical study report based on the protocol 
deviation log. 
Protocol deviations will be listed, including their classification as major or minor for the Safety 
Set. 
6.3. 
Demographic and Baseline Characteristics 
Demographic and baseline characteristics: age at informed consent in years, categorical age (<65 
years, ≥65 years), race, ethnicity, height in cm, weight in kg, and BMI in kg/m2 will be 
summarized by cohort for the safety set, the evaluable set, and the per protocol set. 
6.4. 
Medical History, including Prostate Cancer History  
Medical history will be summarized by MedDRA system organ class (SOC) and preferred term 
(PT) using frequencies and percentages. 
Prior prostate cancer history will also be summarized using summary statistics for months since 
most recent prostate cancer staging, PSA (ng/mL) and testosterone (ng/dL).  Frequencies and 
percentages will be presented for whether PSA results were captured within 30 days from 
Baseline, PSA groups, primary Gleason grade, secondary Gleason grade, Gleason total score, 
primary tumor stage (T), regional lymph node stage (N), distant metastasis stage (M) and renal 
impairment status.   
Medical history and prostate cancer history will be presented for the safety set, the evaluable set 
and the per-protocol set. 
6.5. 
Prior Prostate Cancer Therapies and Surgeries 
For prior prostate cancer therapies, each line of therapy is captured into a group ranging from A-
O, where A is the first line of therapy and O is the last line of therapy.  The drugs within each are 
collected.   Prior to locking the database, these drugs will be categorized into groups. An 
additional categorization will also be performed to show types of prostate cancer therapies.   
These therapies will be summarized overall for the drugs within the different lines of therapies.  
The number of therapy regimens received, and types of prostate cancer therapies will be 
summarized.      


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Radiation therapy will be presented to show whether it was prostate related or not, and radiated 
site. 
Months since last reported surgery will also be summarized.  Surgeries will also be presented by 
system organ class and preferred term. 
All prior prostate cancer therapies and surgeries will be presented for the safety set, the evaluable 
set and the per protocol set. 
6.6. 
Prior Medication History and Medications Present at Entry 
Prior medications will be summarized by ATC4 class and generic name using frequencies and 
percentages.  Prior medications will also be listed. 
Prior medication history will be presented for the safety set, the evaluable set and the per 
protocol set.   
6.7. 
Conventional Imaging at Baseline 
Type of bone scans, bone scans obtained within 10 hours of dosing, MRI/CT performed, and 
type of MRI/CT will be summarized by the safety set, the evaluable set and the per protocol set. 
7. 
EFFICACY  
7.1. 
General Considerations 
Statistical tests and their corresponding confidence intervals will be two-sided at the 0.05 
significance level. 
The estimation of sensitivity and specificity rely on the central imaging core lab independent 
readers.  Each reader’s assessments will be summarized separately. 
7.2. 
Testing Statistical Assumptions Including Comparability at Baseline 
7.2.1. 
Test of Proportions 
The assumption underlying the normal approximation to the binomial distribution, used in the 
computation of confidence intervals for sensitivity, specificity, PPV, and NPV, 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.  
It is expected that the sample size for each statistic will be sufficient to meet this assumption.  In 
the event that the sample size is not sufficient, Agresti-Coull exact tests will be used.  As there is 
only one treatment in this study, there will be no testing of baseline comparability. 
7.2.2. 
Test of means 
The assumption of normality of the data may be violated when testing for differences in means.  
If data fail the Shapiro-Wilk test for normality within each group, then a Wilcoxon rank sum test 
will be used for the comparison of 2 groups and a Kruskal-Wallis test for comparison of 3 groups 
to test for differences in the distribution between groups.  For 2 group comparisons, an exact 
95% confidence interval will be generated for the difference scores. For a 1-way repeated 


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measures ANOVA, if the assumption of normality is not met then a Friedman test will be 
performed.  
7.3. 
Statement of the Null and Alternate Hypotheses 
The null and alternative hypotheses are stated in Section 4.3.  
7.4. 
Subgroup Analyses 
No subgroup analyses are planned, but they may be examined for exploratory purposes. 
7.5. 
Multiple Comparisons and Multiplicity 
Within Cohort A, the type I error rate will be preserved by requiring that both null hypotheses be 
rejected in order to draw the conclusion that 18F-DCFPyL is efficacious for imaging.  In addition, 
the three readers from the central imaging core laboratory are independent and requiring that the 
same 2 of 3 readers agree about sensitivity and specificity (Cohort A) will control for type I 
error.  
7.6. 
Analysis of the Primary Efficacy Endpoint 
7.6.1. 
Primary Efficacy Analysis of Primary Endpoints 
The primary analysis for subjects in Cohort A will be addressed by computing point estimates 
and 95% two-sided confidence intervals (CIs) for specificity first and if the null hypothesis is 
rejected for specificity then sensitivity will be tested next. Both outcomes are assessed on the 
subject level (one overall outcome per subject) in the evaluable set.  If the per protocol set exists, 
then this analysis will be performed on the per protocol set as a supplemental analysis.   The 
normal approximation to the binomial distribution is planned assuming the assumptions have 
been met (See Section 7.2). Sensitivity and specificity will be computed for each of three central 
imaging core lab independent PET/CT readers. 
The null hypothesis for specificity will be rejected if the lower limit of the 95% CI exceeds 80% 
for at least two of the three independent central PET/CT readers.  If statistical significance is 
achieved for specificity where the null hypothesis is rejected, then sensitivity will be tested 
where the null hypothesis will be rejected if the lower limit of the 95% CI exceeds 40% for the 
same two readers who rejected the null hypothesis for specificity.  
7.6.2. 
Sensitivity Analyses of the Primary Endpoints 
A sensitivity analysis of the primary endpoint will be performed allowing any 2 of the 3 central 
PET/CT readers to reject the null hypothesis for sensitivity only after specificity has been 
deemed a success. This analysis will require agreement of at least 2 readers, but they do not need 
to be the same 2 central readers to reject the null hypothesis for specificity and sensitivity. This 
analysis will be performed for the evaluable and per protocol sets. 


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7.7. 
Analysis of Secondary Efficacy Endpoints 
Analysis of secondary efficacy endpoints will be conducted regardless of the outcomes of the 
primary analyses.  Diagnostic testing and imaging detection rates will be analyzed for the 
evaluable set.  The PK parameters will be summarized for the PK blood set. 
7.7.1. 
NPV and PPV in Cohort A 
Point estimates and two-sided 95% CIs for PPV and NPV will be computed for the prostate 
gland and the lymph nodes in Cohort A subjects in the Evaluable Set.  The normal 
approximation to the binomial distribution is planned assuming the assumptions have been met 
(See Section 7.2).  PPV and NPV will be computed for each of the three central imaging core lab 
independent PET/CT readers. 
7.7.2. 
PPV and Sensitivity in Cohort B 
Point estimates and two-sided 95% CIs for PPV and Sensitivity will be computed from the 
conventional guided biopsy obtained from subjects in Cohort B for the Evaluable Set.  The 
normal approximation to the binomial distribution is planned assuming a null hypothesis of 0.5. 
If the assumptions are not met, then confidence intervals derived from an Agresti-Coull exact 
test will be used (See Section 7.2).  Results will be computed for each of the three central 
imaging core lab independent readers. 
7.7.3. 
Detection Rates for Lesion Counts in both Cohorts Combined 
For subjects in Cohort A and B combined, the sum of the lesions per tissue type and overall per 
subject will be summarized showing the N, mean, median, standard deviation, minimum and 
maximum values for each central imaging core lab reader including the reader of conventional 
scans. 18F-DCFPyL images and conventional images will be summarized separately and the 
mean of each reader’s results from 18F-DCFPyL PET/CT will be compared to conventional 
imaging using a one-way repeated measures ANOVA. If the assumptions are not met for this test 
(see Section 7.2), then a Friedman’s test will be performed to determine if there is a difference 
between any of the groups.  If significant is determined from either the ANOVA or the 
Friedman’s test, then a Dunnett’s test will be performed to show where the difference exists 
between each reviewer and the conventional scan.  A p-value and 95% confidence interval for 
the difference in means will be presented for each 18F-DCFPyL PET/CT reviewer versus 
conventional imaging. This analysis will be performed on the Evaluable Set. 
7.7.4. 
PK 
Blood, plasma, and urine collection at each nominal time will be collected twice per patient.  The 
mean of the values at each nominal time will be used in the creation of parameters used in the 
analysis.  For each subject, blood concentration-time data using actual blood draw times rather 
than nominal times will be computed by non-compartmental analysis and pharmacokinetic 
parameters will be generated.  Additional blood concentration-time data will be fitted into a two-
compartment model to calculate T1/2-alpha and T1/2-beta.  Summary statistics for blood will be 
presented for maximum concentration (Cmax), area under the (activity-time) curve (AUC), body 
weight normalized clearance (CL), volume of distribution at steady-state (Vss), time to maximum 
concentration (Tmax), half-life(T1/2) [noncompartmental analysis], T1/2-alpha and T1/2-beta [2-


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compartment modelling], and mean residence time (MRT).  Since there are two values collected 
per nominal time, the mean of these values within nominal time will be derived prior to 
generating the PK parameters.  These PK parameters will be derived by an external analyst then 
summarized for the PK blood set.  PSA groups, eGFR groups and eGFR will also be summarized 
for the PK blood set.   
Summary statistics for urinary excretion will be presented for Tmax, Rate max, Rate last, 
T1/2elim, and Cumulative Urine Recovery. For % of injected dose recovered per each urine 
collection interval per subject will be used to calculate Tmax, Rate max, Rate last, T1/2elim, and 
cumulative urine recovery by 4 and 8 hours post-administration if feasible. These PK parameters 
will be derived by an external analyst then summarized for the PK urine set.  eGFR groups as 
defined in Section 5.5.16 and eGFR will also be summarized for the PK urine set. 
The ratio of plasma-to-blood concentrations will be calculated per subject/time-point. 
7.8. 
Analysis of Exploratory Endpoints 
Sensitivity and specificity of the prostate gland as well as SUVmax, SUVpeak and SUVr will all be 
analyzed on the evaluable set.  Change in Management defined from the questionnaire will be 
summarized on the safety set.  The PPV endpoint will be analyzed on the Change in Planned 
Protocol Procedure Set. 
 SUVmax, SUVpeak, SUVmean, and volume will be summarized for each tissue location 
(bone, lymph nodes, soft tissue, and prostate gland) and each of the 3 central imaging 
core lab independent readers using the evaluable set from both cohorts.  SUVr will be 
summarized in the same manner including a reference lesion also.  A 95% confidence 
interval for the mean or distribution will be presented for each reader based on the 
assumption on normality defined in Section 7.2.   
 Differences in the average across all 3 reviewers for SUVmax, SUVpeak, SUVr, SUVmean, 
and volume will be compared between histology outcomes using a t-test that assumes 
unequal variances. If the assumptions for the t-test are not met then a Wilcoxon rank sum 
test will be performed with corresponding exact 95% confidence intervals defined in 
section 7.2. 
 The average SUVmax, SUVpeak, SUVr, SUVmean, and volume values across all reviewers 
will be compared between Gleason Score groups at time of radical prostatectomy, 
Baseline PSA groups and testosterone groups split at the median value.  The comparisons 
of means between groups will be performed using a generalized linear model.  If 
normality cannot be assumed then a Kruskal-Wallis test will be performed instead.  
Within each group a 95% confidence interval will be presented.   
 Point estimates and two-sided 95% CIs for Specificity and Sensitivity will be computed 
from the prostate gland for Cohort A in the Evaluable Set.  The normal approximation to 
the binomial distribution is planned assuming a null hypothesis of 0.5. If the assumptions 
are not met then confidence intervals derived from an Agresti-Coull exact test will be 
used (See Section 7.2).  Results will be computed for each of the 3 central imaging core 
lab independent readers.  


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 Clinical management questions pre- and post 18F-DCFPyL PET/CT imaging will be 
summarized from the questionnaire evaluated by a central reader.  The proportion of 
subjects in Cohort A who had a change in intended clinical management plan from pre- 
to post PyL scans will be analyzed using a one sample binomial test. 
 Point estimates and two-sided 95% CIs for PPV will be computed for the change of 
management set.  An Agresti-Coull 95% confidence interval will be used will be used 
assuming a null hypothesis of 0.5.  Results will be computed for each of the 3 central 
imaging core lab independent readers.  
7.9. 
Reader Reliability  
There are four imaging readers who were trained to perform our central reads used in much of 
the analyses.  Only three of these readers will perform these reads with the fourth reader as an 
alternative if needed.  Variability of these readers regarding the primary endpoint for the 
evaluable set will be tested as described below.  The following is assumed: 
Ni=total number of subjects with the primary endpoint in the evaluable set (i=1, 2,…N) 
K=number of readers (3) 
Rj= number of responses (j=1,2) 
nij=number of times subject i is in response group j 
 
7.9.1. 
Intra-Reader Reliability 
Prior to reading any images, a random subset of 30 PyL images will be randomly selected by the 
Imaging vendor.  Once the reads start, this subset will be re-introduced to each reader no sooner 
than 3 weeks after the original read. They will be read under identical conditions as the original 
read (same criteria evaluation, same analysis reporting, same analysis platform).  The rate of 
agreement between the original reads and the re-reads for the primary endpoint in this subset will 
be compared using the intra-rater variability defined from Cohen’s Kappa5.  This calculation will 
be performed for each reader separately.   
𝐶𝑜ℎ𝑒𝑛ᇱ𝑠 𝐾𝑎𝑝𝑝𝑎= 𝑝௔ି 𝑝௘
(1 −𝑝௘) 
                                                       where  pa = ∑
௡ೕೕ
௡
ோ
௝ୀଵ
 
𝑝௘= ෍ 𝑛௝ା
𝑛
ோ
௝ୀଵ
𝑛ା௝
𝑛 
The standard error of Kappa σk will be calculated as: 
 
 
 
 
 
σk = ට
௉ೌ(ଵି௉ೌ)
ே(ଵି௉೐)మ 
It is assumed that the concordance rate between time points for each reader will be at minimum 
of 93% with a Kappa of 86%. This would yield a 95% confidence interval of (0.68, 1) for a 
sample of 30 subjects.   
7.9.2. 
Inter-Reader Reliability 
For the primary analysis of the primary endpoint the inter-reader reliability will be estimated 
using the multiple-reader generalized kappa statistic developed by Fleiss6,7.   


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𝐾𝑎𝑝𝑝𝑎= 𝑝 ̅ − 𝑝̅௘
1 −𝑝̅௘
 
 
                                    Variance: 
ଶ
ே௄(௄ିଵ)
∑
௣ೕ
మା(∑
௣ೕ
మ)
ೃ
ೕసభ
మିଶ∑
௣ೕ
య
ೃ
ೕసభ
ೃ
ೕసభ
(ଵି∑
௣ೕ
మ
ೃ
ೕసభ
)మ
 
 
Where  
 
 
𝑝௝= 
ଵ
ே௄∑
𝑛௜௝
ே
௜ୀଵ
 
 
 
𝑝௜= 
∑
௡೔ೕ(௡೔ೕିଵ)/ଶ
ೃ
ೕసభ
௄(௄ିଵ)/ଶ
 
 
𝑝̅ = 
∑
௣೔
ಿ
೔షభ
ே
      (overall agreement) 
 
 
𝑝̅௘= ∑
𝑝௝
ଶ
ோ
௝ୀଵ
  (expected chance agreement) 
 
The generalized Kappa statistic and a 95% confidence interval will be computed.   
8. 
SAFETY AND TOLERABILITY 
All safety data will be summarized by cohort. 
8.1. 
Adverse Event Preferred Term and System Organ Class Summary 
Tables 
An overall summary of frequency and percentage of treatment-emergent adverse events 
(TEAEs), most frequent (>5%) overall TEAEs, serious TEAEs, severe TEAEs (grade ≥ 3), 
TEAEs by grade, and treatment-related TEAEs will be presented by cohort and overall using the 
safety set. 
8.1.1. 
Summaries of Adverse Event Incidence Rates for All Subjects 
Treatment-emergent adverse events will be summarized by SOC and PT using the frequency and 
percentage of subjects experiencing any adverse event, experiencing each SOC and experiencing 
each PT within each SOC, using the safety set.  The number of occurrences of each adverse 
event will be included. 
Treatment-emergent adverse events will be summarized by severity and for subjects who report 
adverse events with severity grades 3 or higher.  The most severe occurrence of each event will 
be summarized by SOC and PT using the frequency and percentage of subjects experiencing any 
adverse event, experiencing each SOC and experiencing each PT within each SOC by cohort and 
overall, using the safety analysis set.    


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Treatment-emergent adverse events will be summarized by relationship to study drug.  The most 
closely related occurrence of each event will be summarized by SOC and PT using the frequency 
and percentage of subjects experiencing any adverse event, experiencing each SOC and 
experiencing each PT within each SOC by cohort and overall, using the safety analysis set.  
8.1.2. 
Summaries of Adverse Incidence Rates for Serious Adverse Events (SAE), 
Adverse Event Discontinuations, and Death 
The overall summary table includes incidences of serious adverse events, adverse events that led 
to discontinuation and deaths. 
Separate listings for serious adverse events, adverse events that led to discontinuation and deaths 
will be created.   
8.2. 
Exposure to Study Drug 
Exposure to study drug will be summarized using summary statistics for volume administered, 
location of injection, correction factor at pre and post dose, the decay corrected dose in mCi and 
MBq at time of administration, and any dose change due to an AE for the safety set. 
8.3. 
Concomitant and Other Medications 
Concomitant medications will be summarized by ATC4 class and generic term using frequencies 
and percentages for the safety analysis set. 
8.4. 
Routine Laboratory Data 
Summary statistics for observed and change from baseline values of each laboratory analyte will 
be presented by visit for the safety set.  Labs will include hematology and chemistry.  A shift 
table will also be presented showing the shift in values from Baseline to follow up (below LLN, 
within LLN and ULN, above ULN, and missing).  The following parameters will be created and 
summarized also: 
Leukocytes = sum of Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils 
Basophils/leukocytes = (Basophils/leukocytes)*100 
Eosinophils/leukocytes = (Eosinophils /leukocytes)*100 
Lymphocytes/leukocytes = (Lymphocytes /leukocytes)*100 
Monocytes/leukocytes = (Monocytes /leukocytes)*100 
Neutrophils/leukocytes = (Neutrophils /leukocytes)*100 
8.5. 
Vital Signs 
Summary statistics for observed and change from baseline values of each vital sign (systolic and 
diastolic blood pressures, heart rate, respiratory rate, and temperature) will be presented by visit 
and cohort for the safety set. 


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8.6. 
ECG 
Summary statistics for observed and change from baseline values of each ECG parameter will be 
presented by visit and cohort using the safety set.  For QT interval, adjudicated QTc-Bazett and 
adjudicated QTc-Fidericia, the following groups will be summarized at Baseline and the pre-
imaging visit:  values above 450, above 480 and above 500. For these same parameters the 
following will be summarized at the pre-imaging time point only:  Increase 31-50, increase >60, 
decrease 31-60, and decrease >60. 
8.7. 
Physical Examination 
Not applicable 
9. 
PHARMACOKINETICS 
Summary statistics for blood will be presented for maximum concentration (Cmax), area under 
the (activity-time) curve (AUC), clearance (CL), volume of distribution at steady-state (Vss), 
time to maximum concentration (Tmax), half-life(T1/2) [noncompartmental analysis], T1/2-
alpha and T1/2-beta [2-compartment modelling], and mean residence time (MRT). Clearance 
and Vss will be body-weight normalized. 
Percent of dose recovered in urine will be presented by collection intervals for the PK urine set.  
The following urinary kinetics will also be presented for this set:  Tmax, Rate max, Rate last, T1/2 
elim, and cumulative urine recovery by 4 and 8 hours post administration as % injected dose.  The 
ratio of plasma-to-blood concentrations will be calculated per each subject/time-point. 
9.1. 
Derived Data 
 Concentration of Reference Standard, Ci/mL = 
 (Decay Corrected pre injection reference standard of syringe prior to injection into flask– 
Decay Corrected post injection reference standard of syringe after injection into 
flask)/1000mL. 
 Reference Standard CPM = 18F-DCFPyL reference standard (CPM) from PK*Decay 
Correction factor for measurement time defined for 0-4 hours 
 Average CPM  for Reference standard= Average of 3 CPM results collected for 18F-
DCFPyL std for 0-4 hours.  
 Average CPM/ml for reference standard= Average CPM for reference standard/0.3  
 Concentration of Reference Standard in CPM/Ci = Average CPM/ml for reference 
standard/concentration of reference standard (Ci/mL) 
 For each blood, plasma and urine sample time, calculate: 
  18F-DCFPyL CPMb = 18F-DCFPyL CPM result at sample time*correction factor 
for measurement time  defined for the PK period the sample is drawn in 
 CPMb(ml) = CPMb/0.3 


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 CPM concentration(Ci/ml) = CPMb (ml) / Concentration of Sample in CPM 
(Ci) 
 Average CPM Ci/ml = average CPM Ci/ml within each unique nominal time 
 Ratio of plasma to blood = Average CPM (Ci/ml) for plasma/ Average CPM (Ci/ml) for 
blood per unique sample nominal time 
 For each urine sample, calculate: 
 Radioactivity excreted per collection interval (µCi) = CPM (Ci/ml) from 
urine*urine collection volume (ml) 
 % Dose excreted = (Sum of Radioactivity exerted per collection interval(µCi)  
/(administered dose(mCi)*1000))*100 
 Average % dose excreted = average of individual % dose excreted per unique 
urine collection interval 
 Cumulative Average % dose excreted = sum of average % dose excreted over all 
unique urine collection intervals: 
 0-4 hours = sum of average % dose excreted over  0-2 and 2-4 hours urine 
collection intervals 
 0-8 hours = sum of average % dose excreted over all unique 0-2 and 2-4 hours 
urine collection intervals (0-2, 2-4, and 4-8 hours) 
  
Pharmacokinetic analyses will be conducted on pooled cohorts using the PK blood set and PK 
urine set.   


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10. 
PLANNED TREATMENT SAP CHANGES THAT DIFFER FROM 
THE PROTOCOL 
 Screened population renamed to consented population as the definition states all 
subjects need to provide consent and not screening data. 
 The Evaluable set was updated to state that subjects in Cohort A are required to have 
a prostatectomy and lymphadenectomy.  
 The Change in Planned Protocol Procedure Set was added as a subject population to 
capture the subjects who had a change in the planned protocol procedure. 
 The PK Evaluable set was divided into two groups:  The PK Blood Set and the PK 
Urine set, as a subject could meet the criteria for one of these, but not the other. 
 ‘PPV of 18F-DCFPyL PET/CT imaging in subjects with corresponding 
histopathology that is outside the planned protocol surgical template or biopsy site’ 
was updated to ‘PPV of 18F-DCFPyL PET/CT imaging in subjects with 
corresponding histopathology for subjects who had a change in planned treatment per 
Cohort assignment’.  Subjects may undergo a planned protocol procedure defined per 
the other cohort. 
 The number of lesions per subject plotted against PSA and baseline testosterone for 
each of the 3 central imaging core lab readers will no longer be performed. 
 SUVmax, SUVpeak, SUVr will no longer be summarized by subgroups: Previous 
radiation therapy (yes/no), Previous hormonal therapy (yes/no), or Previous 
chemotherapy (yes/no).  Most subjects will be from cohort B only. 
 Sensitivity will no longer be summarized by previous radiation therapy, previous 
hormonal therapy or previous chemotherapy.  Since it is no longer the primary 
endpoint and it’s not appropriate to combine cohorts for this analysis, it is no longer 
of interest. 
 The following was added for PK: Additional blood concentration time data will be 
fitted into a two-compartmental model to calculate T1/2-alpha and T1/2-beta.  For % of 
injected dose recovered per each urine collection interval per subject will be used to 
calculate Tmax, Rate max, Rate last, T1/2elim, and cumulative urine recovery if 
feasible. 
11. 
REFERENCES 
1. ICH E6: Good Clinical Practice: Consolidated Guidance 
2. ICH E9: Statistical Principles for Clinical Trials 
3. Fleiss, J. L.; Levin, B.; Paik, M.C. (2003). Statistical Methods for Rates and Proportions 
(3rd ed.). New York: John Wiley & Sons 
4. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, 3rd, Feldman HI, et al. A 
new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604-12 
5. Gwet, K.; Intrarater Reliability. Wiley Encyclopedia of Clinical Trials, Copyright 2008 
John Wiley & Sons, Inc. 


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6. Woolson, R.; Statistical Methods for the Analysis of Biomedical Data. Copywright 1987 
John Wiley & Sons, Inc. 
7. Fleiss, J. L., Nee, J. C. M., and Landis, J. R. Ž1979. The large sample variance of 
kappa in the case of different sets of raters. Psychol. Bull., 86, 974_977. 
 
 


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12. 
APPENDIX 
12.1. 
Table of Contents for Data Display Specifications 
Table 4 contains a list of tables, listings and figures proposed for this study.  
Table 4: 
List of Tables, Listings and Figures 
Number 
Title 
14.1-1 
Subject Enrollment and Disposition, Consented Subjects 
14.1.1:  Baseline Summaries – Safety Set 
14.1.1-1 
Demographics and Baseline Characteristics, Safety Set 
14.1.1-2 
Prostate Cancer History, Safety Set 
14.1.1-3 
Medical History, Safety Set 
14.1.1-4 
Prior Prostate Cancer Therapies, Safety Set 
14.1.1-5 
Prior Surgery, Safety Set 
14.1.1-6 
Conventional Imaging at Baseline, Safety Set 
14.1.1-7 
Baseline Medication Use, Safety Set 
14.1.2:  Baseline Summaries – Evaluable Set 
14.1.2-1 
Demographics and Baseline Characteristics, Evaluable Set 
14.1.2-2 
Prostate Cancer History, Evaluable Set 
14.1.2-3 
Medical History, Evaluable Set 
14.1.2-4 
Prior Prostate Cancer Therapies, Evaluable Set 
14.1.2-5 
Prior Surgery, Evaluable Set 
14.1.2-6 
Conventional Imaging at Baseline, Evaluable Set 
14.1.2-7 
Baseline Medication Use, Evaluable Set 
14.1.3:  Baseline Summaries – Per Protocol Set 
14.1.3-1 
Demographics and Baseline Characteristics, Per Protocol Set 
14.1.3-2 
Prostate Cancer History, Per Protocol Set 
14.1.3-3 
Medical History, Per Protocol Set 
14.1.3-4 
Prior Prostate Cancer Therapies, Per Protocol Set 
14.1.3-5 
Prior Surgery, Per Protocol Set 
14.1.3-6 
Conventional Imaging at Baseline, Per Protocol Set 
14.1.3-7 
Baseline Medication Use, Per Protocol Set 
14.2.1:  Primary Efficacy – Evaluable Set 
14.2.1-1 
Sensitivity and Specificity of the Pelvic Lymph Nodes for the Subjects in Cohort A, 
Evaluable Set 


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14.2.2:  Secondary Efficacy- Evaluable Set or PK Serum Set 
14.2.2-1 
Diagnostic Testing for Secondary Endpoints, Evaluable Set 
14.2.2-2 
Summary of Imaging Detection Rates for Lesion Counts by Region- Evaluable Set 
14.2.2-3 
Summary of Pharmacokinetic Parameters for Cycle 1, Day1- PK Blood Set 
14.2.3:  Exploratory Efficacy 
14.2.3-1 
SUV Responses at Baseline- Evaluable Set 
14.2.3-2 
SUVR Responses at Baseline – Evaluable Set 
14.2.3-3 
SUV Responses by Histology Outcomes- Evaluable Set 
14.2.3-4 
SUV Responses and Volume at Baseline by PSA Groups- Evaluable Set 
14.2.3-5 
SUV Responses and Volume at Baseline by Gleason Score Groups at Time of 
Prostatectomy- Evaluable Set 
14.2.3-6 
SUV Responses and Volume at Baseline by Testosterone Groups-Evaluable Group 
14.2.3-7 
Specificity and Sensitivity of the Prostate Gland for Cohort A- Evaluable Set 
14.2.3-8 
Shift in Change of Management Questionnaire- Safety Set 
14.2.3-9 
Analysis of Change in Management Questionnaire- Safety Set 
14.2.3-10 
PPV and Positive Imaging from any tissue compared to histology for both Cohorts 
Combined -Change in Management Set 
14.2.3-11 
Summary of Imaging Results-Safety Set 
14.2.3-12 
Summary of Histology Results- Safety Set 
14.2.3-13 
Summary of Procedures- Safety Set 
14.2.3-14 
Inter-Reader and Intra-Reader Variability for Cohort A- Evaluable Set 
14.2.4:  Efficacy- Per Protocol Set 
14.2.4-1 
Specificity and Sensitivity of the Pelvic Lymph Nodes for the Subjects in Cohort A- Per-
Protocol Set 
14.3.1:  Adverse Events- Safety Set 
14.3.1-1 
Summary of Treatment Emergent Adverse Events, Overall and by Cohort -Safety Set 
14.3.1-2 
Most Frequent (>5% Overall) Treatment Emergent Adverse Events, Overall and by Cohort- 
Safety Set 
14.3.1-3 
Treatment Emergent Adverse Events Overall and by Cohort- Safety Set 
14.3.1-4 
Serious Treatment Emergent Adverse Events Overall and by Cohort- Safety Set 
14.3.1-5 
Drug Related Treatment Emergent Adverse Events Overall and by Cohort- Safety Set 
14.3.1-6 
Treatment Emergent Adverse Events where Severity Grade>=3, Overall and by Cohort- 
Safety Set 
14.3.1-7 
Treatment Emergent Adverse Events by Severity Grade, Overall – Safety Set 


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14.3.2:  Listing of Deaths and Other Serious and Significant Adverse Events- Safety Set 
14.3.1-1 
Listing of Treatment Emergent Adverse Event Leading to Discontinuation or Death- Safety 
Set 
14.3.1-2 
Listing of Treatment Emergent Adverse Events Deemed Serious or With a Grade 3 or 
Above- Safety Set 
14.3.4:  Abnormal Laboratory Value Listing 
14.3.4-1 
Listing of Abnormal Hematology Results – Safety Set 
14.3.4-2 
Listing of Abnormal Chemistry Results- Safety Set 
14.3.5:  Vital Signs 
14.3.5-1 
Summary and Change from Baseline in Vital Signs- Safety Set 
14.3.6:  Other Safety Data 
14.3.6-1 
Summary and Change from Baseline in Hematology Results- Safety Set 
14.3.6-2 
Summary and Change from Baseline in Chemistry Results- Safety Set 
14.3.6-3 
Clinical Laboratory Shift Table: Chemistry- Safety Set 
14.3.6-4 
Clinical Laboratory Shift Table: Hematology- Safety Set 
14.3.6-5 
Summary and Change from Baseline in ECG Parameters- Safety Set 
14.3.6-6 
Concomitant Medications- Safety Set 
14.3.6-7 
Study Drug Exposure- Safety Set 
14.4:  PK Evaluations 
14.4-1 
Percent of Dose Recovered in Urine per Collection Interval -PK Urine Set 
14.4-2 
Summary of Urinary Kinetics- PK Urine Set 
Listings 
16.2.1-1 
Listing of Discontinuations – Consented Population 
16.2.2-1 
Listing of Protocol Deviations – Safety Set 
16.2.3-1 
Listing of Subjects Excluded from the Evaluable Set Used for Efficacy- Safety Set 
16.2.4-1 
Listing of Demographics- Consented Set 
16.2.5-1 
Listing of Blood PK by Nominal Blood Draw Times – PK Blood Set 
16.2.5-2 
Listing of Plasma PK by Nominal Blood Draw Times- PK Blood Set 
16.2.5-3 
Listing of Blood PK Parameters- PK Blood Set 
16.2.5-4 
Listing of Urinary Kinetics- PK Urine Set 
16.2.5-5 
Listing of Urine PK by Collection Intervals- PK Urine Set 
16.2.5-6 
Listing of Decay Corrected Dose – Safety Set 
16.2.5-7 
Listing of Compliance- Safety Set 
16.2.6-1 
Listing of Diagnostic Performance – Evaluable Set 


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16.2.7-1 
Listing of Adverse Events- Safety Population 
16.2.8-1 
Listing of Laboratory Parameters- Safety Set 
Figures 
14.4.1 
PK Concentrations by Nominal Time- PK Blood Set