A Multicenter, Open-Label, Exploratory Platform Study to Evaluate Biomarkers and Immunotherapy Combinations for the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer
Phase: PHASE1
Conditions: Metastatic Castration-resistant Prostate Cancer
Sponsor: Parker Institute for Cancer Immunotherapy

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1
 
 
Protocol Title:  A Multicenter, Open-Label, Exploratory Platform Study to Evaluate Biomarkers 
and Immunotherapy Combinations for the Treatment of Patients with Metastatic Castration-
resistant Prostate Cancer 
Appendix Cohort C 
Protocol Number:  PICI0033 
Amendment Number:  1 
Compound Number:  CDX-301, INO-5151, Nivolumab 
Short Title:  Platform Study for Prostate Researching Translational Endpoints Correlated to 
Response to Inform Use of Novel Combinations (PORTER) 
Sponsor Name and Legal Registered Address:   
Parker Institute for Cancer Immunotherapy 
1 Letterman Drive 
Suite D3500 
San Francisco, CA 94129 
Tel: 415-985-7311 
 
Regulatory Agency Identifying Number(s):  
IND NUMBER: 18853 
EudraCT NUMBER:  Not applicable 
Approval Date:  Final Protocol: 26 February 2019 
 
Amendment 1: 30 April 2019 
 
CONFIDENTIAL 
This document and its contents are the property of and confidential to Parker Institute for Cancer 
Immunotherapy. Any unauthorized copying or use of this document is prohibited. 
 
 

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INVESTIGATOR PROTOCOL AGREEMENT PAGE 
I agree: 
• 
To assume responsibility for the proper conduct of the study at this site. 
• 
To conduct the study in compliance with this protocol, any future amendments, and with 
any other study conduct procedures provided by Parker Institute for Cancer 
Immunotherapy. 
• 
Not to implement any changes to the protocol without written agreement from Parker 
Institute for Cancer Immunotherapy and prior review and written approval from the 
Institutional Review Board or Independent Ethics Committee except where necessary to 
eliminate an immediate hazard to participants. 
• 
That I am thoroughly familiar with the appropriate use of the study drug(s), as described 
in this cohort appendix and any other information provided by Parker Institute for Cancer 
Immunotherapy including, but not limited to, the current Investigator’s Brochure(s). 
• 
That I am aware of, and will comply with, the International Conference on 
Harmonisation for Good Clinical Practices (GCP) and all applicable regulatory 
requirements. 
• 
To ensure that all persons assisting me with the study are adequately informed about the 
study drugs, the Parker Institute for Cancer Immunotherapy study protocol, and of their 
study-related duties and functions as described in the protocol. 
• 
That I agree that persons debarred from conducting or working on clinical studies by any 
court or regulatory agency will not be allowed to conduct or work on studies for the 
Parker Institute for Cancer Immunotherapy or for a partnership in which the Parker 
Institute for Cancer Immunotherapy is involved, and that I will immediately disclose in 
writing to the Parker Institute for Cancer Immunotherapy if any person who is involved 
in the study is debarred, or if any proceeding for debarment is pending. 
 
 
Signature: 
 
 
Date: 
 
 
Name 
(print): 
 
  
 
Site 
Number: 
Principal Investigator 
 
___________ 
  
 
 
  
 

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Amendment(s) to Appendix Cohort C 
Text revisions resulting from the amendment(s) are incorporated in the synopsis and body of the 
Appendix Cohort Amendment. Major changes to the appendix cohort are summarized below. 
Key Revisions in Amendment 1 (30 April 2019) 
Section # and Name 
Description of Change 
Study Design 
1.2 Schema, Figure 1 
Modified to improve identification of key research procedure time points. 
1.3 Schedule of Activities 
Updated collection schedule for circulating tumor cells and cfDNA to 
remove complexity in collection timing and amount of material collected 
from participants. 
Study Intervention 
6.6.1 Dose Modifications for 
CDX-301, INO-5151, and 
Nivolumab 
Added text stating enrollment for the initial 6 participants will be split 
into 2 groups (of 3 participants each) separated by an 8 week enrollment 
hold to allow for safety monitoring with this first-in-human combination. 
Additionally, a second 8 week enrollment hold will follow the second 
group enrolled to continue monitoring for safety risks before the 
remaining participants are enrolled. 
Clarification of Document 
General Revisions 
Document updated to address minor typographical errors and editorial 
changes for clarity. 
 
 

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TABLE OF CONTENTS 
 
TABLE OF CONTENTS .................................................................................................................4 
LIST OF TABLES ...........................................................................................................................8 
LIST OF FIGURES .........................................................................................................................8 
1 
PROTOCOL SUMMARY ...................................................................................................9 
1.1 
SYNOPSIS ...............................................................................................................9 
1.2 
SCHEMA ...............................................................................................................10 
1.3 
SCHEDULE OF ACTIVITIES..............................................................................12 
2 
INTRODUCTION .............................................................................................................17 
2.1 
STUDY RATIONALE ..........................................................................................17 
2.2 
BACKGROUND ...................................................................................................17 
2.2.1 
Background on INO-5151 (PSA, PSMA, Interleukin-12) DNA Delivered 
via Intramuscular Electroporation (Inovio Pharmaceuticals) ..................18 
2.2.1.1 
PSA and PSMA Immunotherapy ...........................................18 
2.2.1.2 
Interleukin-12 Plasmid with DNA Vaccines .........................20 
2.2.1.3 
Rationale for Use of Electroporation .....................................21 
2.2.2 
Background on rhuFLT3L/CDX-301 (Celldex Therapeutics, Inc.) ........22 
2.2.3 
Background on Nivolumab (Bristol-Myers Squibb Company) ...............24 
2.2.4 
Rationale for CDX-301 + INO-5151 + Nivolumab Immunotherapy 
Combination ............................................................................................24 
2.3 
BENEFIT/RISK ASSESSMENT ..........................................................................28 
3 
OBJECTIVES AND ENDPOINTS ...................................................................................30 
4 
STUDY DESIGN...............................................................................................................31 
4.1 
OVERALL DESIGN .............................................................................................31 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN ...........................................31 
4.3 
JUSTIFICATION FOR DOSE ..............................................................................31 
4.3.1 
Rationale for Nivolumab Dose and Schedule .........................................32 
4.3.2 
Rationale for INO-5151 Dose and Schedule ...........................................33 
4.3.3 
Rationale for CDX-301 Dose and Schedule ............................................33 
4.4 
TREATMENT BEYOND DISEASE PROGRESSION ........................................34 
4.5 
END OF STUDY DEFINITION ...........................................................................34 
5 
STUDY POPULATION ....................................................................................................35 

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5.1 
INCLUSION CRITERIA.......................................................................................35 
5.1.1 
Common Inclusion Criteria .....................................................................35 
5.1.2 
Combination-specific Inclusion Criteria .................................................37 
5.2 
EXCLUSION CRITERIA .....................................................................................37 
5.2.1 
Common Exclusion Criteria ....................................................................37 
5.2.2 
Combination-specific Exclusion Criteria ................................................39 
5.3 
LIFESTYLE CONSIDERATIONS .......................................................................39 
5.4 
SCREEN FAILURES ............................................................................................39 
6 
STUDY INTERVENTION ................................................................................................39 
6.1 
STUDY INTERVENTION(S) ADMINISTERED ................................................39 
6.1.1 
Investigational Device .............................................................................41 
6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY ......................41 
6.3 
RANDOMIZATION AND BLINDING................................................................41 
6.4 
STUDY INTERVENTION COMPLIANCE .........................................................41 
6.5 
CONCOMITANT THERAPY...............................................................................42 
6.5.1 
Permitted Therapy ...................................................................................42 
6.5.2 
Prohibited Therapy ..................................................................................42 
6.6 
DOSE MODIFICATIONS ....................................................................................42 
6.6.1 
Dose Modifications for CDX-301, INO-5151, and Nivolumab ..............42 
6.6.1.1 
Potential for Overlapping Toxicities with CDX-301, INO-
5151, and Nivolumab ............................................................44 
6.6.1.2 
Dose Modifications and Toxicity Management for Adverse 
Events Associated with CDX-301, INO-5151, and Nivolumab
 ...............................................................................................45 
6.6.1.3 
Dose Modifications and Toxicity Management for 
Infusion/Injection-related Reactions Associated with the 
Administration of CDX-301, INO-5151, and/or Nivolumab 46 
6.6.1.4 
Dose Delays and Interruptions of CDX-301, INO-5151, and 
Nivolumab .............................................................................48 
6.6.2 
Dose Modifications for Nivolumab .........................................................48 
6.6.3 
Dose Modifications for INO-5151 ..........................................................50 
6.6.4 
Dose Modifications for CDX-301 ...........................................................50 
7 
DISCONTINUATIONS OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL..........................................................................51 
7.1 
DISCONTINUATION OF STUDY INTERVENTION ........................................51 

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7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM STUDY ........51 
7.3 
LOST TO FOLLOW-UP .......................................................................................52 
8 
STUDY ASSESSMENTS AND PROCEDURES .............................................................52 
8.1 
EFFICACY ASSESSMENTS ...............................................................................52 
8.1.1 
Laboratory Assessments of Clinical Activity ..........................................52 
8.2 
SAFETY ASSESSMENTS ....................................................................................52 
8.2.1 
Clinical Safety Laboratory Assessments .................................................52 
8.2.1.1 
Local Laboratory Assessments ..............................................52 
8.3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS ..............................53 
8.3.4 
Regulatory Reporting Requirements for SAEs .......................................53 
8.3.7 
Adverse Events of Special Interest ..........................................................54 
8.4 
TREATMENT OF OVERDOSE ...........................................................................54 
8.5 
PHARMACOKINETICS .......................................................................................54 
8.6 
IMMUNOGENICITY AND ANTI-DRUG ANTIBODIES ..................................54 
8.7 
BIOMARKERS .....................................................................................................54 
8.8 
MEDICAL RESOURCE UTILIZATION AND HEALTH ECONOMICS ..........54 
9 
STATISTICAL CONSIDERATIONS...............................................................................54 
9.5.1 
Interim Safety Monitoring .......................................................................55 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ....56 
10.1 
APPENDIX C-1: MANAGEMENT ALGORITHMS ..........................................57 
10.2 
APPENDIX C-2: LISTS OF TERMINOLOGY AND ABBREVIATIONS .........65 
10.2.1 
List of Terminology .................................................................................65 
10.2.2 
List of Abbreviations ...............................................................................65 
10.3 
APPENDIX C-3: APPENDIX COHORT C AMENDMENT HISTORY ............69 
11 
REFERENCES ..................................................................................................................70 
 

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LIST OF TABLES 
Table 1: 
Schedule of Activities ............................................................................................13 
Table 2 
Adverse Events Reported in Studies of Inovio DNA Delivered IM with 
Electroporation Occurring in at Least 5% of Subjects ...........................................22 
Table 3: 
Clinical Studies Supporting the Co-administration of Components of this Study 
Intervention ............................................................................................................27 
Table 4: 
Cohort-Specific Objectives and Corresponding Endpoints ...................................30 
Table 5: 
Study Intervention ..................................................................................................39 
Table 6: 
Toxicity Criteria Requiring Permanent Treatment Discontinuation ......................44 
Table 7:  
Dose Modification and Toxicity Management Guidelines for Infusion/Injection-
related Reactions Associated with the Administration of CDX-301, INO-5151, 
and/or Nivolumab ..................................................................................................47 
Table 8: 
Dose Modification and Toxicity Management Guidelines for Adverse Events 
Associated with Nivolumab ...................................................................................49 
Table 9: 
Dose Modification and Toxicity Management Guidelines for Adverse Events 
Associated with CDX-301 .....................................................................................51 
Table 10: 
Laboratory Tests Sent to the Study Site’s Local Laboratory for Analysis of 
Disease-related Endpoints ......................................................................................52 
Table 11: 
Laboratory Tests Sent to the Study Site’s Local Laboratory for Analysis of Safety
................................................................................................................................53 
Table 12: 
Probability of Proceeding to Full Enrollment ........................................................55 
Table 13: 
Incidence with 95% Confidence Intervals of Possible Observed Adverse Events 
Described in Table 6 ..............................................................................................55 
 
 
LIST OF FIGURES 
Figure 1: 
Study Schema.........................................................................................................11 
 

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1 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS 
Protocol Title: 
A Multicenter, Open-Label, Exploratory Platform Study to Evaluate Biomarkers and 
Immunotherapy Combinations for the Treatment of Patients with Metastatic Castration-resistant 
Prostate Cancer 
Appendix Cohort C 
Short Title: 
Platform Study for Prostate Researching Translational Endpoints Correlated to Response to 
Inform Use of Novel Combinations (PORTER) 
Note to Investigators:  This cohort appendix is intended to supplement the core protocol, and as 
such, will focus on combination-specific (CDX-301, INO-5151, and nivolumab) information that 
is not already available in the core protocol. 
Rationale: 
This study cohort is designed to explore a multi-pronged approach to stimulate antitumor 
immunity by enhancement of a deoxyribonucleic acid (DNA) vaccination targeting prostate 
cancer tumor antigens through electroporation (EP), cytokine adjuvants, mobilization and 
activation of dendritic cells (DCs), and relieving immune suppression of cytotoxic T cells by 
administration of an anti-programmed cell death 1 (PD-1) monoclonal antibody (mAb) in 
metastatic castration-resistant prostate cancer (mCRPC): 
• Flt-3 ligand (CDX-301) to induce mobilization, activation and/or expansion of DCs 
• DNA vaccine INO-5151 encoding human prostate-specific membrane antigen (PSMA), 
human prostate-specific antigen (PSA), and human interleukin-12 (IL-12) to stimulate 
antitumor-directed CD8 T-cell responses to castration-resistant prostate cancer (CRPC)-
specific tumor antigens 
• Anti-PD-1 mAb (nivolumab) to overcome immune suppression of tumoral T cells 
 
Objectives and Endpoints: 
Refer to the core protocol. 
Combination-specific exploratory objectives include: 

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Combination-specific Exploratory Objectives 
Endpoints 
• To evaluate the PK of CDX-301 and/or nivolumab. 
• To evaluate the immunogenicity of INO-5151, 
CDX-301, and/or nivolumab. 
• Sparse PK analysis. 
• Presence of immune response against PSA and/or 
PSMA 
• ADA against CDX-301 and/or nivolumab. 
ADA = anti-drug antibodies; IL-12 = interleukin-12; PK = pharmacokinetics; PSA = prostate-specific antigen; 
PSMA = prostate-specific membrane antigen 
 
Overall Design, Number of Participants, Follow-up, and Data Monitoring Committee: 
Refer to the core protocol. 
Intervention Groups and Duration: 
Participants will be assigned to receive one of the enrolling immunotherapy combination study 
interventions. In this cohort, participants will receive CDX-301, INO-5151, and nivolumab as 
follows: 
Intervention 
Dose 
Frequency 
Route 
Schedule 
CDX-301 
75 µg/kg 
QD x 5 days x 2 
(ie, twice) 
SC 
Immune-priming Lead-in 
Days 1-5 and 22-26 
INO-5151 
3 mg 
Immune-priming 
dose, followed by 
 
Q4W x 3 doses,  
then Q12W 
IM followed by EP 
Day 8 of 
Immune-priming Lead-in 
 
Starting Day 1 of Cycle 1a 
Nivolumab 
480 mg 
Q4W 
IV over 30 minutes 
Starting Day 1 of Cycle 1 
IV = intravenous(ly); IM = intramuscular(ly); EP = electroporation; QD = daily; Q4W = every 4 weeks; 
Q12W = every 12 weeks; SC = subcutaneous(ly) 
a Day 1 of Cycle 1 follows 1 week after Day 22 of the Immune-priming Lead-in 
 
CDX-301 will be administered during the Immune-priming Lead-in only. INO-5151 and 
nivolumab will be administered for up to 2 years, unless the participant: is no longer clinically 
benefiting (as evidenced by symptomatic or radiographic disease progression and/or clinical 
deterioration); experiences any toxicity meeting specified discontinuation criteria (see Section 
6.6) or unacceptable toxicity in the best clinical discretion of the treating physician (ie, 
Investigator discretion); reaches the maximum duration of study intervention; or withdraws 
consent. In this cohort, a cycle is defined as 4 calendar weeks. 
1.2 
SCHEMA 
The study schema is depicted in Figure 1. 

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Figure 1: 
Study Schema 
 
EP = electroporation; IM = intramuscularly; IV = intravenously; mCRPC = metastatic castration-resistant prostate cancer; Q4W = every 4 weeks; 
Q12W = every 12 weeks; SC = subcutaneously 
Note: The horizontal axis is not linearly scaled, so the interval for Immune-priming Lead-in appears to be much longer than for the subsequent cycles. 
a INO-5151 will be administered IM followed by EP. 
b Day 1 of Cycle 1 follows 1 week after Day 22 of the Immune-priming Lead-in. 
CDX-301 will be administered during the Immune-priming Lead-in only. INO-5151 and nivolumab will be administered for up to 2 years, unless the 
participant: is no longer clinically benefiting (as evidenced by symptomatic or radiographic disease progression and/or clinical deterioration); experiences any 
toxicity meeting specified discontinuation criteria (see Section 6.6) or unacceptable toxicity in the best clinical discretion of the treating physician; reaches the 
maximum duration of study intervention; or withdraws consent. A cycle is defined as 4 calendar weeks. Participants will be followed for up to 2.5 years from 
the time of the initiation of study intervention. 
This study design is applicable to Stage 1, as well as Stage 2 if the cohort is expanded. 

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1.3 
SCHEDULE OF ACTIVITIES 
The Schedule of Activities (SOA) shown in Table 1 is specific for this combination and 
supersedes the SOA provided in the core protocol. 

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Table 1: 
Schedule of Activities 
Tests & Procedures 
Screening/ 
Enrollmenta 
On-Treatment: CDX-301 + INO-5151 + Nivolumab 
End of 
Treatment 
Visitc 
Follow up 
Immune-priming Lead-in 
Cycle 1b (Q4W) 
Cycles 
2,3, and 4 
Cycle 5 
Onward 
Day 
Day -28 to 
Day -1 
Days 
1 - 5  
Day 
8 
Day 
15 
Days 
22 - 26 
Day 1 
Day 8 
Day 1 
Day 1 
14 - 28 
days after 
last dose 
110 days 
after last 
dose 
Q3Md 
Window (days) 
-28 
 
 
± 1 
± 1 
± 1 
± 1 
± 3 
± 3 
± 7 
± 10 
± 14 
Informed consente 
X 
 
 
 
 
 
 
 
 
 
 
 
Review of I/E criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical/cancer history 
X 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
X 
 
 
 
X 
 
X 
X 
X 
 
 
ECOG performance 
status 
X 
X 
 
 
 
X 
 
X 
X 
X 
X 
 
Vital signs (see Core 
Protocol Section 8.2.3) 
X 
X 
 
 
 
X 
 
X 
X 
X 
 
 
Body weight 
X 
X 
X 
X 
X 
X 
 
X 
X 
(Cycles 5, 
8, 11, 14, 
17, 20, 23, 
and 26) 
X 
 
 
Hematology (see Table 
11) 
X 
Xf 
(Day 1) 
Xf 
X 
Xf 
(Day 22) 
Xf 
X 
Xf 
Xf 
X 
X 
 
Clinical chemistry (see 
Table 11) 
X 
Xf 
(Day 1) 
Xf 
X 
Xf 
(Day 22) 
Xf 
X 
Xf 
Xf 
X 
X 
 
Urinalysis 
X 
 
 
 
 
 
 
 
 
X 
 
 
Prostate-specific 
antigen 
X 
X 
(Day 1) 
 
 
X 
(Day 22) 
X 
 
X 
X 
X 
X 
 
Testosterone level 
X 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECG 
X 
 
 
 
 
 
 
X 
(Cycles 2 
and 4) 
 
 
 
 

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Tests & Procedures 
Screening/ 
Enrollmenta 
On-Treatment: CDX-301 + INO-5151 + Nivolumab 
End of 
Treatment 
Visitc 
Follow up 
Immune-priming Lead-in 
Cycle 1b (Q4W) 
Cycles 
2,3, and 4 
Cycle 5 
Onward 
Day 
Day -28 to 
Day -1 
Days 
1 - 5  
Day 
8 
Day 
15 
Days 
22 - 26 
Day 1 
Day 8 
Day 1 
Day 1 
14 - 28 
days after 
last dose 
110 days 
after last 
dose 
Q3Md 
Window (days) 
-28 
 
 
± 1 
± 1 
± 1 
± 1 
± 3 
± 3 
± 7 
± 10 
± 14 
Circulating tumor cellsg 
 
Xf 
(Day 1) 
 
 
 
Xf 
 
Xf 
Xf 
X 
 
 
cfDNA (blood)h 
 
 
 
 
 
Xf 
 
Xf (Cycles 
2, 3, and 4) 
 
X 
 
 
Circulating soluble 
analytes/PK/ADAi 
X 
Xf 
(Day 1, 
Day 5) 
Xf 
Xf 
Xf 
(Day 26) 
Xf 
Xf 
Xf (Cycles 
2, 3, and 4) 
 
X 
X 
 
Blood immune 
biomarkersi 
X 
Xf 
(Day 1, 
Day 5) 
Xf 
Xf 
Xf 
(Day 26) 
Xf 
Xf 
Xf (Cycles 
2, 3, and 4) 
 
X 
 
 
Archival tumor tissue 
X 
 
 
 
 
 
 
 
 
 
 
 
Tumor biopsyj 
X 
 
 
 
 
 
 
X 
(Cycle 2) 
 
X (at PD 
[optional])j 
 
 
Stool collectionk 
X 
 
 
 
 
 
 
X 
(Cycle 2)k 
 
 
 
 
Concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Adverse events 
All AEs and SAEs will be collected for at least 100 days after the last dose of study interventionl 
 
CDX-301 
administrationm 
 
X 
 
 
X 
 
 
 
 
 
 
 
INO-5151 
administrationn 
 
 
X 
 
 
X 
 
X 
(Cycles 
2 and 3) 
X 
(Cycles 6, 
9, 12, 15, 
18, 21, 
and 24) 
 
 
 

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Tests & Procedures 
Screening/ 
Enrollmenta 
On-Treatment: CDX-301 + INO-5151 + Nivolumab 
End of 
Treatment 
Visitc 
Follow up 
Immune-priming Lead-in 
Cycle 1b (Q4W) 
Cycles 
2,3, and 4 
Cycle 5 
Onward 
Day 
Day -28 to 
Day -1 
Days 
1 - 5  
Day 
8 
Day 
15 
Days 
22 - 26 
Day 1 
Day 8 
Day 1 
Day 1 
14 - 28 
days after 
last dose 
110 days 
after last 
dose 
Q3Md 
Window (days) 
-28 
 
 
± 1 
± 1 
± 1 
± 1 
± 3 
± 3 
± 7 
± 10 
± 14 
Nivolumab 
administrationo 
 
 
 
 
 
X 
 
X 
X 
 
 
 
Radiographic disease 
assessment 
X 
 
 
 
 
 
 
X (prior 
to 
Cycle 3) 
At Week 8 (± 1 week), repeat every 8 weeks (± 1 
week) for the first 24 weeks, and every 12 weeks 
(± 1 week) thereafter until radiographic PD or 
start of subsequent therapy 
Review of alternate 
anticancer therapyp 
 
 
 
 
 
 
 
 
 
 
X 
X 
Follow up for overall 
survival 
 
 
 
 
 
 
 
 
 
 
X 
X 
ADA = anti-drug antibodies; AE(s) = adverse event(s); cfDNA = cell-free deoxyribonucleic acid; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; 
EOT = end of treatment; EP = electroporation; I/E = inclusion/exclusion; IV = intravenously; PD = progressive disease; PK = pharmacokinetics; Q3M = every 3 months; 
Q4W = every 4 weeks; QD = daily; SAE(s) = serious adverse event(s); SC = subcutaneously 
a Tests/procedures performed as standard of care prior to obtaining informed consent and within 28 days prior to the first dose of study intervention do not have to be repeated at 
screening. 
b Day 1 of Cycle 1 follows 1 week after Day 22 of the Immune-priming Lead-in. 
c The End of Treatment Visit will be completed following the last dose of study intervention, either at the completion of the on-treatment phase or at early discontinuation. 
d For up to 2.5 years from the initiation of study intervention, participants in the follow up phase will be contacted by the site to collect alternate anticancer therapy information 
and determine survival status. 
e Informed consent must be obtained prior to any study-specific procedures and may be obtained prior to the 28-day screening window. 
f Blood samples should be collected prior to administration of any study intervention. 
g Circulating tumor cells will be collected at baseline (ie, Day 1 of the Immune-priming Lead-in prior to study intervention administration), Day 1 of each cycle (prior to study 
intervention administration), and EOT. 
h cfDNA (blood) will be collected Day 1 of Cycle 1-Cycle 4, and EOT. 
i Circulating soluble analytes, PK and ADA blood sample, and/or blood immune biomarkers will be collected at baseline (ie, screening and/or Day 1 of Cycle 1 prior to study 
intervention administration), prior to study intervention administration on Days 1. 5, 8, 15, and 26 of the Immune-priming Lead-in, Days 1 and 8 of Cycle 1, Day 1 of Cycles 2-4, 
at EOT, and the first follow up visit. 
j Participants will undergo 2-3 tumor biopsies: prior to beginning protocol therapy (ie, baseline biopsy, mandatory for all participants, including those with bone only disease if 
medically feasible), and during treatment (ie, on-treatment biopsy during Cycle 2, if medically feasible). On- treatment biopsy should occur as early as possible after the second 

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dose (Day 2 – Day 10 of Cycle 2); however, any on treatment biopsy after Day 1 of Cycle 2 will be accepted. An optional biopsy may be obtained at the time of disease 
progression, including from participants who respond and subsequently progress. Every attempt should be made for the on-treatment biopsies to be taken from the same lesion as 
the pre-treatment biopsy when feasible. 
k Stool will be collected at screening and during Cycle 2, if possible. Otherwise, any on-treatment stool sample will be acceptable. The stool sample may be collected at the clinic 
or at the participant’s home. 
l All SAEs will be collected from the time the participant signs informed consent. Prior to initiation of study intervention, only SAEs that are related to a protocol-mandated 
intervention, including those that occur prior to the assignment of study procedures should be reported. All AEs will be collected from the start of study intervention. All AEs 
and SAEs will be collected for at least 100 days after the last dose of study intervention. Refer to Section 8.3 of the core protocol for details regarding safety reporting for this 
study. 
m CDX-301 will be administered at a dose of 75 µg/kg subcutaneously (SC) QD x 5 days [ie, Monday – Friday] twice during the Immune-priming Lead-in (Days 1 – 5 and 
Days 22 – 26). 
n INO-5151 will be administered at a dose of 3 mg intramuscularly (IM) followed by EP on Day 8 of the Immune-priming Lead-in, Starting with Cycle 1, INO-5151 will be given 
on the same day as nivolumab on Day 1 of Cycle 1, Cycle 2, and Cycle 3, and every 12 weeks (ie, every 3 cycles) thereafter. A cycle is defined as 4 calendar weeks. 
o Nivolumab will be administered at a dose of 480 mg IV over 30 minutes Q4W starting on Day 1 of Cycle 1 and will continue for up to 2 years unless the participant: is no 
longer clinically benefiting (as evidenced by symptomatic or radiographic disease progression and/or clinical deterioration); experiences any toxicity meeting specified 
discontinuation criteria (see Section 6.6) or unacceptable toxicity in the best clinical discretion of the treating physician; reaches the maximum duration of study intervention; or 
withdraws consent. A cycle is defined as 4 calendar weeks. The time between nivolumab doses must not be less than 24 days. 
p Collection of information related to any post-study intervention alternate anticancer therapy. 
 

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2 
INTRODUCTION 
Refer to the core protocol. 
2.1 
STUDY RATIONALE 
Refer to the core protocol. 
2.2 
BACKGROUND 
Immune checkpoint blockade, particularly with programmed cell death 1 (PD-1) or programmed 
cell death ligand 1 (PD-L1) antibodies, has changed the landscape for the treatment of a variety 
of advanced solid tumors. Though the majority of patients with a specific tumor type don’t 
respond to treatment, a notable subset of patients across tumor types achieve durable responses 
in the context of relatively well tolerated therapy leading to the substantial enthusiasm for this 
therapeutic class. However, not only is there intra-tumor-type variability in the likelihood of 
response to PD-1/PD-L1 blockade but there is also substantial inter-tumor type heterogeneity 
(Yarchoan et al., 2017). Prostate cancer has been among the tumor types for which single-agent 
PD-1/PD-L1 blockade has been associated with relatively rare responses, and the responses that 
do occur are typically in the context of a genomically-defined subset of cancers (ie, mismatch 
repair deficient tumors) (Graff et al; 2016). Therefore, there is a critical need to develop rational 
combination strategies to extend the benefits of PD-1/PD-L1 blockade to patients with metastatic 
castration-resistant prostate cancer (mCRPC). Strategies that mobilize immune cells to the tumor 
microenvironment, stimulate cytotoxic CD8 T cells to recognize tumor specific antigens, and 
induce tumor cell killing offer a potential way to extend those benefits. 
Deoxyribonucleic acid (DNA) immunization has been recognized as a promising vaccine 
platform for almost 20 years for a number of reasons (Hokey and Weiner, 2006). Both DNA 
vaccines and various viral vector vaccines have been explored for diseases where a potent T-cell 
response may be required to achieve clinical improvement. Prophylactic and therapeutic DNA 
vaccines have generated immunogenicity that is similar to what has been achieved with viral 
vectors (Morrow and Weiner, 2010). Potent T-cell immune responses can be generated to 
virtually any antigenic sequence after antigen processing and presentation. Although traditional 
live attenuated and viral vector vaccines may also elicit potent T-cell responses, these viral 
approaches bear safety concerns associated with their vector backbone, which DNA vaccines 
should and do circumvent. In addition, as opposed to viral-based vaccines which carry a risk of 
mutation back to a virulent state or spread to unintended individuals, DNA vaccines are not 
based on an intact natural pathogen and therefore cannot revert to a virulent form. Finally, 
repeated dosing of viral-based vaccines may be hindered by neutralization of targeted viral 
vector sequences. The plasmid backbones of DNA vaccines are associated with virtually no 
immune response, thus allowing repeated dosing to increase or maintain the immune responses 

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against the DNA encoded antigen over long periods. Additionally, toxicology studies have found 
no evidence of genome integration as measured by polymerase chain reaction (PCR) in two 
previous studies of several DNA vaccine products (Sheets et al., 2006a; Sheets et al., 2006b) 
expressing a variety of inserts, such as human immunodeficiency virus (HIV), Ebola, severe 
acute respiratory syndrome (SARS), West Nile Virus and malaria antigens (INO-5151/INO-5150 
and INO-9012 Investigator’s Brochure, 2019). In contrast, pre-existing anti-vector immunity can 
reduce the immunogenicity and ability to utilize the viral vector for future immunizations. 
Finally, DNA vaccines are simple and relatively inexpensive to construct, are readily produced 
in large quantities, and are generally stable for long periods of time. These advantages make 
DNA-based immunization a desirable immune-based modality for the prevention or treatment of 
disease. 
2.2.1 
Background on INO-5151 (PSA, PSMA, Interleukin-12) DNA 
Delivered via Intramuscular Electroporation (Inovio 
Pharmaceuticals) 
2.2.1.1 
PSA and PSMA Immunotherapy 
Prostate-specific antigen (PSA) is a protein member of the kallikrein-related peptidase family 
and is secreted by the epithelial cells of the prostate gland. PSA is present in small quantities in 
the serum of normal men with healthy prostates, but is often elevated in the presence of prostate 
cancer or other prostate disorder (Williams et al., 2007). Serum PSA has been utilized as one 
prostate cancer biomarker in conjunction with other techniques for diagnosis, prognosis, prostate 
cancer disease recurrence and progression. Previous studies also indicate a role of PSA in the 
initiation and progression of prostate cancer, making it a potential functional target (Williams et 
al., 2007). 
Prostate specific membrane antigen (PSMA) is a multi-domain protein expressed in either an 
integral membrane or cytoplasmic form in a variety of cell types, including the neovasculature of 
several types of solid tumors. Further, PSMA expression is increased in prostate cancer cells as 
the disease progresses making it a highly relevant target for tumors that are diagnosed later in 
disease progression rather than earlier (Schmittgen et al, 2003). In a study examining 
intratumoral PSMA expression in 902 subjects at prostatectomy, Kasperzyk et al. found a 
positive association between PSMA levels and risk of lethal prostate cancer, which was not 
independent of the clinical parameters examined, and therefore, did not support the clinical 
utility of PSMA expression as a biomarker for lethal prostate cancer (Kasperzyk et al., 2013). 
Much like PSA, previous studies have indicated that PSMA is preferentially expressed in the 
prostate compared to normal tissues (Cunha et al., 2006). PSMA-specific T cell mediated 
responses can confer antitumor effects and an increase in the percentage of PSMA-specific T 

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cells producing interferon gamma (IFN-γ) correlates with clinical improvement in prostate 
cancer patients (Tjoa et al., 1999; Mincheff et al., 2001). 
In contrast to PSA, PSMA expression is more prevalent in extraprostatic tissues (Cunha et al., 
2006). PSMA messenger ribonucleic acid (mRNA) and protein expression have been found in 
both normal tissue and prostate cancer tissue by quantitative PCR and immunohistochemistry, 
respectively, although the actual levels and location of PSMA expression in normal tissue remain 
unclear (Cunha et al., 2006; Silver et al., 1997). Despite its reported limited extraprostatic 
expression, PSMA has also been reported in the brain, duodenum, colon, liver, proximal kidney 
tubules, and salivary gland (Horoszewicz et al., 1987; Israeli et al., 1994; Lopes et al., 1990; 
Luthi-Carter et al., 1998; Sácha et al., 2007). Cunha et al. found PSMA mRNA expression in the 
brain, liver and kidney, although the levels in these organs were approximately 12-18-fold less 
than the mRNA expression level in the prostate (Cunha et al., 2006). Silver et al. also reported 
PSMA immunoreactive tissue in prostate epithelium, kidney (luminal site of the proximal renal 
tubules), duodenum and colon (Silver et al., 1997). This study did not show any PSMA 
immunoreactivity in the brain as was shown by other groups, and the differentiated prostate 
tissue expression and over expression of PSMA in metastatic tissues support the study of this 
unique prostate tumor-associated biomarker for developing new strategies for immune therapy of 
prostate cancer. Because of its relevance in metastatic prostate cancer, this antigen has been 
targeted in a variety of both diagnostic evaluations (eg, PSMA positron emission tomography 
[PET]), as well as therapeutic targets such as antibody drug conjugates (ADC), vaccine therapies, 
and nanoparticles. 
Immunotherapy is a promising approach to develop tumor antigen-specific therapies for prostate 
cancer (Gulley and Drake, 2011; Troyer et al., 1995; Rice et al., 2008). In antigen-specific 
approaches, a tumor-associated antigen is directly targeted, either by loading that antigen onto 
antigen-presenting cells (APC) ex vivo or by incorporating the antigen into a vaccine cellular 
delivery system at a protein or DNA level. In the absence of immunotherapy, however, T-cell 
response to tumor antigens such as PSA are difficult to detect in patients, which indicates that 
some level of pre-existing tolerance may exist (Drake, 2010). 
Approximately 1,400 human subjects have been treated or are being enrolled in clinical trials to 
evaluate immunotherapy based on DNA or viral vectors that encode various prostate-specific 
antigens (INO-5151/INO-5150 and INO-9012 Investigator’s Brochure, 2019). While 
measurable, anti-prostate tumor-specific immunoglobulin has been difficult to detect, the T-cell 
antigen-specific activity has been measured somewhat consistently. Measurable tumor responses 
(National Prostate Cancer Project [NPCP] criteria) to these immunotherapies have also been 
reported. In general, safety and tolerability has been shown to be acceptable (Drake, 2010; Felici 

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et al., 2012). Local injection site reactions were the most common safety event observed. 
Additionally, cellular based vaccines were associated with acceptable systemic safety profile. 
In a recently-reported phase 1 study of 62 biochemically recurrent prostate cancer patients, 
INO-5150 (PSA and PSMA), with and without INO-9012 (interleukin-12 [IL-12] plasmid), was 
demonstrated to be safe and immunogenic, with observed humoral and cellular responses, 
including generation of functional antigen-specific CD8 T cells (Shore et al., 2018b). In addition, 
clinical activity was observed in the form of significantly increased PSA doubling times and 
reduced percent rise in PSA, which was significantly different in the patients with demonstrated 
immunogenicity to INO-5150 (Shore et al., 2018a; Shore et al., 2018b).The INO-5151 to be used 
in this clinical trial is a single-vial combination of INO-5150 and INO-9012, which will facilitate 
administration. 
Refer to the Investigator’s Brochure (IB; INO-5151/INO-5150 and INO-9012 Investigator’s 
Brochure, 2019) for additional background information. 
2.2.1.2 
Interleukin-12 Plasmid with DNA Vaccines 
IL-12 is an immune cytokine that is produced by dendritic cells (DCs), macrophage, neutrophils, 
and B cells in response to antigen stimulation. IL-12 plays an important role in the eliciting 
effective immune responses through activation of antigen-presenting activity of DCs and 
promoting the cytotoxic activity of CD8 T cells and natural killer (NK) cells. Thus, IL-12 is an 
important cytokine in promoting an antitumor immune response. Given its immunomodulatory 
and additionally anti-angiogenic function, recombinant IL-12 has been evaluated in clinical 
studies as an anti-cancer agent. A review of clinical applications of recombinant IL-12 lists 17 
separate clinical studies conducted in more than 500 patients with advanced solid tumors and 
various hematologic malignancies (Del Vecchio et al., 2007). Recombinant human IL-12 
(rhIL-12) has been evaluated both as monotherapy and in combination with vaccines, other 
cytokines, or antitumor monoclonal antibodies in these clinical studies. Systemic delivery of 
rhIL-12 protein can cause significant toxicity (Gollob et al., 2000). In contrast, IL-12 DNA 
therapy has minimal toxic effects in non-human primates and human subjects (Shore et al., 
2018a; Shore et al., 2018b; Schadeck et al., 2006; Boyer et al., 2005; Chong et al., 2007; Kalams 
et al., 2012; Kalams et al., 2013; Daud et al., 2008). In a recent human trial, the combination of 
INO-5150 ± INO-9012 was shown to be safe, well tolerated and immunogenic (Shore et al., 
2018a; Shore et al., 2018b). 
In preclinical studies, use of IL-12 plasmid with DNA vaccines has been shown to substantially 
increase the immunogenicity of DNA vaccines (Hanlon et al., 2001; Kim et al., 1998a; Kutzler et 
al., 2005; Operschall et al., 1999; Chattergoon et al., 2004; Egan et al., 2006; Kim et al., 1998b; 
Calarota and Weiner, 2004; Umemura et al., 2001). Co-administration of cytokine plasmids with 
DNA vaccines has been studied in rodents (Kim et al., 1997) and have demonstrated a dramatic 

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increase in specific cytotoxic T-lymphocyte (CTL) activity and provides the basis for evaluation 
of INO-5151 in the proposed clinical trial. These preclinical studies demonstrated a dramatic 
increase in specific CTL activity when plasmid DNA was co-administered with an IL-12 
plasmid, as compared with results in animals receiving plasmid alone (Chattergoon et al., 2004; 
Egan et al., 2006; Kim et al., 1998b; Calarota and Weiner, 2004). In summary, DNA vaccine 
administration in combination with IL-12 DNA has been shown to be generally safe and well 
tolerated, and possibly more immunogenic, although further studies need to be done (Kalams et 
al., 2013). 
2.2.1.3 
Rationale for Use of Electroporation 
Several groups are developing methods to improve the immune responses of DNA vaccines 
using genetic optimization (including use of highly concentrated DNA formulations, multiple 
ribonucleic acid (RNA) optimizations and addition of improved leader sequences), cytokine 
adjuvants, and alternative cellular delivery (ie, electroporation [EP]) (Kutzler and Weiner, 2008). 
The approach being studied in this trial employs all these methods with delivery of IL-12 as an 
immune cytokine and an emphasis on improving the transfection of DNA using EP. EP is the 
application of a localized electrical field at the site of injection to facilitate cell uptake of DNA 
by permeabilizing cell membranes and may also induce local inflammation (Kutzler and Weiner, 
2008; Sardesai and Weiner, 2011). This physical process exposes the target tissue to a brief 
electric field pulse that induces temporary and reversible pores in the cell membrane to enhance 
the cellular uptake of large molecules such as DNA. By temporarily increasing the permeability 
of cell membranes, EP has been shown to be an efficient way to introduce DNA into cells 
(Aihara and Miyazaki, 1998; Gehl and Mir, 1999) and to increase the expression level of 
antigens encoded by DNA (Hirao et al., 2008). The EP technology has been used for more than 
three decades by molecular biologists for in vitro cell transfection. Clinical applications of EP 
have been used in human studies of gene therapy and more recently in cancer (Sardesai and 
Weiner, 2011). 
The hypothesis is that EP will increase the uptake and expression of plasmid DNA (pDNA), 
generating significantly increased immunogenicity. Electroporation enhances both cellular and 
humoral immune responses, using less DNA than intramuscular immunizations alone (Schoenly 
and Weiner, 2008). Studies have demonstrated the ability of EP to augment specific cellular 
immune responses in mice (Liu et al., 2008) and in macaques (Luckay et al., 2007). Luckay et al. 
found that delivering simian immunodeficiency virus (SIV) DNA vaccines intramuscularly (IM) 
followed by EP increased the potency of these vaccines 50-200 fold (Luckay et al., 2007). There 
are various means of delivering EP (ie, constant current vs. constant voltage) and testing these 
strategies in mice and pigs has shown a constant current device may be the most effective at 
generating immune responses (Draghia-Akli et al., 2008). Studies in macaques found that EP of 

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SIV DNA + IL-12 plasmids yielded 10-fold higher responses than DNA injections without EP 
(Hirao et al., 2008), and that this immune response was boosted with additional doses. The 
magnitude of achievable responses is similar to that seen with natural SIV infection, in the order 
of 10,000 spot forming units (SFU)/million peripheral blood mononuclear cells (PBMC) in an 
enzyme-linked immunospot (ELISpot) assay. These responses are also polyfunctional, as defined 
by the ability of immune cells from treated animals to generate IFN-γ, tumor necrosis factor 
alpha (TNF-α) and interleukin-2. Furthermore, the functional consequence of EP delivery of 
DNA encoding an antigen in combination with IL-12 includes an improved ability of specific 
CD8+ T-cells to proliferate in cell culture in response to antigenic stimulation compared to 
delivery without EP (Hirao et al., 2008). 
As of 30-Jun-2018, 3,319 doses had been administered to 1,096 subjects via the CELLECTRA® 
2000 by either IM or intradermal administration. Among subjects who received PSA, PSMA, 
and plasmids with a DNA backbone identical to that of INO-5150 and delivered IM followed by 
EP alone or in combination with IL-12 plasmid DNA (eg, INO-9012), the most commonly 
reported adverse event reported was injection site pain (Table 2). 
Table 2 
Adverse Events Reported in Studies of Inovio DNA Delivered IM with 
Electroporation Occurring in at Least 5% of Subjects 
Adverse Event Preferred Term 
Number of Subjects (%) 
(N = 1022) 
Injection site pain 
570 (55.8) 
Fatigue 
228 (22.3) 
Injection site erythema 
190 (18.6) 
Headache 
187 (18.3) 
Myalgia 
148 (14.5) 
Upper respiratory tract infection 
130 (12.7) 
Injection site swelling 
128 (12.5) 
Injection site pruritus 
110 (10.8) 
Nausea 
110 (10.8) 
Arthralgia 
  89 (  8.7) 
Injection site bruising 
  81 (  7.9) 
Malaise 
  76 (  7.4) 
Source: INO-5151/INO-5150 and INO-9012 Investigator’s Brochure, 2019 
 
2.2.2 
Background on rhuFLT3L/CDX-301 (Celldex Therapeutics, Inc.) 
rhuFLT3L/CDX-301 is the soluble recombinant human (rhu) protein form of the FMS-related 
tyrosine kinase 3 ligand (Flt3L), a hematopoietic cytokine. CDX-301 represents the 153 

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N-terminal amino acids of the human Flt3L extracellular domain after the cleavage of the 
N-terminal signal peptide. 
Flt3L is a hematopoietic growth factor that plays an important role in the mobilization and 
expansion of stem cells and progenitors (Lyman and Jacobsen, 1998). In particular, it has been 
shown to facilitate the differentiation of both DCs and natural killer cells from hematopoietic 
stem cell precursors (Blom et al., 2000; Chen et al., 2005; Gilliet et al., 2002; Miller et al., 1999). 
Specifically, Flt3L directly induces the differentiation of a proportion of CD34+ CD45RA- early 
progenitor cells into pre-DCs, and results in increased numbers of activated DCs (Blom et al., 
2000; Breton et al., 2016). In healthy human volunteers it has been demonstrated that Flt3L 
administration increases the number of DCs, as well as CD14+ monocytes (Chen et al., 2005; 
Anandasabapathy et al., 2015; Maraskovsky et al., 1996; Pulendran et al., 1997). 
Numerous preclinical models have shown the ability of Flt3L administration to mobilize a range 
of immune cell subsets, DCs predominant among these (Brasel et al., 1996; Fernandez et al., 
1998; Kutzler and Weiner, 2004; Miller et al., 2003). Flt3L administration has demonstrated 
antitumor activity in a variety of tumor models including melanoma, lymphoma, leukemia, 
breast, colon, prostate, lung and hepatocellular carcinoma (Averbook et al., 2002; Ciavarra et al., 
2000; Drexler et al., 1999; Esche et al., 1998; Hou et al., 2007; Wang et al., 2000; Chakravarty et 
al., 1999). Preclinical models have also shown that Flt3L administration can enhance the 
antitumor immunity of checkpoint inhibitors such as PD-1 and cytotoxic T-lymphocyte-
associated protein 4 (CTLA-4) antibodies to promote tumor regression of non-immunogenic 
tumors (Lynch et al., 1997).  
Flt3L has been used in many early phase human clinical trials of different immunotherapeutic 
approaches—as an adjuvant or in order to mobilize DCs for collection to produce a cellular 
vaccine—in patients with colorectal cancer, non-small cell lung cancer, mesothelioma, and 
prostate cancer among others and demonstrated safety with minimal toxicity from Flt3L 
administration through multiple routes of administration (Fong et al., 2001; Freedman et al., 
2003; Higano et al., 2004; Morse et al., 2000).  
A study in 31 patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) 
evaluated the impact of Flt3L administration on peripheral blood DCs and post-treatment 
changes in PSA (Higano et al., 2004). DCs increased markedly from baseline to Day 15, and the 
increase was consistently observed after administration of Flt3L in each cycle. Mean percentages 
of DCs in peripheral blood ranged from 1.4% to 1.9% pre-cycle and from 10.1% to 13.9% on 
Day 15, and after the first cycle, absolute counts on Day 15 were approximately 29-fold higher 
than pre-cycle levels. NK cell counts (CD56+) were found to be elevated after cycle 1 (154% 
increase versus 2.8% decrease in placebo group at Day 22). The most frequently experienced 
toxicity was injection site reaction, followed by asthenia, rash, and diarrhea. Although median 

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PSA levels did not vary during any cycle, a significant slowing in velocity of PSA was observed 
while patients were on-study (relative velocity = 0.002) compared with prestudy PSA velocity 
(relative velocity = 0.007). Given that Flt3L consistently produced an increase in DC numbers 
and the slowing of PSA velocity after administration, the authors concluded that Flt3L warrants 
further study for the immunotherapy of prostate cancer. Furthermore, mobilization of DCs by 
administration of Flt3L followed by exposure to IL-12, PSA, and PSMA may lead to improved 
activation of DCs and antigen presentation for eliciting a robust antitumor immune response to 
vaccination with tumor antigens. 
Refer to the IB (CDX-301/Recombinant Human Flt3 Ligand [rhuFlt3L] Investigator’s Brochure, 
2018) for detailed background information on rhuFLT3L/CDX-301. 
2.2.3 
Background on Nivolumab (Bristol-Myers Squibb Company) 
Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the PD-1 
receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated 
inhibition of the immune response, including the antitumor immune response. Opdivo® 
(nivolumab) is approved in the United States (US) for the treatment of several cancer types, 
including unresectable or metastatic melanoma (as monotherapy or in combination with 
ipilimumab) and as monotherapy in previously-treated metastatic non-small cell lung cancer 
(NSCLC), advanced renal cell carcinoma (RCC), relapsed or refractory classical Hodgkin 
lymphoma (cHL), locally advanced or metastatic urothelial carcinoma (UC), recurrent or 
metastatic squamous cell carcinoma of the head and neck (SCCHN), microsatellite instability-
high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC), and 
hepatocellular carcinoma (HCC). In phase 1 investigation, nivolumab did not demonstrate 
clinical activity in 17 participants with advanced mCRPC. This is consistent with mCRPC 
having a low level of immune cell infiltrate and tumor mutational burden (TMB). Treatment 
strategies to increase antigen presentation and immune infiltration and activation may improve 
the immune responsiveness of mCRPC to nivolumab. 
Refer to the IB (Nivolumab Investigator’s Brochure, 2018) and approved US prescribing 
information (Opdivo [nivolumb] US Prescribing Information [USPI], 2018) for detailed 
background information on nivolumab. 
2.2.4 
Rationale for CDX-301 + INO-5151 + Nivolumab Immunotherapy 
Combination 
This study cohort is designed to explore a multi-pronged approach to stimulate antitumor 
immunity by enhancement of a DNA vaccination targeting prostate cancer tumor antigens 
through EP, cytokine adjuvants, mobilization and activation of DCs, and relieving immune 

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suppression of cytotoxic T cells by administration of an anti-PD-1 monoclonal antibody (mAb) 
in mCRPC: 
• Flt3L (CDX-301) to induce mobilization, activation, and/or expansion of DCs 
• DNA vaccine INO-5151 for expression of human PSMA, PSA, and IL-12 to stimulate 
antitumor directed CD8 T-cell responses to CRPC-specific tumor antigens 
• Anti-PD-1 mAb (nivolumab) to overcome immune suppression of tumoral T cells 
 
Flt3L binds CD135 (Flt3 receptor) and induces proliferation, differentiation, and mobilization of 
hematopoietic stem cells, early progenitor cells, and DCs. Flt3L is a key regulator of DCs, 
inducing marked increases and activation of both myeloid and plasmacytoid DCs. Immunologic 
analyses have shown 10 to 100+ fold increase in DCs (including CD141+ DCs), as well as 
augmentation of humoral and cellular responses to the NY-ESO-1 vaccine; however, no clear 
activity as monotherapy was noted in patients with advanced cancer (Ohri et al., 2018), 
suggesting CDX-301 promotes antitumor immunity but not sufficiently to result in clinical 
benefit. These observations suggest that combination of CDX-301 with immunotherapies 
generating effective CD8 T cell responses, such as INO-5151, may lead to an effective antitumor 
response, specifically in the presence of a checkpoint inhibitor. The combination of CDX-301, 
which increases innate immune cells, with a DNA-encoding vaccine and immune-stimulatory 
cytokine IL-12 is hypothesized to induce potent antitumor immunity (Shore et al., 2018a; 
Schadeck et al., 2006; Boyer et al., 2005; Chong et al., 2007; Kalams et al., 2012; Kalams et al., 
2013; Daud et al., 2008; Gollob et al., 2000; Bhardwaj et al., 2016, Gao et al., 2018). A 29-fold 
increase in DCs was seen at Day 15 in a trial of CDX-301 in nmCRPC, which support the 
rationale for this agent in the immune-priming period prior to vaccination. INO-5151 is a DNA 
based vaccine encoding PSA and PSMA, 2 antigens that are widely expressed in advanced 
prostate cancer and also encodes IL-12, an adjuvant cytokine with preclinical and clinical data 
supporting that it increases CD8 T cell responses (Shore et al., 2018a; Shore et al., 2018b). These 
plasmids will be administered IM followed by EP to enhance cellular uptake of DNA and 
increase potency. In a recently reported phase 1 study in patients with non-metastatic 
biochemically recurrent prostate cancer, INO-5150, with and without INO-9012, was safe and 
immunogenic with demonstrated clinical activity (Shore et al., 2018a; Shore et al., 2018b). The 
majority of patients experienced a slowing of pre-treatment PSA doubling times (a reflection of 
disease activity). Patients who experienced disease stabilization by Week 27 continued to Week 
72, and importantly, this trend was seen in those with a pre-study PSA doubling time (DT) of 
< 6 months. PSA DT of < 6 months in a biochemically recurrent population are associated with a 
worse prognosis and greater likelihood of developing overt metastatic disease. The final 
component of this regimen, nivolumab, an anti-PD-1 agent, will be given as systemic therapy to 

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target adaptive resistance pathways and provide ongoing immune stimulation throughout the 
vaccine regimen cycle. 
Further, ongoing clinical studies support this combination approach. The combination of 
vaccines and anti-PD-(L)1 therapy is being assessed in ongoing studies in several tumor types, 
including SCCHN, glioblastoma, UC, and human papillomavirus cancers (Table 3). CDX-301, in 
combination with a vaccine (CDX-1401) and polyinosinic-polycytidylic acid stabilized with 
polylysine and carboxymethylcellulose (poly-ICLC), has been studied in patients with melanoma 
(Table 3). Results of the study demonstrated that subjects receiving CDX-301 pretreatment 
showed substantial increases in DC, monocytes, and NK cells. Further, subjects receiving 
CDX-301 developed higher anti-vaccine antibody titers than those who did not receive 
CDX-301. The authors concluded that DC mobilization with Flt3L is safe and may enhance 
responses to DC-targeted vaccines (Bhardwaj et al., 2016). 
While each component is unlikely to yield clinical benefit on its own in mCRPC, these 
individual components (CDX-301, INO-5151, and nivolumab) provide different mechanisms to 
target and enhance immunogenicity by activating innate and adaptive immune mechanisms in 
order to elicit an antitumor immune response. 

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Table 3: 
Clinical Studies Supporting the Co-administration of Components of this Study Intervention 
Study 
Disease Site 
N 
Combination 
Findings  
Vaccine + Anti-PD-(L)1 Combinations 
NCT03162224 
SCCHN 
(HPV associated) 
50 
MEDI0457 (INO-3112) 
vaccine + durvalumab 
Single arm, open-label study ongoing to assess safety and tolerability, antitumor 
activity (ORR, PFS, DCR, OS), and immunogenicity. 
NCT03439085 
HPV cancers 
77 
MEDI0457 (INO-3112) 
vaccine + durvalumab 
Non-randomized, parallel assignment, open-label study to assess efficacy (ORR, 
PFS, DCR, OS) and safety. 
NCT03491683 
Glioblastoma 
52 
INO-5401 + INO-9012 
vaccine + cemiplimab + 
XRT + temozolomide (if 
clinically indicated) 
Non-randomized, parallel assignment, open-label study ongoing to assess safety, 
immunogenicity, and preliminary efficacy (OS). 
NCT03502785 
UC 
85 
INO-5401 + INO-2012 
vaccine + atezolizumab 
Non-randomized, parallel assignment, open-label study ongoing to assess safety, 
immunogenicity, and preliminary efficacy (ORR, DoR, PFS, OS). 
Vaccine + CDX-301 Combinations 
NCT02129075 
Melanoma 
60 
CDX-1401 vaccine + 
Poly-ICLC ± CDX-301 
Randomized study (CDX-301 + CDX-1401+ poly-ICLC vs CDX-1401+ poly-
ICLC) demonstrated DC mobilization with Flt3L is safe and may enhance 
responses to DC-targeted vaccines. Preliminary analyses showed substantial 
(between ~15- to ~200-fold) increases of PBMC innate immune cells (DC, 
monocytes and NK cells) in subjects with CDX-301 pretreatment vs subjects 
without CDX-301. Further, there was development of higher anti-NY-ESO-1 
antibody titers in subjects with CDX-301 pretreatment vs subjects without 
CDX-301. (Bhardwaj et al., 2016) 
CDX-1401 = DEC-201/NY-ESO-1 fusion protein vaccine; DC = dendritic cell; DCR = disease control rate; DoR = duration of response; Flt3L = FMS-related 
tyrosine kinase 3 ligand; HPV = human papillomavirus; NK = natural killer; ORR = objective response rate; OS = overall survival; PBMC = peripheral blood 
mononuclear cell; PD-(L)1 = programmed cell death 1 or anti-programmed cell death ligand 1; PFS = progression-free survival; poly-ICLC = polyinosinic-
polycytidylic acid stabilized with polylysine and carboxymethylcellulose; SCCHN = squamous cell carcinoma of the head and neck; UC = urothelial carcinoma; 
XRT = radiation therapy 
 
 

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2.3 
BENEFIT/RISK ASSESSMENT 
There are data supporting the use of the individual components of the study intervention in this 
cohort (ie, CDX-301, INO-5151, and nivolumab); however, the combination has not been 
previously studied in animal models or in human studies. Each component has been studied 
specifically in prostate cancer and was well tolerated (Higano et al., 2004; Brahmer et al., 2010; 
Topalian et al., 2012; Shore et al., 2018a; Shore et al., 2018b). Toxicity profiles are non-
overlapping. 
Nivolumab 
Nivolumab has demonstrated durable responses exceeding 6 months as monotherapy in several 
tumor types, including NSCLC, melanoma, RCC, and SCCHN. In confirmatory trials, 
nivolumab demonstrated a statistically significant improvement in OS as compared with the 
current standard of care in subjects with advanced or metastatic NSCLC, unresectable or 
metastatic melanoma, advanced RCC, or SCCHN. 
The monotherapy safety profile is similar across tumor types. Most adverse events (AEs) were 
low-grade (Grade 1 to 2) with relatively few related high-grade (Grade 3 to 4) AEs. There is no 
pattern in the incidence, severity, or causality of AEs to nivolumab dose level. Clinically relevant 
AEs typical of stimulation of the immune system were infrequent and manageable by delaying or 
stopping nivolumab treatment and timely immunosuppressive therapy or other supportive care 
(Nivolumab Investigator’s Brochure, 2018).  
In several ongoing clinical trials, the safety of nivolumab in combination with other therapeutics 
such as ipilimumab, cytotoxic chemotherapy, anti-angiogenics, and targeted therapies is being 
explored. Most studies are ongoing and, as such, the safety profile of nivolumab combinations 
continues to evolve. 
Overall, these findings support a favorable benefit-risk profile for nivolumab across various 
tumor types. More detailed information about the known and expected benefits and risks and 
reasonably expected AEs of nivolumab may be found in the prescribing information (Opdivo 
USPI, 2018). 
INO-5151 
DNA vaccines are simple and relatively inexpensive to construct, are readily produced in large 
quantities, and are generally stable for long periods of time, making them a desirable immune-
based modality for the prevention or treatment of disease. Additionally, nonclinical studies have 
demonstrated no evidence of genome integration as measured by PCR in 2 previous studies of 
several DNA vaccine products expressing a variety of inserts (INO-5151/INO-5150 and INO-
9012 Investigator’s Brochure, 2019). In contrast, pre-existing anti-vector immunity can reduce 
immunogenicity and ability to utilize the viral vector for future immunizations. 

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The plasmid backbones of DNA vaccines are associated with limited, if any, immune response, 
allowing repeated dosing to increase or maintain immune responses over long periods. Repeated 
dosing of viral-based vaccines may be hindered by neutralization of targeted viral vector 
sequences. As opposed to viral-based vaccines, which carry a risk of mutation back to a virulent 
state or spread to unintended individuals, DNA vaccines are not based on an intact natural 
pathogen, and therefore, cannot revert to a virulent form. 
The combined safety data from completed and ongoing trials with IL-12 plasmid DNA have 
demonstrated that there have been no significant safety concerns identified in the studies in 
which IL-12 (eg, INO-9012) is used as an adjuvant in combination with other plasmids. In 
addition, up to 5.8 mg of IL-12 DNA has been administered intratumorally followed by EP, and 
no safety signals were observed. 
In contrast to high-dose intravenous (IV) recombinant human IL-12 protein, IL-12 plasmid DNA 
has showed an acceptable safety profile in clinical studies when delivered intramuscularly either 
alone or when followed by EP. The use of IL-12 DNA has also been associated with expansion 
of antigen-specific IFN-γ positive effector cells, as well as granzyme B production. The induced 
immunity included both a CD8+ as well a CD4+ component. 
The most frequently reported AEs across studies in which PSA, PSMA and plasmids with a 
DNA backbone identical to that of INO-5150 and delivered via IM+EP alone or in combination 
with IL-12 plasmid DNA (eg, INO-9012) are provided in Table 2. Injection site pain was the 
most frequently reported treatment-related AE across all studies. There were few treatment-
related Grade 3 or Grade 4 AEs or serious adverse events (SAEs).  
These data indicate that synthetic consensus antigenic sequences inserted into the plasmid 
backbone generate significant cellular and humoral immune responses, without compromising 
the acceptable safety profile of naked DNA delivery (Doukas et al., 2011; Ledwith et al., 2000). 
The generally acceptable benefit/risk profile of DNA vaccines delivered using EP supports 
further study in selected diseases, such as prostate cancer. 
CDX-301 
Conclusions regarding the benefit/risk of CDX-301 should be considered in the context of a drug 
in the early stages of development, and therefore by definition, is uncertain and evolving. 
CDX-301 has been well-tolerated and demonstrates the potential for utility in a number of life-
threatening disease states by mobilizing and increasing the number of hematopoietic stem cells 
and DCs in healthy volunteers and cancer patients. CDX-301 administered in combination with 
vaccines was well tolerated, without SAEs, and promoted integrated immunity (Bhardwaj et al., 
2016). Data collected to date indicate that CDX-301 has an acceptable toxicity profile, and the 

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overall benefit/risk remains in favor of continued clinical evaluation (CDX-301/Recombinant 
Human Flt3 Ligand [rhuFlt3L] Investigator’s Brochure, 2018). 
CDX-301, INO-5151, and Nivolumab 
Data from studies of the individual components of the study intervention in this cohort, as well 
as clinical studies of the co-administration of the components of the combination, provide 
support for the study of this immunotherapy combination. Nonclinical data and clinical 
experience indicate the potential for improvement of response compared with nivolumab 
monotherapy. Thus, the potential benefit of this immunotherapy combination appears to 
outweigh the known risks of these agents and warrants clinical investigation. 
3 
OBJECTIVES AND ENDPOINTS 
The cohort-specific objectives and endpoints are listed in Table 4. 
Table 4: 
Cohort-Specific Objectives and Corresponding Endpoints 
Objectives 
Endpoints 
Primary 
 
• To determine the safety of CDX-301 + INO-5151 
followed by INO-5151 + nivolumab in participants 
with mCRPC. 
Refer to the core protocol. 
Secondary 
 
• To determine the ORR of CDX-301 + INO-5151 + 
nivolumab in participants with measurable mCRPC. 
• To determine the DCR ≥ 9 months of CDX-301 + 
INO-5151 + nivolumab in participants with 
measurable mCRPC. 
• To evaluate the rPFS of CDX-301 + INO-5151 + 
nivolumab in participants with mCRPC. 
• To estimate the OS of CDX-301 + INO-5151 + 
nivolumab in participants with mCRPC. 
Refer to the core protocol. 
Exploratory 
 
• To evaluate the PK of CDX-301 and/or nivolumab. 
• To evaluate the immunogenicity of INO-5151, 
CDX-301, and/or nivolumab. 
 
Refer to the core protocol for overall exploratory 
objective(s). 
• Sparse PK analysis. 
• Presence of immune response against PSA and/or 
PSMA 
• ADA against CDX-301 and/or nivolumab. 
 
Refer to the core protocol for overall exploratory 
endpoint(s). Note that biomarker evaluation for this 
cohort will include immune profiles, including 
dendritic cells. 
ADA = anti-drug antibodies; DCR = disease control rate; IL-12 = interleukin-12; mCRPC = metastatic castration-
resistant prostate cancer; ORR = objective response rate; OS = overall survival; PK = pharmacokinetics; 

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PSA = prostate-specific antigen; PSMA = prostate-specific membrane antigen; rPFS = radiographic progression-free 
survival 
 
4 
STUDY DESIGN 
4.1 
OVERALL DESIGN 
In this study intervention cohort, INO-5151 and CDX-301 will be administered during the 
Immune-priming Lead-in. CDX-301 will be administered on Days 1-5 and Days 22-26 and INO-
5151 will be administered on Day 8 of the Immune-priming Lead-in. Thereafter, INO-5151 will 
be administered in Cycle 1, Cycle 2, and Cycle 3 and every 12 weeks (Q12W; ie, every 3 cycles) 
thereafter for up to 2 years, concurrent with nivolumab. Nivolumab will be administered every 4 
weeks (Q4W) starting in Cycle 1 for up to 2 years (Figure 1), unless the participant: is no longer 
clinically benefiting (as evidenced by symptomatic or radiographic disease progression and/or 
clinical deterioration); experiences any toxicity meeting specified discontinuation criteria (see 
Section 6.6) or unacceptable toxicity in the best clinical discretion of the treating physician; 
reaches the maximum duration of study intervention; or withdraws consent. The preferred 
sequence when INO-5151 and nivolumab are administered on the same day is:  INO-5151 via EP 
followed by nivolumab infusion. 
Participants will be monitored for safety and response and will be followed on-study for up to 
2.5 years from the time of the initiation of study intervention. All participants will be followed 
for safety for at least 100 days after discontinuation of study intervention. Approximately 15 
participants, including a minimum of 7 with a non-bone metastatic lesion that can be biopsied, 
will be enrolled in Stage 1. An additional approximately 15 participants, including a minimum of 
7 with a non-bone metastatic lesion, will be enrolled in Stage 2, if the cohort is expanded. 
A pre-treatment biopsy of a metastatic lesion is required for all participants, including those with 
bone only disease, if medically feasible. Participants must also provide consent for archival 
tissue from a prior biopsy or surgery for prostate cancer. An on-treatment biopsy is required, 
when medically feasible, usually after the second dose of nivolumab (ie, Cycle 2). An optional 
biopsy may be obtained at the time of disease progression, including from participants who 
respond and subsequently progress following a response to treatment. The on-treatment biopsies 
should be taken from the same lesion as the pre-treatment biopsy when feasible. 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
The scientific rationale for this combination is provided in Section 2.2.4. 
4.3 
JUSTIFICATION FOR DOSE 
The doses of INO-5151 and CDX-301 proposed for this study have established as being safe in 
previous and ongoing clinical trials (Section 4.3.2 and Section 4.3.3, respectively). Nivolumab 

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will be administered as a fixed dose of 480 mg intravenously Q4W, an established dosing 
regimen and US Food and Drug Administration (FDA)-approved for a majority of approved 
nivolumab indications (Section 4.3.1).  
All agents are being administered at the recommended dose determined in prior studies in cancer 
patients and based on the safety profiles of the individual components, there does not appear to 
be overlapping toxicities. Therefore, the combination of CDX-301, INO-5151, and nivolumab at 
the doses proposed is considered warranted for the evaluation of safety and clinical activity in 
this population. 
4.3.1 
Rationale for Nivolumab Dose and Schedule 
In the US, single-agent nivolumab was approved in 2014 at a dose of 3 mg/kg every 2 weeks 
(Q2W). Subsequently, population pharmacokinetics (PPK) and exposure response analyses were 
performed to support use of flat dosing regimens (ie, nivolumab 240 mg Q2W, 360 mg every 
3 weeks [Q3W], and 480 mg Q4W) in participants with cancer. A flat dose of nivolumab 240 mg 
Q2W was selected since it is identical to a dose of 3 mg/kg for participants weighing 80 kg, the 
observed median body weight in nivolumab-treated cancer patients, while the nivolumab 360 mg 
Q3W and 480 mg Q4W regimens allow flexibility of dosing with less frequent visits and in 
combination with other agents using alternative dosing schedules to Q2W, such as ipilimumab. 
Using a PPK model, the overall distributions of nivolumab exposures (average steady-state 
concentration [Cavgss], minimum steady-state plasma concentration [Cminss], maximum steady-
state plasma concentration [Cmaxss], and trough concentration after the first dose [Cmin1]) are 
comparable after treatment with either nivolumab 3 mg/kg or 240 mg Q2W (Nivolumab 
Investigator’s Brochure, 2018). 
Following nivolumab 480 mg Q4W, Cavgss are expected to be similar to those following 
nivolumab 3 mg/kg or 240 mg Q2W, while Cminss are predicted to be ~16% lower and are not 
considered to be clinically relevant. Cmaxss are predicted to be approximately ~43% greater 
relative to that following nivolumab 3 mg/kg Q2W dosing. However, the range of nivolumab 
exposures (median and 90% prediction intervals) following administration of 240 mg flat Q2W, 
360 mg Q3W, and 480 mg Q4W regimens across the 35 to 160 kg weight range are predicted to 
be maintained well below the corresponding exposures observed with the well tolerated 10 
mg/kg nivolumab Q2W dosing regimen (Nivolumab Investigator’s Brochure, 2018) 
The 240 mg Q2W dose was approved in the USPI in September 2016 for use in metastatic 
melanoma, NSCLC, and RCC indications. In March 2018, the 480 mg Q4W dose was approved 
in the USPI for use in metastatic melanoma, NSCLC, RCC, cHL, SCCHN, UC, and HCC 
indications (Opdivo USPI, 2018). 

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4.3.2 
Rationale for INO-5151 Dose and Schedule 
INO-5151 will be administered at a dose of 3 mg followed by EP in Immune-priming Lead-in, 
followed by 3 doses administered Q4W starting at Cycle 1, and then Q12W thereafter. 
Administration of INO-5151 will commence on Day 8 of the Immune-priming Lead-in, based on 
doses studied in the phase 1 clinical study (PCa-001) and a schedule that has been modified to 
Q4W by the inclusion of a dose at Cycle 2. The PCa-001 study which assessed the safety, 
tolerability, and antigen-specific immune responses of INO-5150 with or without INO-9012 
delivered via IM EP at 2 doses of INO-5150 (high-dose: 8.5 mg or low-dose: 2 mg) alone or in 
combination with INO-9012 1 mg in patients with prostate cancer (INO-5151/INO-5150 and 
INO-9012 Investigator’s Brochure, 2019). The doses selected for Study PCa-001 were based on 
previous human experience with other DNA vaccines and preclinical data with INO-5150 and 
INO-9012. A total dose of 8.5 mg INO-5150 DNA was selected for Study PCa-001 based on the 
safety and immunogenicity data generated in Studies HPV-001 and FLU-001, where 6 mg of 
DNA were delivered via IM+EP, which showed trends toward higher response rates and 
magnitudes of IFN-γ ELISpot responses in the high dose cohort compared to the low (0.6 mg) 
and mid-dose (2 mg) cohorts without significant safety issues (INO-5151/INO-5150 and INO-
9012 Investigator’s Brochure, 2019). In combination with INO-9012 1 mg (ie, the same dose 
equivalent of INO-9012 proposed for this study), the mid-dose of 2 mg proved effective at 
generating an immune response (Shore et al., 2017). 
Grade 1 – 3 AEs were reported in 82% of the 62 patients enrolled in study PCa-001, including 
75% treated with low-dose INO-5150 and 87% treated with low-dose INO-5150 in combination 
with INO-9012. Common AEs included injection site pain, swelling, and erythema, all of which 
were Grade 1 – 2. Grade 3 SAEs of presyncope, cardiac disorder, fall, neoplasm, and alanine 
aminotransferase (ALT) and aspartate aminotransferase (AST) elevation occurred in 5 patients, 
and none were considered treatment-related; there were no Grade 4 or 5 SAEs (Shore et al., 
2017). 
Among the 61 evaluable patients across the 4 cohorts in study PCa-001, 77% demonstrated T 
cell immunogenicity, 60% had IFN-γ reactivity by ELISpot, 10% and 8% had antibody titers 
against PSA and PSMA, respectively, and 38% exhibited CD38, perforin + CD8 T cell 
responses. A clinical effect was demonstrated by evidence of dampening of the percent rise in 
PSA and increased PSA doubling times in the majority of patients (Shore et al., 2018a; Shore et 
al., 2018b). 
4.3.3 
Rationale for CDX-301 Dose and Schedule 
CDX-301 will be administered as a subcutaneous (SC) injection at a dose of 75 μg/kg daily (QD) 
for 5 days, the highest dose studied using the 5-day schedule in the phase 1 clinical study in 
healthy volunteers (CDX301-02), which assessed the safety, tolerability, pharmacokinetic and 

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pharmacodynamic profile of daily SC injections of CDX-301 at multiple dose levels 
(1 μg/kg/day to 75 μg/kg/day) and durations (5 to 10 days; CDX-301/Recombinant Human Flt3 
Ligand [rhuFlt3L] Investigator’s Brochure, 2018). 
Results of CDX301-02 showed that CDX-301 exhibited a typical absorption profile for SC 
administration with mean times to maximum serum concentration (Tmax) of 19.8 hours at 
75 μg/kg/day for 5 days. Mean maximum serum concentrations (Cmax) increased linearly with 
dose across the dose range when administered over 5 days and was 667.4 ng/mL following 
75 μg/kg/day for 5 days. Similarly, area under the curve (AUC) values increased across the entire 
range in a dose-independent manner. The half-life was 28 hours at 75 μg/kg/day for 5 days. 
Treatment-related toxicity was infrequent and reported only at the 25 and 75 μg/kg/day dose 
levels (number of subjects at these dose levels was 9 and 15, respectively). One Grade 3 event, 
community acquired pneumonia, was considered treatment-related. However, no additional 
infections, dose-limiting toxicities, SAEs, or Grade 3 toxicities were reported. All other 
treatment-related AEs were Grade 1; these included lymphadenopathy in 6 subjects and single 
cases of diarrhea, injection site erythema, folliculitis and dry mouth. There were no reported 
clinically significant laboratory toxicities attributed to CDX-301. 
As of October 2018, of 89 subjects (cancer patients, healthy volunteers, and stem cell donors) 
tested from 5 studies (Celldex-sponsored and investigator-initiated), 1 patient (receiving 
CDX-301 25 μg/kg/day for 10 days) has tested positive for the presence of specific 
anti-CDX-301 antibodies. Subsequent characterization of this patient’s serum has shown the 
response to be non-neutralizing. 
Dosing with 75 μg/kg daily for 5 days was sufficient to increase CD34+ stem cells and DCs by at 
least 10-fold over baseline values. 
Refer to the IB (CDX-301/Recombinant Human Flt3 Ligand [rhuFlt3L] Investigator’s Brochure, 
2018) for an additional description of overall safety, immunogenicity, and efficacy in humans. 
4.4 
TREATMENT BEYOND DISEASE PROGRESSION 
Refer to the core protocol. 
4.5 
END OF STUDY DEFINITION 
Refer to the core protocol for the end of study definition. 
The total length of this study cohort, from screening of the first participant to the end of the 
cohort, is expected to be approximately 3 years, 9 months. 

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5 
STUDY POPULATION 
Prospective requests for approval of protocol deviations to recruitment and enrollment criteria, 
also known as waivers or exemptions, is not allowed. 
5.1 
INCLUSION CRITERIA 
Participants are eligible to be included in the study only if all the following criteria apply: 
5.1.1 
Common Inclusion Criteria 
1. Participant must be ≥ 18 years of age at the time the informed consent is signed. 
2. Participants must agree to use an adequate method of contraception as outlined in 
Appendix 6 of the core protocol starting with the first dose of study intervention and for 
at least 7 months after the last dose of study intervention and refrain from donating sperm 
during this period. 
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for 
the participant. 
3. Participants must be able and willing to comply with the study visit schedule and study 
procedures. 
4. Histologically documented adenocarcinoma of the prostate. 
5. Metastatic castration resistant prostate cancer with castrate-level testosterone 
(< 50 ng/dL) at screening. 
6. Have received and progressed on prior secondary androgen receptor signaling inhibitor 
therapy (eg, abiraterone, enzalutamide, apalutamide). Progression is defined by one or 
more of the following 3 criteria: 
a. Prostate-specific antigen (PSA) ≥ 1.0 ng/mL and rising PSA by at least 2 
consecutive measurements a minimum of 1-week apart. 
b. Soft tissue progression as defined by Response Evaluation Criteria in Solid 
Tumors (RECIST) version 1.1 (Eisenhauer et al., 2009). 
c. Bone disease progression as defined by 2 new bone lesions (as per Prostate 
Cancer Clinical Trials Working Group 3 [PCWG3; Scher et al., 2016]).  
7. Have measurable disease or non-measurable disease based on PCWG3-modified 
RECIST 1.1. 
8. Provide fresh pre-treatment core needle or incisional biopsy of a metastatic tumor lesion 
not previously irradiated. Fine needle aspiration is not acceptable. 
a. Additionally, if a pre-treatment biopsy is not medically feasible for participants 
with bone only disease, formalin-fixed paraffin-embedded (FFPE) tumor 
specimen in a paraffin block (preferred) or at least 10 slides containing unstained, 
freshly cut, serial sections must be provided. 
b. For all participants, in addition to fresh pre-treatment biopsy, consent for archival 
tissue is required. 

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9. Must be willing to undergo tumor biopsy(ies) on treatment, if medically feasible. 
10. Participants must discontinue antiandrogen therapy (ie, bicalutamide, flutamide, 
nilutamide) at least 4-6 weeks prior to registration with no evidence of PSA decline after 
washout. 
a. Bicalutamide: Washout period at least 6 weeks 
b. Flutamide and nilutamide: Washout period at least 4 weeks 
11. Participants must discontinue therapies for mCRPC for 5 half-lives or 28 days, whichever 
is shorter. 
a. Participants will remain on gonadotropin-releasing hormone (GnRH) agents 
throughout this study. 
b. Prior chemotherapy is allowed if no progression of disease on chemotherapy as 
defined by PCWG3-modified RECIST 1.1.  
c. Prior treatment with sipuleucel-T, radium-223, or poly adenosine diphosphate 
(ADP)-ribose polymerase (PARP) inhibitor (eg, olaparib) is allowed. 
d. Tissue biopsy may be performed during washout period. 
12. Participants with prior or concurrent malignancies are permitted if any one of the 
following applies: 
a. Previously treated malignancy for which all treatment of that malignancy was 
completed at least 2 years before enrollment and no evidence of disease exists, or 
b. With agreement from the Medical Monitor and Principal Investigator (PI), 
participants who have a concurrent malignancy that is clinically stable and does 
not require tumor-directed treatment are eligible to participate if the risk of the 
prior malignancy interfering with either safety or efficacy endpoints is very low, 
or 
c. With agreement from the Medical Monitor and PI, other malignancies may be 
permitted if the risk of the prior malignancy interfering with either safety or 
efficacy end points is very low. 
13. Have a performance status of 0 or 1 according to the Eastern Cooperative Oncology 
Group (ECOG) scale. 
14. Demonstrate adequate organ function on screening laboratory tests performed within 
14 days of treatment initiation and as evidenced by: 
a. Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L without transfusion or erythropoietin 
(EPO) dependency (within ≤ 7 days of assessment) 
b. Absolute neutrophil count ≥ 1,500/mm3 without growth factor support (within 
< 28 days of assessment) 
c. Platelet count ≥ 100,000/mm3 
d. Estimated glomerular filtration rate (GFR) ≥ 45 mL/min using the Cockcroft-
Gault formula 

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e. Serum total bilirubin < 1.5 x upper limit of normal (ULN) or ≤ 2.0 x ULN for 
participants with liver metastases 
i. Participants with Gilbert's syndrome must have ≤ 3 x ULN and no liver 
lesions 
f. Aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) 
(SGPT) ≤ 3.0 x ULN or ≤ 5.0 x ULN for participants with liver metastases. 
g. Albumin ≥ 2.5 mg/dL. 
h. International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN 
unless participant is receiving anticoagulant therapy, as long as PT is within 
therapeutic range of intended use of anticoagulants. 
i. Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless participant is 
receiving anticoagulant therapy, as long as PTT is within therapeutic range of 
intended use of anticoagulants. 
15. Willing and capable of giving signed informed consent as described in Appendix 1 of the 
core protocol, which includes compliance with the requirements and restrictions listed in 
the informed consent form (ICF) and in this protocol. 
 
5.1.2 
Combination-specific Inclusion Criteria 
1. No known histologic evidence of neuroendocrine differentiation or small cell histology. 
 
5.2 
EXCLUSION CRITERIA 
Participants are excluded from the study if any of the following criteria apply: 
5.2.1 
Common Exclusion Criteria 
1. Is currently participating and receiving study therapy or has participated in a study of an 
investigational agent and received study therapy or used an investigational device within 
4 weeks of the first dose of treatment. 
a. Recent or concurrent non-therapeutic investigational agents that are not 
anticipated to interfere with study intervention, such as certain investigational 
imaging tracers, may be permitted with written agreement from the Medical 
Monitor. 
2. Has a diagnosis of immunodeficiency or conditions that need systemic corticosteroid 
replacement therapy > 10 mg/day prednisone (or equivalent) or other immunosuppressive 
medications within 28 days prior to the first dose of study intervention. Inhaled steroids 
are permitted if necessary. 
3. Has any active known or suspected autoimmune disease. Participants with vitiligo, type I 
diabetes mellitus, controlled autoimmune hypothyroidism, psoriasis not requiring 
systemic treatment, or other conditions under control are permitted to enroll. 
Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement 

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therapy ≤ 10 mg of prednisone/day for adrenal or pituitary insufficiency, etc.) is not 
considered a form of systemic treatment.  
4. Has a known history of active TB (Bacillus Tuberculosis). 
5. Has known history of, or any evidence of active, non-infectious pneumonitis. 
6. Has an active infection requiring systemic therapy. 
7. Has a history or current evidence of any condition, therapy, or laboratory abnormality 
that might confound the results of the trial, interfere with the participant’s participation 
for the full duration of the trial, or is not in the best interest of the participant to 
participate, in the opinion of the treating Investigator. 
8. Has known psychiatric or substance abuse disorders that would interfere with cooperation 
with the requirements of the trial. 
9. Is expecting to father children within the projected duration of the trial, starting with the 
pre-screening or screening visit through 7 months after the last dose of study intervention. 
10. Known history of testing positive for human immunodeficiency virus (HIV), known 
acquired immunodeficiency syndrome (AIDS), or any positive test for hepatitis B or 
hepatitis C virus representing acute or chronic disease. 
11. Has received a live vaccine within 30 days of planned start of study intervention. 
Note:  Seasonal influenza vaccines for injection are generally inactivated flu vaccines and 
are allowed; however intranasal influenza vaccines (eg, Flu-Mist®) are live attenuated 
vaccines, and are not allowed. 
12. Has known active central nervous system (CNS) metastases and/or carcinomatous 
meningitis. Participants with previously treated brain metastases may participate provided 
they are stable (without evidence of progression by imaging for at least 4 weeks prior to 
the first dose of study intervention and any neurologic symptoms have returned to 
baseline), have no evidence of new or enlarging brain metastases, and are not using 
steroids for at least 7 days prior to study intervention.  This exception does not include 
carcinomatous meningitis which is excluded regardless of clinical stability.   
13. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study 
Day 1 or who has not recovered (ie, ≤ Grade 1 or at baseline) from AEs due to agents 
administered more than 4 weeks earlier. 
a. Participants with controlled autoimmune disease as described in exclusion 
criterion #3 are permitted to enroll. 
14. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 
2 weeks prior to study Day 1 or who has not recovered (ie, ≤ Grade 1 or at baseline) from 
AEs due to a previously administered agent. 
a. Note:  Participants with ≤ Grade 2 neuropathy and/or hearing loss are an 
exception to this criterion and may qualify for the study. 
b. Note:  If a participant received major surgery, he must have recovered adequately 
from the toxicity and/or complications from the intervention prior to starting 
therapy.   

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15. History of allergy to any of the study intervention components. 
 
5.2.2 
Combination-specific Exclusion Criteria 
1. Has had prior therapy with any anti-PD-1 or anti-PD-L1 antibody (prior therapy with an 
anti-CTLA-4 antibody is permitted). 
2. Has had prior cancer vaccine therapy. 
3. Has a history of acute myeloid leukemia (AML). 
4. History of unstable or deteriorating cardiac disease within the previous 6 months prior to 
screening including but not limited to the following: 
a. Unstable angina or myocardial infarction 
b. Congestive heart failure (New York Heart Association [NYHA] Class III or IV) 
c. Uncontrolled clinically significant arrhythmias 
5. Any pre-excitation syndromes (eg, Wolff-Parkinson-White syndrome). 
 
5.3 
LIFESTYLE CONSIDERATIONS 
No lifestyle considerations/restrictions are required for this cohort. 
5.4 
SCREEN FAILURES 
Refer to the core protocol. 
6 
STUDY INTERVENTION 
Study intervention is defined as any investigational intervention(s), marketed product(s) or 
placebo intended to be administered to a study participant according to the study protocol. 
6.1 
STUDY INTERVENTION(S) ADMINISTERED 
The study interventions to be administered in this study are summarized in Table 5. 
Table 5: 
Study Intervention 
Study 
Intervention 
Name 
Dosage Formulation 
Unit Dose 
Strength(s) 
Dosage 
Level(s) 
Route of 
Administration 
Sourcing 
CDX-301 
Sterile solution for single 
use. Single-use vial 
containing CDX-301 in 
buffered solution 
composed of sodium 
phosphate and sodium 
chloride, with a pH of 7.0 
2.5 mg/mL 
75 µg/kg 
SC 
Celldex 
Therapeutics 

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Study 
Intervention 
Name 
Dosage Formulation 
Unit Dose 
Strength(s) 
Dosage 
Level(s) 
Route of 
Administration 
Sourcing 
INO-5151 
Single-use vial containing 
pGX1101 (plasmid 
encoding PSA; INO-5101), 
pGX1108 (plasmid 
encoding PSMA; INO-
5108), and pGX6001 
(plasmid encoding IL-12) 
(1:1:1 ratio w/w) in 1x 
SSC, pH 7 for injection 
3 mg/mL 
3 mg 
IM followed 
by EP 
Inovio 
Pharmaceuticals 
Nivolumab 
Aqueous solution 
10 mg/mL 
480 mg 
IV infusion 
Bristol-Myers 
Squibb 
EP = electroporation; IL-12 = interleukin-12; IM = intramuscular(ly); IV = intravenous(ly); PSA = prostate-specific 
antigen; PSMA = prostate-specific membrane antigen; SC = subcutaneous(ly); SSC = Saline Sodium Citrate 
formulation 
 
The preferred sequence when INO-5151 and nivolumab are administered on the same day (eg, 
Day 1 of Cycle 1) is:  INO-5151 via electroporation (EP) followed by infusion of nivolumab. 
Study intervention will be administered as follows: 
• CDX-301 will be administered only during the Immune-priming Lead-in at a dose of 
75 µg/kg SC QD x 5 days (Immune-priming Lead-in Days 1 – 5 and Days 22 – 26 [ie, 
Monday – Friday on the weeks administered]). 
• INO-5151 will be administered intramuscularly (IM) at a dose of 3 mg followed by EP 
(Section 6.1.1) on Day 8 of the Immune-priming Lead-in, Day 1 of Cycles 1, 2, and 3, 
and every 12 weeks thereafter (ie, Cycles 6, 9, 12, etc. for up to 2 years) on the same day 
as nivolumab. 
• Nivolumab will be administered at a dose of 480 mg IV over approximately 30 minutes 
Q4W, starting on Day 1 of Cycle 1, for up to 2 years, unless the participant: is no longer 
clinically benefiting (as evidenced by symptomatic or radiographic disease progression 
and/or clinical deterioration); experiences any toxicity meeting specified discontinuation 
criteria (see Section 6.6) or unacceptable toxicity in the best clinical discretion of the 
treating physician; reaches the maximum duration of study intervention; or withdraws 
consent. 
Note: Day 1 of Cycle 1 follows 1 week after Day 22 of the Immune-priming Lead-in. A 
cycle is defined as 4 calendar weeks. 
 

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Administration of study intervention will be performed in a monitored setting in which there is 
immediate access to trained personnel and adequate equipment and medicine to manage 
potentially serious reactions. 
6.1.1 
Investigational Device 
The CELLECTRA® 2000 device is intended for the enhanced uptake and expression of plasmid 
DNA-based biologics in order to enhance vaccine efficacy (ie, via EP). The system is battery 
powered and includes a pulse generator, applicator, and disposable sterile needle array. The 
plasmid is delivered manually by IM injection. All device components are designed to fulfill 
international standards, where applicable, and manufactured in accordance to Inovio design and 
quality specifications. 
CELLECTRA® 2000 generates minimally-controlled, pulsed electrical currents that temporarily 
and reversibly increase cellular membrane permeability without damaging the tissue. An injected 
plasmid DNA formulation can be introduced into the cells with enhanced uptake during the 
period of increased permeability. 
Refer to the IB (INO-5151/INO-5150 and INO-9012 Investigator’s Brochure, 2019) and the 
CELLECTRA® 2000 User’s Manual for complete information and instructions on the use of this 
device. 
6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
Refer to the core protocol for general guidance on handling, storage, and accountability. 
INO-5151 should be stored in a secure, locked area at 2-8°C. 
CDX-301 should be stored in a secure, locked area at 2-8°C and protected from light. CDX-301 
should not be frozen, and CDX-301 vials should not be shaken. CDX-301 liquid should be 
withdrawn from vial gently, avoiding foaming and excess shearing. 
Nivolumab must be stored at 2°-8°C and protected from light and freezing.  
The instructions for reconstitution and administration of the study intervention are described in 
the Pharmacy Manual(s). 
6.3 
RANDOMIZATION AND BLINDING 
This is not a randomized study, and study intervention will be administered in an open-label 
fashion. 
6.4 
STUDY INTERVENTION COMPLIANCE 
Study intervention will be administered by authorized site personnel and tracked using drug 
accountability records. No additional measures of compliance will be instituted. 

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6.5 
CONCOMITANT THERAPY 
Refer to the core protocol. 
6.5.1 
Permitted Therapy 
Refer to the core protocol. 
6.5.2 
Prohibited Therapy 
Refer to the core protocol. 
6.6 
DOSE MODIFICATIONS 
6.6.1 
Dose Modifications for CDX-301, INO-5151, and Nivolumab 
There will be no dose escalation or dose reduction in this study. 
An 8-week enrollment hold will be implemented following treatment of the first 3 participants in 
order to monitor for acute and sub-acute adverse events and ensure that no unanticipated safety 
risks are identified. If no unanticipated safety risks are identified, 3 additional participants may 
be enrolled and initiated on study intervention. After treatment of the 6th participant, another 8-
week enrollment hold will be implemented. During this enrollment hold, new participants may 
be consented and screened, but not initiated on study intervention. 
The initial 6 participants treated in this cohort will be observed for the occurrence of any of the 
AEs described in Table 6 that are observed from the beginning of treatment through completion 
of the first cycle of nivolumab (ie, 8 weeks) and that are considered by the Investigator to be 
possibly, probably, or definitely related to CDX-301, INO-5151, nivolumab, or the 
immunotherapy combination, unless there is a clear alternative explanation. If 1 or no AEs 
described in Table 6 are observed in the first 6 participants, enrollment will continue as planned 
until a total of approximately 15 participants are enrolled. If AEs described in Table 6 are 
observed in 2 or more of the first 6 participants, enrollment into the cohort will be suspended, 
and the Safety Assessment Committee (refer to Section 9.5.1 of the core protocol) will be 
convened to review the available data and provide a recommendation, which may include, but is 
not limited to, modification or discontinuation of the cohort. 
Participants who experience any AE described in Table 6 will be discontinued from all study 
intervention and should continue follow-up assessments as outlined in the SOA (Section 1.3). 
Grade 3 and 4 toxicities are observed in all trials of nivolumab in multiple tumor types. As such 
toxicities are anticipated; however, given the unique nature of this protocol, monitoring for AEs 
described in Table 6 will continue throughout the study. 
The Investigator may attribute each AE to the combination or any individual component of the 
study intervention. Study participants may not have any dose escalations or reductions of 

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CDX-301, INO-5151, or nivolumab in this study. If an Investigator believes a toxicity is 
uniquely related to one agent drug, then appropriate documentation is required regarding the 
drug to which the Investigator is attributing the AE. The following retreatment requirements will 
apply: 
• During the Immune-priming Lead-in if, in the opinion of the Investigator, the toxicity is 
related to CDX-301, then CDX-301 should be withheld (eg, skipped) according to 
recommended dose modifications. 
o If CDX-301-related toxicities prevent the administration of CDX-301 on Days 
22 – 26, administration may be held for up to 1 week to allow for recovery.  
• Cycle 1 may commence following the completion of the Immune-priming Lead-in 
provided the participant meets the retreatment criteria for INO-5151. 
o Starting with Cycle 1 if, in the opinion of the Investigator, the toxicity is related to 
INO-5151 and/or nivolumab then both drugs should be held according to 
recommended dose modifications. If toxicity does not resolve or the criteria for 
resuming study intervention are not met within 8 weeks after the last dose, the 
participant must be discontinued from the combination therapy, unless written 
approval to restart therapy is provided by the Medical Monitor. 
 
The anticipated important safety risks associated with the administration of CDX-301, 
INO-5151, and/or nivolumab, as well as the measures to be taken, are outlined in the following 
sections. Refer to the Investigator’s Brochures for CDX-301, INO-5151, and nivolumab for 
complete summaries of safety information. 

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Table 6: 
Toxicity Criteria Requiring Permanent Treatment Discontinuation 
Participants should be monitored for the occurrence of any of the following AEs that are considered by the 
Investigator to be possibly, probably, or definitely related to CDX-301, INO-5151, nivolumab, or the 
immunotherapy combination. Treatment with all study intervention should be permanently discontinued for the 
following: 
• 
Grade 4 non-hematological toxicity (not laboratory) 
• 
Grade 4 hematologic toxicity lasting ≥ 7 days 
• 
Grade 3 thrombocytopenia in the presence of clinically significant active bleeding (eg, requiring 
transfusion or hospitalization) 
• 
Any non-hematologic toxicity ≥ Grade 3 in severity, with the following exceptions: 
o 
Grade 3 fatigue lasting ≤ 3 days 
o 
Grade 3 nausea, vomiting, or diarrhea lasting ≤ 3 days 
o 
Grade 3 rash without use of corticosteroids or anti-inflammatory agents per standard of care 
o 
Grade 4 fever 
o 
Grade 4 flu-like symptoms lasting ≤ 48 hours 
• 
Any new Grade 3 or Grade 4 non-hematologic laboratory abnormality, if 
o 
the abnormality leads to hospitalization, or 
o 
the abnormality persists for > 1 week and is believed to be clinically significant. For example, 
exceptions would include asymptomatic pancreatitis. 
• 
Febrile neutropenia Grade 3 or Grade 4 
• 
Any elevated AST or ALT laboratory value that is ≥ 3 × ULN and an elevated total bilirubin lab value that 
is ≥ 2 × ULN and an alkaline phosphatase lab value that is < 2 × ULN, in which no alternative reasons can 
be found to explain the combination of increased AST/ALT and total bilirubin, such as viral hepatitis A, B 
or C, preexisting or acute liver diseases, pre-existing known liver metastases, or another drug capable of 
causing the observed injury 
• 
Grade 5 toxicity 
ALT = alanine aminotransferase; AST = aspartate aminotransferase; ULN = upper limit of normal 
 
6.6.1.1 
Potential for Overlapping Toxicities with CDX-301, INO-5151, 
and Nivolumab 
In general, the toxicities associated with the monotherapy administration of CDX-301, 
INO-5151, and nivolumab are not expected to be overlapping when administered in combination. 
The safety data for nivolumab are described in the USPI (Opdivo USPI, 2018). Nivolumab 
therapy is associated with immune-mediated adverse reactions, which can be severe and fatal in 
some cases. With appropriate medical therapy, immune-related adverse reactions resolved in 
most cases. Immune-mediated adverse reactions may involve any organ system; however, the 
most common severe immune-mediated adverse reactions are enterocolitis, endocrinopathies, 
hepatitis, dermatitis (including toxic epidermal necrolysis [TEN] and Stevens-Johnson syndrome 
[SJS]), and neuropathy. The safety profile of nivolumab combination therapy varies with the 
agent combined with nivolumab but is generally consistent with the safety profiles observed with 
either agent alone and, in some cases, both frequency and severity of AEs were greater than that 
observed with either agent alone. 

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The most common toxicity reported with the administration of INO-5151 has been mild to 
moderate administration site pain, which often resolves spontaneously within 5 to 10 minutes 
and may be accompanied by swelling and erythema. Evaluation of creatine phosphokinase for 
risk of muscle damage and electrocardiogram for risk of cardiac conduction abnormalities has 
been clinically unremarkable, and no EP-related safety issues have been identified other than 
transient injection site pain as mentioned above. 
In human studies to date, rhuFlt3L has been well tolerated, with many AEs attributable to 
patients’ underlying malignancy or other compounds/therapies being administered 
concomitantly, and no dose reductions of Flt3L for toxicity were reported in any of these trials. 
Erythematous nodules of up to 1 to 2 cm at the skin injection sites lasting several days were the 
only manifestation of toxicity in most patients. One patient who injected doses into the same area 
daily for 3 consecutive days developed diffuse erythema of the upper arm and adenopathy in the 
axilla that resolved spontaneously. Arthralgias, myalgias, and fever were not reported, nor were 
liver function test abnormalities. With CDX-301 administration, specifically, leukocytosis, 
especially monocytosis, is expected during administration. Injection site reactions have been 
reported and are generally mild to moderate, but occasionally severe. Lymphadenopathy 
occurred in < 20% of study participants, was not associated with AEs, and resolved after 
discontinuation of treatment. When administered in combination with CDX-1401, a DEC-
201/NY-ESO-1 fusion protein, treatment was well tolerated, with the most commonly reported 
AEs being Grade 1-2 chills, injection site erythema and pain, fever, and myalgias. 
6.6.1.2 
Dose Modifications and Toxicity Management for Adverse Events 
Associated with CDX-301, INO-5151, and Nivolumab 
Immuno-oncology agents are associated with AEs that can differ in severity and duration from 
AEs caused by other therapeutic classes. Early recognition and management of AEs associated 
with immuno-oncology agents may mitigate severe toxicity. Management algorithms (Appendix 
C-1) have been developed to assist Investigators in assessing and managing the following groups 
of drug-related AEs: 
• Immune-mediated colitis 
• Immune-mediated nephritis and renal dysfunction 
• Immune-mediated pneumonitis 
• Immune-mediated hepatitis 
• Immune-mediated endocrinopathies (hypophysitis, adrenal insufficiency, hypothyroidism 
and hyperthyroidism, Type 1 diabetes mellitus) 
• Immune-mediated skin adverse reactions 

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• Immune-mediated encephalitis 
 
6.6.1.3 
Dose Modifications and Toxicity Management for 
Infusion/Injection-related Reactions Associated with the 
Administration of CDX-301, INO-5151, and/or Nivolumab 
Interrupt or slow the rate of infusion in participants with mild or moderate infusion reactions. 
Discontinue the immunotherapy combination in participants with severe or life-threatening 
infusion reactions. 
All Grade 3 or 4 infusion reactions must be reported within 24 hours to the study Medical 
Monitor and reported as an SAE if it meets the criteria. Infusion reactions should be graded as 
described in Section 10.5.3 of the core protocol. 
Dose modification and toxicity management guidelines for infusion/injection-related reactions 
are provided in Table 7.  

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Table 7:  
Dose Modification and Toxicity Management Guidelines for Infusion/Injection-related Reactions Associated 
with the Administration of CDX-301, INO-5151, and/or Nivolumab 
Grade 
(NCI CTCAE v 5.0) 
 
Treatment 
Premedication at 
Subsequent Dosing 
Grade 1 
Mild reaction; infusion interruption not indicated; 
intervention not indicated 
Increase monitoring of vital signs as medically indicated until the participant is 
deemed medically stable in the opinion of the Investigator 
None 
Grade 2 
Requires therapy or infusion interruption but responds 
promptly to symptomatic treatment (eg, antihistamines, 
NSAIDs, narcotics, IV fluids); prophylactic medications 
indicated for ≤ 24 hours 
Stop Infusion 
Additional appropriate medical therapy may include but is not limited to: 
IV fluids 
Antihistamines 
NSAIDs 
Acetaminophen 
Narcotics 
Increase monitoring of vital signs as medically indicated until the participant is 
deemed medically stable in the opinion of the Investigator 
If symptoms resolve within 1 hour of stopping drug infusion, the infusion may 
be restarted at 50% of the original infusion rate (eg, from 100 mL/h to 50 mL/h). 
Otherwise dosing will be held until symptoms resolve and the participant should 
be premedicated for the next scheduled dose 
Participants who develop Grade 2 toxicity related to the study intervention, 
and not related to electroporation, despite adequate premedication should 
be permanently discontinued from further study intervention 
Participant may be premedicated 
according to local treatment 
guidelines 
Grades 3 or 4 
Grade 3: 
Prolonged (ie, not rapidly responsive to symptomatic 
medication and/or brief interruption of infusion); 
recurrence of symptoms following initial improvement; 
hospitalization indicated for other clinical sequelae (eg, 
renal impairment, pulmonary infiltrates) 
Grade 4: 
Life-threatening; pressor or ventilatory support indicated 
Stop Infusion 
Administer urgent medical therapy as appropriate/clinically indicated 
Increase monitoring of vital signs as medically indicated until the participant is 
deemed medically stable in the opinion of the Investigator 
Hospitalization may be indicated 
**In cases of anaphylaxis, epinephrine should be used immediately 
Participant is permanently discontinued from further study intervention 
No subsequent dosing 
Appropriate resuscitation equipment should be available at the bedside and a physician readily available during the period of drug administration. 
For further information, please refer to the Common Terminology Criteria for Adverse Events v5.0 (CTCAE) at http://ctep.cancer.gov 
CTCAE = Common Terminology Criteria for Adverse Events; NCI = National Cancer Institute; NSAIDs = nonsteroidal anti-inflammatory drugs; IV = intravenous 
 

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6.6.1.4 
Dose Delays and Interruptions of CDX-301, INO-5151, and 
Nivolumab 
Dose delays and interruptions are permitted for toxicity reasons (see Section 6.6.2, Section 6.6.3, 
and Section 6.6.4). 
The Investigator may attribute each AE to the combination or to either individual intervention. 
• If, in the opinion of the Investigator, the toxicity is related to the combination of the 
agents, then all drugs should be held according to recommended dose modifications. 
• If the toxicity is considered clearly related to 1 agent, but not the others, 
o then the other agents can continue unless toxicity related to that study intervention 
would warrant a dose delay.  
 
Appropriate documentation is required regarding the drug to which the Investigator is attributing 
the AE. If toxicity does not resolve or the criteria for resuming study intervention are not met 
within 8 weeks after the last dose, the participant must be discontinued from the combination 
therapy. 
Dose delays and interruptions for reasons other than toxicity, such as surgical procedures, may 
be allowed with Medical Monitor approval. The acceptable length of interruption will depend on 
agreement between Investigator and Medical Monitor. 
6.6.2 
Dose Modifications for Nivolumab 
This study will include set dosing for nivolumab (480 mg Q4W). Dose escalation or reduction of 
nivolumab will not be allowed. If toxicity does not resolve or the criteria for resuming study 
intervention are not met within 8 weeks after the last dose, the participant must discontinue study 
intervention, unless written approval to restart therapy is provided by the Medical Monitor. 
Specific anticipated or potential toxicities associated with the administration of nivolumab, as 
well as the measures to be taken to avoid or minimize such toxicity in this trial, are described in 
Table 8. 
AEs associated with nivolumab exposure may represent an immunologic etiology. These 
immune-related adverse events (irAEs) may occur shortly after the first dose or several months 
after the last dose of treatment and may affect more than one body system simultaneously. 
Therefore, early recognition and initiation of treatment is critical to reduce complications. Based 
on existing clinical study data, drug-related AEs have included pulmonary toxicity, renal toxicity 
(including acute renal failure), endocrine abnormalities, gastrointestinal toxicity, dermatologic 
toxicity (including rash), and hepatotoxicity. For nivolumab monotherapy, as well as when 
administered in combination, the majority of these AEs have been managed successfully with 

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supportive care and, in more severe cases, a combination of dose delay, permanent 
discontinuation, and/or use of corticosteroids or hormone replacement therapy 
(endocrinopathies). For suspected irAEs, ensure adequate evaluation to confirm etiology or 
exclude other causes. Additional procedures or tests such as bronchoscopy, endoscopy, and skin 
biopsy may be included as part of the evaluation. 
Dose modification and toxicity management guidelines for irAEs associated with nivolumab are 
provided in Table 8. 
Table 8: 
Dose Modification and Toxicity Management Guidelines for Adverse Events 
Associated with Nivolumab 
Adverse Reaction 
Severitya 
Dose Modifications 
Colitis 
Grade 2 diarrhea or colitis 
Withhold doseb 
Grade 3 diarrhea or colitis 
Withhold doseb 
Grade 4 diarrhea or colitis 
Permanently discontinue 
Pneumonitis 
Grade 2 pneumonitis 
Withhold doseb 
Grade 3 or 4 pneumonitis 
Permanently discontinue 
Hepatitis/non-HCC 
Aspartate aminotransferase (AST) or alanine 
aminotransferase (ALT) more than 3 and up 
to 5 times the upper limit of normal (ULN) 
or total bilirubin more than 1.5 and up to 3 
times the ULN 
Withhold doseb 
AST or ALT more than 5 times the ULN or 
total bilirubin more than 3 times the ULN 
Permanently discontinue 
Hepatitis/HCC 
• If AST/ALT is within normal limits at 
baseline and increases to more than 3 and 
up to 5 times the ULN 
• If AST/ALT is more than 1 and up to 3 
times ULN at baseline and increases to 
more than 5 and up to 10 times the ULN 
• If AST/ALT is more than 3 and up to 5 
times ULN at baseline and increases to 
more than 8 and up to 10 times the ULN 
Withhold dosec 
If AST or ALT increases to more than 10 
times the ULN or total bilirubin increases to 
more than 3 times the ULN 
Permanently discontinue 
Hypophysitis 
Grade 2 or 3 hypophysitis 
Withhold doseb 
Grade 4 hypophysitis 
Permanently discontinue 
Adrenal insufficiency 
Grade 2 adrenal insufficiency 
Withhold doseb 
Grade 3 or 4 adrenal insufficiency 
Permanently discontinue 
Type 1 diabetes mellitus 
Grade 3 hyperglycemia 
Withhold doseb 
Grade 4 hyperglycemia 
Permanently discontinue 
Nephritis and renal 
dysfunction 
Serum creatinine more than 1.5 and up to 6 
times the ULN 
Withhold doseb 

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Adverse Reaction 
Severitya 
Dose Modifications 
Serum creatinine more than 6 times the 
ULN 
Permanently discontinue 
Skin 
Grade 3 rash or suspected Stevens-Johnson 
syndrome (SJS) or toxic epidermal 
necrolysis (TEN) 
Withhold doseb 
Grade 4 rash or confirmed SJS or TEN 
Permanently discontinue 
Encephalitis 
New onset moderate or severe neurologic 
signs or symptoms 
Withhold doseb 
Immune-mediated encephalitis 
Permanently discontinue 
Other 
Other Grade 3 adverse reaction 
• First occurrence 
• Recurrence of the same Grade 3 adverse 
reaction 
 
Withhold doseb 
Permanently discontinue 
Life-threatening or Grade 4 adverse reaction 
Permanently discontinue 
Grade 3 myocarditis 
Permanently discontinue 
Requirement for 10 mg per day or greater 
prednisone or equivalent for more than 12 
weeks 
Permanently discontinue 
Persistent Grade 2 or 3 adverse reactions 
lasting 12 weeks or longer 
Permanently discontinue 
Source: Opdivo USPI, 2018  
ALT = alanine aminotransferase; AST = aspartate aminotransferase; HCC = hepatocellular carcinoma; 
SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis; ULN = upper limit of normal 
a Guidelines based on toxicity graded per National Cancer Institute Common Terminology Criteria for Adverse 
Events (NCI CTCAE), where applicable. 
b Resume treatment when adverse reaction improves to Grade 0 or 1. 
c Resume treatment when AST/ALT return(s) to baseline. 
 
6.6.3 
Dose Modifications for INO-5151 
Dose modifications of INO-5151 will not be allowed in this study. If toxicity does not resolve or 
the criteria for resuming study intervention are not met within 8 weeks after the last dose, the 
participant must discontinue the combination therapy, unless written approval to restart therapy 
is provided by the Medical Monitor. 
6.6.4 
Dose Modifications for CDX-301 
Dose escalation or reduction of CDX-301 will not be allowed in this study. Doses of CDX-301 
that are withheld (eg, skipped) for toxicity attributed to CDX-301 (Table 9), and doses that are 
skipped should not be made up. If CDX-301-related toxicities prevent the administration of 
CDX-301 on Days 22 – 26 of the Immune-priming Lead-in, administration may be held for up to 
1 week to allow for recovery. 

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Leukocytosis, especially monocytosis, is expected during administration of CDX-301 and may 
be particularly pronounced when combined with other hematopoietic growth factors. 
Hematological parameters, including white blood cell (WBC) and differential, should be 
monitored in participants receiving CDX-301. 
Specific anticipated or potential toxicities associated with the administration of CDX-301, as 
well as the measures to be taken to avoid or minimize such toxicity in this trial, are described in 
Table 9. 
Table 9: 
Dose Modification and Toxicity Management Guidelines for Adverse Events 
Associated with CDX-301 
Adverse Reaction 
Severity 
Dose Modifications 
Leukocytosis 
WBC count > 50,000 cells/mm3 
Withhold (skip) dosea 
Injection site reaction 
Grade 1 or 2 
No action required regarding CDX-301 
dose. 
Pre-medication with diphenhydramine 
may be considered for participants who 
experience local reactions after treatment 
with CDX-301  
Grade 3 
Permanently discontinue 
Grade 4 
Permanently discontinue 
Other ≥ Grade 2 adverse 
reaction 
• First occurrence 
Withhold (skip) dosea 
• Recurrence of the same 
≥ Grade 2 adverse reaction 
Permanently discontinue 
WBC = white blood cell 
a Resume treatment at the same CDX-301 dose level when adverse reaction returns to baseline, except for instances 
where the potential recurrence of the event poses an undue risk for the participant. Doses that are withheld (eg, 
skipped) should not be made up. 
 
7 
DISCONTINUATIONS OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1 
DISCONTINUATION OF STUDY INTERVENTION 
Refer to the core protocol. 
In addition to the discontinuation criteria described in the core protocol, refer to Table 6, 
Section 6.6.2, Section 6.6.3, and Section 6.6.4 for toxicities requiring permanent discontinuation 
of nivolumab, INO-5151, and/or CDX-301. 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM 
STUDY 
Refer to the core protocol. 

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7.3 
LOST TO FOLLOW-UP 
Refer to the core protocol. 
8 
STUDY ASSESSMENTS AND PROCEDURES 
Refer to the core protocol. Any combination-specific supplementary information or 
modifications from the core protocol are described in the following sections. 
In this study cohort, the time between nivolumab doses must not be less than 24 days. 
8.1 
EFFICACY ASSESSMENTS 
Refer to the core protocol. 
8.1.1 
Laboratory Assessments of Clinical Activity 
Samples for the laboratory assessments of clinical activity and hormone levels in Table 10 will 
be sent to the study site’s local laboratory for analysis: 
Table 10: 
Laboratory Tests Sent to the Study Site’s Local Laboratory for Analysis of 
Disease-related Endpoints 
Profile 
Laboratory Test 
Clinical activity 
PSA 
Hormone levels 
testosterone 
PSA = prostate-specific antigen 
 
 
8.2 
SAFETY ASSESSMENTS 
Refer to the core protocol. 
8.2.1 
Clinical Safety Laboratory Assessments 
8.2.1.1 
Local Laboratory Assessments 
Samples for the laboratory tests in Table 11 will be sent to the study site’s local laboratory for 
analysis: 

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Table 11: 
Laboratory Tests Sent to the Study Site’s Local Laboratory for Analysis of 
Safety 
Profile 
Laboratory Test 
Hematology 
RBC count 
hemoglobin 
hematocrit 
WBC count with automated differential (neutrophils, eosinophils, basophils, 
monocytes, lymphocytes, other cells) 
platelet count 
manual differential, if clinically indicated 
Clinical Chemistry 
(Serum or Plasma) 
sodium 
potassium 
chloride 
bicarbonate 
glucose 
BUN or urea 
creatinine 
total protein 
albumin 
calcium 
total bilirubin 
alkaline phosphatase 
ALT 
AST 
LDH 
TSH (T3 and FT4 should be checked if TSH is outside the normal range) 
coagulation assessments (PT, PTT, INR)a 
Urinalysis 
 
ALT = alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; 
INR = international normalized ratio; LDH = lactate dehydrogenase; PT = prothrombin time; PTT = partial 
thromboplastin time; RBC = red blood cell; TSH = thyroid stimulating hormone; WBC = white blood cell 
a Coagulation assessment not required during treatment phase unless indicated 
 
8.3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
Refer to the core protocol for the SAE and AE collection periods and for details regarding safety 
reporting. 
8.3.4 
Regulatory Reporting Requirements for SAEs 
Refer to the core protocol for the regulatory reporting requirements for SAEs. 
For this cohort, the Parker Institute for Cancer Immunotherapy Pharmacovigilance Group will 
report SAEs to regulatory authorities, the overall PI, Bristol-Myers Squibb, Inovio 
Pharmaceuticals, Celldex Therapeutics, and the Institutional Review Board/Independent Ethics 
Committee (IRB/IEC), as appropriate. The process for such reporting, including contact 

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information and specific instructions for reporting to each of these organizations, is described in 
the Safety Monitoring Plan. 
8.3.7 
Adverse Events of Special Interest 
There are no identified adverse events of special interest for this immunotherapy combination. 
8.4 
TREATMENT OF OVERDOSE 
Refer to the core protocol. 
8.5 
PHARMACOKINETICS 
Sparse pharmacokinetics (PK) blood sampling will be collected according to the SOA to assess 
the PK of CDX-301 and/or nivolumab. 
PK profiles for CDX-301 and/or nivolumab will be performed using a validated assay method 
under the supervision of the Sponsor’s designee. 
8.6 
IMMUNOGENICITY AND ANTI-DRUG ANTIBODIES 
Immunogenicity samples will be collected according to the SOA to enable evaluation of immune 
response against PSMA and/or PSA and anti-drug antibodies (ADA) to CDX-301 and/or 
nivolumab. Additionally, blood samples should also be collected at the final visit from 
participants who discontinued study intervention or were withdrawn from the study. These 
samples may be tested by the Sponsor's designee. 
The detection and characterization of antibodies to CDX-301 and/or nivolumab may be 
performed using a validated assay method under the supervision of the Sponsor’s designee.  
The detection and characterization of immune response against PSA and/or PSMA may be 
performed using enzyme-linked immunospot (ELISpot) assays or other assays. 
8.7 
BIOMARKERS 
Refer to the core protocol. 
Immune profiling may be performed, including evaluation of dendritic cell numbers and 
activation using flow cytometry or other assays. Additionally, immune response against PSMA 
and PSA maybe be evaluated by ELISpot. 
8.8 
MEDICAL RESOURCE UTILIZATION AND HEALTH 
ECONOMICS 
Refer to the core protocol. 
9 
STATISTICAL CONSIDERATIONS 
Refer to the core protocol. 

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9.5.1 
Interim Safety Monitoring 
Refer to the core protocol for details related to the Safety Assessment Committee (SAC), the 
committee charged with safety review for this study. 
With the inclusion of a safety period for the first 6 participant for this study cohort (see 
Section 6.6.1), the likelihood of proceeding to full enrollment decreases as the risk of toxicity 
from an AEs described in Table 6, as demonstrated in Table 12. 
Table 12: 
Probability of Proceeding to Full Enrollment 
True Risk of Toxicity 
0.10 
0.20 
0.30 
0.40 
0.50 
0.60 
Probability of Full Enrollment 
0.89 
0.66 
0.42 
0.23 
0.11 
0.04 
Assumes P(X≤1) where X is a binomial random variable with sample size n = 6 and p = true risk of toxicity. 
 
Table 13 shows the width of 95% confidence intervals calculated for possible observed rates of 
AEs described in Table 6 within the study. 
Table 13: 
Incidence with 95% Confidence Intervals of Possible Observed Adverse 
Events Described in Table 6 
Number of Participants with Adverse 
Eventsa/Number of Participants 
Incidence of Adverse Eventsa 
95% Confidence Intervalb 
0/6 
0 
[0, 0.39] 
1/6 
0.17 
[0.03, 0.56] 
2/6 
0.33 
[0.10, 0.70] 
3/6 
0.50 
[0.19, 0.81] 
a Adverse events described in Table 6  
b Wilson method for computing confidence interval 
 
 

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10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
Refer to the core protocol for the following appendices: 
Appendix 1: Regulatory, Ethical and Study Oversight Considerations 
Appendix 2: Eastern Cooperative Oncology Group (ECOG) Performance Status 
Appendix 3: RECIST Criteria (Version 1.1) with Modifications as Recommended by 
PCWG3 
Appendix 4: Clinical Laboratory Tests 
Appendix 5: Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-
up, and Reporting 
Appendix 6: Contraceptive Guidance and Collection of Pregnancy Information 
Appendix 7: Genetics 

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10.1 
APPENDIX C-1: MANAGEMENT ALGORITHMS 
Management algorithms have been developed to provide guidance for Investigators in assessing 
and managing immune-mediated events in participants receiving nivolumab. Section 6.6.2 
describes the criteria for dose delay and discontinuation to be followed for nivolumab in this 
cohort. These algorithms are intended to provide clinical recommendations. In cases in which the 
modification criteria in Section 6.6.2 and the algorithms differ, the criteria in Section 6.6.2 
should take precedence.  
The management algorithms are provided for the following groups of drug-related AEs: 
• Immune-mediated gastrointestinal adverse events (diarrhea, colitis) 
• Immune-mediated renal adverse events (nephritis and renal dysfunction) 
• Immune-mediated pulmonary adverse events (pneumonitis) 
• Immune-mediated hepatic adverse events (hepatitis) 
• Immune-mediated endocrinopathy adverse events (hypophysitis, adrenal insufficiency, 
hypothyroidism and hyperthyroidism, Type 1 diabetes mellitus) 
• Immune-mediated skin adverse events 
• Immune-mediated neurologic adverse events (encephalitis) 
 
 

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10.2 
APPENDIX C-2: LISTS OF TERMINOLOGY AND 
ABBREVIATIONS 
10.2.1 
List of Terminology 
Terminology 
Description 
Cohort 
A group of participants receiving the same immunotherapy 
combination. 
Cohort appendix 
A document that guides the treatment of participants in a given 
cohort. The cohort appendices are identified using a letter 
designation (eg, Appendix Cohort C).  
Core protocol 
The master document that provides the elements common 
across the study and among all cohorts, unless otherwise 
specified. 
Immunotherapy combination 
Two or more study interventions administered to a cohort of 
participants. 
 
10.2.2 
List of Abbreviations 
Abbreviation 
Definition 
ADA 
anti-drug antibody(ies) 
ADC 
antibody drug conjugates 
ADP 
adenosine diphosphate 
AE(s) 
adverse event(s) 
AIDS 
acquired immunodeficiency syndrome 
ALT 
alanine aminotransferase 
AML 
acute myeloid leukemia 
APC 
antigen-presenting cells 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
BUN 
blood urea nitrogen 
C 
cycle 
Cavgss 
average steady-state concentration 
CDX-1401 
DEC-201/NY-ESO-1 fusion protein vaccine 
cfDNA 
cell-free deoxyribonucleic acid 
cHL 
classical Hodgkin lymphoma 
Cmax 
maximum observed drug concentration 
Cmaxss 
maximum steady-state plasma concentration 
Cminss 
minimum steady-state plasma concentration 
Cmin1 
trough concentration after the first dose 

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Abbreviation 
Definition 
CNS 
central nervous system 
CRC 
colorectal cancer 
CRPC 
castration-resistant prostate cancer 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTL 
cytotoxic T-lymphocyte 
CTLA-4 
cytotoxic T-lymphocyte-associated protein 4 
D 
day 
DC(s) 
dendritic cell(s) 
DCR 
disease control rate 
dMMR 
mismatch repair deficient 
DNA 
deoxyribonucleic acid 
DoR 
duration of response 
DT 
doubling time 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
ELISpot 
enzyme-linked immunospot 
EOT 
end of treatment 
EP 
electroporation 
EPO 
erythropoietin 
FDA 
Food and Drug Administration 
FFPE 
formalin-fixed paraffin-embedded 
Flt3L 
FMS-related tyrosine kinase 3 ligand 
GCP 
Good Clinical Practice 
GFR 
glomerular filtration rate 
HCC 
hepatocellular carcinoma 
HIV 
human immunodeficiency virus 
HPV 
human papillomavirus 
I/E 
inclusion/exclusion 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
IFN-γ 
interferon gamma 
IgG4 
immunoglobulin G4 
IM 
intramuscular(ly) 
IL-12 
interleukin-12 
INR 
international normalized ratio 
irAE(s) 
immune-related AE(s) 
IRB/IEC 
Institutional Review Board/Independent Ethics Committee 
IV 
intravenous(ly) 

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Abbreviation 
Definition 
LDH 
lactate dehydrogenase 
mAb 
monoclonal antibody 
mCRPC 
metastatic castration-resistant prostate cancer 
mRNA 
messenger ribonucleic acid 
MSI-H 
microsatellite instability-high 
NCI 
National Cancer Institute 
NK 
natural killer 
nmCRPC 
nonmetastatic castration-resistant prostate cancer 
NPCP 
National Prostate Cancer Project 
NSAIDs 
nonsteroidal anti-inflammatory drugs 
NSCLC 
non-small cell lung cancer 
NYHA 
New York Heart Association 
ORR 
objective response rate 
OS 
overall survival 
PARP 
poly ADP ribose polymerase 
PBMC 
peripheral blood mononuclear cell 
PCR 
polymerase chain reaction 
PCWG3 
Prostate Cancer Clinical Trials Working Group 3 
PD 
progressive disease 
PD-1 
programmed cell death 1 
PD-L1 
programed cell death ligand 1 
pDNA 
plasmid DNA 
PET 
positron emission tomography 
PFS 
progression-free survival 
PI 
Principal Investigator 
PK 
pharmacokinetics 
poly-ICLC 
polyinosinic-polycytidylic acid stabilized with polylysine and 
carboxymethylcellulose 
PORTER 
Prostate Researching Translational Endpoints Correlated to Response 
PPK 
population pharmacokinetics 
PSA 
prostate-specific antigen 
PSMA 
prostate-specific membrane antigen 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
Q2W 
every 2 weeks 
Q3M 
every 3 months 
Q3W 
every 3 weeks 
Q4W 
every 4 weeks 

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Abbreviation 
Definition 
Q12W 
every 12 weeks 
QD 
daily 
RBC 
red blood cell 
RCC 
renal cell carcinoma 
RECIST 
Response Evaluation Criteria in Solid Tumors 
rhIL-12 
recombinant human IL-12 
rhu 
recombinant human 
rhuFlt3L 
recombinant human Flt3 ligand 
RNA 
ribonucleic acid 
rPFS 
radiographic progression-free survival 
S 
screening 
SAC 
Safety Assessment Committee 
SAE(s) 
serious adverse event(s) 
SARS 
severe acute respiratory syndrome 
SC 
subcutaneous(ly) 
SCCHN 
squamous cell carcinoma of the head and neck 
SFU 
spot forming units 
SGOT 
serum glutamic-oxaloacetic transaminase 
SGPT 
serum glutamic-pyruvic transaminase 
SIV 
simian immunodeficiency virus 
SJS 
Stevens-Johnson syndrome 
SOA 
Schedule of Activities 
TB 
tuberculosis 
TEN 
toxic epidermal necrolysis 
Tmax 
mean time to maximum serum concentration 
TMB 
tumor mutational burden 
TNF-α 
tumor necrosis factor alpha 
TSH 
thyroid stimulating hormone 
UC 
urothelial carcinoma 
ULN 
upper limit of normal 
US 
United States 
USPI 
US Prescribing Information 
WBC 
white blood cell 
XRT 
radiation therapy 
 

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10.3 
APPENDIX C-3: APPENDIX COHORT C AMENDMENT 
HISTORY 
 
DOCUMENT HISTORY 
Documents 
Date of Issue 
Amendment 1 
30 Apr 2019 
Original Appendix Cohort C 
26 Feb 2019 
 
 
 

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11 
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