Clinical trial NCT03956056
Conditions: Pancreas Cancer Pancreatic Cancer Cancer of the Pancreas
Sponsor: Washington University School of Medicine
Start date: 2020-02-13; Completion date: 2023-07-06
Enrollment: 12 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a phase 1 open-label study to evaluate the safety and immunogenicity of a neoantigen peptide vaccine strategy in pancreatic cancer patients following surgical resection and adjuvant chemotherapy. The neoantigen peptide vaccines will incorporate prioritized neoantigens and personalized mesothelin epitopes and will be co-administered with poly-ICLC. The hypothesis of this study is that neoantigen peptide vaccines will be safe and capable of generating measurable neoantigen-specific CD4 and CD8 T cell responses.

Detailed description:

Arms: arm 1: The schedule for vaccination will be Days 1, 4, 8, 15, and 22 (delays of up to 96 hours are allowed for each dose based on the adverse events experienced). Additional vaccinations will be given on Days 50 and 78 (+/- 2 weeks). The first vaccine dose may be administered following confirmation of disease-free status and within 90 days following date of repeat imaging. All study injections will be given subcutaneously and co-administered with poly-ICLC by a trained healthcare provider.
Interventions: intervention 1: Neoantigen Peptide Vaccine intervention 2: Poly ICLC intervention 3: Blood for immune monitoring
Intervention descriptions: intervention 1: • Each pool of vaccine study drug + poly IC:LC will be administered to one of the four limbs (A - Right Arm, B - Left Arm, C - Right Leg, D - Left Leg) by subcutaneous (SC) injection. intervention 2: • Each pool of vaccine study drug + poly IC:LC will be administered to one of the four limbs (A - Right Arm, B - Left Arm, C - Right Leg, D - Left Leg) by subcutaneous (SC) injection. intervention 3: -Baseline, day 1, day 22, day 50, day 78, week 25, and week 73

Protocol documents:
Prot_SAP_000.pdf: 
Washington University School of Medicine 
Protocol Date 02/22/22 (A2) 
Siteman Cancer Center 
Pancreatic Cancer Peptide Vaccine 
Neoantigen peptide vaccines  
 
Page 1 of 61 
A PHASE 1 CLINICAL TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY 
OF A NEOANTIGEN PEPTIDE VACCINE STRATEGY IN PANCREATIC CANCER 
PATIENTS FOLLOWING SURGICAL RESECTION AND ADJUVANT 
CHEMOTHERAPY 
HRPO #: 201908124 
Version date: 02/22/2022 
IND #: 19125 
ClinicalTrials.gov #: NCT03956056 
 
INVESTIGATORS 
Principal Investigators: 
Daniel A. Laheru, MD 
Medical Oncologist 
Johns Hopkins School of Medicine 
401 N. Broadway 
Baltimore, MD 21231 
Telephone: 410-955-8974 
E-mail: Laherda@jhmi.edu 
 
William E. Gillanders, M.D. 
IND Sponsor, Surgical Oncologist 
Washington University School of Medicine 
660 South Euclid, Box 8109 
St. Louis, MO 63110 
Telephone: 314-747-0072 
E-mail: gillandersw@wustl.edu 
 
Co-Investigators: 
Robert D. Schreiber, Ph.D. 
Immunobiologist 
Washington University School of Medicine 
660 South Euclid, Box 8118 
St. Louis, MO 63110 
Telephone: 314-362-8747 
E-mail: Schreiber@wustl.edu  
 
Christopher A. Miller, Ph.D. 
Genome Scientist 
The Genome Center at WUSM 
660 South Euclid, Box 8501 
St. Louis, MO 63110 
Telephone: 314-286-0263 
E-mail: c.a.miller@wustl.edu 
 
Elizabeth Jaffee, M.D. 
Medical Oncologist 
Johns Hopkins School of Medicine 
1650 Orleans Street, Cancer Research Bldg #4M07 
Baltimore, MD 21231 
Telephone: 410-614-8216 
E-mail: ejaffee@jhmi.edu 
 
Feng Gao, M.D., Ph.D. 
Biostatistician 
Washington University School of Medicine 
660 South Euclid, Box 8067 
St. Louis, MO 63110 
Telephone: 314-362-3682 
E-mail: feng@wustl.edu 
 
S. Peter Goedegebuure, Ph.D. 
Immunologist 
Washington University School of Medicine 
660 South Euclid, Box 8109 
St. Louis, MO 63110 
Telephone: 314-362-8612 
E-mail: goedegep@wustl.edu 
 
William Hawkins, M.D. 
Surgical Oncologist 
Washington University School of Medicine 
660 South Euclid, Box 8109 
St. Louis, MO 63110 
Telephone: 314-362-7046 
E-mail: hawkinsw@wudosis.wustl.edu 
 
Kian H. Lim, MD 
Medical Oncologist 
Washington University School of Medicine 
660 South Euclid, Box 8089 
St. Louis, MO 63110 
Telephone: 314-747-9320 
E-mail: klim@dom.wustl.edu 
 
Marianna Ruzinova, M.D., Ph.D. 
Pathologist 
Washington University School of Medicine 
BJCIH 03303 
St. Louis, MO 63110 
Telephone: 314-362-7704 
E-mail: mruzinova@wustl.edu  
 
C. Alston James, MD 
Surgical Oncology Research Fellow 
Washington University School of Medicine 
660 South Euclid, Box 8109 
St. Louis, MO 63110 
Telephone: 314-333-1831 
E-mail: jamesc@wustl.edu 
 


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Pancreatic Cancer Peptide Vaccine 
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SUMMARY 
Protocol: 
A PHASE 1 CLINICAL TRIAL TO EVALUATE THE SAFETY AND 
IMMUNOGENICITY OF A NEOANTIGEN PEPTIDE VACCINE STRATEGY IN 
PANCREATIC CANCER PATIENTS FOLLOWING SURGICAL RESECTION 
AND ADJUVANT CHEMOTHERAPY 
Study Design: 
This is a phase 1 open-label study to evaluate the safety and immunogenicity of 
a neoantigen peptide vaccine strategy in pancreatic cancer patients following 
surgical resection and adjuvant chemotherapy. The neoantigen peptide vaccines 
will incorporate prioritized neoantigens and personalized mesothelin epitopes 
and will be co-administered with poly-ICLC. The hypothesis of this study is that 
neoantigen peptide vaccines will be safe and capable of generating measurable 
neoantigen-specific CD4 and CD8 T cell responses. The primary objective of this 
study is to demonstrate the safety and feasibility of the neoantigen peptide 
vaccine strategy. The secondary objective is to evaluate the immunogenicity of 
the neoantigen peptide vaccine strategy as measured by ELISPOT analysis and 
multi-parametric flow cytometry, surrogates for T cell function. 
Product Description: The neoantigen peptide vaccines are composed of synthetic long peptides which 
are 25-30 amino acids in length and designed to express mutant tumor specific 
antigens identified by exome sequencing. These are processed by the immune 
system differently than minimal peptide vaccines, prolonging the duration of 
peptide presentation, and T cell activation. Peptide vaccines will be administered 
subcutaneously and will be co-administered with poly-ICLC. 
Subjects: 
Pancreatic cancer patients who have completed surgical resection and adjuvant 
chemotherapy without evidence of recurrent disease are eligible. Patients 
enrolled into the protocol must provide consent for exome sequencing and 
dbGAP-based data sharing and provide germline and tumor DNA samples of 
adequate quality for sequencing. 
Study Plan: 
Fifteen pancreatic cancer patients will be enrolled. Subjects will be treated with 
synthetic long peptides corresponding to prioritized neoantigens in combination 
with poly-ICLC, a synthetic toll-like receptor ligand. The peptides and poly-ICLC 
will be mixed prior to injection. Peptide and poly-ICLC will be administered 
subcutaneously at days 1, 4, 8, 15, 22, 50, and 78 with at least 24 hours between 
injection days. 
Study Duration: 
Each subject will be followed for 12 months following the last vaccination. 
Additional follow-up visits or telephone contact will be scheduled annually 
thereafter if the patient is alive and available for follow-up. 
Study Endpoints: 
The primary endpoint is safety of the neoantigen peptide vaccine regimen. Safety 
will be closely monitored after injection with eight or more clinical and laboratory 
assessments in the first six months of the trial. Toxicity will be graded according 
to the National Cancer Institute Common Terminology Criteria for Adverse 
Events version 5.0. The secondary endpoint is immunogenicity of the vaccine 
regimen as measured by ELISPOT analyses and multiparametric flow cytometry. 
Exploratory analyses will include other measures of immune function, including 
CYTOF analysis. 
 


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SCHEMA 
 
 


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PROTOCOL SIGNATURE PAGE 
 
A PHASE 1 CLINICAL TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY 
OF A NEOANTIGEN PEPTIDE VACCINE STRATEGY IN PANCREATIC CANCER 
PATIENTS FOLLOWING SURGICAL RESECTION AND ADJUVANT 
CHEMOTHERAPY 
 
I have read the attached clinical protocol and agree to conduct this trial in accordance with all the 
stipulations of the protocol and in accordance with the Declaration of Helsinki/Tokyo/Venice on 
Experimentation in Humans as required by the United States Food and Drug Administration regulations, 
Code of Federal Regulations Title 21 parts 50, 56, 312, 800, Title 45 part 46 and all applicable guidelines. 
 
Name of Investigator: 
 
 
Signature 
Date 
 


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TABLE OF CONTENTS 
SUMMARY _________________________________________________________________ 2 
SCHEMA ___________________________________________________________________ 3 
PROTOCOL SIGNATURE PAGE ______________________________________________ 4 
1 
OBJECTIVES ___________________________________________________________ 7 
 
PRIMARY OBJECTIVE ________________________________________________________________ 7 
 
SECONDARY OBJECTIVE ______________________________________________________________ 7 
 
EXPLORATORY OBJECTIVES ___________________________________________________________ 7 
2 
BACKGROUND _________________________________________________________ 8 
 
PANCREATIC CANCER _______________________________________________________________ 8 
 
MUTATIONAL LANDSCAPE IN PANCREATIC CANCER _________________________________________ 8 
 
TUMOR MICROENVIRONMENT _________________________________________________________ 8 
 
TUMOR ANTIGENS __________________________________________________________________ 8 
 
NEXT GENERATION SEQUENCING _______________________________________________________ 9 
 
PERSONALIZED CANCER VACCINES _____________________________________________________ 9 
 
PRIORITIZATION OF SEQUENCING-IDENTIFIED NEOANTIGENS __________________________________ 9 
 
SYNTHETIC LONG PEPTIDE VACCINES ___________________________________________________ 10 
 
CLINICAL TRIAL DESIGN AND DOSE CONSIDERATIONS ______________________________________ 10 
 
CHALLENGES OF SEQUENCING PANCREATIC CANCERS ______________________________________ 11 
3 
PATIENT SELECTION _________________________________________________ 12 
 
INCLUSION CRITERIA _______________________________________________________________ 12 
 
EXCLUSION CRITERIA _______________________________________________________________ 12 
 
STEP 1 ELIGIBILITY ________________________________________________________________ 13 
 
INCLUSION OF WOMEN AND MINORITIES ________________________________________________ 13 
4 
REGISTRATION PROCEDURES _________________________________________ 14 
 
PRIOR TO REGISTRATION ____________________________________________________________ 14 
 
REGISTRATION PROCEDURES _________________________________________________________ 14 
 
CONFIRMATION OF PATIENT ELIGIBILITY ________________________________________________ 15 
 
PATIENT REGISTRATION IN THE SITEMAN CANCER CENTER ONCORE DATABASE _________________ 15 
 
ASSIGNMENT OF UPN ______________________________________________________________ 15 
5 
INVESTIGATIONAL AGENT ____________________________________________ 16 
 
NEOANTIGEN PEPTIDE VACCINE ______________________________________________________ 16 
 
POLY-ICLC (HILTONOL) ____________________________________________________________ 24 
 
NONCLINICAL STUDIES _____________________________________________________________ 25 
 
SEQUENCING PIPELINE ______________________________________________________________ 28 
 
EPITOPE PREDICTION ALGORITHM _____________________________________________________ 28 
6 
TREATMENT PLAN ____________________________________________________ 30 
 
PEPTIDE VACCINE ADMINISTRATION ___________________________________________________ 30 
 
CONCOMITANT MEDICATION GUIDELINES _______________________________________________ 30 
 
DEFINITIONS OF EVALUABILITY _______________________________________________________ 30 
 
DURATION OF THERAPY _____________________________________________________________ 31 
 
DURATION OF FOLLOW UP ___________________________________________________________ 31 
7 
POTENTIAL TOXICITY AND DOSE MODIFICATIONS ____________________ 32 
 
POTENTIAL TOXICITY _______________________________________________________________ 32 
 
TOXICITY MONITORING AND MANAGEMENT _____________________________________________ 32 


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DOSE MODIFICATIONS ______________________________________________________________ 32 
8 
STUDY CALENDAR ____________________________________________________ 33 
9 
CRITERIA FOR RESPONSE _____________________________________________ 34 
 
PRIMARY OBJECTIVE: SAFETY ________________________________________________________ 34 
 
SECONDARY OBJECTIVES: EVALUATION OF THE IMMUNE RESPONSE ___________________________ 34 
 
EXPLORATORY OBJECTIVES __________________________________________________________ 35 
10 REMOVAL OF SUBJECTS FROM PROTOCOL THERAPY _________________ 37 
 
REMOVAL OF SUBJECTS FROM PROTOCOL THERAPY ________________________________________ 37 
 
VOLUNTARY SUBJECT WITHDRAWAL ___________________________________________________ 37 
 
PROCEDURE FOR DISCONTINUATION ___________________________________________________ 37 
11 REGULATORY AND REPORTING REQUIREMENTS ______________________ 39 
 
SPONSOR-INVESTIGATOR REPORTING REQUIREMENTS _____________________________________ 39 
 
SECONDARY SITE REPORTING REQUIREMENTS ___________________________________________ 40 
 
EXCEPTIONS TO EXPEDITED REPORTING ________________________________________________ 41 
12 DATA AND SAFETY MONITORING _____________________________________ 42 
 
DEVELOPMENTAL THERAPEUTICS _____________________________________________________ 43 
 
PROTOCOL STOPPING CRITERIA _______________________________________________________ 43 
13 STATISTICAL CONSIDERATIONS ______________________________________ 44 
 
EXPERIMENTAL DESIGN _____________________________________________________________ 44 
 
DATA ANALYSIS __________________________________________________________________ 45 
14 DATA MANAGEMENT _________________________________________________ 47 
 
ADVERSE EVENT COLLECTION IN THE CASE REPORT FORMS ________________________________ 48 
15 AUDITING ____________________________________________________________ 48 
16 MULTICENTER REGULATORY REQUIREMENTS ________________________ 49 
17 REGULATORY AND ETHICAL OBLIGATIONS ___________________________ 50 
 
INFORMED CONSENT _______________________________________________________________ 50 
 
INSTITUTIONAL REVIEW BOARD ______________________________________________________ 50 
 
SUBJECT CONFIDENTIALITY __________________________________________________________ 50 
18 ADMINISTRATIVE AND LEGAL OBLIGATIONS _________________________ 51 
 
STUDY DOCUMENTATION AND RETENTION OF RECORDS ____________________________________ 51 
 
POLICY REGARDING RESEARCH-RELATED INJURIES ________________________________________ 51 
 
STUDY TERMINATION _______________________________________________________________ 51 
19 REFERENCES _________________________________________________________ 52 
20 APPENDICES __________________________________________________________ 55 
 
ABBREVIATIONS __________________________________________________________________ 55 
 
ECOG/ZUBROD PERFORMANCE STATUS SCALE ___________________________________________ 56 
 
NATIONAL CANCER INSTITUTE COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS _________ 56 
 
DEFINITIONS FOR ADVERSE EVENT REPORTING __________________________________________ 57 
 
REPORTING TIMELINES _____________________________________________________________ 59 
 
WASHINGTON UNIVERSITY UNANTICIPATED PROBLEM REPORTING COVER SHEET _______________ 61 
 


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1 OBJECTIVES 
This is a phase 1 open-label study to evaluate the safety and immunogenicity of a neoantigen peptide 
vaccine strategy. The neoantigen peptide vaccine strategy is designed to target prioritized neoantigens 
that are present in an individual patient’s pancreatic cancer but not in corresponding normal tissues. The 
vaccines will be formulated as synthetic long peptides and will be administered subcutaneously in 
conjunction with poly-ICLC. The hypothesis of this study is that the neoantigen peptide vaccine strategy 
will be safe for human administration and capable of generating measurable T cell responses to the 
neoantigens. 
 Primary objective 
The primary objective is to assess the safety and feasibility of the neoantigen peptide vaccine approach. 
This trial will be considered feasible if we are able to successfully perform tumor/normal exome 
sequencing, identify at least 3 neoantigens per patient, and manufacture and administer neoantigen 
vaccines to more than 50% of enrolled patients. 
 Secondary objective 
The secondary objective, and primary scientific endpoint, is to assess the prevalence of antigen-specific T 
cells in the peripheral blood of patients pre- and post-vaccination as measured by flow cytometry and 
ELISPOT.  
 Exploratory objectives 
Exploratory objectives include measurement of immune response, including the phenotype and functional 
status of neoantigen-specific T cells as measured by CYTOF analysis. 
An exploratory clinical endpoint is to assess clinical response as measured by disease-free survival and 
overall survival. 
 
 


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2 BACKGROUND 
 Pancreatic cancer 
Pancreatic adenocarcinoma is currently the 4th leading cause of cancer related death with the incidence 
of disease expected to increase by 2030 [1, 2]. Despite recent advances in conventional chemotherapy 
regimens for pancreatic cancer there has been little improvement in outcomes for patients facing this 
recalcitrant disease [3, 4]. Currently, surgical resection remains the only curative treatment. However, 5-
year survival is achieved in only 20-25% of those with operative disease at time of diagnosis. 
 Mutational landscape in pancreatic cancer 
Next generation sequencing technologies have been used to characterize the mutational landscape in 
pancreatic cancer. Exome sequencing studies have revealed an average of 63 genetic alterations 
affecting 12 core cellular pathways [5]. The majority of these alterations were point mutations with the 
most frequently mutated genes being KRAS, TP53, and SMAD4. Tumors demonstrated heterogeneity in 
regard to the genomic alterations present, indicating that a spectrum of mutations are present across 
individual patients. 
 Tumor microenvironment 
Pancreatic cancer has a robust desmoplastic stroma with an abundant leukocyte infiltrate [6, 7]. This 
stroma is implicated in resistance to conventional therapies by limiting effective delivery of therapies to 
malignant cells [8]. The immune infiltrate is predominantly tumor promoting cells derived from the bone 
marrow, including tumor associated macrophages and myeloid derived suppressor cells (MDSC) [9, 10]. 
Furthermore, effector tumor infiltrating lymphocytes are scarce with the majority of tumor infiltrating 
lymphocytes being immunosuppressive FoxP3+ regulatory T-cells (Tregs). 
 Tumor antigens 
Tumor antigens are often classified as shared tumor antigens and tumor-specific antigens (neoantigens). 
The majority of tumor-specific antigens are now believed to be the result of somatic mutations present in 
the tumor. 
Shared tumor antigens are expressed in multiple cancers, and are often self-differentiation antigens that 
are expressed in a limited subset of normal tissues, but overexpressed in cancers. Examples of shared 
tumor antigens include MAGE (melanoma) [11], prostatic acid phosphatase (prostate cancer) [12], and 
HER2/neu (breast cancer) [13]. Mesothelin is a shared tumor antigen that is highly expressed in 
pancreatic adenocarcinoma [14]. A listeria modified to express mesothelin has been used in pancreatic 
cancer clinical trials and has demonstrated safety and efficacy [15]. Jaffee et al. have characterized the 
immunogenic epitopes for mesothelin for the HLA-A1, HLA-A2, HLA-A3, and HLA-A24 alleles [16, 17]. 
Tumor-specific antigens (or neoantigens) are uniquely expressed in individual cancers, and are typically 
the result of point mutations or other genetic changes that are present only in the tumor (reviewed in [18, 
19]). As such, tumor-specific antigens represent the only antigens that are truly unique to the tumor and 
not expressed in normal tissues. The first human mutant tumor-specific antigen was described in 1995, 
resulting from a point mutation of cyclin-dependent kinase (CDK4) [20]. Since that time additional 
publications have described the expression of neoantigens in melanoma [21], non-small cell lung cancer 
[22] and other human cancers [23]. 
Cancer vaccine strategies targeting neoantigens have substantial theoretical advantages over strategies 
targeting shared tumor antigens. Theoretical advantages include: (1) Targeting neoantigens is potentially 
safer. Neoantigens are expressed only in the tumor, decreasing the risk of autoimmunity. (2) Targeting 
neoantigens is potentially more effective. T cell responses to neoantigens are high in affinity and are not 
limited by central mechanisms of self-tolerance. (3) Targeting neoantigens potentially limits antigen-loss, 
a common tumor escape mechanism. One of the hallmarks of cancer is genome instability, and one clear 
weakness of cancer vaccines that target a single shared tumor antigen is antigen-loss. Targeting multiple 
neoantigens may preclude antigen loss. In addition, many neoantigens play a functional role in neoplastic 
transformation (driver mutations). (4) Targeting neoantigens is likely to be universally applicable in 
epithelial cancers, including pancreatic cancer. Epithelial cancers appear to have significant numbers of 


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nonsynonymous mutations present, suggesting that a personalized vaccine approach could be used in 
most patients with pancreatic cancer, regardless of HLA type.  
We have recently used next generation sequencing technologies to identify and study neoantigens in 
more detail as described in the sections below [24, 25]. 
 Next generation sequencing 
Robust next-generation sequencing strategies for the identification of neoantigens will be required for the 
successful clinical translation of personalized cancer vaccine strategies. As such, a major focus of our 
research studies has been the development of cost-effective and accurate next-generation sequencing 
strategies to identify neoantigens and validate the expression of these antigens at the mRNA level. 
Initially a cancer genome sequencing approach was used. While cancer whole genome sequencing is 
informative and provides comprehensive information about both the coding and noncoding regions of the 
genome, this level of information may not be necessary for identifying neoantigens, or prioritizing antigens 
for immune intervention. We have now confirmed that tumor/normal exome sequencing is a robust and 
accurate strategy for the identification of neoantigens [24, 25]. Of note, recent studies suggest that 
approximately 40% of mutations identified by cancer exome sequencing are not expressed at the mRNA 
level, so it is important to confirm expression of the mutant allele at the mRNA level. To evaluate mRNA 
expression, we have performed cDNA-capture sequencing analyses. We have confirmed that cDNA-
capture sequencing can be used to successfully confirm expression of sequencing-identified neoantigens 
at the mRNA level. This analysis also provides an estimation of how highly expressed the mutated allele 
is expressed relative to other genes in the tumor. For the phase 1 clinical trial proposed, tumor/normal 
exome sequencing analysis will be used to identify mutations (single nucleotide variants, insertions and 
deletions) present only in the tumor, and cDNA-capture sequencing will be used to confirm mutant allele 
expression and expression level in the tumor mRNA. 
 Personalized cancer vaccines 
There are two conceptual strategies for creating personalized cancer vaccines targeting neoantigens: a 
candidate epitope strategy, and an unbiased strategy. The candidate epitope strategy uses computer 
algorithms [26, 27] and in vitro studies to predict immunodominant epitopes, which are then integrated 
into a personalized vaccine. In the unbiased strategy, no attempt is made to identify the immunodominant 
epitopes, and all candidate neoantigens are integrated into a personalized vaccine. 
We have considered both the candidate epitope strategy and the unbiased strategy. We believe that the 
candidate epitope strategy is superior to the unbiased strategy for the following reasons. (1) Preliminary 
data from preclinical models and human correlative studies suggest that relatively few sequencing-
identified neoantigens are processed, presented and effectively recognized by the immune system. (2) 
We have now developed and validated algorithms for the prediction and prioritization of sequencing-
identified neoantigens [24, 25]. (3) Targeting a limited number of prioritized sequencing-identified 
neoantigens will facilitate vaccine design and manufacture and streamline immune monitoring. 
 Prioritization of sequencing-identified neoantigens 
Of note, we have now developed and validated an epitope prediction algorithm for the prioritization of 
sequencing-identified neoantigens. Once somatic mutations have been identified and mutant mRNA 
expression confirmed/quantified using the sequencing strategies outlined above, neoantigens will be 
prioritized using an epitope prediction algorithm that has been designed to select and prioritize the most 
promising sequencing-identified neoantigens. Currently, the most commonly used CD8 T cell epitope 
prediction algorithm is NetMHC. However, collaborative work conducted by Robert Schreiber, Elaine 
Mardis, Max Artyomov and William Gillanders has shown that a much more accurate prediction comes 
from calculating a median affinity for each sequencing-predicted mutant epitope using multiple available 
epitope prediction algorithms (i.e. NetMHC Pan; ANN; and SMM). We have significantly improved this 
epitope prediction algorithm by applying these filters to the initial prioritized output list: (a) elimination of 
hypothetical proteins; (b) use of an antigen processing algorithm to eliminate epitopes that are not likely 
to be proteolytically produced by constitutive proteasomes or immunoproteasomes; and (c) prioritization 
of “neo-epitopes” identified by a higher affinity binding of the mutant peptide sequence compared to the 
wildtype peptide sequence. The final output of these analyses is a rank-ordered list of the highest to 


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lowest priority sequencing-identified neoantigens for each individual patient. In experiments performed 
using preclinical mouse sarcoma models, this refined prediction algorithm has successfully identified the 
major tumor rejection antigens in three out of three tumors tested to date [24, 25]. To our knowledge, this 
is the only algorithm that has been successfully applied to date to cancer vaccine development. Additional 
information about the preclinical validation of the epitope prediction algorithm is provided in Section 5.2 
Nonclinical Studies. MHC class II epitopes can also be accurately predicted using a similar algorithm 
(Artimov, unpublished data). 
Once a rank-ordered list of the highest to lowest priority sequencing-identified mutant tumor-specific 
peptide antigens is generated, we will generate tetramers corresponding to the top 5-10 class I 
neoantigens using a photo-activated peptide tetramer protocol. We will stain T cells from the peripheral 
blood of subjects using a state-of-the-art CyTOF processor. Mutant epitopes associated with positive 
tetramer staining will be prioritized for the generation of neoantigen peptide vaccines. Once the candidate 
mutant epitopes have been verified, multivalent peptide vaccine construction will commence. 
 Synthetic long peptide vaccines 
The neoantigen peptide vaccine strategy is based on the synthetic long peptide vaccine platform. We 
have focused on this platform because of the established safety and documented efficacy of this platform. 
First generation peptide-based cancer vaccines have typically included "minimal epitope" peptides, i.e. 
peptides of 9-10 amino acids in length known to bind to specific MHC class I alleles. First generation 
peptide-based cancer vaccines have an excellent safety profile and have been successful in inducing 
peptide-specific T cell responses in the peripheral blood of cancer patients, as measured by ELISPOT or 
tetramer analysis.  
These initially promising results with first-generation peptide-based cancer vaccines prompted 
investigators to explore improvements to the platform. These investigations have resulted in "next-
generation" peptide-based cancer vaccines [28] including synthetic long peptide vaccines. Synthetic long 
peptide vaccines are 25-30 amino acids in length and are processed by the immune system differently 
than minimal epitope peptide vaccines. This prolongs the duration of peptide presentation and T cell 
activation [29, 30]. Synthetic long peptide vaccines have proven to be both safe and remarkably effective 
in clinical translation [31]. In our previous experience, we have been able to successfully design and 
manufacture neoantigen synthetic long peptide vaccines in > 85% of cases. Processing of synthetic long 
peptides and T cell activation can be further enhanced through the activation of toll-like receptors on the 
surface of APC. In particular, the TLR3 agonist, poly-ICLC is commonly used as an adjuvant to enhance 
the efficacy of peptide-based cancer vaccines, including synthetic long peptide-based vaccines [31].  
 Clinical trial design and dose considerations 
The early clinical development paradigm for chemotherapeutic agents has significantly influenced the 
development of therapeutic cancer vaccines. However, there are major differences between these two 
classes of therapeutics that have important implications for early clinical development. Specifically, the 
phase 1 concept of dose escalation to find a maximum-tolerated dose does not apply to most therapeutic 
cancer vaccines. Most therapeutic cancer vaccines are associated with minimal toxicity at a range that is 
feasible to manufacture or administer, and there is little reason to believe that the maximum-tolerated 
dose is the most effective dose. 
In a recent article from the biostatistics literature, Simon et al. write that "the initial clinical trial of many 
new vaccines will not be a toxicity or dose-ranging trial but rather will involve administration of a fixed 
dose of vaccine … in most cases the dose selected will be based on preclinical findings or practical 
considerations. Using several dose levels in the initial study to find the minimal active dose or to 
characterize the dose-activity relationship is generally not realistic" [32]. 
The peptide vaccine will integrate multiple peptides corresponding to prioritized neoantigens in 
combination with the molecular adjuvant poly IC:LC. We propose to test a fixed dose of peptide 
consistent with recent reports [33]. The final peptide concentration is 300 µg/mL of each peptide after 
mixture with poly-ICLC 


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 Challenges of sequencing pancreatic cancers 
The challenges of performing massively parallel sequencing (MPS) assays from clinical pancreatic cancer 
samples are considerable. At its essence, pancreatic adenocarcinoma has a low cellularity, with many 
stromal cells interspersed with the pancreatic cancer cells. A pathologist who is a specialist in 
gastrointestinal cancers will survey the tumor to identify islands of high tumor cellularity and take 1mm 
punches from formalin fixed paraffin embedded (FFPE) tissues. By selecting these areas for sequencing 
we are able to enrich the tumor purity to the level that allows neoantigen identification. Additionally, since 
the tissues have been previously subjected to FFPE, some degradation of the nucleic acids may result, 
further complicating the sample quality toward MPS. 
Nevertheless, our group has worked extensively to optimize MPS library construction techniques that 
enable high diversity libraries to be constructed from as little as 10 ng of input DNA. In particular, we 
currently utilize the Swift Biosciences Accel-NGS 2S kit that is optimized for low input DNA from FFPE 
samples with an input range of 10-50 ng of isolated DNA. The resulting libraries have proven suitable for 
subsequent exome capture by hybridization such as the Integrated DNA Technologies (IDT) Rapid 
Exome reagent. This commercially available reagent has superior performance on FFPE-derived DNA 
libraries, and has a rapid hybridization time of only 4 hours, permitting a one-day turn around for library 
construction, quantitation, and hybrid capture prior to sequencing. 
Another challenge of pancreatic adenocarcinoma is the rapid degradation of RNA that often occurs during 
surgery. Our surgical team has been evaluating whether the RNA stability can be influenced by changes 
to the surgical procedure that reduce ischemia time during surgery. In our early experience with several 
samples, this alteration in the surgical procedure leads to dramatic improvements to the RNA stability as 
gauged by RNA integrity (RIN) values obtained from our post-isolation QC procedures. In turn, the MPS 
libraries generated from these pancreatic RNAs are of high quality and diversity. 
 
 


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3 PATIENT SELECTION 
 Inclusion criteria 
A patient will be eligible for evaluation and sequencing of tissue for vaccine development (Step 0) and 
vaccine administration (Step 1) only if ALL of the following criteria apply: 
1. Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma; mixed 
histology will be included as long as the predominant histology is adenocarcinoma. 
2. Completed an R0 or R1 surgical resection as determined by pathology  
3. Pathology review demonstrates tumor cellularity no less than 30% in quantities sufficient to 
obtain 6-8 1mm biopsies from the original FFPE blocks.  
4. At least 18 years of age. 
5. Life expectancy of > 12 months. 
6. ECOG performance status ≤ 2 
7. Normal bone marrow and organ function as defined below: 
a. WBC 
≥3,000/μL 
b. absolute neutrophil count 
≥1,500/μL 
c. platelets 
≥100,000/μL 
d. total bilirubin 
≤1.5 X institutional upper limit of normal 
(Subjects with Gilbert’s syndrome may be 
enrolled despite a total bilirubin level >1.5 mg/dL 
if their conjugated bilirubin is <1.5 x ULN) 
e. AST/ALT 
≤2.5 X institutional upper limit of normal 
f. 
creatinine 
≤1.5 X institutional upper limit of normal 
8. International Normalized Ratio (INR) and activated partial thromboplastin time (PTT) < 1.5 x 
ULN provided the patient is not on anticoagulation therapy. 
9. Patients who have had a stent placed for biliary obstruction can be included in the study 
provided serum bilirubin at time of enrollment is within protocol limits. 
10. Women of child-bearing potential and men must agree to use adequate contraception (hormonal 
or barrier method of birth control, abstinence) prior to study entry and for the duration of study 
participation. Should a woman become pregnant or suspect she is pregnant while participating 
in this study, she must inform her treating physician immediately. 
11. Able to understand and willing to sign an IRB approved written informed consent document. 
 Exclusion criteria 
A patient will be ineligible for inclusion in this study if ANY of the following criteria apply: 
1. Evidence of neuroendocrine tumor, duodenal adenocarcinoma, or ampullary adenocarcinoma.  
2. Received neoadjuvant chemotherapy for their pancreatic adenocarcinoma. 
3. Evidence of disease recurrence or metastasis following surgical resection at any time prior to the 
first vaccination administration. Most patients will undergo restaging midway through adjuvant 
chemotherapy and at the completion of therapy; however, timing of imaging is at the discretion of 
the patient’s medical oncologist. 
4. History of other malignancy ≤ 3 years previous with the exception of basal cell or squamous cell 
carcinoma of the skin which were treated with local resection only, carcinoma in situ of the cervix, 
or LCIS/DCIS of the breast. 
5. Known allergy, or history of serious adverse reaction to vaccines or TLR agonists such as 
anaphylaxis, hives, or respiratory difficulty. 


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6. Acute or chronic, clinically significant hematologic, pulmonary, cardiovascular, hepatic renal, 
and/or other functional abnormality that would jeopardize the health and safety of the participant 
as determined by the investigator based on medical history, physical examination, laboratory 
values, and/or diagnostic studies. 
7. A psychiatric illness/social situations that would limit compliance with study requirements as 
determined by the investigator from the medical history, physical exam, and/or medical record 
8. Prior or currently active autoimmune disease requiring management with immunosuppression. 
This includes inflammatory bowel disease, ulcerative colitis, Crohn’s disease, systemic vasculitis, 
scleroderma, psoriasis, multiple sclerosis, hemolytic anemia, immune-mediated 
thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, 
sarcoidosis, or other rheumatologic disease or any other medical condition or use of medication 
(e.g., corticosteroids) which might make it difficult for the patient to complete the full course of 
treatments or to generate an immune response to vaccines. In the case of asthma or chronic 
obstructive pulmonary disease taking inhaled corticosteroids that does not require daily systemic 
corticosteroids is acceptable. Additionally, local acting steroids (topical, inhaled, or intraarticular) 
will be allowed. Patients on intermittent or short course steroids will be allow if the dose does not 
exceed 4 mg of dexamethasone (or equivalent) per day for > 7 consecutive days. Any patients 
receiving steroids should be discussed with the PI to determine if eligible. 
9. Pregnant and/or breastfeeding. 
10. Known HIV-positive status. These patients are ineligible because of the potential inability to 
generate an immune response to vaccines. 
 Step 1 eligibility 
At Step 1 eligibility confirmation prior to vaccination, the above criteria must be met plus: 
1. Completed adjuvant chemotherapy: 
a. Initiation of adjuvant chemotherapy within 16 weeks of surgery 
b. Completion of at least 4 months of adjuvant chemotherapy with 
gemcitabine/capecitabine  FOLFIRINOX, or similar adjuvant chemotherapy at the 
discretion of the patient’s medical oncologist.  
c. Additional chemoradiation therapy as recommended by the patient’s medical oncologist. 
d. Reimaging post-completion of chemotherapy demonstrates no evidence of recurrent 
disease and CA 19-9 is less than 92.5 u/mL. 
e. Dose modifications and/or delays in adjuvant chemotherapy is at the discretion of the 
treating physician 
2. There is a 1 week washout prior to Day 1 of vaccine for patients on daily systemic steroids at 
doses exceeding 10 mg prednisone. 
3. Receiving any other investigational agents, or has received an investigational agent within the 
last 30 days. 
 Inclusion of women and minorities 
Both men and women and members of all races and ethnic groups are eligible for this trial. 
 
 


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Pancreatic Cancer Peptide Vaccine 
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4 REGISTRATION PROCEDURES 
 Prior to registration 
4.1.1 
Subject recruitment 
The methods used for recruitment of subjects in the study will be devoid of any procedures that may be 
construed as coercive. The recruitment process will not involve any restrictions based on social or 
demographic factors including age, or ethnic characteristics of the subject population. However, the 
composition of the study subject population will depend on patient sources available to the investigators. 
Subjects will be identified and recruited for this study as follows: 
Patients will be recruited from Washington University’s Siteman Cancer Center and Johns Hopkins 
Sidney Kimmel Comprehensive Cancer Center outpatients or patient referrals by our community 
oncologists to the principal investigator and co-investigators. Patients must be willing and able to give 
their written informed consent indicating that they are aware of the investigational nature of the study. 
After a patient is deemed eligible for study, the principal investigator (or co-investigators) will discuss the 
Washington University/Johns Hopkins IRB-approved informed consent with the patient. This written 
informed consent will be signed and dated by the patient and the principal investigator (or co-
investigators). The original consent will be placed in the patient’s permanent record and a copy will be 
given to the patient. 
Washington University School of Medicine (WUSM)/Johns Hopkins Medicine (JHM) has an approved 
Multiple Project Assurance of Compliance with Department of Health and Human Services Regulations 
for the Protection of Human Research Subjects on file with the Office for Human Research Protection 
(OHRP). The Human Research Protection Office Policies and Procedures for Protection of Human 
Research Subjects details all policies and procedures for the protection of human research subjects and 
can be obtained upon request from the Human Research Protection Office. 
4.1.2 
Compliance and understanding 
All patients who present with a diagnosis of pancreatic cancer will be screened for eligibility for entry into 
the study at their postoperative follow up with their surgeon or initial postoperative appointment with their 
medical oncologist. As in all trials, the goal is to achieve a high level of compliance with protocol 
requirements by assuring, during the eligibility assessment, that the potential subject is fully informed and 
agrees to the protocol requirements. In addition, subjects with a strong likelihood of non-adherence such 
as difficulties in adhering to follow-up schedule due to geographic distance from the Siteman Cancer 
Center/Sidney Kimmel Comprehensive Cancer Center, should not knowingly be registered. Adherence of 
the Siteman Cancer Center/Sidney Kimmel Comprehensive Cancer Center staff to careful assessment of 
the subject’s understanding of the trial and a clinical center environment which supports the continued 
commitment of the subjects are essential for the trial to be successfully completed. 
4.1.3 
Presentation of informed consent 
Consent will be obtained by either the principal investigator or by individuals approved by the principal 
investigator and whose names and copy of their curriculum vitae have been filed. The initial consent 
should be the IRB-approved version corresponding to the version of the protocol approved when the 
screening was initiated. Informed consent is to be obtained from the subject according to Section 17.1 
Informed Consent of this protocol. 
 Registration procedures 
Patients must not start any protocol intervention prior to registration through the Siteman Cancer 
Center. 
Registration for this trial will be a two-step process. Step 0 will be screening and confirmation of eligibility 
for vaccine creation. Step 1 will be screening and confirmation of eligibility for vaccine administration. See 
Section 3: Patient Selection for eligibility criteria for each step and Section 8: Study Calendar for 
screening procedures for each step. 


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Step 0 screening must occur within 16 weeks of surgical resection, and Step 0 enrollment can occur up to 
four weeks after initiation of adjuvant chemotherapy. Step 1 screening will occur when the patient’s 
vaccine is ready or nearly ready, but must be within 14 days of the first vaccine administration. 
The following steps must be taken before registering patients to this study: 
(1) 
Confirmation of patient eligibility by Washington University (applies to both Step 0 and Step 1) 
(2) 
Registration of patient in the Siteman Cancer Center database (This will be done by Washington 
University research coordinator. Step 0 enrollment will be “On Study” in the OnCore database, and Step 1 
enrollment will be “On Treatment” in the OnCore database.) 
(3) 
Assignment of unique patient number (UPN) 
Once the patient has been entered in the Siteman Cancer Center OnCore database, the WUSM 
coordinator will forward verification of enrollment and the UPN via email. 
 Confirmation of patient eligibility 
Confirm patient eligibility for both Step 0 and Step 1 by collecting the information listed below and 
scanning and emailing it to the research coordinator listed in the Siteman Cancer Center Clinical Trials 
Core Protocol Procedures for Secondary Sites packet at least two business days prior to registering 
patient (if a quicker turnaround is needed, please contact primary study coordinator at Washington 
University): 
(1) 
Your name and contact information (telephone number, fax number, and email address) 
(2) 
Your site PI’s name, the registering MD’s name, and your institution name 
(3) 
Patient’s race, sex, and DOB 
(4) 
Three letters (or two letters and a dash) for the patient’s initials 
(5) 
Currently approved protocol version date 
(6) 
Copy of signed consent form (patient name may be blacked out) 
(7) 
Planned date of enrollment 
(8) 
Completed eligibility checklist, signed and dated by a member of the study team 
(9) 
Copy of appropriate redacted source documentation confirming patient eligibility 
 Patient registration in the Siteman Cancer Center OnCore database 
Registrations may be submitted Monday through Friday between 8am and 5pm CT. Urgent late afternoon 
or early morning enrollments should be planned in advance, and coordinated with the Washington 
University research coordinator. Registration will be confirmed by the research coordinator or his/her 
delegate by email within two business days. Verification of eligibility and registration should be kept in the 
patient chart. 
All patients at all sites must be registered through the Siteman Cancer Center OnCore database at 
Washington University. 
 Assignment of UPN 
Each patient will be identified with a unique patient number (UPN) for this study. Patients will also be 
identified by first, middle, and last initials. If the patient has no middle initial, a dash will be used on the 
case report forms (CRFs). All data will be recorded with this identification number on the appropriate 
CRFs. 
 
 


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5 INVESTIGATIONAL AGENT 
 Neoantigen Peptide Vaccine 
5.1.1 
Physical, chemical and biological characteristics 
The personalized synthetic long peptide vaccine strategy is based on the synthetic long peptide vaccine 
platform. Synthetic long peptides will be 16-35 amino acids in length. The peptides will be designed to 
generate an immune response to neoantigens found in an individual patient’s tumor. The amino acid 
sequence of the synthetic long peptides will correspond to the amino acid sequence of the prioritized 
candidate neoantigens. Synthetic long peptide vaccines will be designed in the Gillanders laboratory 
based on the following general steps:  
(1) Pancreatic adenocarcinoma tissue and normal lymphocytes will be obtained from pancreatic cancer 
patients who are eligible for the phase 1 clinical trial.  
(2) A pancreas specific pathologist will review the operative specimen slides to verify tumor cellularity 
and quantity sufficient for proceeding 
(3) The corresponding FFPE blocks will be punched with a disposable 1mm biopsy punch. 6-8 full 
thickness punches will be taken from areas of high tumor cellularity and divided evenly into two DNA 
LoBind Eppendorf tubes (one tube for DNA and one for RNA).  
(4) DNA and RNA are subsequently extracted in the Washington University Center for Human 
Immunology and immunotherapy Programs (CHIIPS) core.  
(5) Tumor/normal exome sequencing and tumor cDNA-capture sequencing, if feasible, will be performed 
to identify candidate neoantigens.  
(6) Candidate neoantigens will be prioritized based on epitope prediction algorithms and in vitro studies 
as outlined previously.  
(7) Mesothelin expression will be confirmed by RNA analysis, if patients are confirmed to express 
mesothelin and are HLA-A1, HLA-A2, HLA-A3, or HLA-24, the corresponding mesothelin epitopes will 
be added to the vaccine.  
(8) Synthetic long peptides corresponding to the prioritized neoantigens will be designed. For single 
nucleotide variants, the mutant amino acid will be at or near the center of the synthetic long peptide 
and the entire minimal epitope will be included. The exact length and sequence of the synthetic long 
peptide will also integrate manufacturing considerations in consultation with peptide chemists at 
CSBio.  
(9) The neoantigen peptide vaccines will be manufactured and vialed at CSBio. 
5.1.2 
Manufacturing facility 
Synthetic long peptides supplied by CSBio will be manufactured according to the process described 
below. The sequencing pipeline to identify candidate neoantigens and the epitope prediction algorithms to 
prioritize candidate neoantigens are described in the IND. 
Synthetic long peptides supplied from CSBio will be provided to WUSM with a Certificate of Analysis of 
product specifications to confirm product quality prior to release. Release specification criteria will include: 
1) Appearance; 2) Identity by Mass Spectral Analysis (MW); 3) Peptide Content by Nitrogen Elemental 
Analysis; 4) Residual Solvents By Gas Chromatography; 5) Peptide Purity by Analytical HPLC; 6) 
Trifuoracetic Acid Content by analytical HPLC. The pooled peptides will also be tested with the Bacterial 
Endotoxins and Microbial Limit Test and the results provided to WUSM. 
5.1.2.1 
Manufacturing Process for CSBio Peptides 
The CSBio solid phase Fmoc peptide synthesis is based on sequential addition of alpha-amino and side 
chain protected amino acid residues to an insoluble polymeric support (see Production Scheme below for 
detailed method). Synthesis is carried out in a batchwise manner using a CS Bio automated peptide 
synthesizer. Resin is contained in a filter reaction vessel and reagents added and removed under 


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computer control. Synthesis is performed by the stepwise addition of activated amino acids to the solid 
support starting from the carboxy terminus to the amino terminus. The activation and coupling of amino 
acids is performed by HBTU/HOBT chemistry and dimethylformamide is used as the main wash solvent.  
At the end of synthesis, the peptide is cleaved off the resin by reagent K (TFA + Scavengers) for 2-5 
hours at room temperature, and subjected to multiple ether extractions. Crude peptides are subjected to 
vacuum filtration followed by RP-HPLC purification using a C18 column. HPLC purification is performed 
on a system that is qualified by a trained specialist to comply with FDA standards. The purity and identity 
of the peptide is confirmed by running analytical HPLC and mass spectrum analysis. The final purified 
peptides will be shell frozen in glass jars using liquid nitrogen, lyophilized, and packaged at the GMP 
facility as a dry lyophilized powder under environmentally controlled conditions.  
Solid Phase Fmoc Peptide Production Scheme: 
A. Synthesis: 
Resin: MBHA Resin, Wang Resin, ClTrt Resin or AM Resin 
Resin Scale: mmol 
AA: Arg(Pbf), Asn/Gln/Cys/His (Trt), Asp/Glu (OtBu), Lys/Trp (Boc), Ser/Thr/Tyr (tBu), 
Met/Gly/Ile/Leu/Phe/Pro/Val/Ala 
Coupling Method (Fmoc Chemistry) 
Coupling Reagent:  
Rx/DIC/HOBt/AA, in DMF (First Coupling) 
Rx/DIC/HOBt/AA and/or DIEA/HBTU/AA, in DMF (Optional, Double Coupling) 
Capping with Ac2O and DIEA in DMF (Optional) 
Coupling time (water-jacketed, with heat): 
46 minutes for each AA attachment (First Coupling) 
46 minutes (HOBt/DIC) or 20 to 46 minutes (HBTU/DIEA) for each AA attachment (Optional, Double 
Coupling) 
2 minutes (Optional, Capping) 
Coupling time (no heat): 
2 to 6 hours for each AA attachment (First Coupling) 
2 to 6 hours (HOBt/DIC) or 1 to 2 hours (HBTU/DIEA) for each AA attachment (Optional, Double 
Coupling) 
5 minutes (Optional, Capping) 
B. Cleavage Method: 
Reagent K (TFA/EDT/TIS/H2O, 94/2/2/2), 2 ~ 5 hours at room temperature 
C. Purification: 
Column: C18, 4.1-10 cm x 22.5-27.5 cm 
Column Equilibration: 2-10% Buffer B for NLT 1.5 Column Volumes 
Sample Loading: Dilute with purified water or Buffer A as necessary to drop Acetonitrile level below 
elution percentage. Load to column maintaining a system pressure ≤ 1500 PSI. 
Preparative HPLC Run Gradient: 
The starting %B at or above equilibration %B but lower than peptide elution percentage 
The ending %B above elution but below wash method percentage 
Typical gradient has a change of 0.3-1.0 %B change per minute over a 50 to 80 minute period. 
Mobile Phase: Aqueous Buffer A (0.1% TFA or 1% TEAP or 0.1% NH4OH, or 50-100mM NH4OAc or 0.5-
1% AcOH) and Organic Buffer B (Acetonitrile). 
D. Ion-exchange: 
Column: C18, 4.1-10 cm x 22.5-27.5 cm 
Column Equilibration: 2-10% Buffer B for NLT 1.5 Column Volumes  
Mobile Phase (pre-gradient):  
1.) Buffer A, 1 % TEAP; Buffer B, ACN  
2.) Buffer A, 50-100mM NH4OAc; Buffer B, ACN 


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3.) Buffer A, 0.5-1% AcOH; Buffer B, ACN 
Preparative HPLC Run Gradient: 
The starting %B at or above equilibration %B but lower than peptide elution percentage 
The ending %B above elution but below wash method percentage 
Typical gradient has a change of 0.3-1.5 %B change per minute over a 40 to 70 minute period. 
Mobile Phase: Aqueous Buffer A (0.5-1% AcOH) and Organic Buffer B (Acetonitrile). 
E. Lyophilization: 
Shell frozen in 1 L glass jars using liquid nitrogen and lyophilized on Virtis Freezemobile 35 L. 
Condenser Temperature: < -55 °C 
Vacuum: ≤ 1000 mT after attaching jar 
5.1.2.2 
Product Formulation for CSBio Peptides 
Peptides will be reconstituted at CSBio immediately prior to product release tests. Random vials will 
be selected for product release testing. The recommended methods for identity, purity and contents 
for testing of peptides produced as Active Pharmaceutical Ingredients (APIs) under cGMP, will be 
performed as outlined in Table 1: 
TABLE 1: Synthetic long peptide product release tests 
Criteria 
Method 
Specification 
Test Site/SOP # 
Appearance 
Visual inspection 
White to off-
white powder 
CS Bio / SOP 08-16 
Molecular Weight 
Determination 
Identification by Mass Spectral 
Analysis 
MW+/- 1.0 up 
to 2000d 
CS Bio / SOP 08-08 
Peptide content by CHN 
Analysis 
Nitrogen Elemental Analysis Report result 
CS Bio / SOP 08-10 
Primary Counter Ion 
Analytical HPLC 
Report result 
CS Bio / SOP 08-13 or  
SOP 08-111 
Secondary Counter 
Ion 
Analytical HPLC 
Report result 
CS Bio / SOP 08-13 or  
SOP 08-111 
Residual Organic 
Solvents 
Gas chromatography 
Within ICH 
guidelines 
CS Bio / SOP 08-12 
Peptide Purity 
Analytical HPLC 
≥ 95% 
CS Bio / SOP 08-06 
Visual Inspection of Appearance: Physical appearance testing can be the most subjective but 
important test performed on drug substances that can give valuable information about the color and 
solid state of the peptide. Typical testing involves viewing the material against a white background 
under good lighting and reporting the color and solid state. Thus, ensuring that the sample products 
have the appropriate visual characteristics based on established specifications. 
Identification by Mass Spectral Analysis: Mass spectrometry provides key tools for the analysis of 
peptides and a powerful technique for the identification and elucidation the structure of peptides.  
Molecular weight analysis is determined by flow injection analysis – mass spectrometry (FIA-MS) 
using a single quadrupole detection. The peptide sample is dissolved in a mixture of MeOH/Water 
and Acetonitrile (ACN) which is further injected into the MS system.  
Peptide Content by CHN Nitrogen Elemental Analysis: The content of the peptide can be easily 
determined by Nitrogen determination by CHN elemental analysis. Briefly, Carbon, Hydrogen, and 
Nitrogen are determined using a 2400 Perkin-Elmer CHN Analyzer. The analyzer uses combustion 
to convert the sample elements to simple gasses, i.e. CO2, H2O, and N2. Upon entering the analyzer, 


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the sample is combusted in pure oxygen environment at high temperatures of ~ 1000°C. Peptide 
content is calculated from the determined content of nitrogen in the sample compared to the 
theoretical nitrogen content of the specified peptide.  
Primary and Secondary Counter ion by RP-HPLC: The quantitation of counter ions of 
trifluoroacetate (TFA) and acetate can be determined by RP-HPLC. The primary counter ion TFA is 
exchanged under acidic conditions and separated by gradient Reverse-Phase HPLC using a C18 
column and a mobile phase. The mobile phase normally consists of Phosphoric acid (H3PO4), 
Methanol (MeOH) and deionized water. UV detection at 210nm is normally used for this 
measurement. 
Residual Organic Solvents by Gas Chromatography: Residual organic solvents of Acetonitrile 
(ACN), and N,N-Dimethylformamide (DMF) are extracted using DMSO and separated by headspace 
has chromatography (HS-GC) using a Zebron capillary column. The mobile phase or gas carrier is 
normally Helium. Measurement is by Flame Ionization Detector (FID). Quantitation of residual 
solvents in sample peptides is by determined by comparing to reference standards for each residual 
solvent. Other solvents can be easily added to residual solvents testing if they were used in the 
manufacturing process. 
Peptide Purity by RP-HPLC: The peptide purity is normally determined using RP-HPLC, which is 
the most common, widely used and well-established tool universally used in quality control. The 
separation of sample peptides by RP-HPLC involve continuous partitioning of the molecules 
between the mobile phase and the hydrophobic stationary phase. The mobile phase consists of 
various amounts of Trifluoroacetic acid, Acetonitrile and Water and normally measurements is by UV 
absorption at ~ 214nm. 
The above described attributes are considered essential components of a peptide specification. 
Stability assays are not likely to be appropriate for this project, as peptides synthesized for use in the 
phase 1 clinical trial will be used within weeks of their synthesis.  
5.1.2.3 
Labels 
CSBio pooled peptides will be provided with the following labels:  
Peptide Synthesis Facility 
Product Name: Study # - PPI # - Peptide Pool ( A, B, C, etc) 
Component: 
1PP-XXXX, SLP name, PP-XXXX, SLP name …. 
2Process Lot #: PLYY-XXX 
Manufacture Date: mm/yyyy 
Quantity: 25.0 +/- 5.0 mL 
Concentration:  0.4 mg/mL 
Store ≤ -75oC ± 10oC 
Not for human use without sterile processing 
Note: 
1Part Numbers will include the number for each of the peptides in the pool that will be reflected on 
the corresponding peptide sequence located in the shipping manifest. 
2Process Lot # reflects the batch production record for all pools in a batch order 
5.1.3 
Product Formulation 
Synthetic long peptides manufactured by CSBio will be supplied to WUSM as low bioburden pooled 
peptide solutions. The low bioburden, pooled peptides will be supplied in a 50 mL conical tube at a final 


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Neoantigen peptide vaccines  
 
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concentration of 0.4 mg/mL in 26.7% DMSO, and shipped to the Biologic Therapy Core Facility (BTCF) at 
Washington University School of Medicine on dry ice and will be stored at -75°C +/- 10°C. The peptide 
pools will then be sterile filtered and aliquoted into sterile cryovials (Step 1), representative cryovials will 
be selected for sterility and endotoxin testing (Step 2), and then transferred or shipped to the appropriate 
investigational pharmacy (Step 3). 
Steps 1-3 are summarized and then described in detail below. 
(1) The peptide pools will be sterile filtered and aliquoted into sterile cryovials 
(2) Representative cryovials will be selected for sterility and endotoxin testing 
(3) Cryovials will be transferred to the investigational pharmacy at WUSM (or shipped to the 
appropriate investigational pharmacy at participating sites). The vialed product will be stored at -
75°C +/- 10°C prior to use. 
Specifically: 
Step 1. The peptide pools will be sterile filtered and aliquoted into sterile cryovials. 
Each diluted peptide pool will then be sterile filtered with a 0.2 micron DMSO-compatible filter (for 
example, a 0.2 micron DSMO-safe Acrodisc syringe filter; Pall Corporation: Product# 4433 or equivalent). 
Each peptide pool will then be aliquoted into 12 x 1.8 mL sterile cryovials (1.5 mL per 1.8 mL sterile 
cryovial). 7 cryovials will be designated for injection, 3 cryovials will be designated for product release 
tests, and 2 cryovials will be held in reserve. Cryovials will be stored at -75°C +/- 5°C. 
Each patient will have 12-48 cryovials depending on the number of peptides that were successfully 
manufactured (Table 1). For example, if 16 peptides are successfully manufactured, there will be 48 
cryovials (4 peptide pools x 12 cryovials per peptide pool). 
Step 2. Representative cryovials will be selected for sterility and endotoxin testing. 
Representative cryovials from each peptide pool will be tested for sterility and endotoxin (two cryovials will 
be tested for sterility and one cryovial will be tested for endotoxin). Sterility testing will be performed using 
the USP <71> sterility test method. The DMSO concentration has been tested to ensure it will not 
interfere with the sterility test. The release criteria for the sterility test is no growth at 14 days. The release 
criteria for endotoxin is < 5 EU/mL. If the peptide pools pass these product release tests, the cryovials will 
be transferred to the investigational pharmacy at WUSM, or shipped to the appropriate investigational 
pharmacy at participating sites.  
Step 3. Cryovials will be transferred to the investigational pharmacy at WUSM (or shipped to the 
appropriate investigational pharmacy at participating sites). 
Following sterility and endotoxin testing, the BTCF will transfer cryovials on dry ice to the WUSM 
investigational pharmacy, or the BTCF will ship cryovials on dry ice to the appropriate investigational 
pharmacy at participating sites. Cryovials will be packaged and shipped in temperature monitoring 
containers. 
Step 4. At each vaccination timepoint, peptide pools will be mixed with poly ICLC immediately 
prior to administration. 
Step 4 is the final step in product formulation and will be performed on the day of vaccine administration 
by an investigational pharmacist. Additional details are provided in the Investigational Agent 
Administration section, below. 
At each vaccination timepoint, one cryovial from each peptide pool will be mixed with poly ICLC.  
Each  peptide pool will be drawn up into a syringe to facilitate mixture with poly ICLC and administration. 
Up to four syringes will be prepared at each vaccination time point corresponding to each peptide pool.  
Each prepared syringe will contain both the  synthetic long peptides and poly-ICLC. 0.75 mL of the  
peptide pool will be mixed with 0.25 mL of poly ICLC.  


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The adjuvant, poly-ICLC is formulated with clinical grade poly I; poly C stabilized with 
carboxymethylcellulose and poly-L-Lysine. 
Poly-ICLC is composed of the following: 
• 
0.6 to 3% DMSO 
• 
3.6 to 3.7% dextrose in water 
• 
3.6 to 3.7 mM sodium succinate 
• 
0.5 mg/mL polyL:polyC 
• 
0.375 mg/mL poly-L-Lysine 
• 
1.25 mg/mL sodium carboxymethylcellulose 
• 
0.225% sodium chloride solution 
The final peptide concentration is 300 μg/mL of each peptide after mixture with poly ICLC.  
5.1.4 
Packaging and Labeling 
Up to four peptide pools (A, B, C, D) are prepared for each patient. 
Seven cryovials per peptide pool (up to 28 cryovials total) will be transferred to the investigational 
pharmacy at WUSM or shipped to the investigational pharmacy at the appropriate clinical site. 
Each peptide pool will be in a separate labeled case. Each cryovial contains a single peptide pool 
containing up to four peptides (with each individual peptide at a concentration of 400 mcg/mL, 1.5 mL/vial  
in 26.7% DMSO). Each cryovial will be labeled. 
An example of the label for the pooled peptides is presented below. 
Patient ID: Study #, INT designates the appropriate subject study ID number and initials. 
Vial #XX designates the appropriate vial number. 
Peptide Pool Y designates the appropriate peptide pool (A, B, C, D).  
For CTEP studies, the appropriate NCI Protocol Number will be inserted onto the label as shown. 
 
WUSM Neoantigen Vaccine 
NCI Protocol Number (if applicable) 
 
Patient ID: Study#, INT 
Lot # 00X, Vial #XX 
                                   Date of Manufacture: MM/DD/YY 
Peptide Pool: Y 
Concentration 0.4 mg/mL, 1.5 mL/vial  
Store at -75 ºC ± 10 ºC 
NSC 804336 
CAUTION: Investigational drug - Limited 
by Federal Law to investigational use 
 
An example of the case label is presented below.  
Patient ID: Study #, INT designates the appropriate subject study ID number and initials. 
Peptide Pool Y designates the appropriate peptide pool (A, B, C, D).  
X Total vials indicates the number of vials/case 


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For CTEP studies, the appropriate NCI Protocol Number will be inserted onto the label as shown. 
WUSM Neoantigen Vaccine 
Contents: Synthetic long peptides for injection 
Patient ID: Study#, INT 
Date of Manufacture: MM/DD/YY 
NCI Protocol Number (if applicable) 
Peptide Pool: Y, Lot 00X 
Concentration 0.4 mg/mL, 1.5 mL/vial 
X Total vials 
NSC 804336 
Directions: Administer as directed in the protocol 
Store at -75°C +/- 10°C 
Store vials in carton until time of use 
CAUTION: Investigational drug - Limited  
by Federal Law to investigational use 
 
5.1.5 
Storage conditions 
The low bioburden, lyophilized synthetic long peptides provided by CSBio will be received by designated 
personnel in the Biologic Therapy Core Facility at Washington University School of Medicine, handled 
and stored safely and properly, and kept in a secure, limited-access location. Once formulated into a drug 
product, the synthetic long peptides may be dispensed only by the Investigator or designated personnel 
specifically authorized by the Investigator. 
Upon receipt, the low bioburden, lyophilized synthetic long peptides will be stored in a controlled access 
location according to the instructions specified on the package labels. Similarly, once formulated into a 
drug product, the synthetic long peptides will be stored in a controlled access location according to the 
instructions specified on the package labels. 
• 
The synthetic long peptides will be stored frozen at -75°C +/- 5°C 
• 
The poly-ICLC vials (Hiltonol) are to be stored refrigerated between 2°C to 8°C. 
The investigator will be notified of any expiry or retest date extension of clinical study material during the 
study conduct. It is not anticipated that the expiration date of the synthetic long peptides will change as no 
stability tests are planned. 
Changes to the retest date of the poly-ICLC will be communicated via memo from Oncovir, or a designee. 
The retest dates of the poly-ICLC may be updated throughout the study. On expiry date notification site 
personnel must complete all instructions outlined in the notification, including segregation of expired 
clinical study material for return to the sponsor or its designee for destruction. 
All study drugs are for investigational use only and are to be used only within the context of this study. 
5.1.6 
Dispensation and Accountability 
The investigator and study pharmacist must maintain 100% up-to-date written records of the vaccine 
study drug dispensing activities for each patient. Accountability for all study medication received and 
dispensed during the entire study are recorded for each patient using Patient Drug Accountability Logs. If 
any dispensing errors or discrepancies are discovered you should notify the Clinical Research Associate 
(CRA) monitor or Principal Investigator immediately. 


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The Patient Drug Accountability Logs must accurately reflect the drug accountability of the study 
medication at all times. The following information will be recorded as a minimum: 
• 
Protocol number and title 
• 
Name of the investigator and site identifier/number 
• 
Description of study medication 
• 
Expiry and/or retest date (if not recorded elsewhere) and kit number 
• 
The date and amount dispensed, including the initials of the person dispensing study medication 
• 
The log should include all required information as a separate entry for each patient for whom 
study medication is dispensed 
5.1.7 
Safety and Handling 
The Material Safety Data Sheets (MSDS) for Hiltonol are provided in Section 5.2. Refer to the appropriate 
MSDS for safety and handling guidelines. 
Due to the personalized nature of the vaccine study drug (WU-PVAX), the potential toxicity has not been 
evaluated. Universal precautions should be used when handling a patient’s vaccine. All preparation 
should be performed within a biosafety cabinet. 
5.1.8 
Vaccine Preparation 
Each vaccination consists of up to 4 separate injections, with each syringe containing peptides from one 
of the up to four peptide pools combined with adjuvant. 
• 
The vaccine should be prepared in a biosafety cabinet and using aseptic handling procedures to 
prevent contamination. Place the peptide pool vials, poly-ICLC vial, mixing syringes, needles, and 
dosing syringe into the biosafety cabinet. 
• 
Remove one cryovial of pooled peptides for each of the up to four peptide pools (i.e. Pool A, Pool 
B, Pool C, Pool D) from the box and allow to thaw and warm to ambient conditions (15°C to 30°C) 
by placing them at room temperature for 1 to 4 hours. Accelerating aids such as a water bath 
should not be used. Each 1.5 mL pooled peptide vial contains 400 µg/mL of each peptide in the 
pool in a solution of 26.7% DMSO/sterile water. 
• 
Remove one vial of the poly-ICLC (adjuvant) from the refrigerated storage and allow it to warm to 
room temperature for at least 1 hour and a maximum of 4 hours prior to dose preparation. One 
vial of poly-ICLC will provide enough adjuvant for each of the four peptide pools. 
• 
The peptide pools and poly-ICLC will be mixed by using two connected syringes and passing the 
suspension back and forth between the syringes for a minimum of 5 full passes (1 pass = back 
and forth). The suspension will have an opaque white appearance. 
 
Gently swirl each thawed peptide pool vial. Using a syringe with a luer-lock dispensing needle 
withdraw 0.75 mL from the peptide pool vial. 
 
Gently swirl the poly-ICLC vial. DO NOT INVERT the poly-ICLC vial. The vial must remain 
upright and tipped to an approximately 30-degree angle to remove enough adjuvant for each 
of the four pools. One vial of poly-ICLC will provide enough adjuvant for each of the four 
peptide pools. Insert a new syringe with a luer-lock 21gauge 1½ inch needle into the vial 
placing the tip of the needle near the bottom of the vial. Withdraw the poly-ICLC to the 0.25 
mL mark on the syringe. An air bubble may be in place between the stopper of the plunger 
and the 0.25mL mark on the syringe. Please DO NOT attempt to remove the air bubble. This 
air bubble will be removed during the next mixing step. Removing the air bubble at this step 
will limit the amount of poly-ICLC which can be removed from the vial. 
 
The contents of the two syringes (peptide and poly-ICLC) are connected to a Braun Medical 
(Bethlehem, PA) Fluid Dispensing Connector, Product code FDC 1000, REF 415080 or FDC 


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2000, REF 4150810. The peptides and poly-ICLC are mixed by gently transferring the 
contents back and forth between the syringes, thru the Fluid Dispensing Connector. 
 
Draw the entire 1 mL into one of the syringes, remove the syringe from the device and attach 
a 27 gauge 1/2-inch or 5/8-inch stainless steel needle for SC administration. 
• 
Label the syringe to correspond with the peptide pool of the vaccine along with the protocol 
number, patient name, and ID number. 
• 
Repeat steps for the remaining peptide pool vials and adjuvant. There will be up to four peptide 
pools as identified on the pooled peptides label. Prepared dosing syringes may be stored at room 
temperature for up to 6 hours prior to administration. 
5.1.9 
Route of Administration 
Each pool of peptides + poly IC:LC will be administered to one of the four limbs (Pool A – Right Arm, Pool 
B - Left Arm, Pool C – Right Leg, Pool D – Left Leg) by subcutaneous (SC) injection. In the setting where 
a limb is unavailable for injection, the injection should be administered to the nearest flank. The same 
pool should be administered to the same limb across doses. 
 Poly-ICLC (Hiltonol) 
5.2.1 
Poly-ICLC Description 
Polyinosinic-Polycytidylic acid stabilized with poly-L-lysine and carboxymethylcellulose (Poly-ICLC, 
Hiltonol ® ) is a synthetic double-stranded ribonucleic acid (dsRNA) ‘host-targeted’ therapeutic vial-mimic 
and Pathogen-associated molecular pattern (PAMP) with broad innate and adaptive immune enhancing, 
vaccine adjuvant, antiviral and antiproliferative effects 
5.2.2 
Clinical Pharmacology 
Poly-ICLC stimulates at least 4 interrelated systems, any of which (alone or in combination) might be 
responsible for its possible antitumor and antiviral activity; induction of IFN, a broad immune-enhancing 
effect, direct antiviral/antineoplastic effect, and modulation of gene expression.  
Poly-ICLC induces a ‘natural mix’ of Interferons, cytokines and chemokines, including IFN production. As 
expected, the amount of these measurable in serum is dose dependent, although biologically significant 
induction likely occurs locally. In previous studies, the minimal serum IFN levels induced by the currently 
recommended low doses of Poly-ICLC have not been associated with antitumor or antiviral action. A 
study of the immunomodulatory effect of Poly-ICLC in cancer patients showed no detectable serum IFN in 
patients receiving 1 mg/m2 Poly-ICLC by IM injection. In contrast, IFN was detectable in the serum of 
patients receiving 4 mg/m2 IV Poly-ICLC. 
Low-dose Poly-ICLC directly stimulates the immune system through activation of NK cells, myeloid 
dendritic cells via TLR3 and MDA5, T-cells, macrophages and by inducing a ‘natural mix of interferons, 
cytokines and chemokines. Some of these actions are related to the potent PAMP-adjuvant actions of 
Poly-ICLC with various vaccine platforms, as well as to the broad antiviral state induced by the drug. 
The third action of Poly-ICLC is a more direct broad host-targeted antiviral and perhaps antineoplastic 
effect mediated by the two IFN-inducible nuclear enzyme systems, the 2’5’-OAS and the P1/eIF2a kinase, 
also known as the PKR, as well as RIG-I helicase and MDA5. The concentration of the 2’5’-OAS was 
elevated in the peripheral blood mononuclear cells of all Poly-ICLC-treated patients. Intramuscular 
administration of low-dose Poly-ICLC increased NK cells and growth inhibitory activities and 2’5’-OAS 
levels to a greater extent than high-dose IV infusion. Clinically, a maximal OAS response was observed at 
an IM dose of 30 μg/kg Poly-ICLC, and was greatly decreased at greater than 100 μg/kg in normal 
volunteers. The hypothesis that OAS and/or PKR may be involved in the antineoplastic effect of Poly-
ICLC may thus explain the relative ineffectiveness of high dose Poly-ICLC in early cancer trials. However, 
further studies are needed to confirm this. 
A fourth aspect of the action of Poly-ICLC involves modulation of the expression of a broad range of 
innate immune and other genes in a pattern closely paralleling that of a live virus vaccine. Some of these 
genes play critical roles in the body’s natural defenses against a variety of neoplasms and microbial 


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infections, and in controlling other cell functions, including protein synthesis, programmed (apoptotic) cell 
death, cell metabolism, cellular growth, the cytoskeleton and the extracellular matrix. For example, 
preliminary studies have confirmed marked clinical elevation of the p56 gene in white blood cells some 24 
hours after administration of 20 mcg/kg poly-ICLC in glioma patients. The clinical significance of these 
findings is not known, although there was no evidence of significant clinical toxicity in these patients 
5.2.3 
Pharmacokinetics and Drug Metabolism 
Poly-ICLC is normally metabolized by a serum endonuclease. 
Four monkeys were injected with 1 mg/kg of poly-ICLC and 4 others at 3 mg/kg IV. Serum samples were 
obtained at 1, 5, 10, and 30 minutes, and at 1, 2, 3, 4, 8, 12, and 24 hours. Poly-ICLC was assayed in 
loRK cells. Serum poly-ICLC levels had decreased to 5% of peak values 4 hours after injection. There 
was no change in clearance rate after six additional injections over a two-week period. 
Preclinical data on nasal use of poly-ICLC or poly-IC in various murine viral challenge studies is reported 
in several publications. These indicate a dose-dependent increase in lung and bronchial lavage interferon 
and TLR3 expression in response to drug alone, independent of viral challenge. Preliminary data from 
very recent unpublished studies of poly-ICLC applied rectally or nasally to macaque monkeys also 
confirm induction of various cytokines and chemokines. 
Poly-ICLC is not detectable in serum 24 hours after administration. However, the clinical half-life of the 
OAS response to 30 μg/kg IM poly-ICLC in healthy human volunteers is about 2.5 days, suggesting an 
optimum dose schedule of two or three times per week. 
Twenty-four of 29 patients treated with 10 to 20 μg/kg poly-ICLC by IM injection showed at least a 300% 
increase in serum OAS. A significant association of serum OAS with tumor response has been observed 
in patients with malignant glioma participating in an open pilot trial. 
5.2.4 
Supplier 
Poly-ICLC will be supplied by Oncovir, Inc. 
5.2.5 
Dosage Form and Preparation 
Poly-ICLC is supplied by Oncovir in single-dose vials containing 1 mL of 2 mg/mL opalescent white 
suspension. Each milliliter of poly-ICLC for injection contains 2 mg/mL poly-IC, 1.5 mg/mL poly-L-lysine, 
and 5 mg/mL sodium carboxymethylcellulose in 0.9% sodium chloride solution and adjusted to pH 7.6-7.8 
with sodium hydroxide. 
 
Poly-ICLC is withdrawn from the vial under sterile conditions as detailed above. 
5.2.6 
Storage and Stability 
Poly-ICLC is stable at room temperature for brief periods (days). It is normally refrigerated at about 40ºF 
(2-8°C) but should not be frozen 
5.2.7 
Administration 
Poly-ICLC will be mixed with the synthetic long peptide vaccines as detailed above. 
 Nonclinical studies 
5.3.1 
Overview 
We propose a phase 1 clinical trial of a neoantigen peptide vaccine strategy. The neoantigen peptide 
vaccine strategy is designed to target neoantigens present in the pancreatic cancer, but absent in normal 
tissues. 
One of the reasons that we have pursued clinical development of a neoantigen peptide vaccine strategy 
targeting neoantigens is because we believe that this strategy has the potential to be safer than strategies 
targeting shared tumor antigens. Shared tumor antigens are typically expressed at high levels in the 
tumor, but are also typically expressed at lower levels in some normal tissues. Expression of shared 
tumor antigens in normal tissues may increase the risk of autoimmunity. Neoantigens are present only in 


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the tumor. In addition, our next-generation sequencing-based epitope prediction algorithm prioritizes 
epitopes where the mutant epitope (but not the wildtype epitope) can bind to restricting HLA molecules. 
This decreases the potential that immune responses targeting neoantigens will be cross-reactive with 
wildtype antigens. 
We do not think that GLP safety and toxicology studies will provide significant insight into the safety of the 
neoantigen peptide vaccine strategy. First, it is impossible to know a priori what mutations will be present 
and/or prioritized in individual patients. We estimate that there are as many as 7 million potential 
neoantigens that could be targeted by our approach. Only a limited number of mutations could be 
targeted in GLP safety and toxicology studies. Second, to our knowledge, no mammary tumor models 
exist that would be relevant for GLP safety and toxicology studies.  
5.3.2 
Nonclinical studies 
It has long been known that there is a dynamic relationship between the immune system and cancer. This 
dynamic relationship has been studied in detail, ultimately resulting in the establishment of the cancer 
immunoediting concept [34-41].  
We have recently focused on defining the antigens recognized by the immune system during the cancer 
immunoediting process. These studies, summarized below, demonstrate that neoantigens are important 
tumor rejection antigens, and provide strong support for our personalized pancreatic cancer vaccine 
strategy. Specifically, we have developed next-generation sequencing and epitope prediction algorithms 
to identify and prioritize neoantigens. We will use these algorithms in the proposed clinical trial. The 
preclinical data supporting the use of these algorithms are presented below. 
In initial studies we used a combination of next-generation sequencing and epitope prediction algorithms 
to identify neoantigens in the d42m1 MCA sarcoma line. These algorithms identified one particular 
mutation (an R913L mutation of SPTBN2) as a top candidate, and subsequent analyses confirmed that 
this mutant tumor-specific antigen functioned as an immunodominant tumor rejection antigen. These 
studies were published in Nature [24]. 
The d42m1 MCA sarcoma is an unedited tumor, and would therefore be expected to express strong 
tumor rejection antigens. We have since turned our attention to examining the epitope landscape in 
edited MCA sarcomas that develop in immunocompetent wildtype mice. Specifically, we have asked the 
following questions: (1) Can the next-generation sequencing and epitope prediction algorithms be used 
more broadly to identify and prioritize important neoantigens in less immunogenic tumors? (2) Can the 
next-generation sequencing and epitope prediction algorithms be used to prioritize antigens for immune 
targeting and/or personalized vaccine therapy? 
To address these questions we focused initial efforts on d42m1-T3. d42m1-T3 is a clone of d42m1 that 
lacks the immunodominant rejection antigen, mutant SPTBN2, and forms progressively growing tumors in 
wildtype mice. We specifically chose the d42m1-T3 clone because d42m1-T3 shares with naturally edited 
sarcomas the ability to form progressively growing tumors in wildtype mice and shows a similar sensitivity 
to checkpoint blockade.  
To identify and prioritize mutant tumor specific antigens from the d42m1-T3 we used optimized next-
generation sequencing and epitope prediction algorithms. Specifically, we pipelined the candidate mutant 
tumor-specific antigen sequences into four different MHC class I epitope prediction algorithms and 
calculated the median predicted affinity for binding to the relevant class I MHC alleles. We then applied 
filters that account for proteasomal processing of the antigen and differences in MHC class I binding 
affinity between mutant and native sequences to prioritize the neoantigens. We also deprioritized 
hypothetical Riken proteins.  
Of the top 61 prioritized candidates, 20 were eliminated by the filtering process; including two of the top 
four candidates. Of those that remained, two [G1254V Laminin subunit α4 (mLama4) and A506T alpha-
1,3 glucosyltransferase (mAlg8)] were clearly favored above the others based on predicted binding 
affinity.  
To test whether these two “best” neoantigens were biologically relevant, we generated tumor-specific 
CD8 T cell lines from the spleens of three independent mice that had rejected d42m1-T3 cells after anti-
PD-1 therapy and showed that each T cell line (CTL-62, CTL-73, CTL-74) displayed specificity for d42m1-


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T3 but not an unrelated sarcoma, F244. To determine if the “prioritized” neoantigens were recognized by 
anti-d42m1-T3 T cell lines, we incubated 8 amino acid synthetic peptides corresponding to each of the 
top 61 initially predicted H-2Kb neoantigens with irradiated splenocytes and CTL-74 T cells and monitored 
IFNγ production. The mLama4 and mAlg8 peptides strongly stimulated CTL-74 T cells, with mLama4 
inducing ~10x more IFNγ than mAlg8. No other predicted mutant epitope induced significant levels of 
IFNγ production in this assay. Similar results were obtained with the other two d42m1-T3 specific CD8 T 
cell lines. Subsequent dose response experiments showed that mLama4 stimulated the tumor-specific T 
cell lines to a greater extent than mAlg8 and that the T cells reacted specifically with mutant but not native 
peptides.  
We then used four experimental systems to confirm that our optimized epitope prediction algorithms 
accurately prioritized neoantigens. First, together with the groups of Hans-Georg Rammensee in 
Tübingen and Ruedi Abersold in Zurich we detected mLama4 and mAlg8 peptides bound to H-2Kb on 
d42m1-T3 tumor cells. To our knowledge this is the first time that mutant class I epitopes have been 
detected bound to tumor cell-associated MHC class I. Second, using PE-labeled H-2Kb tetramers carrying 
mLama4 or mAlg8 peptides, CD8 T cells with specificities for these two epitopes were found to 
accumulate in d42m1-T3 tumors in αPD-1 treated mice and reached peak values just prior to tumor 
rejection on day 12. Consistent with the results of the T cell stimulation experiments, mLama4-specific T 
cells were present in significantly higher numbers in the tumor than mAlg8-specific T cells. No mLama4- 
or mAlg8-specific T cells were observed in irrelevant, checkpoint blockade-sensitive F244 tumors. Third, 
vaccination of naïve WT mice with mutant-Lama4 or mutant-Alg8 short peptide vaccines (8mer) induced 
strong CD8 T cell responses that were specific for the mutant, but not the WT epitope (mLama4 = 1650 
SFC/106 cells vs. wtLama4 = 75 SFC/106 cells; mAlg8 =606 SFC/106 cells vs. wtAlg8 = 50 SFC/106 cells). 
Fourth, prophylactic vaccination of mice with long peptides (~30mer) corresponding to either the mLama4 
epitope alone, or both the mLama4 and mAlg8 epitopes induced protection against subsequent challenge 
with d42m1-T3 tumor cells. The combined peptide vaccine was more protective than the vaccine 
containing the mLama4 long peptide alone (Figure 5). 
Of note, immune responses to both mLama4 and mAlg8 were also observed after vaccination with a 
polyepitope DNA vaccine encoding mLama4, mAlg8, and several additional epitopes. Mice were 
vaccinated three times and the immune response to mLama4, mAlg8 and control peptides was assessed 
by ELISPOT using splenocytes from vaccinated mice. Vaccination with polyepitope DNA vaccines 
induced responses that were similar in magnitude as synthetic long peptide vaccines encoding mLama4 
or mAlg8 (data not shown). 
5.3.3 
Rationale for no GLP safety studies 
We do not think that GLP safety and toxicology studies will provide significant insight into the safety of the 
neoantigen peptide vaccine strategy. 
First, it is impossible to know a priori what mutations will be present and/or prioritized in patients. Next-
generation sequencing of epithelial cancers has demonstrated that there are very few recurrent mutations 
present. Mutations can be present in any one of the approximately 20,000 protein-coding genes present 
in the human genome. Even more problematic is that the mutations targeted could be anywhere in the 
corresponding protein. It has been estimated that the average length of a protein in humans is 362 AA. 
Thus, there are potentially 7,240,000 potential neoantigens that could be targeted by our approach. This 
includes only point mutations and does not include mutations resulting from indels. If studies are 
performed in a preclinical model, only a limited number of mutations will be targeted. For example if we 
design a neoantigen peptide vaccine specific for a murine epithelial cancer targeting 5 genes, this would 
represent only 5 of 7,240,000 potential neoantigens. Even if 1000 GLP safety and toxicology studies were 
performed, each targeting 5 neoantigens, it would still provide information on < 0.07% of potential 
neoantigens. 
Second, to our knowledge, no pancreatic cancer models exist that would be relevant for the proposed 
preclinical studies. In order to study neoantigens, sequencing analyses of paired tumor/normal tissues are 
required. As such, we would need to study spontaneous tumors in mice, as tumors propagated as cell 
lines do not have corresponding normal DNA to evaluate. There are very few models of spontaneous 
pancreatic cancer development in wildtype mice. Spontaneous tumors do develop in genetically 
engineered mice, but these oncogene-driven tumors in genetically engineered murine models of cancer 


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typically have a very limited number of mutations. We have performed extensive studies in genetically 
engineered mice, and have found that there are very few mutations present in tumors derived from these 
mice. For example, we have performed extensive studies in the p53-null transplant mammary tumor 
model. p53 is a tumor suppressor gene and plays an important role in maintaining genome stability. As 
such one might expect that there would be a significant number of mutations present in p53-null 
transplant mammary tumors. However, we have sequenced > 10 p53-null transplant mammary tumors 
and have found that there are only a limited number of mutations present in each tumor. This is not at all 
representative of human pancreatic cancers where significantly more mutations are present. Of note, a 
significant number of mutations must be present to reliably identify neoantigens that are immunogenic, as 
many candidate neoantigens are not processed and presented by the immune system, or cannot be 
recognized efficiently by T cells. If only a limited number of mutations is present, it is possible that no 
neoantigens will be identified that are immunogenic. For meaningful GLP safety and toxicology studies of 
a neoantigen peptide cancer vaccine, one of the key considerations is to assess any potential toxicity 
associated with immune responses to the vaccine. If no neoantigens are identified that are immunogenic, 
the GLP safety and toxicology studies will have only limited value as no immune response to the mutant 
tumor-specific antigen will be generated. As such, we are not aware of any pancreatic cancer tumor 
models in mice that would be appropriate for the GLP safety and toxicology studies. 
 Sequencing pipeline 
Robust next-generation sequencing strategies for the identification of neoantigens will be required for the 
successful clinical translation of personalized cancer vaccine strategies. As such, a major focus of our 
research studies has been the development of cost-effective and accurate next-generation sequencing 
strategies to identify neoantigens and validate the expression of these antigens at the mRNA level.  
The first step in the sequencing pipeline is exome sequencing of pancreatic cancer and normal DNA. 
Exome fragments are captured using Nimblegen's "VCRome" exome capture reagent. Background DNA 
is washed away while the bound exome DNA is eluted and sequenced. Separate libraries are made from 
the pancreatic cancer and normal DNA and processed independently. Exome sequencing is performed 
using the Illumina platform. 
Exome sequences from pancreatic cancer and normal DNA are compared separately to the human 
reference sequence and then to one another to identify somatic variation. VarScan 2 software is used to 
detect misaligned sequences and identify structural variants in the pancreatic cancer DNA.  
The second step in the sequencing pipeline is cDNA-capture sequencing. To validate the results of the 
exome sequencing, and confirm expression of the somatic mutations in the pancreatic cancer, cDNA-
capture sequencing of the pancreatic cancer RNA will be performed. cDNA-capture sequencing is very 
similar to RNA sequencing, but cDNA is captured prior to sequencing to enrich for mRNA. cDNA-capture 
sequencing is a sensitive and accurate methodology to detect expression of somatic mutations at the 
mRNA level in pancreatic cancer. cDNA-capture sequencing is performed using the Illumina platform.  
Additional details are included in the “Sequencing Pipeline” section of IND 16509.  
 Epitope prediction algorithm 
We have developed and optimized an epitope prediction algorithm for the identification and prioritization 
of neoantigens. This optimized epitope prediction algorithm is described below and in the Gubin 2014 
manuscript [25]. We have established this algorithm is collaboration with Dr. Robert Schreiber, an 
internationally-known expert in tumor immunology [24, 34-41]. Schreiber was one of the first to use next 
generation sequencing technologies to identify neoantigens, demonstrating that these antigens are 
important tumor rejection antigens [24]. Schreiber and Gillanders have now optimized the epitope 
prediction algorithm and have demonstrated that cancer vaccines targeting neoantigens are associated 
with antitumor immunity [25].  
The goal of the optimized epitope prediction algorithm is to identify and prioritize up to 20 neoantigens. 
The algorithm uses a combination of binding algorithms, processing algorithms and in vitro binding 
assays. 


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Mutations that are expressed in the pancreatic cancer will be identified using the sequencing pipeline 
outlined in the document titled “Sequencing Pipeline.” The predicted amino acid sequences 
corresponding to the expressed mutations will be pipelined through multiple class I and class II MHC 
epitope-binding algorithms provided by the Immune Epitope Database and Analysis Resource 
(http://www.immuneepitope.org) including but not limited to (i) Stabilized Matrix Method (SMM) [42], (ii) 
Artificial Neural Network (ANN) [43], and (iii) NetMHCpan [44]. 
A prioritized list of binding epitopes (i.e. IC50 < 500 nM) will be generated after calculating the median 
binding affinity value for each mutant sequence (affinity value expressed as 1/IC50 x 100).  
Filters will be applied to the list to (a) eliminate epitopes that are not processed efficiently by the 
immunoproteosome based on the NetChop algorithm [45] (peptides with a NetChop score > 0.6 will be 
prioritized), (b) deprioritize epitopes from hypothetical proteins or that form a weaker predicted binding 
epitope than that expressed by the corresponding wild type sequence, (c) prioritize mutant epitopes that 
have the highest difference in predicted binding affinity compared to their wild type counterpart, and (d) 
incorporate expression profiles of wild type genes that correspond to the mutant antigen candidates in 
normal vs tumor cells.  
Additional details are included in the “Epitope Prediction Algorithm” section of IND 16509. 
 
 


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6 TREATMENT PLAN 
 Peptide Vaccine administration 
All subjects will be treated as outpatients in the Siteman Cancer Center/Sidney Kimmel Comprehensive 
Cancer Center. 
Patients with pathologically verified R0/R1surgical resection and no evidence of recurrent and/or 
metastatic disease will be identified for tissue procurement and sequencing. Patients will initiate 
gemcitabine/capecitabine or comparable adjuvant chemotherapy no more than 16 weeks following 
resection. Adjuvant chemotherapy will be administered for a total of six cycles as per the NCCN 
recommendations for adjuvant chemotherapy following surgical resection. Additional chemoradiation, 
dose modifications, reductions, and supportive care will be performed at the discretion of the treating 
medical oncologist. After completion of adjuvant chemotherapy, patients will undergo repeat imaging by 
CT scan and/or MRI to evaluate for disease recurrence. Patients with no evidence of disease as 
determined by a board certified radiologist and without rising levels of tumor markers will be eligible for 
vaccination. If vaccine production is unable to be completed for a particular patient, that patient will 
discontinue participation in this study and will be replaced. 
The schedule for vaccination will be Days 1, 4, 8, 15, and 22 (delays of up to 96 hours are allowed for 
each dose based on the AEs experienced). Additional vaccinations will be given on Days 50 and 78 (+/- 2 
weeks). The first vaccine dose may be administered following confirmation of disease-free status and 
within 90 days following date of repeat imaging. All study injections will be given subcutaneously and co-
administered with poly-ICLC by a trained healthcare provider. At each vaccination time point, patients will 
receive up to four injections of the neoantigen peptide vaccine + adjuvant. The peptides and poly-ICLC 
will be mixed prior to injection. Standard aseptic technique and precautions will be utilized in site 
preparation, vaccine administration, and medical waste disposal to ensure maximal safety of subjects and 
study personnel. Please refer to Section 5.10 for Vaccine preparation instructions. 
At the discretion of the treating physician, patients may be pre-medicated with lorazepam 1mg PO at least 
30 minutes but no greater than 60 minutes prior to the first injection. Patients may also receive a second 
dose of lorazepam (1 mg PO) 10 minutes prior to injection. Patients may also receive acetaminophen 
650mg PO at least 30 minutes but no greater than 60 minutes prior to the first injection. 
Following study injections, subjects will be observed for a minimum of 30 minutes. Vital signs 
(temperature, blood pressure, pulse and respiratory rate) will be taken at 30-45 minutes post-
immunization. The injection sites will be inspected for evidence of local reaction. 
On each injection day (prior to injection), study subjects will be evaluated by clinical exam and laboratory 
tests. Post-vaccination follow-up visits are at 4 weeks following last injection (± 7 days) and 1 year 
following last injection (± 14 days). Additional follow-up visits or telephone contact will be scheduled 
annually thereafter if the patient is alive and available for follow-up. 
At intervals throughout the study (both before and after vaccination) subjects will have blood drawn for 
immunologic assays. Any cells, serum or plasma not used will be stored for future immunological assays. 
Please see Section 8 Study Calendar for details on study visit procedures and monitoring. 
 Concomitant Medication Guidelines 
Patients may receive other vaccinations while on study, including influenza and pneumococcal. 
Patients will be treated for toxicities at the discretion of the physician. Growth factor support with either 
filgrastim or pegfilgrastim is at the discretion of the investigator. 
There are no prohibited medications. 
 Definitions of Evaluability 
All enrolling patients are evaluable for the primary objective of feasibility, even patients whose 
tumor/normal exome sequencing is not completed or who are unable to have vaccine manufactured or 
administered. 


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A patient must have received at least one injection of vaccine in order to be evaluable for the primary 
objective of safety and the secondary objective (prevalence of antigen-specific T cells in peripheral 
blood). 
 Duration of therapy 
In the absence of treatment delays due to adverse events, treatment may continue for 7 doses of 
neoantigen peptide pancreatic cancer vaccines. Under certain circumstances, a subject will be terminated 
from participating in further injections. Subjects who are discontinued from additional study injections will 
continue to be followed according to the schedule of safety and immunogenicity evaluations. Please see 
Section 10 Removal of Patients from Protocol Therapy for additional details. 
 Duration of follow up 
Patients will examined at 4 and 52 weeks following the final vaccination. Additional follow-up visits or 
telephone contact will be scheduled every year thereafter if the patient is alive and available for follow-up. 
Patients removed from study for unacceptable adverse events will be followed until resolution or 
stabilization of the adverse event. 
 
 


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7 POTENTIAL TOXICITY AND DOSE MODIFICATIONS 
 Potential toxicity 
7.1.1 
Potential toxicity related to the neoantigen peptide vaccine 
This is the one of the first times that mutant tumor-specific antigens identified by next generation 
sequencing have been targeted for immune therapy in humans, and one of the first times that 
personalized synthetic long peptide vaccines have been administered to humans. However, clinical trials 
of similar investigational peptide vaccines suggest that these vaccines will be very safe. We expect that 
most of the toxicity to be limited to local grade 1 or 2 reactions at the site of vaccination. 
Please note that the risks detailed below are based on the risks of injections, the risks of vaccines in 
general, and the results of previous studies with investigational DNA vaccines. 
Risks associated with subcutaneous injections include acute bleeding and/or bruising. Although highly 
unlikely, intradermal injection can result in injection site infection. As with any immunization, discomfort or 
redness at the injection site in the days following vaccine administration may be expected.  
Subjects may exhibit general signs and symptoms associated with administration of a vaccine injection, 
including fever, chills, rash, aches and pains, nausea, headache, dizziness and fatigue. These side 
effects will be monitored, but are generally short term and do not require treatment. 
 Toxicity monitoring and management 
Toxicity will be characterized according to the National Cancer Institute Common Terminology Criteria for 
Adverse Events version 5.0 (CTCAE). Subjects who are immunized with the peptide vaccine will be 
evaluated at the time of each vaccination on days 1, 4, 8, 15, 22, 50 and 78. Adverse events will be 
reported to the Quality Assurance and Safety Monitoring Committee of the Siteman Cancer 
Center/Sidney Kimmel Comprehensive Cancer Center, the Institutional Review Board, the Institutional 
Biosafety Committee, the Office of Biotechnology Activities and the Food and Drug Administration as 
detailed in Section 11 Adverse Event Reporting. 
Significant local inflammation will be treated with cold packs and oral analgesics as indicated. Skin 
ulceration at the vaccine site will be treated with local wound care and antibiotics as indicated. 
Development of signs and/or symptoms of autoimmune involvement will be initially treated conservatively 
with analgesics. More aggressive intervention (systemic corticosteroids) will be used as necessary and 
will result in termination of future vaccine inoculation. 
 Dose modifications 
No dose modifications are planned. If a subject develops an adverse event that is classified as possibly, 
probably, or definitely associated with protocol therapy, this may result in removal of the subject from 
protocol therapy as outlined in Section 10 Removal of Subjects from Protocol Therapy. Protocol 
Stopping Criteria are outlined in Section 12 Data and Safety Monitoring. 
 


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8 STUDY CALENDAR 
The window for Step 0 screening procedures is up to 28 days prior to enrollment. Enrollment must occur 
within 28 days of the patient starting on adjuvant therapy. The window for Step 1 screening procedures is 
14 days prior to first vaccine dose. 
 
Step 0 
Screening 
Step 1 
Screening 
Day 
1 
Day 4f 
Day8f 
Day15f 
Day 22f 
Day 50 
(+/-2wk) 
Day 78 
(+/-2wk) 
EOT 
F/Uh 
Neoantigen peptide 
vaccinea,i 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
Physical exam 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concurrent Meds 
X ------------------------------------------------------------------------------------------------------------------------ X 
 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Performance Status 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
CBC w/diff, plts 
X 
X 
X 
 
 
 
X 
X 
X 
 
 
CMPb 
X 
X 
X 
 
 
 
X 
X 
X 
 
 
INR, PTT 
X 
X 
 
 
 
 
 
 
 
 
 
EKG  
X 
X 
 
 
 
 
 
 
 
 
 
Radiologic 
evaluation 
Radiologic measurements will be performed as clinically indicated. Documentation of tumor recurrence or metastatic 
disease must be provided for patients removed from study for progressive disease. 
Adverse event 
evaluation 
 
 
Xg 
Xg 
Xg 
Xg 
Xg 
Xg 
X 
X 
 
B-HCG 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
Xe 
 
 
Immune monitoringc 
X 
 
X 
 
 
 
X 
X 
X 
 
Xj 
Pathology Reviewd 
X 
 
 
 
 
 
 
 
 
 
 
Eligibility 
Confirmation 
X 
X 
 
 
 
 
 
 
 
 
 
a: Personalized synthetic long peptide pancreatic cancer vaccine 
b: Albumin, alkaline phosphatase, total bilirubin, bicarbonate, BUN, calcium, chloride, creatinine, glucose, LDH, phosphorus, potassium, total 
protein, SGOT [AST], SGPT [ALT], sodium. 
c: Immune monitoring labs to consist of seven 10mL green top heparin tubes for isolation of PBMCs. During adjuvant therapy, the mid and 
end of chemo draws are optional. Generally, these should occur at a clinic visit associated with the restaging scan, as well as at each follow 
up visit. This will yield approximately 50-200 x106 PBMCs per collection. 
d: Pathology review to confirm diagnosis of adenocarcinoma and evaluate tumor cellularity.  
e: Serum or urine pregnancy test (women of childbearing potential). 
f: +/- 1 days with at least 24 hours between vaccinations  
g: Adverse event evaluation on day of vaccine  
h: ± 28 days; follow-up or telephone contact at 4 weeks and 1 year after last injection and annually thereafter if the patient is alive and 
available for follow-up. F/U visits may be done at the participant’s local MD office. 
i: patients may discontinue participation if vaccine production is unable to be completed 
j: optional based on patient availability 


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9 CRITERIA FOR RESPONSE 
 Primary objective: safety 
Assessment of synthetic long peptide safety will include both clinical observation and laboratory 
evaluation. Safety will be closely monitored after injection with eight or more clinical and laboratory 
assessments in the first 24 weeks of the trial. The following parameters will be assessed following 
vaccination: 
(1) 
Local signs and symptoms 
(2)  
Systemic signs and symptoms 
(3) 
Laboratory evaluations, including blood counts and serum chemistries 
(4) 
Adverse, and serious adverse events 
Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for 
Adverse Events v5.0. 
 Secondary objectives: evaluation of the immune response 
9.2.1 
Introduction to immune monitoring 
The secondary endpoint is to evaluate the immunogenicity of the neoantigen peptide vaccine. 
Immunogenicity will be measured by ELISPOT analysis, a surrogate for CD4 and CD8 T cell function, and 
multiparametric flow cytometry. In both assays the quantity and quality of antigen-specific T cells is 
determined; the ELISPOT analysis is based on measuring the frequencies of IFN-γ producing T cells in 
response to polyepitope antigen, whereas the multiparametric flow cytometry assesses phenotypic as 
well as functional characteristics of epitope-specific T cells. In the proposed study, blood samples will be 
collected at multiple time points (n=8) and PBMC isolated and cryopreserved. Upon completion of the 
vaccination protocol, all samples will be analyzed simultaneously in order to minimize assay-to-assay 
variation. 
9.2.2 
Sample collection and processing 
During Step 0 enrollment, tumor samples will be reviewed by a pathologist with expertise in pancreatic 
cancer who will review the operative specimen slides to verify tumor cellularity and quantity sufficient for 
proceeding. Once tissue viability is confirmed, specimens from outside Washington University will be 
shipped to the Gillanders lab at the following address: Gillanders Lab, 425 S. Euclid Ave. CSRB 3339, St. 
Louis, MO 63110. The corresponding FFPE blocks will be punched with a disposable 1mm biopsy punch. 
6-8 full thickness punches will be taken from areas of high tumor cellularity and divided evenly into two 
DNA LoBind Eppendorf tubes (one tube for DNA and one for RNA). To identify somatic mutations, DNA 
and RNA will be extracted from the FFPE preserved tissue by the Center for Human Immunology and 
Immunotherapy Programs (CHiiPS) core. All tissue selected for sequencing will be processed into a 
single-cell suspension by mechanical and enzymatic digestion, and used to extract nucleic acids. Tumor 
DNA + RNA will then undergo tumor exome and tumor cDNA-capture sequencing, respectively at the 
Genome Institute. Normal genomic DNA will be isolated from PBMCs by the CHiiPS core or Gillanders 
laboratory personnel for normal exome sequencing at The Genome Institute.  
Patients will undergo their first blood draw during Step 0 screening to establish a baseline for immune 
monitoring and for creation of the vaccine. This first blood draw will be shipped ambient same day of draw 
to the Gillanders lab at the following address: Gillanders Lab, 425 S. Euclid Ave. CSRB 3339, St. Louis, 
MO 63110.   Additional optional pre-vaccine blood samples will be obtained midway through 
chemotherapy and at the end of chemotherapy. Immune monitoring labs will be draw prior to vaccination 
on Days 1, 22, 50, and 78. Post- vaccine immune monitoring labs will be drawn at the first two follow-up 
time points (4 weeks after last injection and 1 year after last injection). Seven collection tubes (BD 
Vacutainer® sodium heparin (green top), REF 367874, 10 mL each for a total of approximately 70 mL) 
are filled by venipuncture at each time point. Blood samples will be transported to Dr. Gillanders’/JHU 
equivalent laboratory (6th floor Clinical Sciences Research Building, room 3339) within one hour of 
collection. PBMC will be obtained by Ficoll-Hypaque gradient centrifugation and cryopreserved in 10% 


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DMSO according to standard procedures. Blood will be batch shipped to the Gillanders lab at the address 
listed above. Exome sequencing of PBMC will be performed to obtain germline sequences. 
9.2.3 
ELISPOT Analysis 
ELISPOT analysis, will be performed as previously described [46-50]. PBMC from subjects in the phase 
1b clinical trial will be tested for secretion of IFN-γ by ELISPOT assay. PBMC will be plated at various 
concentrations starting at 300,000 cells per well, in triplicate, following the protocol previously described 
by Dr. Mohanakumar and colleagues. PBMC will be co-cultured with the mutant and mesothelin peptides 
encoded by the polyepitope construct. As negative controls, PBMC will be incubated in medium alone or 
stimulated with matching wild type peptides. As a positive control we will include a mix of viral peptides, 
CEF, containing immunodominant epitopes for multiple common HLA alleles from influenza virus, 
cytomegalovirus, and Epstein-Barr virus. After 24-48 hours, the plates will be developed and the spots 
counted in an ImmunoSpot Series I analyzer (Cellular Technology). 
9.2.4 
Multi-parametric flow cytometry 
Patient-derived PBMC will be used for functional assays to characterize immunity to personalized 
pancreatic cancer DNA vaccines. Polyfunctional CD8 T cell responses will be determined after stimulation 
of cultured PBMC with polyepitope pulsed autologous PBMC using muti-parameter flow cytometry. 
Fluorescently labeled MHC class I tetramers expressing vaccine-encoded peptides will be used to gate 
on peptide-specific T cells. The choice of tetramers to be used in these analyses will be dictated by the 
neoantigens and mesothelin antigens used for a given patient’s personalized vaccine, and the patient’s 
HLA phenotype. We will also simultaneously stain tetramer-positive and tetramer-negative CD8 T cells for 
a variety of well-accepted markers that report the functional status of antigen specific CD8 T cells. These 
include the cell surface markers PD-1, CTLA-4, LAG-3, and TIM-3 (markers of T cell inactivation), the 
proliferation marker Ki-67, and the cellular activation markers ICOS, granzyme B, TNF-α and IFN-γ. We 
have already validated all of our staining reagents and demonstrated that specific combinations of mAb 
labeled with different fluorescent tags can be used together allowing for multi-color analysis in a single 
run. Analyses will be performed using either a BD Fortessa (6-color analysis) or BD LSR II cytometers 
(11-color analysis). A positive effect of immunotherapy is expected to show increased numbers of 
tetramer-positive cells that also display decreased expression of PD-1, CTLA-4, LAG3, and TIM3, and 
increased staining for Ki-67, ICOS, granzyme B, TNF-β and IFN-γ.  
PBMC aliquots (2x106 cells/mL) will be stimulated with individual peptides encoded by the polyepitope 
vaccine and cultured in the presence of IL-2 (50U/mL). Ten days after activation, cells will be harvested, 
washed and restimulated with irradiated (10,000 rads) peptide-pulsed autologous PBMC for 16h (in the 
presence of Brefeldin A) and stained with antibodies for the various markers listed above. Cells will be 
analyzed by the Immune Monitoring Core, also known as the Center for Human Immunology and 
Immunotherapy Programs (CHiiPs), headed by Dr. Robert Schreiber. Cultured cells stimulated with 
unpulsed PBMC will be used as negative control, and cells stimulated with CEF-pulsed PBMC will be 
used as positive controls using an appropriate tetramer. One advantage of using 10 day 
activated/antigen-driven PBMC to measure polyfunctional responses is the expected relative high 
frequency of polyepitope-specific T cells providing a larger sample size for statistically significant data 
analysis. 
 Exploratory objectives 
We will also monitor the function and phenotype of antigen-specific T cells using time-of-flight mass 
spectrometry (CyTOF). The CyTOF is a next-generation technology based on inductively coupled plasma 
mass spectrometry (ICP-MS) that employs antibodies or peptide-MHC tetramers labeled with heavy metal 
isotopes instead of fluorophores to identify cell associated proteins of interest [51, 52]. This instrument 
permits investigators to probe up to 49 parameters simultaneously on individual cells thus allowing for 
cellular phenotyping at unprecedented depth. In addition, it facilitates the effective analysis of 
lymphocytes whose numbers may be limited such as those derived from human cancer patients. The 
Washington University Center for Human Immunology and Immunotherapy Programs has now obtained 
and installed two CyTOF2 instruments that are being used successfully under the guidance of Dr. 
Stephen Oh, Assistant Professor of Medicine and Director of Mass Cytometry for CHiiPs. 


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Clinical responses and time to disease progression will be evaluated with physical examination and 
diagnostic imaging as clinically indicated. 


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10 REMOVAL OF SUBJECTS FROM PROTOCOL THERAPY 
 Removal of subjects from protocol therapy 
Subjects may be removed from protocol therapy if any one or more of the following events occur: 
(1) 
Development of recurrent or metastatic disease prior to the initial vaccination will result in 
stopping vaccine development at its current stage; 
(2) 
Development of recurrent or metastatic disease during the vaccination period will result in 
stopping further vaccinations. Due to the high recurrence rate associated with pancreas cancer, it 
is expected that some percentage of patients will recur during the period of vaccine production 
and administration. Due to the poor response to traditional chemotherapeutics, patients who recur 
or develop metastatic disease may still benefit from vaccine administration, vaccine 
administration in combination with chemotherapy, and/or checkpoint blockade.  The decision to 
continue or discontinue vaccine administration will be left to the treating physician. 
(3) 
Intercurrent illness that prevents further administration of protocol therapy; 
(4) 
Pregnancy; 
(5) 
Type 1 hypersensitivity reaction associated with protocol therapy; 
(6) 
Grade 2 systemic or injection site adverse event classified as possibly, probably, or definitely 
associated with protocol therapy that does not resolve to at least grade 1 prior to the next 
scheduled treatment excluding priming vaccine on Days 1, 4, 8, and 15, where dose delays are 
permitted per Section 6); 
(7) 
Grade 3 or 4 systemic or injection site adverse event classified as possibly, probably, or definitely 
associated with protocol therapy; 
(8) 
Any significant autoimmune disease or phenomena presumed to be related to protocol therapy; 
(9) 
Unable to complete vaccine production; 
(10) 
Subject refusal to continue protocol therapy and/or observations; 
(11) 
Significant protocol violation or noncompliance, either on the part of the subject or investigator(s); 
(12) 
The principal investigator or study sponsor believes it is in the subject's best interest to 
discontinue participation in the study; 
(13) 
Administrative reasons, e.g., study termination by the principal investigator, Siteman Cancer 
Center/Sidney Kimmel Comprehensive Cancer Center, HRPO, FDA, or other group. 
Please note that even if a subject is removed from protocol therapy, they will continue to be followed for 
adverse events for 30 days after last injection, and thereafter only report treatment related SAEs or AEs. 
 Voluntary subject withdrawal 
The subject has the right to voluntarily withdraw from the study at any time for any reason without 
prejudice to her future medical care by the physician or at the institution. 
For any subject who withdraws consent, the date and reason for consent withdrawal should be 
documented. Subject data will be included in the analysis up to the date of the consent withdrawal. 
 Procedure for discontinuation 
The procedure to be followed at the time a subject either discontinues participation or is removed from the 
study is: 
(1) 
Check for the development of adverse events. 
(2) 
Complete the End-of-Study form and include an explanation of why the subject is withdrawing or 
withdrawn. 


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(3) 
Attempt to perform follow-up evaluations as outlined above. 


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11 REGULATORY AND REPORTING REQUIREMENTS 
The entities providing oversight of safety and compliance with the protocol require reporting as outlined 
below.  Please refer to Section 20.4 for definitions and Section 20.6 for a grid of reporting timelines. 
Adverse events will be tracked from start of treatment through 30 days following the last day of study 
treatment.  All adverse events must be recorded on the toxicity tracking case report form (CRF) with the 
exception of: 
• 
Baseline adverse events, which shall be recorded on the medical history form 
Refer to the data submission schedule in Section 14 for instructions on the collection of AEs in the EDC. 
Reporting requirements for Washington University study team may be found in Section 11.1.  Reporting 
requirements for secondary site study teams participating in Washington University-coordinated research 
may be found in Section 11.2 
 Sponsor-Investigator Reporting Requirements 
11.1.1 Reporting to the Human Research Protection Office (HRPO) at Washington University 
Reporting will be conducted in accordance with Washington University IRB Policies. 
Pre-approval of all protocol exceptions must be obtained prior to implementing the change. 
11.1.2 Reporting to the Quality Assurance and Safety Monitoring Committee (QASMC) at 
Washington University 
The Washington University Sponsor Investigator (or designee) is required to notify the QASMC of any 
unanticipated problems involving risks to participants or others occurring at WU or any BJH or SLCH 
institution that have been reported to and acknowledged by HRPO.  (Unanticipated problems reported to 
HRPO and withdrawn during the review process need not be reported to QASMC). 
 
QASMC must be notified within 10 days of receipt of IRB acknowledgment via email to 
qasmc@wustl.edu.  Submission to QASMC must include the myIRB form and any supporting 
documentation sent with the form. 
 
For events that occur at secondary sites, the Washington University Sponsor Investigator (or designee) is 
required to notify the QASMC within 10 days of Washington University notification via email to 
qasmc@wustl.edu.  Submission to QASMC must include either the myIRB form and supporting 
documentation or (if not submitted to myIRB) the date of occurrence, description of the event, whether the 
event is described in the currently IRB approved materials, the event outcome, determination of 
relatedness, whether currently enrolled participants will be notified, and whether the informed consent 
document and/or any study procedures will be modified as a result of this event. 
11.1.3 Reporting to the FDA 
The conduct of the study will comply with all FDA safety requirements.  PLEASE NOTE THAT 
REPORTING REQUIREMENTS FOR THE FDA DIFFER FROM REPORTING REQUIREMENTS FOR 
HRPO/QASMC.  It is the responsibility of the Washington University principal investigator to report to the 
FDA as follows: 
• 
Report any unexpected fatal or life-threatening suspected adverse reaction (refer to Section 20.4 
for definitions) no later than 7 calendar days after initial receipt of the information.   
• 
Report a suspected adverse reaction that is both serious and unexpected (SUSAR, refer to 
Section 20.4) no later than 15 calendar days after it is determined that the information qualifies for 
reporting.  Report an adverse event (refer to Section 20.4) as a suspected adverse reaction only 
if there is evidence to suggest a causal relationship between the drug and the adverse event, 
such as: 
o 
A single occurrence of an event that is uncommon and known to be strongly associated 
with drug exposure 


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o 
One or more occurrences of an event that is not commonly associated with drug 
exposure but is otherwise uncommon in the population exposed to the drug 
o 
An aggregate analysis of specific events observed in a clinical trial that indicates those 
events occur more frequently in the drug treatment group than in a concurrent or 
historical control group 
• 
Report any findings from epidemiological studies, pooled analysis of multiple studies, or clinical 
studies that suggest a significant risk in humans exposed to the drug no later than 15 calendar 
days after it is determined that the information qualifies for reporting. 
• 
Report any findings from animal or in vitro testing that suggest significant risk in humans exposed 
to the drug no later than 15 calendar days after it is determined that the information qualifies for 
reporting.  
• 
Report any clinically important increase in the rate of a serious suspected adverse reaction of that 
listed in the protocol or IB within 15 calendar days after it is determined that the information 
qualifies for reporting. 
Submit each report as an IND safety report in a narrative format or on FDA Form 3500A or in an 
electronic format that FDA can process, review, and archive.  Study teams must notify the Siteman 
Cancer Center Protocol Development team of each potentially reportable event within 1 business day 
after initial receipt of the information, and must bring the signed 1571 and FDA Form 3500A to the 
Siteman Cancer Center Protocol Development team no later than 1 business day prior to the due date for 
reporting to the FDA. 
Each notification to FDA must bear prominent identification of its contents (“IND Safety Report”) and must 
be transmitted to the review division in the Center for Drug Evaluation and Research (CDER) or in the 
Center for Biologics Evaluation and Research (CBER) that has responsibility for review of the IND.  
Relevant follow-up information to an IND safety report must be submitted as soon as the information is 
available and must be identified as such (“Follow-up IND Safety Report”). 
11.1.4 Reporting to Secondary Sites 
The Washington University Sponsor-Investigator (or designee) will notify the research team at each 
secondary site of all unanticipated problems involving risks to participants or others that have occurred at 
other sites within 10 working days of the occurrence of the event or notification of the Sponsor-
Investigator (or designee) of the event.  This includes events that take place both at Washington 
University and at other secondary sites, if applicable.  Refer to Section 16.0 (Multicenter Management) for 
more information. 
 
 Secondary Site Reporting Requirements 
The research team at each secondary site is required to promptly notify the Washington University 
Sponsor-Investigator and designee of all serious adverse events (refer to Section 20.4, Section D) within 
1 working day of the occurrence of the event or notification of the secondary site’s PI of the event.  This 
notification may take place via email if there is not yet enough information for a formal written report 
(using FDA Form 3500a (MedWatch) and Washington University’s cover sheet (Appendix C).  A formal 
written report must be sent to the Washington University Sponsor-Investigator and designee within 4 
calendar days (for fatal or life-threatening suspected adverse reactions) or 11 calendar days (for serious 
unexpected suspected adverse reactions) of the occurrence of the event or notification of the secondary 
site’s PI of the event. 
The research team at a secondary site is responsible for following its site’s guidelines for reporting 
applicable events to its site’s IRB according to its own institutional guidelines.  The research team at 
Washington University is responsible for reporting all applicable events to the FDA, CSBio, and Oncovir 
as needed. 


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Washington University pre-approval of all protocol exceptions must be obtained prior to implementing the 
change.  Local IRB approval must be obtained as per local guidelines.  Washington University IRB 
approval is not required for protocol exceptions occurring at secondary sites. 
 Exceptions to Expedited Reporting 
Events that do not require expedited reporting as described in 11.1 include: 
• 
planned hospitalizations 
• 
hospitalization <24 hours 
• 
respite care 
• 
events related to disease progression 
Events that do not require expedited reporting must still be captured in the EDC. 
 
 
 


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12 DATA AND SAFETY MONITORING 
In compliance with the Washington University Institutional Data and Safety Monitoring Plan, an 
independent Data and Safety Monitoring Board (DSMB) will be specifically convened for this trial to 
review toxicity data. A DSMB will consist of no fewer than 3 members including 2 clinical investigators and 
a biostatistician. DSMB members must be employed by Washington University, Barnes-Jewish Hospital, 
or St. Louis Children’s Hospital.  Like investigators, DSMB members are subject to the Washington 
University School of Medicine policies regarding standards of conduct. Individuals invited to serve on the 
DSMB will disclose any potential conflicts of interest to the trial principal investigator and/or appropriate 
university officials, in accordance with institution policies. Potential conflicts that develop during a trial or a 
member’s tenure on a DSMB must also be disclosed. 
Until such a time as the first secondary site enrolls its first patient, a semi-annual DSM report to be 
prepared by the study team will be submitted to the Quality Assurance and Safety Monitoring Committee 
(QASMC) semi-annually beginning six months after study activation at Washington University (if at least 
one patient has been enrolled) or one year after study activation (if no patients have been enrolled at the 
six-month mark). 
The DSM report for the DSMB will be prepared by the study team with assistance from the study 
statistician, will be reviewed by the DSMB, and will be submitted to the QASM Committee.  The DSMB 
must meet at least every six months beginning six months after study activation at Washington 
University/beginning six months after enrollment of the first patient at a secondary site, no more than one 
month prior to the due date of the DSM report to QASMC.  This report will include: 
• 
HRPO protocol number, protocol title, Principal Investigator name, data coordinator name, 
regulatory coordinator name, and statistician 
• 
Date of initial HRPO approval, date of most recent consent HRPO approval/revision, date of 
HRPO expiration, date of most recent QA audit, study status, and phase of study 
• 
History of study including summary of substantive amendments; summary of accrual 
suspensions including start/stop dates and reason; and summary of protocol exceptions, 
error, or breach of confidentiality including start/stop dates and reason 
• 
Study-wide target accrual and study-wide actual accrual including numbers from participating 
sites 
• 
Protocol activation date at each participating site 
• 
Average rate of accrual observed in year 1, year 2, and subsequent years at each 
participating site 
• 
Expected accrual end date and accrual by site 
• 
Objectives of protocol with supporting data and list the number of participants who have met 
each objective 
• 
Measures of efficacy 
• 
Early stopping rules with supporting data and list the number of participants who have met 
the early stopping rules 
• 
Power analysis and/or interim analysis 
• 
Summary of toxicities at all participating sites 
• 
Abstract submissions/publications 
• 
Summary of any recent literature that may affect the safety or ethics of the study  
Further DSMB responsibilities are described in the DSMB charter. 
The study principal investigator and coordinator will monitor for serious toxicities on an ongoing basis. 
Once the principal investigator or coordinator becomes aware of an adverse event, the AE will be 
reported to the HRPO and QASMC according to institutional guidelines (please refer to Section 11). 
Refer to the Washington University Quality Assurance and Safety Monitoring Committee Policies and 
Procedures for full details on the responsibilities of the DSMB.  This is located on the QASMC website at 
https://siteman.wustl.edu/research/clinical-research-resources/protocol-office-prmcqasmc/.  
   


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 Developmental therapeutics 
Given the nature of this human gene transfer protocol, the principal investigator will monitor and analyze 
study data as they become available and will review this data on a monthly basis with the Developmental 
Therapeutics Group at the Siteman Cancer Center. This is an independent group that will provide more 
rigorous oversight than is routinely provided by the QASMC and the HRPO. The director of the 
Developmental Therapeutics group will advise Dr. Gillanders in the proper conduct of this study and will 
review patient treatment and all toxicities in her weekly Phase 1 meeting. In addition, the director of the 
Developmental Therapeutics group will assist in the oversight of the regulatory and data management 
personnel involved in this clinical trial. 
 Protocol stopping criteria 
The principal investigator will closely monitor and analyze study data as they become available and will 
make determinations regarding the presence and severity of adverse events. The administration of study 
injections and new enrollments will be halted and the QASMC promptly notified if any of the following 
events occurs: 
(1) 
One (or more) subject(s) experiences a Grade 3 or 4 adverse event that is classified as probably 
or definitely related to vaccination; 
(2) 
One (or more) subject(s) experiences a vaccine-related SAE; 
(3) 
One (or more) subject(s) experiences death (other than death related to progressive disease) that 
occurs within 30 days of neoantigen vaccine administration; 
(4) 
Two (or more) subjects experience the same Grade 2 or higher adverse event that is classified 
as probably or definitely related to vaccination: this criterion applies to fever, vomiting, laboratory 
abnormalities or other clinical adverse experiences, but does not apply to the subjective local or 
systemic symptoms of pain/tenderness, malaise, fatigue, headache, chills, nausea, myalgia, or 
arthralgia. 
(5) 
Any other observation occurs that in the opinion of the PI results in a recommendation to halt 
enrollment. 
If one of these events does occur, study injections and study enrollments would only resume if review of 
the adverse events that caused the halt resulted in a recommendation to permit further study injections 
and study enrollments. 
The QASMC, in consultation with the principal investigator, will conduct any review and make the 
decision to resume or close the study for any Grade 2 or 3 events leading to a halt in the study. 
The QASMC, with participation by the principal investigator, will consult with the FDA to conduct the 
review and make the decision to resume or close the study for all Grade 4 adverse events leading to a 
halt in the study. 


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13 STATISTICAL CONSIDERATIONS 
 Experimental Design 
This is a phase 1, open-label, trial of a neoantigen peptide vaccine strategy. Twenty patients who have 
had an R0/R1 surgical resection, and who have completed adjuvant chemotherapy will be enrolled. At our 
institution, pancreatic cancer patients undergo routine staging during (three months) and after adjuvant 
chemotherapy. If there is no evidence of disease, patients will be eligible for enrollment. After enrollment, 
exome sequencing of tumor/normal DNA and cDNA-capture sequencing of the tumor will be performed to 
identify somatic mutations present in the tumor and confirm expression of these mutations at the mRNA 
level. Epitope prediction algorithms will then be used to prioritize neoantigens for inclusion in neoantigen 
peptide vaccines, and the neoantigen peptide vaccines will be designed and manufactured. The 
neoantigen peptide vaccines will be administered starting two to four weeks after the completion of 
adjuvant chemotherapy. The neoantigen peptide vaccines will be administered at seven time points, Days 
1, 4, 8, 15, 22, 50, and 78.  
13.1.1 Sample size and accrual 
Development of cancer vaccines is currently an area of intense research interest. The traditional 
paradigm for phase 1 clinical trials has been heavily influenced by phase 1 clinical trials of 
chemotherapeutic agents, where dose escalation designs are appropriate given the rather narrow dose 
versus safety concerns of these agents. However, there are major differences between these two classes 
of therapeutics that have important implications for early clinical development. Specifically, the phase 1 
concept of dose escalation to find a maximum-tolerated dose does not apply to most therapeutic cancer 
vaccines. Most therapeutic cancer vaccines are associated with minimal toxicity at a range that is feasible 
to manufacture or administer, and there is little reason to believe that the maximum-tolerated dose is the 
most effective dose [32]. Consistent with recent recommendations published in the statistical literature, 
the general philosophy of this phase I clinical trial is to facilitate a prompt preliminary evaluation of the 
safety and immunogenicity of a personalized pancreatic cancer DNA vaccine strategy by testing a fixed 
dose of vaccine, instead of performing a dose escalation [32]. The sample size (n=15) is chosen to 
provide a reasonable ability to detect serious adverse events associated with vaccine administration. 
Based on extensive simulations regarding the sample size for pilot or translational studies, Piantadosi [83] 
recommended that a sample size of 10 to 20 patients would provide a reasonable precision for estimating 
preliminary information. We therefor expect that, as detailed below, the proposed sample size for this 
study will be adequate in estimating both safety and preliminary immune efficacy data. The sample size of 
n=15 will consist of EVALUABLE patients. Patients who screen fail due to sequencing issues such as 
poor sample quality will be replaced. 
13.1.2 Sample Size Calculations for Safety 
One of the primary objectives of this study is to evaluate the safety of the neoantigen peptide vaccines. 
We have chosen to power the study to provide a reasonable ability to detect serious adverse events 
associated with vaccine administration. 
Sample size calculations for safety are expressed in terms of the ability to detect serious adverse events. 
The ability of the study to identify serious adverse events is best expressed by the maximum true rate of 
events that would be unlikely to be observed and the minimum true rate of events that would very likely 
be observed. Table below shows the probabilities of observing 0, or 2 or more serious adverse events 
given variety of hypothesized “true” AE rates. If the true rate is at least 15%, for example, there is >90% 
chance of observing at least 1 serious adverse event among a sample size of n=15 evaluable patients. 
Conversely, there is only 10% chance that we would observe 2 or more serious adverse event among 
n=15 evaluable patients if the true rate is less than 3.5%. Although we believe that the true event rate is 
likely to be quite low, this table presents a range of event rates in an attempt to illustrate the sensitivity of 
this study to identify potential safety problems with the neoantigen peptide vaccines. 
 


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Probability of detecting SAE for different safety scenarios if 15 evaluable patients are 
enrolled 
True Event rate 
Pr(0/15) 
Pr(2+/15) 
0.010 
0.860 
0.010 
0.035 
0.586 
0.100 
0.050 
0.463 
0.171 
0.100 
0.206 
0.451 
0.150 
0.087 
0.681 
13.1.3 Sample Size Calculations for Immunogenicity 
The secondary objective and primary scientific endpoint is to assess the prevalence of antigen-specific T 
cells in the peripheral blood of patients pre- and post-vaccination as measured by flow cytometry and 
ELISPOT. A power analysis was performed using paired t-test for over time differences (e.g., changes in 
ELISPOT and multi-parameter flow cytometry). Assuming a moderate correlation between measures 
taken from the same individual, the designed sample size (n=15 evaluable patients) allows us 80% power 
at 1-sided 0.05 alpha level to detect a minimum increase of 0.68*SD, where SD represents the standard 
deviation of measures for immunogenicity. Our preliminary data showed that antigen-specific T cells can 
be measured with a coefficient of variability (CV=SD/Mean) of approximately 20%. Therefore, if assuming 
similar variability in the proposed study, the designed sample size provides 80% power to detect a 
minimal of 15% change in the average antigen-specific T cells. We expect that more power could be 
achieved because multiple measurements will be taken from the same patient and this allows borrowing 
information across different time points. 
 Data Analysis 
As a phase I trial to evaluate the preliminary data on the safety and immunogenicity of a neoantigen 
peptide vaccine strategy, the data analysis for this study is descriptive in nature. Demographic and 
clinical characteristics of the sample, toxicity by grade, as well as response and time to toxicity will be 
listed and summarized using descriptive statistics. 
13.2.1 Primary objective: safety analysis 
Toxicity evaluation is the primary objective of this trial. The data will be descriptive, and standard toxicity 
definitions and criteria will be used as outlined in the National Cancer Institute Common Terminology 
Criteria for Adverse Events version 5.0. 
Since enrollment will be concurrent with the first dose of the personalized pancreatic cancer DNA 
vaccines, all subjects will have received at least one vaccination, and all subjects will provide at least 
some safety data. 
The number and percentage of subjects experiencing each type of adverse event will be tabulated by 
severity, and relationship to treatment. If appropriate, confidence intervals will be used to characterize the 
precision of the estimate. A complete listing of adverse events will also be tabulated, and will provide 
details including severity, relationship to treatment, onset, duration, and outcome. 
Laboratory data measured on a continuous scale will be characterized by summary statistics (mean and 
standard deviation). Boxplots of laboratory data will be generated for baseline values and for values 
measured during and after protocol therapy at each specific time point. Each boxplot will show the 
median, 1st and 3rd quartiles. Outliers will be individually plotted in a separate graph, as appropriate. 
13.2.2 Secondary objective: immune response as measured by ELISPOT analysis and 
multiparametric flow cytometry 


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Immune response as measured by ELISPOT analysis and multiparametric flow cytometry is the 
secondary objective of this trial. The frequency of antigen-specific T cells at each time will be summarized 
using means, standard deviations and medians, and the change over time will also be compared using 
two-ANOVA for repeated measurement data or Friedman rank-sum test as appropriate. The 
immunogenicity of the neoantigen peptide vaccine will also be analyzed qualitatively by summarizing the 
phenotypic and functional characteristics of antigen-specific T cells. Responses will be considered 
positive if the number of T cells after vaccination is greater than two standard deviations above the mean 
before vaccination [50]. The frequency of positive responses at each time point will be assessed and 
binomial response rates with 95% confidence interval estimates will be presented. In addition to 
presenting the binomial response rates, graphical and tabular summaries of the underlying distributions 
will be made. 
13.2.3 Exploratory objectives 
Blood samples will be obtained at multiple time points (prior to vaccination, during, and post-vaccination) 
in order to procure PBMC for correlative studies. Functional studies will include ELISPOT, T cell poly-
functionality by intra-cellular cytokine and degranulation analysis using multi-parametric flow cytometry, 
as detailed in Section 9. 
Time to disease progression will be evaluated with physical examination and diagnostic imaging as 
clinically indicated. The time to disease progression will be described using Kaplan-Meier product limited 
method. The median progression-free survival (PFS), median overall survival (OS), and their 95% CIs will 
be estimated. The association between immunogenicity and PFS or OS will be explored by comparing the 
survival curves between immune responders versus non-responders. To determine whether the observed 
difference is larger than might be expected by chance, a permutation test will be used to compare the 
observed test statistic to the distribution of test statistics that would be seen if there were no difference 
between the two studies. Specifically, we will randomly shuffle the status of response and calculate the 
test statistic from the shuffled data. This procedure will be repeated 10,000 times and the resultant testing 
statistics will provide an accurate representation of the null distribution. The observed test statistics of 
between-study differences will be compared to the null distributions. For each outcome, the permuted p-
value will be the fraction of permuted samples that resulted in a small statistic than the original sample 
[53]. 


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14 DATA MANAGEMENT 
Data collected will be collected using paper case report forms or OnCore electronic data capture forms. 
Forms must be completed within 28 days of time point. 
Case report forms with appropriate source documentation will be completed according to the schedule 
listed in this section. 
Case Report Form 
Submission Schedule 
Original Consent Form 
Prior to registration 
Registration Form 
Eligibility Form 
Demographics Form 
On-Study Form 
Medical History Form 
Prior to starting treatment 
Physical Exam Form 
Enrollment 
Mid chemo 
End of chemo 
Day 1 
Day 4 
Day 8 
Day 15 
Day 22 
Day 50 
Day 78 
4 weeks after last injection 
1 year after last injection 
Vaccine Administration Form 
Day 1 
Day 4 
Day 8 
Day 15 
Day 22 
Day 50 
Day 78 
Immune Monitoring Form 
Enrollment 
Mid chemo 
End of chemo 
Day 1 
Day 22 
Day 50 
Day 78 
Imaging Form 
Mid chemo 
End of chemo 
Toxicity Form 
Day 1 
Day 4 
Day 8 
Day 15 
Day 22 
Day 50 
Day 78 
Concomitant Medications Form 
Continuous through Week 25 
Follow Up Form 
4 weeks after last injection 
1 year after last injection 
Year 2 and annually thereafter  
Death Form 
Time of death 
Progression Form 
Time of disease progression 
MedWatch Form 
See Section 11.0 for reporting requirements 
Any queries generated by Washington University must be responded to within 28 days of receipt by the 
participating site. The Washington University research team will conduct a regular review of data status at 
all secondary sites, with appropriate corrective action to be requested as needed. 


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 Adverse Event Collection in the Case Report Forms 
All adverse events that occur beginning with start of treatment (minus exceptions defined in Section 11.0) 
must be captured in the Toxicity Form.  Baseline AEs should be captures on the Medical History Form. 
 
Participant death due to disease progression should be reported on the Toxicity Form as grade 5 disease 
progression.  If death is due to an AE (e.g. cardiac disorders:  cardiac arrest), report as a grade 5 event 
under that AE.  Participant death must also be recorded on the Death Form. 
 
15 AUDITING 
As coordinating center of this trial, Washington University (via the Quality Assurance and Safety 
Monitoring Committee (QASMC) will monitor each participating site to ensure that all protocol 
requirements are being met; that applicable federal regulations are being followed; and that best practices 
for patient safety and data collection are being followed per protocol. Participating sites will be asked to 
send copies of all audit materials, including source documentation. The audit notification will be sent to 
the Washington University Research Patient Coordinator, who will obtain the audit materials from the 
participating institution. 
Notification of an upcoming audit will be sent to the research team one month ahead of the audit. Once 
accrual numbers are confirmed, and approximately 30 days prior to the audit, a list of the cases selected 
for review (up to 10 for each site) will be sent to the research team. However, if during the audit the need 
arises to review cases not initially selected, the research team will be asked to provide the additional 
charts within two working days. 
Items to be evaluated include: 
• 
Subject screening and enrollment 
• 
Reporting of adverse events 
• 
Maintenance of HIPAA compliance 
• 
Completeness of regulatory documentation 
• 
Completeness of participant documentation 
• 
Acquisition of informed consent 
• 
IRB documentation 
• 
Issues of protocol adherence 
Additional details regarding the auditing policies and procedures can be found at 
https://siteman.wustl.edu/wp-content/uploads/2015/10/QASMC-Policies-and-Procedures-03.31.2015.pdf 
 
 
 


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16 MULTICENTER REGULATORY REQUIREMENTS 
Washington University requires that each participating site sends its informed consent document to be 
reviewed and approved by the Washington University Regulatory Coordinator (or designee) prior to 
IRB/IEC submission.  
Site activation is defined as when the secondary site has received official written documentation from the 
coordinating center that the site has been approved to begin enrollment. At a minimum, each participating 
institution must have the following documents on file at Washington University prior to study activation: 
• 
Documentation of IRB approval of the study in the form of a letter or other official document from 
the participating institution’s IRB. This documentation must show which version of the protocol was 
approved by the IRB. 
• 
Documentation of IRB approval of an informed consent form. The consent must include a statement 
that data will be shared with Washington University, including the Quality Assurance and Safety 
Monitoring Committee (QASMC), the DSMB (if applicable), and the Washington University study 
team. 
• 
Documentation of FWA, signed FDA Form 1572 (if applicable), and the CVs of all participating 
investigators. 
• 
Protocol signature page signed and dated by the investigator at each participating site. 
The coordinating center Principal Investigator (or designee) is responsible for disseminating to the 
participating sites all study updates, amendments, reportable adverse events, etc. Protocol/consent 
modifications and IB updates will be forwarded electronically to the secondary sites within 4 weeks of 
obtaining Washington University IRB approval. Activated secondary sites are expected to submit 
protocol/consent/IB modifications to their local IRBs within 4 weeks of receipt unless otherwise noted. 
Upon the secondary sites obtaining local IRB approval, documentation of such shall be sent to the 
Washington University study team within 2 weeks of receipt of approval. 
Documentation of participating sites’ IRB approval of annual continuing reviews, protocol amendments or 
revisions, all SAE reports, and all protocol violations/deviations/exceptions must be kept on file at 
Washington University. 
The investigator or a designee from each institution must participate in a regular conference call to update 
and inform regarding the progress of the trial. 
 
 
 


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17 REGULATORY AND ETHICAL OBLIGATIONS 
 Informed consent 
In accordance with US FDA regulations (21 CFR 50) and guidelines (Federal Register, May 9, 1997, Vol. 
62, Number 90 - ICH Good Clinical Practice Consolidated Guideline) it is the investigator’s responsibility 
to ensure that witnessed informed consent is obtained from the subject before participating in an 
investigational study, after an adequate explanation of the purpose, methods, risks, potential benefits and 
subject responsibilities of the study. Procedures that are to be performed as part of the practice of 
medicine and which would be done whether or not study entry was contemplated, such as for diagnosis 
or treatment of a disease or medical condition, may be performed and the results subsequently used for 
determining study eligibility without first obtaining consent. On the other hand, informed consent must be 
obtained prior to initiation of any screening procedures that are performed solely for the purpose of 
determining eligibility for research. 
Each subject must be given a copy of the informed consent. The original signed consent must be retained 
in the institution’s records and is subject to review by the sponsor, the HRPO and any other applicable 
regulatory agencies responsible for the conduct of the institution. All elements listed in the ICH Good 
Clinical Practice guidelines must be included in the informed consent. 
Informed consent will be obtained by either the principal investigator or by individuals approved by the 
principal investigator and whose names have been submitted to the IRB. Informed consent will be 
obtained from the subject after the details of the protocol have been reviewed. The individual responsible 
for obtaining consent will assure, prior to signing of the informed consent, that the subject has had all 
questions regarding therapy and the protocol answered. 
 Institutional Review Board 
In accordance with US FDA regulations (21 CFR 56) and guidelines (Federal Register, May 9, 1997 Vol. 
62 Number 90 - ICH Good Clinical Practice Consolidated Guideline) all research involving human 
subjects must be reviewed and approved by the local IRB. All modifications to the protocol, consent 
forms, or other study documents must be reviewed and approved by the local IRB. At Washington 
University School of Medicine, the Human Research Protection Office serves as the local IRB. 
 Subject confidentiality 
In order to ensure subject confidentiality, each subject will be assigned a study number. Subject samples 
and medical information will be de-identified and labeled with the study number. The link between subject 
identification and study number will be safeguarded in a secure file in a locked room, and access will be 
restricted to the principal investigator, study coordinator, and other co-investigators as necessary. 
Collected data will be recorded on case report forms. Case report forms will be safeguarded in a locked 
cabinet and/or a password-protected secure computer drive and access will be restricted to the principal 
investigator, study coordinator, and other co-investigators as necessary. Subject medical information 
related to, or obtained for the purposes of this trial are confidential, and disclosure to third parties is 
prohibited. The exception is regulatory authorities including the FDA, NIH/OBA, and the local IRB. Data 
from this study must be available for inspection on request of regulatory authorities including the FDA and 
the local IRB. 
 
 
 


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18 ADMINISTRATIVE AND LEGAL OBLIGATIONS 
 Study documentation and retention of records 
18.1.1 Study documentation 
Source documents are original documents, data, and records from which the subject’s data are obtained. 
These include but are not limited to hospital records, clinical and office charts, laboratory and pharmacy 
records, diaries, diagnostic imaging studies, and correspondence. 
The principal investigator and staff are responsible for maintaining a comprehensive file of all study-
related documents, suitable for inspection at any time by representatives from the PRMC, HRPO, FDA, 
and any other applicable regulatory agency. 
Pertinent documents in the study file include: 
(1) 
The original protocol with all amendments 
(2) 
Curriculum vitae of principal investigator and co-investigators 
(3) 
Approval notification and any other correspondence with the PRMC, HRPO, NIH RAC and FDA 
Pertinent documents in each individual subject file include: 
(1) 
Informed consent forms 
(2) 
Case report forms 
(3) 
Supporting copies of source documentation 
All original source documentation must be readily available. 
18.1.2 Retention of records 
The principal investigator must retain records related to this study including protocols; amendments; 
IRB/IBC approvals; FDA IND records and other correspondence; completed, signed and dated consent 
forms; patient medical records; case report forms; drug accountability records and any other 
correspondence related to the conduct of the study. 
U.S. FDA regulations (21 CFR 312.62[c]) require that all records pertaining to the conduct of this study, 
must be retained by the responsible investigator for a minimum of 2 years after marketing application 
approval. If no application is filed, these records must be kept 3 years after the investigation is 
discontinued and the U.S. FDA and the applicable local health authorities are notified. 
 Policy regarding research-related injuries 
Washington University School of Medicine investigators and their staffs will try to reduce, control, and 
treat any complications from this research. 
Any subjects who believe that they have been injured as a result of participation in this study will be 
instructed to contact the principal investigator, William E. Gillanders, M.D. at (314) 747-0072. 
Alternatively, they can contact Dr. Amanda Cashen, Chair of the Human Research Protection Office, at 
(800) 438-0445. 
Decisions about payment for medical treatment for research-related injuries will be made by Washington 
University School of Medicine. 
In general, Washington University School of Medicine will provide no long-term medical care or financial 
compensation for research-related injuries. 
 Study termination 
The principal investigator and the Siteman Cancer Center reserve the right to terminate the study. The 
principal investigator will notify the PRMC and HRPO in writing of the study's completion or early 
termination. 


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19 REFERENCES 
1. 
Siegel, R., et al., Cancer statistics, 2014. CA Cancer J Clin, 2014. 64(1): p. 9-29. 
2. 
Rahib, L., et al., Projecting cancer incidence and deaths to 2030: the unexpected burden 
of thyroid, liver, and pancreas cancers in the United States. Cancer Res, 2014. 74(11): p. 
2913-21. 
3. 
Conroy, T., et al., FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N 
Engl J Med, 2011. 364(19): p. 1817-25. 
4. 
Von Hoff, D.D., et al., Increased survival in pancreatic cancer with nab-paclitaxel plus 
gemcitabine. N Engl J Med, 2013. 369(18): p. 1691-703. 
5. 
Jones, S., et al., Core signaling pathways in human pancreatic cancers revealed by 
global genomic analyses. Science, 2008. 321(5897): p. 1801-6. 
6. 
Clark, C.E., G.L. Beatty, and R.H. Vonderheide, Immunosurveillance of pancreatic 
adenocarcinoma: insights from genetically engineered mouse models of cancer. Cancer 
Lett, 2009. 279(1): p. 1-7. 
7. 
Clark, C.E., et al., Dynamics of the immune reaction to pancreatic cancer from inception 
to invasion. Cancer Res, 2007. 67(19): p. 9518-27. 
8. 
Mahadevan, D. and D.D. Von Hoff, Tumor-stroma interactions in pancreatic ductal 
adenocarcinoma. Mol Cancer Ther, 2007. 6(4): p. 1186-97. 
9. 
Porembka, M.R., et al., Pancreatic adenocarcinoma induces bone marrow mobilization 
of myeloid-derived suppressor cells which promote primary tumor growth. Cancer 
Immunol Immunother, 2012. 61(9): p. 1373-85. 
10. 
Sanford, D.E., et al., Inflammatory monocyte mobilization decreases patient survival in 
pancreatic cancer: a role for targeting the CCL2/CCR2 axis. Clin Cancer Res, 2013. 
19(13): p. 3404-15. 
11. 
van der Bruggen, P., et al., A gene encoding an antigen recognized by cytolytic T 
lymphocytes on a human melanoma. Science, 1991. 254(5038): p. 1643-7. 
12. 
Peshwa, M.V., et al., Induction of prostate tumor-specific CD8+ cytotoxic T-lymphocytes 
in vitro using antigen-presenting cells pulsed with prostatic acid phosphatase peptide. 
Prostate, 1998. 36(2): p. 129-38. 
13. 
Peoples, G.E., et al., Breast and ovarian cancer-specific cytotoxic T lymphocytes 
recognize the same HER2/neu-derived peptide. Proc Natl Acad Sci U S A, 1995. 92(2): p. 
432-6. 
14. 
Johnston, F.M., et al., Circulating mesothelin protein and cellular antimesothelin 
immunity in patients with pancreatic cancer. Clin Cancer Res, 2009. 15(21): p. 6511-8. 
15. 
Le, D.T., et al., Safety and survival with GVAX pancreas prime and Listeria 
Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic 
pancreatic cancer. J Clin Oncol, 2015. 33(12): p. 1325-33. 
16. 
Lutz, E., et al., A lethally irradiated allogeneic granulocyte-macrophage colony 
stimulating factor-secreting tumor vaccine for pancreatic adenocarcinoma. A Phase II 
trial of safety, efficacy, and immune activation. Ann Surg, 2011. 253(2): p. 328-35. 
17. 
Thomas, A.M., et al., Mesothelin-specific CD8(+) T cell responses provide evidence of in 
vivo cross-priming by antigen-presenting cells in vaccinated pancreatic cancer patients. 
J Exp Med, 2004. 200(3): p. 297-306. 
18. 
Parmiani, G., et al., Unique human tumor antigens: immunobiology and use in clinical 
trials. J Immunol, 2007. 178(4): p. 1975-9. 


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19. 
Sensi, M. and A. Anichini, Unique tumor antigens: evidence for immune control of 
genome integrity and immunogenic targets for T cell-mediated patient-specific 
immunotherapy. Clin Cancer Res, 2006. 12(17): p. 5023-32. 
20. 
Wolfel, T., et al., A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T 
lymphocytes in a human melanoma. Science, 1995. 269(5228): p. 1281-4. 
21. 
Wang, R.F., et al., Cloning genes encoding MHC class II-restricted antigens: mutated 
CDC27 as a tumor antigen. Science, 1999. 284(5418): p. 1351-4. 
22. 
Echchakir, H., et al., A point mutation in the alpha-actinin-4 gene generates an antigenic 
peptide recognized by autologous cytolytic T lymphocytes on a human lung carcinoma. 
Cancer Res, 2001. 61(10): p. 4078-83. 
23. 
Brandle, D., et al., A mutated HLA-A2 molecule recognized by autologous cytotoxic T 
lymphocytes on a human renal cell carcinoma. J Exp Med, 1996. 183(6): p. 2501-8. 
24. 
Matsushita, H., et al., Cancer exome analysis reveals a T-cell-dependent mechanism of 
cancer immunoediting. Nature, 2012. 482(7385): p. 400-4. 
25. 
Gubin, M.M., et al., Checkpoint blockade cancer immunotherapy targets tumour-specific 
mutant antigens. Nature, 2014. 515(7528): p. 577-81. 
26. 
Parker, K.C., M.A. Bednarek, and J.E. Coligan, Scheme for ranking potential HLA-A2 
binding peptides based on independent binding of individual peptide side-chains. J 
Immunol, 1994. 152(1): p. 163-75. 
27. 
Rammensee, H., et al., SYFPEITHI: database for MHC ligands and peptide motifs. 
Immunogenetics, 1999. 50(3-4): p. 213-9. 
28. 
Yamada, A., et al., Next-generation peptide vaccines for advanced cancer. Cancer Sci, 
2013. 104(1): p. 15-21. 
29. 
Melief, C.J. and S.H. van der Burg, Immunotherapy of established (pre)malignant 
disease by synthetic long peptide vaccines. Nat Rev Cancer, 2008. 8(5): p. 351-60. 
30. 
Bijker, M.S., et al., Superior induction of anti-tumor CTL immunity by extended peptide 
vaccines involves prolonged, DC-focused antigen presentation. Eur J Immunol, 2008. 
38(4): p. 1033-42. 
31. 
Sabbatini, P., et al., Phase I trial of overlapping long peptides from a tumor self-antigen 
and poly-ICLC shows rapid induction of integrated immune response in ovarian cancer 
patients. Clin Cancer Res, 2012. 18(23): p. 6497-508. 
32. 
Simon, R.M., et al., Clinical trial designs for the early clinical development of 
therapeutic cancer vaccines. J Clin Oncol, 2001. 19(6): p. 1848-54. 
33. 
Ott, P.A., et al., An immunogenic personal neoantigen vaccine for patients with 
melanoma. Nature, 2017. 547(7662): p. 217-221. 
34. 
Dunn, G.P., et al., A critical function for type I interferons in cancer immunoediting. Nat 
Immunol, 2005. 6(7): p. 722-9. 
35. 
Dunn, G.P., C.M. Koebel, and R.D. Schreiber, Interferons, immunity and cancer 
immunoediting. Nat Rev Immunol, 2006. 6(11): p. 836-48. 
36. 
Dunn, G.P., L.J. Old, and R.D. Schreiber, The three Es of cancer immunoediting. Annu 
Rev Immunol, 2004. 22: p. 329-60. 
37. 
Shankaran, V., et al., IFNgamma and lymphocytes prevent primary tumour development 
and shape tumour immunogenicity. Nature, 2001. 410(6832): p. 1107-11. 
38. 
Diamond, M.S., et al., Type I interferon is selectively required by dendritic cells for 
immune rejection of tumors. J Exp Med, 2011. 208(10): p. 1989-2003. 


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Neoantigen peptide vaccines  
 
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39. 
Dunn, G.P., et al., Cancer immunoediting: from immunosurveillance to tumor escape. 
Nat Immunol, 2002. 3(11): p. 991-8. 
40. 
Vesely, M.D., et al., Natural innate and adaptive immunity to cancer. Annu Rev 
Immunol, 2011. 29: p. 235-71. 
41. 
Vesely, M.D. and R.D. Schreiber, Cancer immunoediting: antigens, mechanisms, and 
implications to cancer immunotherapy. Ann N Y Acad Sci, 2013. 1284: p. 1-5. 
42. 
Peters, B. and A. Sette, Generating quantitative models describing the sequence 
specificity of biological processes with the stabilized matrix method. BMC 
Bioinformatics, 2005. 6: p. 132. 
43. 
Lundegaard, C., et al., NetMHC-3.0: accurate web accessible predictions of human, 
mouse and monkey MHC class I affinities for peptides of length 8-11. Nucleic Acids Res, 
2008. 36(Web Server issue): p. W509-12. 
44. 
Hoof, I., et al., NetMHCpan, a method for MHC class I binding prediction beyond 
humans. Immunogenetics, 2009. 61(1): p. 1-13. 
45. 
Nielsen, M., et al., The role of the proteasome in generating cytotoxic T-cell epitopes: 
insights obtained from improved predictions of proteasomal cleavage. Immunogenetics, 
2005. 57(1-2): p. 33-41. 
46. 
Jaramillo, A., et al., Identification of HLA-A3-restricted CD8+ T cell epitopes derived 
from mammaglobin-A, a tumor-associated antigen of human breast cancer. Int.J.Cancer, 
2002. 102(5): p. 499. 
47. 
Jaramillo, A., et al., Recognition of HLA-A2-restricted mammaglobin-A-derived epitopes 
by CD8+ cytotoxic T lymphocytes from breast cancer patients. Breast Cancer Res.Treat., 
2004. 88(1): p. 29. 
48. 
Manna, P.P., et al., Generation of CD8+ cytotoxic T lymphocytes against breast cancer 
cells by stimulation with mammaglobin-A-pulsed dendritic cells. Breast Cancer 
Res.Treat., 2003. 79(1): p. 133. 
49. 
Narayanan, K., et al., Response of established human breast tumors to vaccination with 
mammaglobin-A cDNA. J.Natl.Cancer Inst., 2004. 96(18): p. 1388. 
50. 
Hobeika, A.C., et al., Enumerating antigen-specific T-cell responses in peripheral blood: 
a comparison of peptide MHC Tetramer, ELISpot, and intracellular cytokine analysis. J 
Immunother, 2005. 28(1): p. 63-72. 
51. 
Andersen, R.S., et al., Parallel detection of antigen-specific T cell responses by 
combinatorial encoding of MHC multimers. Nat Protoc, 2012. 7(5): p. 891-902. 
52. 
Cheung, R.K. and P.J. Utz, Screening: CyTOF-the next generation of cell detection. Nat 
Rev Rheumatol, 2011. 7(9): p. 502-3. 
53. 
Westfall, P.H. and S.S. Young, Resampling-Based Multiple Testing: Examples and 
Methods for p-Value Adjustment. 1993, New York: John Wiley & Sons, Inc. 


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20 APPENDICES 
 Abbreviations 
AE 
Adverse Event 
CBER 
Center for Biologics Evaluation and Research 
CFR 
Code of Federal Regulations 
CPA 
Cooperative Project Assurance 
CR 
Complete response 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CT 
Computed Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTEP 
Cancer Therapy Evaluation Program 
DNA 
Deoxyribonucleic acid 
DCTD 
Division of Cancer Treatment and Diagnosis 
ELISPOT 
Enzyme-linked immunospot assay 
ECOG 
Eastern Cooperative Oncology Group 
FDA 
Food and Drug Administration 
FWA 
Federal-wide Assurance 
GLP 
Good Laboratory Practice 
GMP 
Good Manufacturing Practice 
GPC 
Gel permeation chromatography 
HIPAA 
Health Insurance Portability and Accountability Act 
HLA 
Human leukocyte antigen 
HRPO 
Human Research Protection Office (Institutional Review Board at WUSM) 
IBC 
Institutional Biosafety Committee 
ICH 
International Conference of Harmonization 
IDB 
Investigational Drug Branch 
IRB 
Institutional Review Board 
LD 
Longest diameter 
MPA 
Multiple Project Assurance 
MRI 
Magnetic Resonance Imaging 
NCI 
National Cancer Institute 
NIH 
National Institutes of Health 
OBA 
Office of Biotechnology Activities 
OHRP 
Office for Human Research Protection 
PBMC 
Peripheral blood mononuclear cell 
PD 
Progressive disease 
PHI 
Protected Health Information 
PR 
Partial response 
RAC 
Recombinant DNA Advisory Committee 
RECIST 
Response Evaluation Criteria in Solid Tumors 
QASMC 
Quality Assurance and Safety Monitoring Committee 
SAE 
Serious Adverse Event 
SAS 
Statistical Analysis System; Analytical software from the SAS Institute, Cary, NC 
SCC 
Siteman Cancer Center 
SCIP 
Siteman Cancer Information Portal 
SD 
Stable disease 
SD 
Standard Deviation 
THF 
Tetrahydrofuran 
UPN 
Universal Product Number 
WUSM 
Washington University School of Medicine 
WUSTL 
Washington University in Saint Louis 


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 ECOG/Zubrod performance status scale 
ECOG/Zubrod Score
Performance Status
0
Asymptomatic
1
Symptomatic, fully ambulatory
2
Symptomatic, in bed < 50% of the day
3
Symptomatic, in bed > 50% of the day but not bedridden
4
Bedridden
5
Dead
 
 National Cancer Institute Common Terminology Criteria for Adverse Events 
This study will collect adverse events using the NCI Common Terminology Criteria for Adverse Events 
v5.0 (CTCAE), if applicable. The CTCAE provides a descriptive terminology that is to be used for adverse 
event reporting. A grading (severity) scale is also provided in the CTCAE for each adverse event term. An 
electronic version of the CTCAE may be accessed through the web at http://ctep.cancer.gov. 
Alternatively, a full copy is available from the principal investigator.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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 Definitions for Adverse Event Reporting 
A. Adverse Events (AEs) 
 
As defined in 21 CFR 312.32: 
Definition: any untoward medical occurrence associated with the use of a drug in humans, whether or 
not considered drug-related. 
Grading: the descriptions and grading scales found in the revised NCI Common Terminology Criteria for 
Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.  A copy of the CTCAE 
version 5.0 can be downloaded from the CTEP website. 
Attribution (relatedness), Expectedness, and Seriousness: the definitions for the terms listed that 
should be used are those provided by the Department of Health and Human Services’ Office for Human 
Research Protections (OHRP).  A copy of this guidance can be found on OHRP’s website: 
http://www.hhs.gov/ohrp/policy/advevntguid.html  
B.  Suspected Adverse Reaction (SAR) 
As defined in 21 CFR 312.32: 
Definition:  any adverse event for which there is a reasonable possibility that the drug caused the 
adverse event.  “Reasonable possibility” means there is evidence to suggest a causal relationship 
between the drug and the adverse event.  “Suspected adverse reaction” implies a lesser degree of 
certainty about causality than adverse reaction, which means any adverse event caused by a drug. 
C. Life-Threatening Adverse Event / Life Threatening Suspected Adverse Reaction 
As defined in 21 CFR 312.32: 
Definition:  any adverse drug event or suspected adverse reaction is considered “life-threatening” if, in 
the view of the investigator, its occurrence places the patient at immediate risk of death. It does not 
include an adverse event or suspected adverse reaction that, had it occurred in a more severe form, 
might have caused death. 
D. Serious Adverse Event (SAE) or Serious Suspected Adverse Reaction 
As defined in 21 CFR 312.32: 
Definition:  an adverse event or suspected adverse reaction is considered “serious” if, in the view of the 
investigator, it results in any of the following outcomes: 
o 
Death 
o 
A life-threatening adverse event 
o 
Inpatient hospitalization or prolongation of existing hospitalization 
o 
A persistent or significant incapacity or substantial disruption of the ability to conduct normal 
life functions 
o 
A congenital anomaly/birth defect 
o 
Any other important medical event that does not fit the criteria above but, based upon 
appropriate medical judgment, may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the outcomes listed above 
E. Protocol Exceptions 
Definition:  A planned change in the conduct of the research for one participant. 
F. Deviation 
Definition:  Any alteration or modification to the IRB-approved research without prospective IRB 
approval.  The term “research” encompasses all IRB-approved materials and documents including the 
detailed protocol, IRB application, consent form, recruitment materials, questionnaires/data collection 
forms, and any other information relating to the research study. 
 


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A minor or administrative deviation is one that does not have the potential to negatively impact the rights, 
safety, or welfare of participants or others or the scientific validity of the study. 
A major deviation is one that does have the potential to negatively impact the rights, safety, or welfare of 
participants or others or the scientific validity of the study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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 Reporting Timelines 
Expedited Reporting Timelines 
Event 
HRPO 
QASMC 
FDA 
Serious AND unexpected 
suspected adverse reaction 
 
 
Report no later than 15 calendar days after it 
is determined that the information qualifies for 
reporting 
Unexpected fatal or life-threatening 
suspected adverse reaction 
 
 
Report no later than 7 calendar days after 
initial receipt of the information 
Unanticipated problem involving 
risk to participants or others 
Report within 10 working days.  If the event 
results in the death of a participant enrolled 
at WU/BJH/SLCH, report within 1 working 
day. 
Report via email after IRB 
acknowledgment 
 
Major deviation 
Report within 10 working days.  If the event 
results in the death of a participant enrolled 
at WU/BJH/SLCH, report within 1 working 
day. 
 
 
A series of minor deviations that 
are being reported as a continuing 
noncompliance 
Report within 10 working days.   
 
 
Protocol exception 
Approval must be obtained prior to 
implementing the change 
 
 
Clinically important increase in the 
rate of a serious suspected adverse 
reaction of that list in the protocol or 
IB 
 
 
Report no later than 15 calendar days after it 
is determined that the information qualifies for 
reporting 
Complaints 
If the complaint reveals an unanticipated 
problem involving risks to participants or 
others OR noncompliance, report within 10 
working days.  If the event results in the 
death of a participant enrolled at 
WU/BJH/SLCH, report within 1 working day.  
Otherwise, report at the time of continuing 
review. 
 
 
Breach of confidentiality 
Within 10 working days. 
 
 
Incarceration 
If withdrawing the participant poses a safety 
issue, report within 10 working days.   
 
If withdrawing the participant does not 
represent a safety issue and the patient will 
 
 


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Routine Reporting Timelines 
Event 
HRPO 
QASMC 
FDA 
Adverse event or SAE 
that does not require 
expedited reporting 
If they do not meet the definition of an 
unanticipated problem involving risks to 
participants or others, report summary information 
at the time of continuing review 
Adverse events will be reported in 
the toxicity table in the DSM report 
which is typically due every 6 
months. 
The most current toxicity table from the DSM 
report is provided to the FDA with the IND’s 
annual report. 
Minor deviation 
Report summary information at the time of 
continuing review. 
 
 
Complaints 
If the complaint reveals an unanticipated problem 
involving risks to participants or others OR 
noncompliance, report within 10 working days.  If 
the event results in the death of a participant 
enrolled at WU/BJH/SLCH, report within 1 
working day.  Otherwise, report at the time of 
continuing review. 
 
 
Incarceration 
If withdrawing the participant poses a safety 
issue, report within 10 working days.   
 
If withdrawing the participant does not represent a 
safety issue and the patient will be withdrawn, 
report at continuing review. 
 
 
 
Expedited Reporting Timelines for Secondary Sites 
Event 
WU (Coordinating Center) 
Local IRB 
FDA 
Serious AND unexpected 
suspected adverse reaction 
Report no later than 11 calendar days after it is 
determined that the information qualifies for reporting. 
Report all applicable events 
to local IRB according to 
local institutional 
guidelines. 
The research team at Washington 
University is responsible for reporting all 
applicable events to the FDA as 
needed. 
Unexpected fatal or life-
threatening suspected adverse 
reaction 
Report no later than 4 calendar days after initial receipt 
of the information. 
Unanticipated problem involving 
risk to participants or others 
Report no later than 4 calendar days after initial receipt 
of the information. 
Adverse event or SAE that does 
not require expedited reporting 
As per routine data entry expectations 
Protocol exception 
Approval must be obtained prior to implementing the 
change. 
be withdrawn, report at continuing review. 


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 Washington University Unanticipated Problem Reporting Cover Sheet 
 
SAE COVER SHEET- Secondary Site Assessment 
 
Washington University HRPO#:  
Sponsor-Investigator:  
Subject Initials:   
Subject ID:  
Treating MD:  
Treating Site:  
EVENT TERM:  
Admission Date:  
EVENT GRADE: 
Date of site’s first notification: 
 
Treating MD Event Assessment:  
 
 
Is this event possibly, probably, or definitely related study treatment? 
 
 yes  
 
 no 
 
If yes, please list which drug (if more than one)______________________________ 
 
       
Explain ______________________________________________________________________ 
 
______________________________________________________________________________ 
 
 
 
_________________________           ___________________________      _________________ 
Physician’s Name 
 
         Physician’s Signature 
 
    Date 
 
 

ICF_001.pdf: 
 
FOR IRB USE ONLY 
IRB ID #: 201908124 
APPROVAL DATE: 06/23/22 
RELEASED DATE: 06/24/22 
EXPIRATION DATE: 06/22/23 
 
INFORMED CONSENT DOCUMENT 
 
Project Title: 
A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of a 
Neoantigen Peptide Vaccine Strategy in Pancreatic Cancer Patients Following Surgical Resection 
and Adjuvant Chemotherapy 
 
Principal Investigator: 
William Gillanders, M.D. 
 
Research Team Contact: 
William Gillanders, M.D. – (314) 362-7201 
 
This consent form describes the research study and helps you decide if you want to participate. It 
provides important information about what you will be asked to do during the study, about the risks and 
benefits of the study, and about your rights and responsibilities as a research participant. By signing this 
form you are agreeing to participate in this study. 
• You should read and understand the information in this document including the procedures, 
risks and potential benefits.  
• If you have questions about anything in this form, you should ask the research team for more 
information before you agree to participate.  
• You may also wish to talk to your family or friends about your participation in this study. 
• Do not agree to participate in this study unless the research team has answered your 
questions and you decide that you want to be part of this study.  
 
KEY INFORMATION 
This is a research study conducted by Dr. Will Gillanders having to do with using an individualized 
vaccine to treat pancreas cancer. You are invited to be in this study because you have recently 
undergone surgery for pancreatic cancer and will be starting or have already started post-surgical 
treatment with chemotherapy. You should carefully consider the information in this consent document 
and discuss it with the research team. You should understand why you might want to participate, or why 
you might not want to participate. It is your choice whether to participate or not. 
 
If you agree and sign this consent, you will be volunteering to participate in the research study. The 
research team must give you a copy of this signed consent document. 
 
1. What is this study about?  
This study is looking at the safety and effects on the immune system of using an individualized 
peptide vaccine to treat people with pancreas cancer. 
 
2. Why should I consider participating? 
The purpose of this study is to learn more about the safety and feasibility of treating pancreas cancer 
with an individualized peptide vaccine. The peptide vaccine is given by injection at several time 
points over the course of approximately 12 weeks. 
 
3. What will I be asked to do?  
If you decide to take part in this study, we will have to confirm that you have enough cancer tissue 
from your surgery to make the peptide vaccine before you begin treatment with standard 
chemotherapy. After that, you will get the individualized vaccine at 7 time points over the course of 


 
FOR IRB USE ONLY 
IRB ID #: 201908124 
APPROVAL DATE: 06/23/22 
RELEASED DATE: 06/24/22 
EXPIRATION DATE: 06/22/23 
 
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Page 2 of 13 
approximately 12 weeks. After you finish your treatment, your doctor and study team will watch you 
for side effects for one year. 
 
This study includes some procedures you might have for your care if you weren’t in this study, such 
as regular physical exams and blood draws to monitor your counts and organ function. When you 
come to the clinic for your study visits, you may be here for a short amount of time (less than an 
hour if you’re just having blood drawn) or a longer amount of time (up to several hours if you’re 
having a study injection). The active part of the study will last for 6 months, with required follow-up 
for another year, and continued long-term yearly follow-up thereafter.  
 
You may choose to stop participating and withdraw from the study at any time. If you withdraw 
from the study, the research team may continue to use the information already collected about you.  
 
4. What are the risks?  
There are some risks to you if you agree to volunteer for this study. The most serious/most common 
risks are vaccine site reaction (including fever and/or pain), soreness, and flu-like symptoms. The 
risks to you are described in more detail later in this consent document.  
 
5. What are the benefits to me? To others?  
There may be no direct benefit to you. It is not possible to know if the peptide vaccine will extend 
your life compared to the usual approach. This study will help the study doctors learn things that will 
help people in the future. 
 
6. Is there any financial cost to me?  
As part of this study you will receive tests and procedures that are similar to what you would receive 
during routine clinical care of your condition. Your health plan/insurance company will be billed for 
some or all of these costs, and you will be responsible for any co-pays and deductibles that are 
normally required by your health plan/insurance.  
 
7. Will my information be confidential?  
Yes, your identity will be kept confidential. Your information will be available only to those who are 
working on this study.  
 
8. Who is the sponsor? 
The study is sponsored by the National Institutes of Health (NIH) and Stand Up to Cancer. 
 
WHAT IS THE PURPOSE OF THIS STUDY? 
This is a research study. We invite you to participate in this research study because you have recently 
undergone surgery for pancreatic cancer and will be starting or have already started post-surgical 
treatment with chemotherapy. 
 
The purpose of this research study is to learn more about the safety and feasibility of injecting an 
individualized peptide vaccine into people with pancreatic cancer. Individualized vaccines include up to 
20 peptides as well as a dose of a drug called Hiltonol, which is a medication that improves the activity 
of the vaccine. A peptide is a naturally occurring biological molecule made up of amino acids. The 
individualized vaccine is designed to target mutations specific to each person’s tumor that are 


 
FOR IRB USE ONLY 
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APPROVAL DATE: 06/23/22 
RELEASED DATE: 06/24/22 
EXPIRATION DATE: 06/22/23 
 
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discovered during genetic testing of the tumor before study procedures start. Injection of this vaccine 
may be a way to generate an immune response to pancreatic cancer cells. An immune response is the 
way your body fights viruses and other infections. There is evidence that an immune response may be a 
way to fight cancer. In addition to evaluating the safety of the individualized vaccine, this study is also 
looking at the immune response that your body has after each injection. 
 
The peptide vaccine injections are considered investigational, which means that they have not been 
approved by the U.S. Food and Drug Administration (FDA). Furthermore, the development of the 
vaccine uses genetic testing and a method for finding the best mutations, and these are both considered 
investigational and are not approved by the FDA. 
 
WHAT WILL HAPPEN DURING THIS STUDY? 
All procedures will be given in the outpatient setting at Siteman Cancer Center unless you have made 
other arrangements with the study team. We feel it is important to remind you that any procedures 
regardless of whether they are tests you would have if you did not take part in the research or are 
research-related will require you to remain at the Siteman Cancer Center up to several hours to complete 
the necessary testing. There may also be a wide variability in the length of clinic visits due to the unique 
characteristics of your medical history and health condition as well as due to clinic factors such as 
physician availability, staffing shortages, and weather delays. This will also vary depending upon your 
needs at the visit as determined by your physician. It is important that you are able to be available to 
complete the procedures at each visit to ensure that your safety and treatment needs are met. 
 
Pre-Study Evaluations: 
Prior to treatment, an overall assessment of your health will need to be taken to see if you are eligible to 
continue to participate in the study. You will have the tests and procedures listed below. 
• Physical examination, including medical history, height, weight, and performance status 
• Routine blood tests to check your blood counts and organ function (about 2 teaspoons of blood 
will be drawn from a vein in your arm) 
• Blood test to check how your blood is clotting (about 1 teaspoon will be drawn from a vein in 
your arm) 
• Pregnancy test (if you are a woman of childbearing potential) 
• Research blood tests to check your immune function (approximately 4 tablespoons of blood will 
be drawn from a vein in your arm) 
• Electrocardiogram (EKG) to check how your heart is functioning 
• Previously taken tumor tissue will be requested for genome sequencing (a process that 
determines the complete DNA sequence of an organism), if it hasn’t already been done as part of 
your routine care. DNA is the molecules inside cells that carry genetic information and pass it 
from one generation to the next. We will also look at your RNA. RNA contains information that 
has been copied from DNA. 
 
If these procedures show that you are eligible to continue participating in this study, and you choose to 
continue, then the process for developing the vaccine will begin while you receive your non-study post-
operative chemotherapy. This process involves accessing the sequencing information from your tumor 
tissue, finding the most promising mutations to target with the vaccine, and then manufacturing that 
vaccine so that you can begin treatment with it. 


 
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RELEASED DATE: 06/24/22 
EXPIRATION DATE: 06/22/23 
 
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While the personalized vaccine is being prepared and you are receiving your post-operative 
chemotherapy, you will have the above tests repeated to ensure that you are still eligible to participate, 
and we will access the routine imaging being done during treatment to check the status of your disease. 
We will also draw approximately 5 tablespoons of blood for research purposes at two time points while 
you are receiving your post-operative chemotherapy. Please know that if your disease recurs during the 
time it takes the scientists to prepare the vaccine (after sequencing of your tumor), you may no longer be 
able to participate in the remainder of the trial. 
 
Administration of Peptide Vaccine: 
You will receive the peptide vaccine at seven time points during the course of your participation in this 
study – Days 1, 4, 8, 15, 22, 50, and 78. You will receive up to 4 subcutaneous injections at each time 
point, one in each of your limbs.  If you are unable to receive a dose in one of your limbs, your left or 
right midriff may be substituted.  The number of injections you receive will depend on the number of 
peptides you will be receiving. 
 
You will be required to remain in the clinic for at least 30 minutes after each injection while a nurse or 
study coordinator monitors your vital signs (temperature, blood pressure, pulse, and respiratory rate).  
 
Study Evaluations: 
• Physical exam, review of medications, and evaluation of any side effects you may be 
experiencing on each injection day and at your end of treatment visit 
• Routine blood tests to check your blood counts and organ function every 4 weeks (approximately 
2 teaspoons of blood will be drawn) 
• Pregnancy test on each injection day 
• Research blood tests to check your immune function on Days 1, 22, 50, and 78 (approximately 5 
tablespoons of blood will be drawn) 
• Routine imaging to check the status of your disease (as per standard care) 
 
Follow-Up: 
You will have follow-up visits 4 weeks after your last vaccine injection and one year after your last 
vaccine injection. At each follow-up visit you will have a physical exam and you may have blood drawn 
for research purposes depending on your availability.  We may follow up with you after that by phone or 
in person (or by review of your medical records) to check on your health status and the status of your 
disease. 
 
Will you save my research information and biospecimens to use in future research studies? 
We would like to use the blood, tissue, and data we are obtaining in this study for studies going on right 
now as well as studies that are conducted in the future. These studies may provide additional 
information that will be helpful in understanding pancreas cancer, or other diseases or conditions, 
including research to develop investigational tests, treatments, drugs or devices that are not yet approved 
by the U.S. Food and Drug Administration. It is unlikely that what we learn from these studies will have 
a direct benefit to you. There are no plans to provide financial compensation to you should this occur. 
By allowing us to use your blood, tissue, and data you give up any property rights you may have in the 
blood, tissue, and data. 


 
FOR IRB USE ONLY 
IRB ID #: 201908124 
APPROVAL DATE: 06/23/22 
RELEASED DATE: 06/24/22 
EXPIRATION DATE: 06/22/23 
 
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We might remove identifiers from your private information and your blood, tissue, and data and then use 
the information and your blood, tissue, and data for future research studies or share them with other 
researchers for their future research. If this occurs we will not ask you for additional consent for these 
uses of your information or blood, tissue, and data.  
 
One way in which we may share your data with others is by putting it into a large database of 
information, called a data repository. If your data is placed in one of these repositories it will be placed 
in the “controlled-access” portion of the repository. This means that only qualified researchers, who 
have received permission from individuals that monitor the access to and use of the data, will be able to 
look at and use your information. Before we put it in this repository, we will remove any information, 
such as your name and birthdate, that might easily identify you. Even though these data will not have 
your name or other identifying information associated with it, it is still possible that someone may be 
able to trace these data back to you because genetic information is unique. Although your individual 
data will only be in the controlled access database, certain summary information may be available to the 
general public. 
 
This future research may include genetic research. Genes are a unique combination of molecules (called 
DNA) that we inherit from our parents. There are millions of tiny differences in our genes that determine 
things like our height or the color of our eyes. Some of these differences may make some people more or 
less likely to develop certain diseases or conditions or to have certain characteristics. The future genetic 
research may include looking at the difference in genes between different groups of people or it may 
include studying your entire DNA sequence. Studying your entire DNA sequence will provide a detailed 
description of your DNA and is sometimes called whole genome sequencing.  
 
If you change your mind and do not want us to store and use your blood, tissue, and data for future 
research, you should contact the research team member identified at the top of this document. The 
blood, tissue, and data will no longer be used for research purposes. However, if some research with 
your blood, tissue, and data has already been completed, the information from that research may still be 
used. Also, if the blood, tissue, and data has been shared with other researchers it might not be possible 
to withdraw the blood, tissue, and data to the extent it has been shared. 
 
Please place your initials in the blank next to Yes or No for each of the questions below: 
 
My blood, tissue, and data may be stored and used for future research as described above. 
 
_____ Yes 
_____ No 
Initials  
Initials 
 
My blood, tissue, and data may be shared with other researchers and used by these researchers 
for the future research as described above. 
 
_____ Yes  
_____ No 
Initials  
Initials 
 
 


 
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HOW MANY PEOPLE WILL PARTICIPATE? 
Approximately 15 people will take part in this study conducted by investigators at Washington 
University and other institutions. 
 
HOW LONG WILL I BE IN THIS STUDY? 
If you agree to take part in this study, your involvement will last for several years. The period of active 
participation will last for approximately 6 months. There is required follow-up for another year, and 
continued long-term yearly follow-up thereafter. 
 
WHAT ARE THE RISKS OF THIS STUDY? 
You may experience one or more of the risks indicated below from being in this study. In addition to 
these, there may be other unknown risks, or risks that we did not anticipate, associated with being in this 
study.  
Some risks described in this consent document, if severe, may cause death.  
 
Risks of Peptide Vaccine 
The experimental vaccine may cause side effects that are mild and a minor inconvenience, or it could 
cause life-threatening reactions or death. You will be watched closely for side effects. Some of the 
suspected risks of the experimental vaccine are listed below. 
 
Likely 
• Redness or swelling in the area where the injection was given lasting a few days at most 
• Soreness at the site of the injection 
• Mild flu-like symptoms such as fever, chills, rash, aches and pains, nausea, headache, dizziness, 
and fatigue 
 
Less likely 
• Immune reaction against normal tissues, meaning that your body may identify your normal tissue 
as foreign and start attacking it; this could cause pain or swelling in your breast, other organs, or 
redness, swelling, or blistering of the skin around the injection site 
• Fever or low blood pressure from parts of the bacteria from which the vaccine is derived 
 
Rare 
• Allergic reaction, such as hives, difficulty breathing, wheezing, high fever, chills 
 
Theoretical risks 
Long-term effects of synthetic long peptide vaccines have not been studied. Possible long-term effects 
include having a stronger local or systemic (of the whole body) reaction if you are exposed to a similar 
disease in the future, than a non-vaccinated person. These effects have been seen with other vaccines but 
not so far with synthetic long peptide vaccines. 
 
Risks of Hiltonol 
Occasional, some may be serious 
• Anemia which may require blood transfusion 
• Diarrhea, nausea, vomiting 


 
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• Chills, tiredness, fever 
• Flu-like symptoms including body aches, muscle pain 
• Swelling and redness at the site of the medication injection 
• Bruising, bleeding 
• Infection, especially when white blood cell count is low 
• Loss of appetite 
 
Risks of Blood Draw  
The blood draw may cause bleeding, bruising, or pain. Some people become dizzy or feel faint. There is 
also a rare risk of infection.  
 
Risks of EKG  
An EKG is considered a non-invasive test. Skin irritation from the EKG electrodes or pain when 
removing the electrodes is a possible risk. Also, you may experience discomfort from lying quietly for a 
long time. 
 
Risks for Women Capable of Becoming Pregnant 
If you are a woman capable of becoming pregnant, we will ask you to have a pregnancy test before 
beginning this study. You must use effective birth control methods and try not to become pregnant while 
participating in this study. If you become pregnant, there may be unknown risks to your unborn child, or 
risks to your unborn child that we did not anticipate. There may be long-term effects of the treatment 
being studied that could increase the risk of harm to an unborn child. You must tell the doctor if your 
birth control method fails while you are on the study. If you believe or know you have become pregnant 
while participating in this research study, please contact the research team member identified at the top 
of this document as soon as possible. Please discuss with the research team how long you need to wait 
before becoming pregnant after completing the treatment or procedures on this study. 
 
Risks for Sexually Active Males 
If you are a sexually active male it is important that your partner not become pregnant during your 
participation in this study. There may be unknown risks to the unborn child or risks we did not 
anticipate. You and your partner must agree to use birth control if you want to take part in this study. If 
you believe or know that your partner has become pregnant during your participation in this study, 
please contact the research team member identified at the top of this document as soon as possible. 
 
Risks of Genetic Research 
There is a federal law called the Genetic Information Nondiscrimination Act (GINA). In general, this 
law makes it illegal for health insurance companies, group health plans and employers with greater than 
15 employees to discriminate against you based on your genetic information. However, it does not 
protect you against discrimination by companies that sell life insurance, disability insurance or long 
term-care insurance.  
 
Risk of Breach of Confidentiality 
One risk of participating in this study is that confidential information about you may be accidentally 
disclosed. We will use our best efforts to keep the information about you secure. Please see the section 
in this consent form titled “How will you keep my information confidential?” for more information. 
 


 
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WHAT ARE THE BENEFITS OF THIS STUDY? 
You may or may not benefit from being in this study.  
 
However, we hope that, in the future, other people might benefit from this study because it will help 
researchers learn more about using personalized DNA vaccines in the treatment of pancreatic cancer. 
 
WHAT OTHER TREATMENT OPTIONS ARE THERE? 
Before you decide whether or not to be in this study, your doctor will discuss the other options that are 
available to you. Instead of being in this study, you could: 
• get treatment or care for your cancer without being in a study 
• take part in another research study 
• get no treatment 
 
WILL IT COST ME ANYTHING TO BE IN THIS STUDY? 
As part of this study you will receive tests and procedures that are similar to what you would receive 
during routine clinical care of your condition. Your health plan/insurance company will be billed for 
some or all of these costs, and you will be responsible for any co-pays and deductibles that are normally 
required by your health plan/insurance. Not all insurance plans cover the costs associated with being in a 
study. Even if they do, you may be responsible for more out-of-pocket expenses, such as co-pays and 
deductibles, when there are more tests and procedures or more expensive tests and procedures involved 
in the study than if you were to receive routine clinical care outside the study.  
 
If you wish to know whether there are more tests and procedures or more expensive tests and procedures 
in the study, you should ask your study doctor.  
 
If you wish to know whether your insurance will pay, you should contact them directly, or speak with 
the study team about obtaining a financial pre-certification prior to enrolling in the study. 
 
WILL I BE PAID FOR PARTICIPATING? 
You will not be paid for being in this research study.  
 
WHO IS FUNDING THIS STUDY? 
The National Institutes of Health (NIH) and Stand Up To Cancer are funding this research study. This 
means that Washington University is receiving payments from the NIH and Stand Up To Cancer to 
support the activities that are required to conduct the study. No one on the research team will receive a 
direct payment or increase in salary from the NIH or Stand Up To Cancer for conducting this study. 
 
WHAT IF I AM INJURED AS A RESULT OF THIS STUDY? 
Washington University investigators and staff will try to reduce, control, and treat any complications 
from this research. If you feel you are injured because of the study, please contact the investigator at 
(314) 747-0072 and/or the Human Research Protection Office at 1-(800)-438-0445.  
 
Decisions about whether payment for medical treatment for injuries relating to your participation in 
research will be made by Washington University. If you need to seek medical care for a research-related 
injury, please notify the investigator as soon as possible.  
 


 
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HOW WILL YOU KEEP MY INFORMATION CONFIDENTIAL? 
Other people such as those indicated below may become aware of your participation in this study and 
may inspect and copy records pertaining to this research. Some of these records could contain 
information that personally identifies you.  
• Government representatives (including the Office for Human Research Protections) to complete 
federal or state responsibilities 
• The U.S. Food and Drug Administration 
• The National Institutes of Health, which is the funding source for this study 
• Stand Up To Cancer, which is the funding source for this study 
• Oncovir, manufacturer of Hiltonol 
• Your primary care physician if a medical condition that needs urgent attention is discovered 
• Hospital or University representatives to complete Hospital or University responsibilities 
• Information about your participation in this study may be documented in your health care records 
and will be available to anyone with access to your health care record, including your health 
insurance company. This information may also be released as part of a release of information 
request. 
• The last four digits of your social security number may be used in hospital or University systems 
to track billing information for research procedures. 
• Washington University’s Institutional Review Board (a committee that oversees the conduct of 
research involving human participants) and the Human Research Protection Office. The 
Institutional Review Board has reviewed and approved this study.  
• Other researchers in other laboratories, to conduct research on cancer or other projects; these 
may be individual researchers at other institutions, or they may be other researchers as part of a 
cooperative group. 
• The Quality Assurance and Safety Monitoring Committee at the Siteman Cancer Center for 
auditing purposes 
• The Siteman Cancer Center Clinical Trials Office 
• Any report or article that we write will not include information that can directly identify you. 
The journals that publish these reports or articles require that we share your information that was 
collected for this study with others to make sure the results of this study are correct and help 
develop new ideas for research. Your information will be shared in a way that cannot directly 
identify you. 
 
To help protect your confidentiality, we will make sure that your study information is kept secure. We 
will keep study information in a secure database that requires a username and password. To help protect 
your confidentiality, no identifying information such as your name, birth date, or social security number 
will be made available to researchers who receive your health information. Furthermore, the study team 
will keep the master code list that links your unique study number with your name and other identifying 
information in locked storage in a locked office (for paper copies) or on a secured network on a 
password-protected computer (for electronic copies). Access to either paper or electronic copies will be 
limited to the Principal Investigator and members of the study team. 
 
Because of the innovative nature of this research, and because you will be among the first people 
receiving this vaccine, there may be interest from the news media and others about this study. 
Washington University, the investigators, and study staff will make every effort to protect your privacy 


 
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if the news media becomes interested in this study. No one outside of the research team and government 
and university regulators will be provided information that could identify you. 
 
The Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital 
is supported by funding from the National Cancer Institute (NCI). To meet NCI requirements, your 
protected health information relating to your participation in this study (including your social security 
number) will be stored in a secure database at the Siteman Cancer Center. This database and also your 
health care records may be reviewed by Siteman Cancer Center personnel. All information will be 
securely and confidentially maintained.  
 
A description of this clinical trial will be available on http://www.clinicaltrials.gov/, as required by U.S. 
law. This website will not include information that can identify you. At most, the website will include a 
summary of the results. You can search this website at any time.  
 
To further protect your privacy, this research is covered by a Certificate of Confidentiality from the 
federal government. This means that the researchers can refuse to disclose information that may identify 
you in any legal or court proceeding or to anyone who is not connected with the research except if:  
• there is a law that requires disclosure, such as to report child abuse and neglect, or harm to self or 
others;  
• 
you give permission to disclose your information, including as described in this consent form; or 
• it is used for other scientific research allowed by federal law. 
You have the right to share your information or involvement in this study with anyone at any time. You 
may also give the research team permission to disclose your information to a third party or any other 
person not connected with the research.  
 
If information about you or your involvement in this research is placed in your medical record the 
information may no longer be protected under the Certificate. However, information in your medical 
records is protected in other ways.   
 
Are there additional protections for my health information? 
Protected Health Information (PHI) is health information that identifies you. PHI is protected by federal 
law under HIPAA (the Health Insurance Portability and Accountability Act). To take part in this 
research, you must give the research team permission to use and disclose (share) your PHI for the study 
as explained in this consent form. The research team will follow state and federal laws and may share 
your health information with the agencies and people listed under the previous section titled, “How will 
you keep my information confidential?” 
 
Once your health information is shared with someone outside of the research team, it may no longer be 
protected by HIPAA.  
 
The research team will only use and share your information as talked about in this form or as permitted 
or required by law. When possible, the research team will make sure information cannot be linked to 
you (de-identified). Once information is de-identified, it may be used and shared for other purposes not 
discussed in this consent form. If you have questions or concerns about your privacy and the use of your 
PHI, please contact the University’s Privacy Officer at 866-747-4975.  
 


 
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Although you will not be allowed to see the study information, you may be given access to your health 
care records by contacting your health care provider.  
 
If you decide not to sign this form, it will not affect 
• your treatment or the care given by your health provider. 
• your insurance payment or enrollment in any health plans.  
• any benefits to which you are entitled. 
However, it will not be possible for you to take part in the study. 
 
If you sign this form: 
• You authorize the use of your PHI for this research 
• This authorization does not expire. 
• You may later change your mind and not let the research team use or share your information 
(you may revoke your authorization).  
• To revoke your authorization, complete the withdrawal letter, found in the Participant section 
of 
the 
Human 
Research 
Protection 
Office 
website 
at 
https://hrpo.wustl.edu/participants/withdrawing-from-a-study/ or you may request that the 
investigator send you a copy of the letter.   
 
 
 
o If you revoke your authorization: 
 The research team may only use and share information already collected for 
the study. 
 Your information may still be used and shared as necessary to maintain the 
integrity of the research, for example, to account for a participant’s 
withdrawal from the research study or for safety reasons. 
 You will not be allowed to continue to participate in the study. 
 
IS BEING IN THIS STUDY VOLUNTARY? 
Taking part in this research study is completely voluntary. You may choose not to take part at all. If you 
decide to be in this study, you may stop participating at any time. Any data that was collected as part of 
your participation in the study will remain as part of the study records and cannot be removed.  
 
If you decide not to be in this study, or if you stop participating at any time, you won’t be penalized or 
lose any benefits for which you otherwise qualify.  
 
What if I decide to withdraw from the study? 
You may withdraw by telling the study team you are no longer interested in participating in the study or 
you may send in a withdrawal letter. A sample withdrawal letter can be found at 
https://hrpo.wustl.edu/participants/withdrawing-from-a-study/ under Withdrawing from a Research 
Study. 
 
If you decide to leave the study early, we will ask you to tell the study doctor if you are thinking about 
stopping so any risks can be evaluated by your doctor. Another reason to tell your doctor that you are 
thinking about stopping is to discuss what follow-up care and testing could be most helpful for you. 
 


 
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Will I receive new information about the study while participating? 
If we obtain any new information during this study that might affect your willingness to continue 
participating in the study, we’ll promptly provide you with that information. 
 
Can someone else end my participation in this study? 
Under certain circumstances, the investigator might decide to end your participation in this research 
study earlier than planned. This might happen for no reason or because staying in the study would be 
harmful, you need treatment that is not allowed while on the study, you fail to follow instructions, you 
become pregnant, or the study is canceled. 
 
WHAT IF I HAVE QUESTIONS? 
We encourage you to ask questions. If you have any questions about the research study itself, please 
contact: Dr. William Gillanders (314) 747-0072. If you experience a research-related injury, please 
contact Dr. Gillanders as well; if this is after hours, you will be directed to the exchange number, which 
will be covered by a resident or fellow on call. Please tell this person that you are a research participant. 
 
If you have questions, concerns, or complaints about your rights as a research participant, please contact 
the Human Research Protection Office 1-(800)-438-0445, or email hrpo@wustl.edu.  General 
information about being a research participant can be found on the Human Research Protection Office 
web site, http://hrpo.wustl.edu. To offer input about your experiences as a research participant or to 
speak to someone other than the research staff, call the Human Research Protection Office at the number 
above. 
 
 
This consent form is not a contract. It is a written explanation of what will happen during the study if 
you decide to participate. You are not waiving any legal rights by agreeing to participate in this study. 
As a participant you have rights and responsibilities as described in this document and including: 
• To be given enough time before signing below to weigh the risks and potential benefits and 
decide if you want to participate without any pressure from the research team or others. 
• To understand all of the information included in the document, have your questions answered, 
and receive an explanation of anything you do not understand. 
• To follow the procedures described in this document and the instructions of the research team to 
the best of your ability unless you choose to stop your participation in the research study. 
• To give the research team accurate and complete information. 
• To tell the research team promptly about any problems you have related to your participation, or 
if you are unable to continue and wish to stop participating in the research study. 


 
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Your signature indicates that this research study has been explained to you, that your questions have 
been answered, and that you agree to take part in this study. You will receive a signed and dated copy of 
this form. 
 
 
Do not sign this form if today’s date is after EXPIRATION DATE: 06/22/23. 
 
 
__________________________________________ 
_______________________________ 
(Signature of Participant) 
 
 
 
 
(Date) 
 
 
____________________________________________ 
(Participant's name – printed) 
 
 
 
Statement of Person Who Obtained Consent 
 
The information in this document has been discussed with the participant or, where appropriate, with the 
participant’s legally authorized representative. The participant has indicated that they understand the 
risks, benefits, and procedures involved with participation in this research study. 
 
 
__________________________________________ 
_______________________________ 
(Signature of Person who Obtained Consent) 
 
(Date) 
 
 
___________________________________________ 
(Name of Person who Obtained Consent - printed)