Stimulating Immune Response With Neoadjuvant Human Papilloma Virus (HPV)-16 Specific Vaccination in HPV-Oropharyngeal Squamous Cell Carcinoma (HPV-OPSCC)
Phase: PHASE1
Conditions: Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Human Papillomavirus-Related Carcinoma, Locally Advanced Oropharyngeal Carcinoma, Stage IVA Oropharyngeal (p16-Negative) Carcinoma AJCC v8, Stage IVB Oropharyngeal (p16-Negative) Carcinoma AJCC v8
Sponsor: Mayo Clinic

MC200710 
Protocol Version Date: 23May2024 
Mayo Clinic Cancer Center 
MC200710 Stimulating Immune Response with Neoadjuvant Human Papilloma Virus (HPV)-16 
specific Vaccination in HPV-Oropharyngeal Squamous Cell Carcinoma (HPV-OPSCC) 
Sponsor/Principal Investigator: 
 
 
 
Co-Principal Investigators: 
 
 
Co-Investigators: 
 
 
 
  
  
 
 
 
 
 
Statistician: 
 
FDA IND #: 27994 
NCT #: NCT5232851 
√Study contributor(s) not responsible for patient care 
Trial Supported by:  
Funding: PDS Biotechnology Corp (Reference number PDS0101-HNC-202) 
Drug Availability:  
Commercial Agents: Pembrolizumab (covered by study funding) 
Drug Company Supplied: PDS0101 (ImmunoMAPK-RDOTAP/HPV-16 E6 & E7 peptides) 
 
Document History 
Approval Date 
Effective Date 
Activation 
06Jan2022 
22Feb2022 
MCCC Amendment 1 
19Aug2022 
23Aug2022 
MCCC Amendment 2 
21Oct2022 
26Oct2022 
MCCC Amendment 3 
04Oct2023 
24Oct2023 
MCCC Amendment 4 
28Jun2024 
03Jul2024 
 

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Protocol Resources 
Questions: 
Contact Name: 
Patient eligibility*, test schedule, 
treatment delays/interruptions/adjustments, 
dose modifications, adverse events, 
forms completion and submission 
  
 
  
Clinical coordinators (lead site first) 
 
Clinical data coordinators (lead site first) 
 
Protocol document, consent form, 
regulatory issues 
 
  
Laboratory Contact for Correlative Studies 
 
 
 
 
 
Serious Adverse Event Reporting 
 
 
*No waivers of eligibility allowed 
 
 

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Table of Contents 
MC200710 Stimulating Immune Response with Neoadjuvant Human Papilloma Virus (HPV)-16 specific 
Vaccination in HPV-Oropharyngeal Squamous Cell Carcinoma (HPV-OPSCC) ........................................ 1 
Protocol Resources ........................................................................................................................................ 2 
Table of Contents .......................................................................................................................................... 3 
Schema .......................................................................................................................................................... 4 
1.0 
Background ................................................................................................................................... 5 
2.0 
Goals ........................................................................................................................................... 10 
3.0 
Patient Eligibility ........................................................................................................................ 11 
4.0  
Study Schedule ............................................................................................................................ 14 
5.0 
Grouping Factor .......................................................................................................................... 16 
6.0 
Registration Procedures .............................................................................................................. 16 
7.0 
Protocol Treatment ...................................................................................................................... 18 
8.0 
Dosage Modification Based on Adverse Events ......................................................................... 20 
9.0 
Ancillary Treatment/Supportive Care ......................................................................................... 22 
10.0 
Adverse Event (AE) Monitoring and Reporting ......................................................................... 25 
11.0 
Treatment Evaluation/Measurement of Effect ............................................................................ 35 
12.0 
Descriptive Factors ..................................................................................................................... 40 
13.0 
Treatment/Follow–up Decision at Evaluation of Patient ............................................................ 41 
14.0 
Body Fluid Biospecimens ........................................................................................................... 42 
15.0 
Drug Information ........................................................................................................................ 44 
16.0 
Statistical Considerations and Methodology ............................................................................... 50 
17.0 
Pathology Considerations/Tissue Biospecimens......................................................................... 54 
18.0 
Records and Data Collection Procedures .................................................................................... 56 
19.0  
Budget ......................................................................................................................................... 57 
20.0 
References ................................................................................................................................... 58 
Appendix I 
ECOG Performance Status ............................................................................................... 59 
Appendix II 
Patient PDS0101 Vaccine Diary ....................................................................................... 60 
Appendix III 
Injection Site Reaction Gauge .......................................................................................... 61 
Appendix IV 
Suggested Contraception Options ..................................................................................... 62 
.

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Schema 
Prior to discussing protocol entry with the patient, contact the Mayo Clinic Research Site 
Management Office  
for dose level and to ensure that a place on the protocol 
is open to the patient. 
 
Registration 
 
 
↓ 
 
 
Cohort is assigned at time of registration* 
Arm A: Vaccine alone (2 cycles) 
Arm B: Vaccine plus IV pembrolizumab (2 cycles)  
 
 
↓ 
 
 
Clinical care: Surgical resection of primary and 
lymph node dissection 
OR 
Definitive chemoradiation 
 
 
↓ 
 
 
Clinical Follow-Up/Observation†:  
(Adjuvant therapy after surgery per MD discretion) 
 
 
↓ 
 
 
Events at any time: 
Disease Progression 
Intolerable adverse effects 
Patient refusal 
 
 
↓ 
 
 
Survival Follow-up/Event Monitoring‡ 
 
*Cohorts are enrolled sequentially in a cohort of 3 design: Arm A 3 patients, followed by Arm B 
3 patients, followed by Arm A 3 patients, followed by Arm B 3 patients, until 18 patients are enrolled. 
Then enrollment will alternate between Arms A and B with each patient until up to 10 evaluable patients 
per arm are enrolled. The goal is to ensure an equal number of evaluable patients on each arm. If one arm 
achieves 10 evaluable patients, we will continue enrollment exclusively to the incomplete arm, with a 
total enrollment of 24 patients maximum. 
†See Section 13.4 
‡See Section 4.2 
Cycle = 21 ±3 days for two cycles 
 
Generic names: Pembrolizumab, 
MK3475 
Brand name(s): KEYTRUDA 
Availability: Commercial 
(covered by study funds) 
Generic names: PDS0101  
(ImmunoMAPK-RDOTAP/HPV-16 E6 & E7 peptides) 
Brand name(s): NA 
Availability: provided by PDS Biotechnology Corp. 

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1.0 
Background 
1.1 
Head and neck cancers
Human papillomavirus-associated oropharynx cancer (HPV-OPSCC) is the most common type of 
head and neck cancer and has a much better prognosis compared to tobacco-related head and 
neck squamous cell carcinoma (HNSCC) with 5 year survival of approximately 90% versus 40%, 
respectively (Ang, Harris, Wheeler, & et al., 2010) 1. As many patients with HPV-OPSCC are 
younger with fewer 
comorbidities and could 
potentially live for years with the 
sequelae of cancer treatment, 
there is great interest in treatment 
“de-intensification.” We and 
others have investigated de-
intensification of standard 
therapy for the HPV-OPSCC. 
The published “Mayo regimen” (Figure 1) investigated a decreased dose of adjuvant 
radiotherapy (RT) to 30 -36 Gy with chemotherapy following curative intent, margin-clearing 
transoral robotic surgery (TORS) for HPV-OPSCC, instead of the standard of care (SOC) 
adjuvant RT dose of 60 Gy. Our study demonstrated overall survival (OS) and loco-regional 
recurrence free survival (LRFS) comparable to historical controls.
The 2-year locoregional 
tumor control rate was 
96.2% (Ma, Price, 
Moore, & et al., 2019) 2.  
Our group has 
subsequently completed 
a randomized phase 3 
study comparing this 
“Mayo regimen” to the 
SOC (60 Gy adjuvant RT, respectively). The trial has completed accrual and the results are 
maturing. This was a Mayo Clinic only study and accrued approximately 250 patients (Figure 2).
We have also 
pioneered the 
use of HPV 
cell-free tumor 
DNA 
(ctHPVDNA) 
in patients 
undergoing 
TORS. It is 
detectable in 
90% of 
patients at 
diagnosis and 
95% of the 
patients are 
HPV16. In 
Figure 2. Schema of MC1675, randomized phase 3 study
Figure 3. (A) Pre and post-op ctHPVDNA, red lines indicate patients with 
positive PCR post-op. (B) Post-op ctHPVDNA was associated with worse 
recurrence-free survival (HR 4.919, p0.012)
A
B
Figure 1. Schema of MC1273 phase 2 study

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addition to clinical factors such as nodal and tumor staging, ctHPVDNA is an independent 
predictor of recurrence-free survival (RFS) (Figure 3) (Routman, et al., 2019, full manuscript 
under review). 
1.2 
Rationale for “intensification” of HPV-OPSCC at high risk of recurrence 
However, contrary to the expectation, not all patients with HPV-OPC have a good prognosis. 
Approximately 10-20% of patients with HPV-OPSCC suffer from locoregional recurrence (LRR) 
or distant metastasis (DM) despite standard therapies (Weller, Ward, Berriochoa, & et al., 2017) 
(Guo, Rettig, & Fakhry, 2016) 3 4. In addition to clinical predictors such as number of lymph 
nodes involved or extranodal extension (ENE), we have identified ctHPVDNA as predictor of 
recurrence (see above). These select patients may need intensification of systemic therapies to 
reduce their risk of recurrence. In Keynote-048, a phase 3 randomized study, pembrolizumab with 
or without cytotoxic chemotherapy has demonstrated improved OS in recurrent/metastatic (R/M)-
HNSCC (Burtness, Harrington, Greil, & et al., 2019) 5. PDS0101 has been shown to induce HPV-
specific immune responses alone and in combination with checkpoint inhibitors in preclinical 
studies and is currently being investigated in recurrent/metastatic setting for HPV-related cancers 
(Investigators brochure PDS0101).  
1.21 
PDS0101 Clinical Experience and Dose Selection 
A phase I clinical study of PDS0101 demonstrating strong clinical HPV16-specific T-cell 
responses and safety has been completed. The results of the study suggest effective 
induction of HPV16-specific T-cell immunogenicity over a broad dose range and no 
SAEs. 
Twelve female subjects entered the study: 3 subjects in Cohort 1 (1.0 mg R-DOTAP dose 
and 2.4 mg HPVmix), 3 subjects in Cohort 2 (3.0 mg R-DOTAP dose and 2.4 mg HPV 
mix), and 6 subjects in Cohort 3 (10 mg R-DOTAP dose and 2.4 mg HPVmix). All 
subjects received all 3 doses of PDS0101 administered by SC injection, as scheduled on 
Days 1, 22, and 43. Per protocol, all subjects were women with confirmed high-risk HPV 
infection and biopsy-proven CIN1. Ages ranged from 24 to 51 years; the median age was 
33.0 years. All subjects had blood draws pre-vaccination and 14 days (±5 days) after each 
vaccination, and once at 90 days after vaccination 3 for immunogenicity testing. 
1.211 
T-cell Immunogenicity: 
Except for 2 subjects (Subject 005-002 in the 1.0 mg R-DOTAP cohort and 
Subject 002-002 in the 3.0 mg cohort), outliers who had unusually high baseline 
HPV16 T cell responses, all remaining 10 subjects had a positive vaccine-
induced response (a ≥3- fold increase over baseline at ≥1 of the 4 post-
vaccination visits by either the IFN-γ or granzyme B ELISpot assays, with 
background counts subtracted). 
By IFN-γ assay (HPV16-specific T-cells), 9 subjects (9/10, 90%) had a positive 
vaccine-induced response; 6 subjects (6 of 9, 67%) had responses by granzyme B 
(1 additional subject had insufficient specimen for granzyme B testing). 
Results from both the IFN-γ and the granzyme B assays strongly suggest that 
there could potentially be an increase in HPV16-specific T-cell responses with 
the 3.0 mg R-DOTAP dose over the 1.0 mg dose but showed no evidence 
suggestive of an increased response of the 3.0 mg R-DOTAP dose over the 10.0 
mg R-DOTAP dose. Greather than 20-fold increases in HPV16-speccific CD8+ 
T cell responses over pre-treaatment levels were observed at the recommemded 
phase 2 R-DOTAP dose of 3.0mg. 

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No clear trend in T-cell response relative to post-vaccination timepoint (14 days 
post-vaccination 1, 2, or 3, or 90 days post-vaccination 3) was observed. All 
doses were active in inducing HPV16-specific T-cell responses. 
IFN-γ (all T-cells) and the granzyme B (CD8+ T-cells) responses were elicited 
across all R-DOTAP doses tested in the study subjects who had various HLA 
types. 
Documented high levels of circulating Granzyme-B CD8+ T-cells prompted an 
IRB-approved retrospective evaluation of clinical outcomes for 24 months 
following the 3rd dose of PDS0101. Clinical responses (reported regression / 
elimination of CIN) determined by cytology and/or colposcopy as available, were 
observed in 60% of evaluable patients across the three tested doses, with the 
timing of these responses documented as early asa 1 to 3 months in some 
patients. 
1.212 
Safety 
All subjects reported treatment-emergent adverse events (TEAEs); the majority 
were administration site reactions. 
All administration site reactions were deemed treatment-related. 
Most administration site reactions were mild or moderate in severity. Some 
severe administration site reactions were reported in the 3.0 and 10.0 mg R-
DOTAP cohorts (grading of serious as per the FDA Toxicity Grading scale for 
Healthy Volunteers in Preventative Vaccine Trials September 2007). Most 
administration site reactions resolved the same day or within a few days, 
although skin discoloration at the injection site took up to several weeks to 
resolve in some subjects. 
Per the Subject Symptoms Diary, administration site reactions were more serious 
and of longer duration in subjects in the 10.0 mg R-DOTAP cohort. 
Administration site reactions (injection site reactions) included: Common events 
(>10%): site swelling, site pain, site skin discoloration or erythema (redness), and 
Uncommon events (1-10%) site fibrosis, site discomfort, site inflammation, site 
pruritis, site papule, site nodule, site paresthesia, site inflammation, site rash. 
No clinically significant differences in the types and pattern of TEAEs were 
observed between vaccinations 1, 2, or 3. 
No DLTs were observed; thus, the maximum tolerated dose (MTD) was the 10.0 
mg R-DOTAP dose. 
No serious adverse events (SAEs), study discontinuations due to adverse events 
(AEs), or deaths occurred. 
No clinically relevant abnormal hematology, blood chemistry, urinalysis, or 
physical findings were observed. 
Other adverse events reported by Oncology patients with relation to PDS0101 
vaccine (Uncommon 1%-10%) include arthralgia, insomnia, tachycardia, 
diarrhea, lymphocyte count decreased, rash, headache. 
The following adverse events were observed in Oncology patients but deemed 
unrelated to the combination (PDS0101+pembrolizumab): hypotension, 
lymphoedema, peripheral ischemia, pain in extremity, compartment syndrome, 
rhabdomyolysis, bradycardia, blood creatine phosphokinase increased, acidosis, 
hyperglycemia, hyperhidrosis, sepsis, acute kidney injury, oropharyngeal pain 

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Other adverse events reported in pre-neoplastic patients (healthy volunteers) 
included Very Common AEs (>10%) headache, and Uncommon AEs (1%-10%) 
fatigue, malaise, pyrexia, diarrhea, nausea, vomiting. myalgia. dizziness. 
lethargy, and insomnia. 
The adverse event assessments are similar whether subjects receive PDS0101 
monotherapy or in combination with pembrolizumab. 
The PDS0101 formulation contains 10% v/v concentration of DMSO in the 
vaccine and was demonstrated to be safe and well-tolerated in both the 
preclinical and human safety studies. Three reported clinical studies of other 
HPV16 peptide vaccines used 20% v/v concentration of DMSO in the 
formulations (Uppaluri, Dunn, & Lewis Jr, 2008); (Chang & et al., 2016); 
(Preston, et al., 2013). One study also used 100% DMSO for 1 of the dose groups 
(Dunn, Dunn, & Curry, 2007).  
1.3 
Rationale for neoadjuvant immune-based therapy 
Neoadjuvant therapy prior to surgery allows for biomarker and pathologic evaluation of disease 
with disease present and appears to be safe and feasible in cancers of the head and neck 
(Schoenfeld, Hanna, Jo, & et al., 2020). In the adjuvant setting, where the majority of patients 
have no discernable evidence of ctHPVDNA (see above) and where tumor antigen may not be 
present, the response to immune based therapies may be less robust and harder to determine. 
Furthermore, many oncologic paradigms utilize initial neoadjuvant response to dictate intensity of 
adjuvant therapies. PDS0101 has been shown to have minimal clinically meaningful toxicity 
(Investigators Brochure PDS0101). Therefore, PDS0101, pending response in the neoadjuvant 
setting, could likewise be used to potentially de-intensify therapy. With response, a patient that 
otherwise would not qualify for RT dose de-escalation or observation may be downstaged and 
qualify for de-intensification, on study. 
1.31 
Addition of pembrolizumab 
Importantly, anti-tumor activity and pathologic regression have been documented using 
checkpoint inhibitors (CPIs) in neoadjuvant treatment of HPV-related and unrelated head 
and neck cancer with varying degrees of pathologic tumor response (pTR) reported 
(Ferrarotto, Bell, Rubin, & et al., 2020) (Uppaluri, Campbell, Egloff, & et al., 2020) 
(Schoenfeld, Hanna, Jo, & et al., 2020). In a study of neoadjuvant and adjuvant 
pembrolizumab in locally advanced, HPV-unrelated HNSCC, 22% (8 of 36) of subjects 
had pTR-2 (> 50% regression) and 22% (8 of 36) had pTR-1 (10%-49% regression) 
(Uppaluri, Campbell, Egloff, & et al., 2020). A major limitation of the effectiveness of 
CPIs is the lack of pre-existing T cell immune infiltration in the tumor microenvironment 
(TME). PDS0101 has been shown to generate high levels of potent, tumor-specific CD8+ 
killer T-cell responses in vivo in both preclinical and human studies. Investigating this 
combination in the neoadjuvant treatment setting will provide an opportunity to further 
maximize anti-tumor responses over those seen with pembrolizumab monotherapy. In 
this study we are proposing to deliver two doses of PDS0101 alone or in combination 
with the immune checkpoint inhibitor pembrolizumab (KEYTRUDA®), prior to 
definitive surgery or chemoradiation with curative intent.  
1.4 
Hypothesis 
We hypothesize that incorporating HPV vaccination with or without checkpoint inhibition 
into the neoadjuvant setting will result in augmentation of immunologic response and 
potentially anti-tumor responses as assessed by ctHPVDNA, imaging, and pathologic 
regression. We propose a proof of principle, pilot prospective study in locally advanced HPV-
OPSCC investigating the efficacy of neoadjuvant PDS0101 and PDS0101 in combination with 

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pembrolizumab in patients who will undergo surgical resection for their HPV-OPSCC. This will 
be a prospective, two-arm, open-label, unblinded study.  
1.41 
Rationale for Definitive Chemoradiation Group 
The majority of patients nationally receive chemoradiation for treatment of H&N 
oropharyngeal carcinoma. Many patients are not candidates for surgical resection. Given 
this situation, understanding of the response rates of PDS0101 with or without 
pembroluzimab in the neoadjuvant setting prior to definitive chemoradiation is important 
and may be more important in a patient population which typically has more advanced 
disease. For patients in this group, ctHPVDNA will be used as the sole primary endpoint. 
For patients without detectable ctHPVDNA at baseline these patients will not count 
towards the primary endpoint. 
1.5 
Correlative Studies 
We will collect tissue and blood to use for correlative studies including tumor micro-
environmental changes and pathologic response, evaluate ctHPVDNA as a marker for tumor 
response, determine HPV16-specific T-cell responses as well as other immune responses. 
We are planning to use various potential methodologies and assessments including antibody 
titers, flow cytometry (e.g., Isoplexis Functional Proteomics), immune profiling (e.g., CyTOF), 
functional ELISPOT assay following exposure to known HPV16 antigens (to quantify 
responders), T-cell receptor (TCR) sequencing (e.g., Adaptive Technologies), and genomic 
analyses. When possible, we will compare pre-treatment and post-treatment results as applicable. 
We will also bank DNA, WBCs, and tissue (fresh and formalin-fixed) for future studies. 
 

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2.0 
Goals  
2.1 
Primary Goal 
To determine pathologic and/or ctHPVDNA response to PDS0101 or PDS0101 plus 
pembrolizumab in patients with high risk HPV-OPSCC. 
NOTE: Pathologic response is defined as necrosis, keratinous debris, giant cell reaction, 
and T cell/immune cell infiltration as a percentage of total tumor bed area. 
2.2 
Secondary Goals 
2.21 
To determine tumor response by RECIST 1.1  
2.22 
To determine progression-free survival and overall survival 
2.3 
Tertiary Goals 
2.31 
To determine the safety of PDS0101 delivered alone or with pembrolizumab 
2.4 
Correlative Research 
2.41 
Determine the changes in tumor microenvironment (TME) with PDS0101 alone 
or with pembrolizumab 
2.42 
Determine circulating ctHPVDNA as a biomarker for tumor response 
2.43 
Determine HPV16-specific T-cell response utilizing multiplex flow cytometry 
and other parameters 
 

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3.0 
Patient Eligibility 
Prior to discussing protocol entry with the patient, contact the Mayo Clinic Research Site 
Management Office  
for dose level and to ensure that a place on the 
protocol is open to the patient. 
3.1 
Registration – Inclusion Criteria 
3.11 
Age ≥18 years 
3.12 
Disease characteristics 
3.121 Locally advanced HPV-OPSCC and high-risk HPV-specific testing with 
at least one of the following: 
• 
Radiology ENE OR 
• 
cN2 (AJCC 8th Edition) disease (contralateral/bilateral nodes) OR 
• 
cN3(AJCC 8th Edition) disease (LN >6 cm) OR 
• 
Radiographic evidence of 2 or more involved lymph nodes 
3.122 Candidate for curative intent surgery or chemo-radiation  
3.13 
Measurable or unmeasurable disease as defined by RECIST 1.1 criteria (See 
Section 11.0)  
3.14 
Eastern Cooperative Oncoloogy Group (ECOG) performance status of 0 or 1. 
3.15 
Adequate organ function as defined below ≤15 days prior to registration: 
• 
White blood cell (WBC) count ≥3,000/mm3 
• 
Platelet count ≥75,000/mm3 
• 
Hemoglobin ≥9.0 g/dL (5.6mmol/L) 
NOTE: Transfusions are not allowed ≤7 days prior to registration 
• 
Total bilirubin ≤1.5 X upper limit of normal (ULN) 
(or total bilirubin ≤3.0 X ULN with direct bilirubin ≤1.5 X ULN in patients 
with well-documented Gilbert’s Syndrome) 
• 
Aspartate transaminase (AST/SGOT) ≤2.5 X ULN 
• 
Creatinine ≤1.5 mg/dL (133 µmol/L) OR 
Calculated creatinine clearance ≥30mL/min/1.73m2 for patients with 
creatinine levels above ULN 
Cockcroft-Gault Equation: 
Creatinine clearance for males =  (140 - age)(weight in kg) 
 
(72)(serum creatinine in mg/dL) 
 
Creatinine clearance for females =  
(140 - age)(weight in kg)(0.85) 
 
(72)(serum creatinine in mg/dL) 
• 
PT/INR/PTT ≤1.5 X ULN OR if patient is receiving anticoagulant therapy 
and PT or PTT is within therapeutic range of intended use of anticoagulants 
3.16 
Negative pregnancy test done ≤3 days prior to registration for persons of 
childbearing potential only. 
3.17 
Persons of childbearing potential or able to father a child must be willing to use 
an effective method of contraceptionfor the course of the study starting with the 

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first dose of study therapy through 120 days after the last dose of study 
medication. (See Section 9.7) 
NOTE: Abstinence is acceptable if this is the usual lifestyle and preferred method 
of contraception for the patient. 
3.18 
Provide written informed consent. 
3.19a 
Willing to return to enrolling institution for follow-up (during the Active 
Monitoring Phase of the study). 
3.19b Willingness to provide mandatory blood specimens for correlative research (see 
Section 14.0).  
3.19c 
Willingness to provide mandatory tissue specimens for correlative research (see 
Section 17.0).  
3.2 
Registration - Exclusion Criteria 
3.21 
Active autoimmune disease requiring systemic treatment, documented history of 
severe autoimmune disease, or a syndrome that requires systemic steroids or 
immunosuppressive agents. 
NOTE: Exceptions are allowed for: 
• 
Vitiligo 
• 
Resolved childhood asthma/atopy 
• 
Intermittent use of bronchodilators or inhaled steroids 
• 
Daily steroids at dose of ≤10mg of prednisone (or equivalent) 
• 
Local steroid injections 
• 
Stable hypothyroidism on replacement therapy 
• 
Stable diabetes mellitus 
• 
Sjögren’s syndrome 
3.22 
Any prior head or neck chemotherapy, radiotherapy, and/or immunotherapy. 
3.23 
Any of the following prior therapies: 
• 
Live vaccine <30 days prior to registration, including intranasal flu vaccine 
(e.g. Flu-Mist®) (Note: Seasonal influenza vaccines for injection are 
generally killed virus vaccines and are allowed). Examples of live vaccines 
include, but are not limited to, the following: measles, mumps, rubella, 
varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin 
(BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are 
generally killed virus vaccines and are allowed; however, intranasal 
influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not 
allowed. 
• 
Chemotherapy or targeted small molecule therapy <21 days prior to 
registration 
• 
Investigational therapy or investigational device <30 days prior to 
registration 
• 
Any prior investigational HPV-specific therapeutic vaccine  
3.24 
Current or prior use of immunosuppressive medication <14 days prior to 
registration  
The following are exceptions to this criterion: 
• 
Intranasal, inhaled, topical steroids, or local steroid injections (e.g., 
intraarticular injection) 

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• 
Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of 
prednisone or its equivalent 
 
Steroids as premedication for hypersensitivity reactions (e.g., premedication 
for CT scans) 
3.25 
Uncontrolled intercurrent illness including, but not limited to:  
• 
Ongoing or active infection requiring systemic therapy 
• 
Interstitial lung disease 
• 
Serious, chronic gastrointestinal conditions associated with diarrhea (e.g., 
Crohn’s disease or others) 
• 
Known active hepatitis B (i.e., known positive HBV surface antigen 
(HBsAg) reactive)  
• 
Known active hepatitis C (i.e., positive for HCV RNA detected by PCR) 
• 
Known HIV (Note: Patients on stable HAART for ≥6weeks with CD4 counts 
≥200 cells/mm3 undetectable HIV viral load by quantitative PCR and no 
opportunistic infections Castlemaan’s Disease ≤12 months prior to 
enrollment are allowed) 
• 
Known active tuberculosis (TB) 
• 
Symptomatic congestive heart failure 
• 
Unstable angina pectoris 
• 
Unstable cardiac arrhythmia or 
• 
Psychiatric illness/social situations that would limit compliance with study 
requirements (e.g., substance abuse) 
3.26 
History of allogeneic hematopoietic transplant or any solid organ transplant 
3.27 
Receiving any other investigational agent which would be considered as a 
treatment for the primary neoplasm. 
3.28 
Other active malignancy <2 years prior to registration.  
EXCEPTIONS: Non-melanotic skin cancer (SCC/BCC), micropapillary thyroid 
cancer, Gleason 6 prostate cancer, carcinoma-in-situ of the breast or cervix 
3.29a 
Any of the following conditions ≤6 weeks prior to registration:  
• Cerebrovascular accident (CVA)  
• Admission for unstable angina  
• Cardiac angioplasty or stenting or coronary artery bypass graft surgery  
• Untreated pulmonary embolism or untreated deep venous thrombosis (DVT)  
• Arterial thrombosis  
3.29b Receipt of immunotherapy/immunomodulatory or immunosuppressive agents 
(e.g., IFNs, tumor necrosis factor, interleukins, immunoglobulins or other 
biologic response modifiers [GM-CSF, GCSF] ≤6 weeks prior to registration.  
 
 

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4.0  
Study Schedule 
4.1 
Test schedule for HPV-OPSCC (all treatment arms) 
 
 
 
Active Monitoring Phase 
 Observation 
Tests and procedures 
≤28 days 
prior to 
Registration 
≤15 days 
prior to 
Registration 
Baseline 
Prior to 
Treatment 
on C1D1 
End of C1 
Prior to 
Treatment 
on C2D1 
End of C21 
End of 
treatment2 
Safety 
follow-
up3 
Clinical 
follow-up4 
Window 
 
 
-3 days 
-3 days 
-7 days 
 
+7 days 
 
History and exam, Wt, PS  
X 
 
X 
X 
X 
X 
X 
X 
Adverse event assessment 
 
 
X 
X 
X 
X 
X 
X 
Consultation with Head and Neck Surgery or 
Radiation Oncology5  
X 
 
 
 
 
 
 
 
Height 
 
X 
 
 
 
 
 
 
Pregnancy test6 
 
X 
 
 
 
 
 
 
Hematology: CBC with 5-part differential 
 
X 
 
X 
X 
X 
X 
 
Chemistry group: Complete metabolic panel (CMP) 
 
X 
 
X 
X 
X 
X 
 
Thyroid testing (TSH; reflex per clinical care) 
 
X 
 
X 
X 
X 
X 
X 
Coagulation test (PT/INR, aPTT) 
 
X 
 
 
 
 
 
 
ctHPVDNA Naveris assay (send out)R 
 
 
X 
X 
X 
 
X 
 
Disease Evaluation/Tumor measurement7 
X 
 
 
 
X8R 
 
 
X9 
Biopsy10 
X 
 
 
 
 
 
 
 
 
Cycle = 21 ±3 days; R = Research funded 
1 NOTE: Surgery if done must be at least 2 weeks after second dose and within 8 weeks after second dose. Definitive radiation therapy if done must be ≥2 weeks after second dose 
and ≤8 weeks after second dose. 
2 End of treatment on this study will be surgery for surgical patients and end of chemo-radiation for chemo-radiation patients (may be combined with Safety Follow-up) 
3 Follow-up visit at least 30 days after last dose for safety monitoring and for surgical patients should be prior to start of adjuvant therapy. If the patient has adjuvant therapy visit 
≥30 days after the second dose, then it could be considered 30-day safety follow up and end of treatment visit 
4 Clinical follow-up beginning approximately 2-6 weeks after surgery for first post-op visit; then 3-6 months post-surgery for surgical patients; and 6 weeks after end of chemo-
radiation for chemo-radiation patients, then 3-6 months post completion of chemoradiation. 
5 See Section 6.9b 
6 For persons of childbearing potential only. Must be done ≤3 days prior to registration and repeated prior to C1D1 if >3 days between registration and treatment. 
7 Standard clinical imaging should be used; CT neck, chest, abdomen, or FDG-PET/CT to rule out distant metastasis. Tumor measurement will happen prior to surgery (end of C2). 
8 If there is no evidence of distant metastasis on baseline screening, then neck CT scan is sufficient at this time point. Tumor measurement will happen prior to surgery (end of C2). 
9 Any imaging done during clinical follow-up period per institutional standards will be used for event monitoring 
10 If clinical biopsy is done, then research tissue can be obtained at the same time. If clinical biopsy is not needed or not done, then research biopsy can be offered. 

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Active Monitoring Phase 
 Observation 
Tests and procedures 
≤28 days 
prior to 
Registration 
≤15 days 
prior to 
Registration 
Baseline 
Prior to 
Treatment 
on C1D1 
End of C1 
Prior to 
Treatment 
on C2D1 
End of C21 
End of 
treatment2 
Safety 
follow-
up3 
Clinical 
follow-up4 
Mandatory research blood specimens11R 
 
 
X 
X 
X 
X 
X 
X 
Mandatory research tissue specimens12,R 
X 
 
 
 
X13 
 
 
 
Patient post-vaccine diary and gauge14 
 
 
 
X 
X 
 
 
 
 
11 Blood samples are collected per Section 14.0 and Lab Manual 
12 Tissue specimens are collected per Section 17.0 and Lab Manual 
13 Research tissue specimens will be collected from surgical sample on the day of the surgery, no separate biopsy needed. For definitive chemoradiation patients, a research biopsy 
may be offered. If patient refuses, there is no protocol violation. 
14 Post-vaccine diary and gauge (Appendices 2-3) should be given to patient on day vaccine is given (C1D1, C1D2). Instruct patients to complete for 7 days after the vaccine using 
the provided gauge for reference. Completed diary must be submitted at the next visit. Please note diary compliance in medical record and confirm AE and conmed data are 
transferred to Medidata Rave. 

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4.2 
Survival Follow-up 
 
Survival Follow-up* 
q. 3 
months 
until PD At PD 
After PD  
q. 6 months 
Death 
New Primary 
Survival Follow-up 
X 
X 
X 
X 
At each occurrence 
If a patient is still alive 2 years after registration, no further follow-up is required. 
NOTE: All timepoints are ±1 month 
5.0 
Grouping Factor 
5.1 
Group Assignment: Arm A (PDS0101 alone) vs. Arm B (PDS0101 with pembrolizumab)  
6.0 
Registration Procedures 
6.1 
Registration by Cohort 
Cohorts will switch every 3 patients for first 18 patients. Then for the last few patients, 
cohorts will switch with every patient until 10 evaluable patients per arm are enrolled to 
ensure an equal number of evaluable patients on both arms. If one arm achieves 10 evalu-able 
patients, we will continue enrollment exclusively in the incomplete arm, until a maximum of 
24 patients have been enrolled. Patients will be registered to the current open cohort. 
6.11 
Prior to discussing protocol entry with the patient, call the Mayo Clinic Research Site 
Management Office 
 
for dose level and to ensure that a place on the protocol is open to the patient.  
6.12 
To register a patient, fax
a completed 
eligibility checklist to the Mayo Clinic Research Site Management Office 
between 8 a.m. and 4:30 p.m. Central Time, Monday through Friday. 
6.2 
Verification of Materials 
Prior to accepting the registration, registration/randomization application will verify the 
following: 
• 
IRB approval at the registering institution 
• 
Patient eligibility 
• 
Existence of a signed consent form 
• 
Existence of a signed authorization for use and disclosure of protected health 
information  
6.3 
Documentation of IRB Approval 
Documentation of IRB approval must be on file in the Registration Office before an 
investigator may register any patients.  
In addition to submitting initial IRB approval documents, ongoing IRB approval 
documentation must be on file (no less than annually) with Research Site Management 
 
If the necessary documentation is not 
submitted in advance of attempting patient registration, the registration will not be 
accepted, and the patient may not be enrolled in the protocol until the situation is resolved. 
When the study has been permanently closed to patient enrollment, submission of annual 
IRB approvals to the Registration Office is no longer necessary. 

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6.4 
Correlative Research - Mandatory 
A mandatory correlative research component is part of this study, the patient will be 
automatically registered onto this component (see Sections 3.0, 14.0 and/or 17.0). 
6.5 
Patient Permissions  
At the time of registration, the following will be recorded: 
• 
Patient has/has not given permission to store and use his/her sample(s) for future 
research on cancer at Mayo Clinic. 
• 
Patient has/has not given permission to store and use his/her sample(s) for future 
research at Mayo Clinic to learn, prevent, or treat other health problems. 
• 
Patient has/has not given permission for MCCC to give his/her sample(s) to 
researchers at other institutions. 
• 
Patient has/has not given permission to store coded genetic and coded medical 
information in secured databases for research analyses. 
6.6 
Treatment on protocol 
Treatment on this protocol must commence at Mayo Clinic in Rochester, Minnesota, 
under the supervision of a medical oncologist 
6.7 
Treatment start 
Treatment cannot begin prior to registration and must begin ≤14 days after registration. 
6.8 
Pretreatment 
Pretreatment tests/procedures (see Section 4.0) must be completed within the guidelines 
specified on the test schedule. 
6.9a 
Baseline symptoms 
All required baseline symptoms (see Section 10.6) must be documented and graded. 
6.9b 
Head and neck surgery or radiation oncology consult required 
A head and neck surgeon or radiation oncologist has seen the patient and confirmed the 
patient is a suitable candidate for this study. (Email or note in medical record will 
suffice.) 
6.9c 
Study drug 
Study drug is available on site.  
6.9d 
Blood draw kits  
Blood draw kit is available on site.  
6.9e 
Study Conduct 
The clinical trial will be conducted in compliance with regulations (21 CFR 312, 50, and 
56), guidelines for Good Clinical Practice (ICH Guidance E6), and in accordance with 
general ethical principles outlined in the Declaration of Helsinki; informed consent will 
be obtained from all participating patients; the protocol and any amendments will be 
subject to approval by the designated IRB prior to implementation, in accordance with 
21 CFR 56.103(a); and subject records will be stored in a secure location and subject 
confidentiality will be maintained. The investigator(s) will be thoroughly familiar with 
the appropriate use of the study drug as described in the protocol and Investigator’s 
Brochure. Essential clinical documents will be maintained to demonstrate the validity of 
the study and the integrity of the data collected. Master files should be established at the 
beginning of the study, maintained for the duration of the study and retained according to 
the appropriate regulations. 
 

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7.0 
Protocol Treatment 
7.1 
Treatment Schedule 
7.11 
Pretreatment medication table (as needed)  
Agent 
Dose 
Route 
Day (±3 days) 
Acetaminophen 
650 mg 
PO 
1 
Diphenhydramine 
25 mg 
PO 
1 
7.12 
Treatment medication table  
Arm Agent 
Dose Level 
Route Day (±3 days) 
A 
PDS0101 
1 mL 
SC 
D1* 
B 
PDS0101  
1 mL 
SC  
D1* 
Pembrolizumab 
200 mg 
IV 
D1* 
*Cycle = 21 ±3 days for two cycles 
7.2 
Pembrolizumab (Arm B only) 
Pembrolizumab will be administered as a 30-minute IV infusion once every 3 weeks for 
two cycles on Day 1 (±3 days). Every effort should be made to target infusion timing to 
be as close to 30 minutes as possible. However, a window of -5 minutes and +10 minutes 
is permitted (i.e., infusion time is 30 minutes: -5 min/+10 min). Pembrolizumab will be 
administered first. 
7.3 
PDS0101 (Arms A and B) 
Each subject will receive PDS0101 (2.7 mg HPV-16 E6 and E7 peptides (400 μg/peptide) 
mixed with 3.0 mg R-DOTAP) administered as a divided dose of two 0.5mL SC 
injections in the upper anterior arm of the same arm. Injection sites should be separated 
by a minimum of 6 centimeters. The first PDS0101 vaccine dose should be administered 
in the non-dominant arm and the second dose should be delivered in the alternate arm. 
For individuals with upper extremity lymphedema, PDS0101 should be delivered in the 
alternate unaffected arm or the anterior thighs (if both upper extremities are affected), 
alternating as previously described. 
For patients receiving both drugs: PDS0101 will be administered between 30-60 min 
after completion of the pembrolizumab infusion. 
For all patients: Following the first vaccination of PDS0101, subjects will have vital signs 
and symptoms monitored for 1 hour (at approximately 0, 15, 30 and 60 minutes). If no 
significant immediate AEs are identified with the first vaccination, patients should be 
monitored after vaccination for at least 15 minutes (at approximately 0 and 15 minutes) 
with subsequent vaccinations. 
Patients should record the occurrence of any AEs, including injection site reactions daily, 
for 7 days post study treatment (monotherapy or combination). A diary is provided in 
Appendix II. Copies of the gauge (Appendix III) printed on acetate will be provided for 
each patient. Please note patient compliance with diary completion in medical record and 
confirm AE and concomitant medication data are transferred to Medidata Rave. 
7.4 
Return to consenting institution 
For this protocol, the patient must return to the consenting institution for evaluation 
during treatment per the study calendar in Section 4.0 (Active Monitoring Phase). 

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7.5 
Treatment by local medical doctor (LMD) 
Treatment for this trial by a local medical doctor (LMD) is not allowed. Treatment by a 
local medical doctor for routine and emergent care is allowed.  
7.6 
Surgery or Chemoradiation per clinical standard of care 
Patients must be candidate for either curative-intent surgery or chemoradiation. 
If the patient is a surgical candidate, definitive surgery will be performed per institutional 
guidelines and procedures at the discretion of the treating oropharyngeal surgeon. 
Treatment with radiation therapy with or without chemotherapy will be with curative 
intent and per enrolling institutional standards at the discretion of the treating radiation 
oncologist. 
 
 

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8.0 
Dosage Modification Based on Adverse Events  
There will be no dose modification for both PDS0101 and Pembrolizumab. Guidelines for the 
management of the adverse events is presented in Tables 8.2 and 8.3. However, if clinically 
indicted the treating physician may hold, omit or discontinue one of the drugs at any time per 
discussion with Study Investigator or Co-Investigator. This information must be documented in 
the patient clinical record.  
→ ALERT: 
ADR reporting may be required for some adverse events (See Section 10.0) ← 
8.1  
Dose Levels (Based on Adverse Events in Tables 8.2 and 8.3) 
There are no dose reductions for PDS0101 or pembrolizumab 
NOTE: 
For Arm A if clinically indicated, treatment may be discontinued for an adverse 
event, and patient may proceed to surgery and/or chemoradiation therapy as 
indicated. 
In Arm B, if either pembrolizumab or PDS0101 is discontinued or omitted, the 
patient can continue the other drug.  
If one of the drugs is held or delayed, the other drug is delayed as well and always 
administered on the same day.  
If both are discontinued, the patient will proceed to surgery and/or chemoradiation 
therapy as indicated. 
  Use the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (November 
27, 2017)* unless otherwise specified   
* 
Located at 
 
8.2 
Dose Modification Guidelines for Second Dose (Cycle 2, Day 1) of Pembrolizumab 
CTCAE 
System/Organ/Class 
(SOC) 
ADVERSE EVENT 
ACTION** 
Cardiac disorders 
Myocarditis 
Hold treatment for Grade 1-2 until it resolves, if 
treatment is delayed ≥2 weeks proceed to surgery or 
chemoradiation; permanently discontinue for Grade 3-
4 
Gastrointestinal 
disorders 
Diarrhea or colitis 
Grade 2-3 hold treatment until Grade 0-1, if treatment 
is delayed ≥2 weeks proceed to surgery or 
chemoradiation; Grade 4 permanently discontinue  
Investigations 
Elevated AST, ALT, or 
total bilirubin 
Hold treatment for Grade 2 until it resolves to 0-1, if 
treatment is delayed ≥2 weeks proceed to surgery or 
chemoradiation; permanently discontinue for Grade 3-
4 
Endocrine disorders 
Endocrine disorders – 
Other, specify: 
Hypophysitis 
Hold treatment for Grade 2-3 until it resolves to 0-1, if 
treatment is delayed ≥2 weeks proceed to surgery or 
chemoradiation; permanently discontinue for Grade 4 
Endocrine disorders 
Hyperthyroidism 
Hold treatment for Grade 3-4 until it resolves to 0-2, if 
treatment is delayed ≥2 weeks proceed to surgery or 
chemoradiation 
Endocrine disorders 
Hypothyroidism 
Therapy with pembrolizumab can be continued while 
thyroid replacement therapy is instituted 

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CTCAE 
System/Organ/Class 
(SOC) 
ADVERSE EVENT 
ACTION** 
Metabolism and 
nutrition disorders 
Glucose intolerance 
(Type 1 diabetes 
mellitus [if new onset]) 
or 
Hyperglycemia 
Hold pembrolizumab for new onset Type 1 diabetes 
mellitus or Grade 3-4 hyperglycemia associated with 
evidence of beta cell failure. Resume pembrolizumab 
when patients are clinically and metabolically stable. If 
treatment is delayed ≥2 weeks proceed to surgery or 
chemoradiation.  
Respiratory, thoracic 
and mediastinal 
disorders 
Pneumonitis 
Hold treatment for Grade 2 until it resolves to 0-1, if 
treatment is delayed ≥2 weeks proceed to surgery or 
chemoradiation;  
Permanently discontinue for Grade 3-4 
 
All Other Immune-
Related Adverse Events 
Hold for Grade 2-3 until AE resolves to Grade 0-1, if 
treatment is delayed ≥2 weeks proceed to surgery or 
chemoradiation or discontinue based on type of event.  
Events requiring discontinuation include but are not 
limited to: Anaphylaxis, Guillain-Barre syndrome, 
Encephalitis.  
Grade 4 permanently discontinue  
 
8.3 
Dose Modification Guidelines for Second Dose (Cycle 2, Day 1) of PDS0101  
CTCAE 
System/Organ/Class (SOC) 
ADVERSE EVENT 
ACTION** 
General disorders and 
administration site conditions Injection site reaction 
Permanently discontinue for Grade 3-4 
Immune system disorders 
Anaphylaxis 
Permanently discontinue 
 
All Other Adverse 
Events considered 
related to PDS0101 
Hold for Grade 2-3 until AE resolves to Grade 0-1, 
if treatment is delayed ≥2 weeks proceed to 
surgery or chemoradiation or discontinue based on 
type of event. 
Grade 4 permanently discontinue  
 

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9.0 
Ancillary Treatment/Supportive Care 
9.1 
Full supportive care 
Patients should receive full supportive care while on this study. This includes blood 
product support, antibiotic treatment, and treatment of other newly diagnosed or 
concurrent medical conditions. All blood products and concomitant medications such as 
antidiarrheals, analgesics, and/or antiemetics received from the first day of study 
treatment administration until 30 days after the final dose will be recorded in the medical 
records. 
9.2 
Blood products and growth factors 
Blood products and growth factors should be utilized as clinically warranted and 
following institutional policies and recommendations. The use of growth factors should 
follow published guidelines of the Journal of Clinical Oncology, Volume 33, No 28 
(October 1), 2015: pp. 3199-3212 (WBC growth factors) AND Journal of Clinical 
Oncology, Volume 28, No 33 (November 20), 2010: pp. 4955-5010 
(darbepoetin/epoetin). 
9.3 
Antiemetics 
Antiemetics may be used at the discretion of the attending physician except for steroids. 
Steroids should be used only if necessary for adverse immune-related events. 
9.4 
Diarrhea 
Patients should be monitored for signs and symptoms of enterocolitis (such as diarrhea, 
abdominal pain, blood, or mucus in stool, with or without fever) and of bowel perforation 
(such as peritoneal signs and ileus). In symptomatic patients, infectious etiologies should 
be ruled out, and if symptoms are persistent and/or severe, endoscopic evaluation should 
be considered. 
All patients who experience diarrhea should be advised to drink liberal quantities of clear 
fluids. If sufficient oral fluid intake is not feasible, fluid and electrolytes should be 
substituted via IV infusion. 
NOTE: Loperamide/diphenoxylate/atropines should NOT be used for diarrhea symptoms 
unless: (1) it is believed that pembrolizumab-related enterocolitis is unlikely to be 
present.  
9.5 
Immunotherapy-related toxicities 
Immunotherapy related toxicities including but not limited to pneumonitis, diarrhea, 
hypophysitis, hyper or hypothyroidism, hepatitis and nephritis will be managed with 
local, systemic steroids or other immunosuppressive agents according to the severity and 
discretion of the treating MD and multidisciplinary team managing the patient. 
9.6 
Concomitant Medications/Vaccination 
Medications or vaccinations specifically prohibited in the exclusion criteria are not 
allowed during the ongoing trial. If there is a clinical indication for any medication or 
vaccination specifically prohibited during the trial, discontinuation from trial therapy or 
vaccination may be required. The final decision on any supportive therapy or vaccination 
rests with the investigator and/or the patient’s primary physician.  

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9.61 
Acceptable Concomitant Medications  
9.611 
General Guidelines 
All treatments that the investigator considers necessary for a subject’s welfare 
may be administered at the discretion of the investigator in keeping with the 
community standards of medical care. All concomitant medication will be 
recorded in the medical record including all prescription, over-the-counter 
(OTC), herbal supplements, and IV medications and fluids. If changes occur 
during the trial period, documentation of drug dosage, frequency, route, and date 
may also be included on the medical record.  
All concomitant medications received within 28 days before the first dose of trial 
treatment and 30 days after the last dose of trial treatment should be recorded. 
Concomitant medications administered 30 days after the last dose of trial 
treatment should be recorded for SAEs and ECIs as defined in Section 10.  
9.612 
Coordination and timing of COVID-19 vaccination 
COVID-19 vaccination timing should be based on local investigator clinical 
assessment and judgment. (Note: Whenever possible, it is recommended to avoid 
COVID vaccination on the day of PDS0101 dosing with or without 
pembrolizumab because it may be difficult to attribute certain AEs (e.g., fever, 
infusion reactions) to the study agent(s) or the COVID vaccine if they are both 
administered on the same day. 
9.62 
Prohibited Concomitant Medications  
The following medications are not permitted during the screening and treatment 
phase (including retreatment for post-complete response relapse) of this trial:  
• Anti-neoplastic systemic cytotoxic chemotherapy or biological therapy  
• Immunotherapy not specified in this protocol  
• Chemotherapy not specified in this protocol  
• Investigational agents other than pembrolizumab  
• Live vaccines within 30 days prior to the first dose of trial treatment and while 
participating in the trial. Examples of live vaccines include, but are not limited to, 
the following: measles, mumps, rubella, varicella/zoster, yellow fever, intranasal 
influenza, rabies, BCG, and typhoid vaccine.  
• Systemic glucocorticoids for any purpose other than to modulate symptoms 
from an event of clinical interest of suspected immunologic etiology.  
NOTE: The Exclusion Criteria describes other medications which are prohibited 
in this trial. There are no prohibited therapies during the Post-Treatment Follow-
up Phase. 
9.7 
Contraception 
PDS0101 and pembrolizumab may have adverse effects on a fetus in utero. Furthermore, 
it is not known if any there are any transient adverse effects on the composition of sperm.  
For this trial, male patients will be considered to be of non-reproductive potential if they 
have azoospermia (whether due to having had a vasectomy or due to an underlying 
medical condition).  
Female patients will be considered of non-reproductive potential if they are either:  
(1) postmenopausal (minimum age 50 years with complete absence of menstruation for at 
least 2 continuous years); in females <45 years of age a high follicle stimulating hormone 
(FSH) level in the postmenopausal range may be used to confirm a post-menopausal state 

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in females not using hormonal contraception or hormonal replacement therapy. In the 
absence of 12 months of amenorrhea, a single FSH measurement is insufficient.)  
OR  
(2) have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or 
bilateral tubal ligation/occlusion, at least 6 weeks prior to screening;  
OR  
(3) has a congenital or acquired condition that prevents childbearing.  
All patients of reproductive potential must agree to avoid becoming pregnant or 
impregnating a partner while receiving study drug and for 120 days after the last dose of 
study drug. (Some suggested methods are included in Appendix IV.) 
Patients should be informed that taking the study medication may involve unknown risks 
to the fetus (unborn baby) if pregnancy were to occur during the study. In order to 
participate in the study patients of childbearing potential must adhere to the contraception 
requirement  from the day of study medication initiation (or 14 days prior to the initiation 
of study medication for oral contraception) throughout the study period up to 120 days 
after the last dose of trial therapy. If there is any question that a patient of childbearing 
potential will not reliably comply with the requirements for contraception, that patient 
should not be entered into the study. 
9.8 
Use in pregnancy 
If a patient inadvertently becomes pregnant while on treatment, the patient will 
immediately be removed from the study. The site will contact the patient at least monthly 
and document the patient’s status until the pregnancy has been completed or terminated. 
The outcome of the pregnancy will be reported to Mayo Clinic, PDS Biotech, and to 
Merck without delay and within 24 hours to Mayo Clinic and within 2 working days to 
PDS Biotech and Merck if the outcome is a serious adverse experience (e.g., death, 
abortion, congenital anomaly, or other disabling or life-threatening complication to the 
mother or newborn).  
The study investigator will make every effort to obtain permission to follow the outcome 
of the pregnancy and report the condition of the fetus or newborn. If a male subject 
impregnates his female partner the study personnel at the site must be informed 
immediately and the pregnancy reported to Mayo Clinic, PDS Biotech, and to Merck, and 
followed as described above. 
9.9 
Use in nursing adults 
Since many drugs are excreted in human milk, and because of the potential for serious 
adverse reactions in the nursing infant, patients who are breast-feeding are not eligible for 
enrollment. 
 
 

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10.0 
Adverse Event (AE) Monitoring and Reporting  
The site Principal Investigator is responsible for reporting any/all serious adverse events to the 
sponsor as described within the protocol, regardless of attribution to study agent or treatment 
procedure. 
The Sponsor/Sponsor-Investigator is responsible for notifying FDA and all participating 
investigators in a written safety report of any of the following: 
• 
Any suspected adverse reaction that is both serious and unexpected. 
• 
Any findings from laboratory animal or in vitro testing that suggest a significant risk for 
human subjects, including reports of mutagenicity, teratogenicity, or carcinogenicity. 
• 
Any findings from epidemiological studies, pooled analysis of multiple studies, or 
clinical studies, whether or not conducted under an IND and whether or not conducted by 
the sponsor, that suggest a significant risk in humans exposed to the drug 
• 
Any clinically important increase in the rate of a serious suspected adverse reaction over 
the rate stated in the protocol or Investigator’s Brochure (IB). 
10.01 Summary of SAE Reporting for this study  
(please read entire section for specific instructions): 
WHAT form: 
WHERE to send: 
Pregnancy Reporting 
 
Attach to MCCC Electronic SAE Reporting Form 
Manually send copies to PDS Biotech at: 
  
NOTE: The MCCC form will automatically be sent 
to 
 
  
Mayo Clinic Cancer Center SAE Reporting Form:  
 
Manually send copies to PDS Biotech at: 
  
NOTE: The MCCC form will automatically be sent 
to 
 
 
Definitions 
Adverse Event 
Any untoward medical occurrence associated with the use of a drug in humans, whether or 
not considered drug related.  
Suspected Adverse Reaction 
Any adverse event for which there is a reasonable possibility that the drug caused the adverse 
event. 
Expedited Reporting 
Events reported to sponsor within 24 hours, 5 days, or 10 days of study team becoming aware 
of the event. 
Routine Reporting 
Events reported to sponsor via case report forms 

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Events of Interest 
Events that would not typically be considered to meet the criteria for expedited reporting, but 
that for a specific protocol are being reported via expedited means in order to facilitate the 
review of safety data (may be requested by the FDA or the sponsor).  
10.1 
Adverse Event Characteristics 
CTCAE term (AE description) and grade: The descriptions and grading scales found 
in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 
5.0 will be utilized for AE reporting. All appropriate treatment areas should have access 
to a copy of the CTCAE version 5.0 A copy of the CTCAE version 5.0 can be 
downloaded from the CTEP web site: 
 
a. Identify the grade and severity of the event using the CTCAE version 5.0. 
b. Determine whether the event is expected or unexpected (see Section 10.2). 
c. Determine if the adverse event is related to the study intervention (agent, treatment or 
procedure) (see Section 10.3). 
d. Determine whether the event must be reported as an expedited report. If yes, 
determine the timeframe/mechanism (see Section 10.4).  
e. Determine if other reporting is required (see Section 10.5). 
f. Note: All AEs reported via expedited mechanisms must also be reported via the 
routine data reporting mechanisms defined by the protocol (see Sections 10.6 and 
18.0). 
NOTE: A severe AE is NOT the same as a serious AE, which is defined in Section 10.4. 
10.2 
Expected vs. Unexpected Events  
Expected events – are those described within the Section 15.0 of the protocol, the study 
specific consent form, package insert (if applicable), and/or the investigator brochure, (if 
an investigator brochure is not required, otherwise described in the general 
investigational plan).  
Unexpected adverse events or suspected adverse reactions are those not listed in Section 
15.0 of the protocol, the study specific consent form, package insert (if applicable), or in 
the investigator brochure (or are not listed at the specificity or severity that has been 
observed); if an investigator brochure is not required or available, is not consistent with 
the risk information described in the general investigational plan. 
Unexpected also refers to adverse events or suspected adverse reactions that are 
mentioned in the investigator brochure as occurring with a class of drugs but have not 
been observed with the drug under investigation. 
An investigational agent/intervention might exacerbate the expected AEs associated with a 
commercial agent. Therefore, if an expected AE (for the commercial agent) occurs with a 
higher degree of severity or specificity, expedited reporting is required. 
NOTE: *The consent form may contain study specific information at the discretion of the 
Principal Investigator; it is possible that this information may NOT be included in the 
protocol or the Investigator Brochure. Refer to protocol or IB for reporting needs. 
10.3 
Attribution to agent(s) or procedure 
When assessing whether an adverse event (AE) is related to a medical agent(s) medical or 
procedure, the following attribution categories are utilized: 
Definite – The AE is clearly related to the agent(s)/procedure. 

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Probable – The AE is likely related to the agent(s)/procedure. 
Possible – The AE may be related to the agent(s)/procedure. 
Unlikely – The AE is doubtfully related to the agent(s)/procedure. 
Unrelated – The AE is clearly NOT related to the agent(s)/procedure. 
10.31 AEs Experienced Utilizing Investigational Agents and Commercial Agent(s) on 
the SAME (Combination) Arm 
NOTE: When a commercial agent(s) is (are) used on the same treatment arm as 
the investigational agent/intervention (also, investigational drug, biologic, 
cellular product, or other investigational therapy under an IND), the entire 
combination (arm) is then considered an investigational intervention for 
reporting. 
• An AE that occurs on a combination study must be assessed in accordance with the 
guidelines for investigational agents/interventions.  
• An AE that occurs prior to administration of the investigational agent/intervention 
must be assessed as specified in the protocol. In general, only Grade 4 and 5 AEs 
that are unexpected with at least possible attribution to the commercial agent require 
an expedited report, unless hospitalization is required. Refer to Section 10.4 for 
specific AE reporting requirements or exceptions. 
An investigational agent/intervention might exacerbate the expected AEs associated 
with a commercial agent. Therefore, if an expected AE (for the commercial agent) 
occurs with a higher degree of severity or specificity, expedited reporting is 
required. 
• An increased incidence of an expected adverse event (AE) is based on the 
patients treated for this study at their site. A list of known/expected AEs is 
reported in the package insert or the literature, including AEs resulting from a 
drug overdose. 
• Commercial agent expedited reports must be submitted to the FDA via MedWatch 
3500A for Health Professionals (complete all three pages of the form). 
10.32 EXPECTED Serious Adverse Events: Protocol Specific Exceptions to Expedited 
Reporting 
For this protocol only, the following Adverse Events/Grades are expected to occur 
within this population and do not require Expedited Reporting. These events must still 
be reported via Routine Reporting (see Section 10.6).* 
*Report any clinically important increase in the rate of a serious suspected 
adverse reaction (at your study site) over that which is listed in the protocol or 
investigator brochure as an expedited event.  
*Report an expected event that is greater in severity or specificity than expected 
as an expedited event. 
*Specific protocol exceptions to expedited reporting should be reported 
expeditiously by investigators ONLY if they exceed the expected grade of the 
event. 

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CTCAE 
System Organ Class 
(SOC) 
Adverse event/ Symptoms 
CTCAE Grade at which the event 
will not be reported in an expedited 
manner1 
General disorders and 
administrations site 
conditions 
Injection site reaction 
≤Grade 2 
Skin and subcutaneous 
tissue disorders 
Pain of skin 
≤Grade 2 
1 These exceptions only apply if the adverse event does not result in hospitalization. If the adverse 
event results in hospitalization, then the standard expedited adverse events reporting 
requirements must be followed.  
The following hospitalizations are not considered to be SAEs because there is no “adverse event” 
(i.e., there is no untoward medical occurrence) associated with the hospitalization: 
● Hospitalizations for respite care 
● Planned hospitalizations and surgery required by the protocol 
● Hospitalization planned before informed consent (where the condition requiring the hospitalization 
has not changed post study drug administration) 
● Hospitalization for elective procedures unrelated to the current disease and/or treatment on this trial 
● Hospitalization for administration of study drug or insertion of access for administration of study 
drug 
● Hospitalization for routine maintenance of a device (e.g., battery replacement) that was in place 
before study entry 
● Hospitalization, or other serious outcomes for signs and symptoms of progression of the cancer. 
 
 

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10.4 
Expedited Reporting Requirements for IND Agents  
10.41 Phase 1 and Early Phase 2 Studies: Expedited Reporting Requirements for 
Adverse Events that Occur on Studies under an IND within 30 Days of the Last 
Administration of the Investigational Agent/Intervention 1, 2 
FDA REPORTING REQUIREMENTS FOR SERIOUS ADVERSE EVENTS (21 CFR Part 312) 
NOTE: Investigators MUST immediately report to the sponsor ANY Serious Adverse Events, whether or not they 
are considered related to the investigational agent(s)/intervention (21 CFR 312.64) 
An adverse event is considered serious if it results in ANY of the following outcomes:  
1) 
Death 
2) 
A life-threatening adverse event  
3) 
An adverse event that results in inpatient hospitalization or prolongation of existing hospitalization for ≥ 24 
hours  
4) 
A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions  
5) 
A congenital anomaly/birth defect.  
6) 
Important Medical Events (IME) that may not result in death, be life threatening, or require hospitalization 
may be considered serious when, based upon medical judgment, they may jeopardize the patient or subject 
and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. (FDA, 
21 CFR 312.32; ICH E2A and ICH E6). 
ALL SERIOUS adverse events that meet the above criteria MUST be immediately reported to the sponsor within 
the timeframes detailed in the table below.  
Hospitalization 
Grade 1 and Grade 2 Timeframes 
Grade 3-5 
Timeframes 
Resulting in 
Hospitalization 
≥24 hrs 
7 Calendar Days 
24-Hour 3 Calendar 
Days 
Not resulting in 
Hospitalization 
≥24 hrs 
Not required 
Expedited AE reporting timelines are defined as: 
o “24-Hour; 3 Calendar Days” – The AE must initially be reported within 24 hours of learning of the AE, 
followed by a complete expedited report within 3 calendar days of the initial 24-hour report. 
o “7 Calendar Days” – A complete expedited report on the AE must be submitted within 7 calendar days 
of learning of the AE. 
1Serious adverse events that occur more than 30 days after the last administration of investigational 
agent/intervention and have an attribution of possible, probable, or definite require reporting as follows:  
Expedited 24-hour notification followed by complete report within 3 calendar days for: 
• All Grade 3, 4, and Grade 5 AEs 
Expedited 7 calendar day reports for: 
• Grade 2 AEs resulting in hospitalization or prolongation of hospitalization 
2 For studies using PET or SPECT IND agents, the AE reporting period is limited to 10 radioactive half-lives, 
rounded UP to the nearest whole day, after the agent/intervention was last administered. Footnote “1” above 
applies after this reporting period. 
Effective Date: May 5, 2011 
NOTE: Refer to Section 10.32 for exceptions to Expedited Reporting 
10.42 General reporting instructions 
The Mayo IND and/or MCCC Compliance will assist the Sponsor-Investigator in 
the processing of expedited adverse events and forwarding of suspected 
unexpected serious adverse reactions (SUSARs) to the FDA and IRB. 
Use Mayo Expedited Event Report form: 

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for investigational agents or 
commercial/investigational agents on the same arm.  
Submit copies of Mayo Expedited Event Report Form by email to PDS Biotech at: 
  
10.43 Reporting of re-occurring SAEs 
ALL SERIOUS adverse events that meet the criteria outlined in Table 10.41 
MUST be immediately reported to the Sponsor within the timeframes detailed in 
the corresponding table. This reporting includes but is not limited to SAEs that 
re-occur again after resolution. 
10.5 
Other Required Reporting 
10.51 Unanticipated Problems Involving Risks to Subjects or Others (UPIRTSOS) 
Unanticipated Problems Involving Risks to Subjects or Others (UPIRTSOS) in 
general, include any incident, experience, or outcome that meets all of the 
following criteria: 
1. Unexpected (in terms of nature, severity, or frequency) given (a) the research 
procedures that are described in the protocol-related documents, such as the 
IRB-approved research protocol and informed consent document; and (b) the 
characteristics of the subject population being studied; 
2. Related or possibly related to participation in the research (in this guidance 
document, possibly related means there is a reasonable possibility that the 
incident, experience, or outcome may have been caused by the procedures 
involved in the research); and 
3. Suggests that the research places subjects or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was 
previously known or recognized. 
Some unanticipated problems involve social or economic harm instead of the 
physical or psychological harm associated with adverse events. In other cases, 
unanticipated problems place subjects or others at increased risk of harm, but no 
harm occurs. 
Note: If there is no language in the protocol indicating that pregnancy is not 
considered an adverse experience for this trial, and if the consent form does not 
indicate that subjects should not get pregnant/impregnate others, then any 
pregnancy in a subject/patient or a male patient’s partner (spontaneously 
reported) which occurs during the study or within 120 days of completing the 
study should be reported as a UPIRTSO. 
Mayo Clinic Cancer Center (MCCC) Institutions: 
If the event meets the criteria for IRB submission as a Reportable 
Event/UPIRTSO, provide the appropriate documentation and use the Mayo 
Clinic Cancer Center Expedited Event Report form 
o submit to 
The Mayo Clinic Compliance Unit will 
review and process the submission to the Mayo Clinic IRB and work with the 
IND Coordinator for submission to FDA. 

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10.52 Death 
Note: A death on study requires both routine and expedited reporting 
regardless of causality, unless as noted below. Attribution to treatment or 
other cause must be provided. 
Any death occurring within 30 days of the last dose, regardless of attribution to 
an agent/intervention under an IND requires expedited reporting within 24-
hours. 
Any death occurring greater than 30 days with an attribution of possible, 
probable, or definite to an agent/intervention under an IND requires expedited 
reporting within 24-hours. 
Reportable categories of Death  
• 
Death attributable to a CTCAE term. 
• 
Death Neonatal: A disorder characterized by cessation of life during the 
first 28 days of life.  
• 
Death NOS: A cessation of life that cannot be attributed to a CTCAE term 
associated with Grade 5. 
• 
Sudden death NOS: A sudden (defined as instant or within one hour of the 
onset of symptoms) or an unobserved cessation of life that cannot be 
attributed to a CTCAE term associated with Grade 5. 
• 
Death due to progressive disease that cannot be attributed to a CTCAE 
term associated with Grade 5 should be reported as Grade 5 “Disease 
progression” under the system organ class (SOC) of “General disorders 
and administration site conditions.” Evidence that the death was a 
manifestation of underlying disease (e.g., radiological changes suggesting 
tumor growth or progression: clinical deterioration associated with a 
disease process) should be submitted 
10.53 Secondary Malignancy 
• 
A secondary malignancy is a cancer caused by treatment for a previous 
malignancy (e.g., treatment with investigational agent/intervention, radiation 
or chemotherapy). A secondary malignancy is not considered a metastasis of 
the initial neoplasm. 
• 
All secondary malignancies that occur following treatment with an agent under 
an IND will be reported. Three options are available to describe the event: 
o Leukemia secondary to oncology chemotherapy (e.g., Acute Myeloctyic 
Leukemia [AML]) 
o Myelodysplastic syndrome (MDS) 
o Treatment-related secondary malignancy 
• 
Any malignancy possibly related to cancer treatment (including AML/MDS) 
should also be reported via the routine reporting mechanisms outlined in each 
protocol. 
10.54 Second Malignancy 
A second malignancy is one unrelated to the treatment of a prior malignancy (and is 
NOT a metastasis from the initial malignancy). Second malignancies require ONLY 
routine reporting unless otherwise specified. 

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10.55 Pregnancy, Fetal Death, and Death Neonatal  
If a female subject (or female partner of a male subject) inadvertently becomes 
pregnant while on treatment with PDS0101 and pembrolizumab (when 
applicable) the subject will immediately be removed from the study. Any 
pregnancy occurring after the subject receives the first PDS0101 vaccine and 
until 30 days after second final PDS0101vaccine must be reported to the 
Investigator within 24 hours of learning of its occurrence. The Investigator will 
contact the subject at least monthly and document the subject’s status until the 
pregnancy has been completed or terminated. The outcome of the pregnancy will 
be reported to the industry partners without delay and within 24 hours if the 
outcome is a serious adverse experience (e.g., death, abortion, congenital 
anomaly, or other disabling or life-threatening complication to the mother or 
newborn). The Study Investigator will make every effort to obtain permission to 
follow the outcome of the pregnancy and report the condition of the fetus or 
newborn to the industry partner.  
Prior to obtaining private information about a pregnant patient and the infant, the 
investigator must obtain consent from the pregnant patient and the newborn 
infant’s parent or legal guardian before any data collection can occur. A consent 
form will need to be submitted to the IRB for these subjects if a pregnancy 
occurs. If informed consent is not obtained, no information may be collected. 
In cases of fetal death, miscarriage or abortion, the mother is the patient. In cases 
where the child/fetus experiences a serious adverse event other than fetal death, 
the child/fetus is the patient. 
NOTE: When submitting Mayo Expedited Adverse Event Report reports for 
“Pregnancy”, “Pregnancy loss”, or “Neonatal loss”, the potential risk of exposure 
of the fetus to the investigational agent(s) or chemotherapy agent(s) should be 
documented in the “Description of Event” section. Include any available medical 
documentation. Include this form: 
10.551 
Pregnancy 
Pregnancy should be reported in an expedited manner as Grade 3 
“Pregnancy, puerperium and perinatal conditions – Other 
(pregnancy)” under the Pregnancy, puerperium and perinatal 
conditions SOC. Pregnancy should be followed until the outcome is 
known. 
10.552 
Fetal Death 
Fetal death is defined in CTCAE as “A disorder characterized by death 
in utero; failure of the product of conception to show evidence of 
respiration, heartbeat, or definite movement of a voluntary muscle after 
expulsion from the uterus, without possibility of resuscitation.” 
Any fetal death should be reported expeditiously, as Grade 4 
“Pregnancy, puerperium and perinatal conditions – Other 
(pregnancy loss)” under the Pregnancy, puerperium and perinatal 
conditions SOC. 

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10.553 
Death Neonatal 
Neonatal death, defined in CTCAE as “A disorder characterized by 
cessation of life occurring during the first 28 days of life” that is felt by 
the investigator to be at least possibly due to the investigational 
agent/intervention, should be reported expeditiously.  
A neonatal death should be reported expeditiously as Grade 4 
“General disorders and administration – Other (neonatal loss)” 
under the General disorders and administration SOC.  
10.56 Adverse Events of Special Interest (AESIs) for PDS0101 
Events of clinical interest related to PDS0101 include: 
1) Possible temporary discoloration (other than redness) of skin at local 
injection sites. Description (hyper- or hypopigmentation) and duration will 
be captured. 
2) Any overdose with either of the compounds. 
10.6 
Required Routine Reporting  
10.61 Baseline and Adverse Events Evaluations 
Pretreatment symptoms/conditions to be graded at baseline and adverse events to 
be graded at each evaluation.  
Grading is per CTCAE v5.0 unless alternate grading is indicated in the table 
below: 
CTCAE  
System/Organ/Class (SOC) 
Adverse event/Symptoms 
Baseline 
Each 
evaluation 
Blood and lymphatic system 
disorders 
Lymph node pain 
X 
X 
Ear and labyrinth disorders 
Ear pain 
X 
X 
General disorders and  
Fatigue 
X 
X 
administration site conditions 
Injection site reaction 
 
X 
Respiratory, thoracic and 
mediastinal disorders 
Sore throat 
X 
X 
Skin and subcutaneous tissue 
disorders  
Rash, maculo-papular  
X 
X  
 
10.62 All other AEs 
Submit via appropriate MCCC Case Report Forms (i.e., paper or electronic, as 
applicable) the following AEs experienced by a patient and not specified in 
Section 10.6: 
10.621 Grade 1 and 2 AEs deemed possibly, probably, or definitely related to the 
study treatment or procedure. 
10.622 Grade 3 and 4 AEs regardless of attribution to the study treatment or 
procedure. 
10.623 Grade 5 AEs (Deaths) 
10.6231 
Any death within 30 days of the patient’s last study 
treatment or procedure regardless of attribution to the study 
treatment or procedure. 

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10.6232 
Any death more than 30 days after the patient’s last study 
treatment or procedure that is felt to be at least possibly 
treatment related must also be submitted as a Grade 5 AE, 
with a CTCAE type and attribution assigned. 
10.7 
Late Occurring Adverse Events 
Refer to the instructions in the Forms Packet (or electronic data entry screens, as 
applicable) regarding the submission of late occurring AEs following completion of the 
Active Monitoring Phase (i.e., compliance with Test Schedule in Section 4.0). 
10.8 
Reporting for PDS Biotech 
Submit copies of all SAE reports on the same day report is completed to PDS Biotech at: 
  
 
 
 

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11.0 
Treatment Evaluation/Measurement of Effect 
This study utilizes ctHPVDNA and pathologic response for treatment response. Objective 
response rate is a secondary endpoint and will be assessed prior to surgery or definitive 
chemoradiation.  
Response and progression will be evaluated in this study using the international criteria proposed 
by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines 
(version 1.1)15. Changes in the largest diameter (unidimensional measurement) of the tumor lesions 
and the short axis measurements in the case of lymph nodes are used in the RECIST guideline. 
11.1 
Schedule of evaluations  
 Screening:  
• Baseline ctHPVDNA, research biopsy and scan to assess the baseline levels of 
ctHPVDNA, baseline pathology and disease status should have been performed 
within 14 days prior to registration.  
• CT scan of neck, chest and abdomen should be obtained. CT scan obtained as 
part of FDG-PET-CT is acceptable, but a at least a dedicated CT neck is preferred. 
NOTE: MRI of the neck is acceptable in lieu of CT-neck but not preferred. If MRI 
of the neck is used at baseline, then MRI should be used to assess the response 
prior to surgery or chemoradiation. 
 Cycle 2, Day 1: The ctHPVDNA levels will be collected again prior to the 
second dose of study treatment.  
 Prior to surgery or definitive chemoradiation (end of Cycle 2):  
• The ctHPVDNA levels will be collected again prior to the surgical resection.  
• The first scan after treatment initiation will be performed prior to surgical 
resection or chemoradiation. If there is no evidence of distant metastasis on 
baseline screening, then CT scan of the neck is sufficient at this time point.  
NOTE:If MRI of the neck is used at baseline, then MRI should be utilized to 
assess the response prior to surgery or chemoradiation.  
NOTE: Following surgical resection, the scans are performed per institutional 
standard of care and at the discretion of treating MD. 
At the time of surgical resection: A research surgical pathology sample will be 
collected during surgery to assess for pathologic response. 
For patients not undergoing surgery, an optional research biopsy may be performed to 
assess for pathologic response. 
11.2 
Definitions of Measurable and Non-Measurable Disease 
11.21 Measurable Disease  
11.211 
A non-nodal lesion is considered measurable if its longest diameter can 
be accurately measured as ≥2.0 cm with chest x-ray, or as ≥1.0 cm 
with CT scan, CT component of a PET/CT, or MRI.  
11.212 
A superficial non-nodal lesion is measurable if its longest diameter is 
≥1.0 cm in diameter as assessed using calipers (e.g. skin nodules) or 
imaging. In the case of skin lesions, documentation by color 
 
15 Eisenhauer EA, Therasse P, Bogaert J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, 
Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria 
in solid tumors: revised RECIST guideline (version 1.1). Eur J Cancer 45(2): 228-247, 2009. 

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photography, including a ruler to estimate the size of the lesion, is 
recommended.  
11.213 
A malignant lymph node is considered measurable if its short axis is 
>1.5 cm when assessed by CT scan (CT scan slice thickness 
recommended to be no greater than 5 mm).  
NOTE: Please collect lymph node level (1, 2, 2a, 2b, 3, 4, 5 and 
retropharyngeal [RP]) 
11.22 Non-Measurable Disease  
11.221 
All other lesions (or sites of disease) are considered non-measurable 
disease, including pathological nodes (those with a short axis ≥1.0 to 
<1.5 cm). Bone lesions, leptomeningeal disease, ascites, pleural/ 
pericardial effusions, lymphangitis cutis/pulmonis, inflammatory breast 
disease, and abdominal masses (not followed by CT or MRI), are 
considered as non-measurable as well.  
Note: ‘Cystic lesions’ thought to represent cystic metastases can be considered as 
measurable lesions, if they meet the definition of measurability described above. 
However, if non-cystic lesions are present in the same patient, these are preferred 
for selection as target lesions. In addition, lymph nodes that have a short axis 
<1.0 cm are considered non- pathological (i.e., normal) and should not be 
recorded or followed. 
11.3 
Guidelines for Evaluation of Measurable Disease  
11.31 Measurement Methods:  
• 
All measurements should be recorded in metric notation (i.e., decimal 
fractions of centimeters) using a ruler or calipers.  
• 
The same method of assessment and the same technique must be used to 
characterize each identified and reported lesion at baseline and during 
follow-up. For patients having only lesions measuring at least 1 cm to less 
than 2 cm must use CT imaging for both pre- and post-treatment tumor 
assessments.  
• 
Imaging-based evaluation is preferred to evaluation by clinical examination 
when both methods have been used at the same evaluation to assess the 
antitumor effect of a treatment.  
11.32 Acceptable Modalities for Measurable Disease:  
• 
Conventional CT and MRI: This guideline has defined measurability of 
lesions on CT scan based on the assumption that CT slice thickness is 5 mm 
or less. If CT scans have slice thickness greater than 5 mm, the minimum 
size for a measurable lesion should be twice the slice thickness.  
• 
As with CT, if an MRI is performed, the technical specifications of the 
scanning sequences used should be optimized for the evaluation of the type 
and site of disease. The lesions should be measured on the same pulse 
sequence. Ideally, the same type of scanner should be used and the image 
acquisition protocol should be followed as closely as possible to prior scans. 
Body scans should be performed with breath-hold scanning techniques, if 
possible.  
• 
PET-CT: CT portion of the PET-CT can be used for RECIST measurements 
and can be used interchangeably with conventional CT in accurately 
measuring cancer lesions over time.  

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• 
FDG-PET: FDG-PET scanning is allowed to complement CT scanning in 
assessment of progressive disease [PD] and particularly possible ‘new’ 
disease. A ‘positive’ FDG-PET scanned lesion is defined as one which is 
FDG avid with an update greater than twice that of the surrounding tissue on 
the attenuation corrected image; otherwise, an FDG-PET scanned lesion is 
considered ‘negative.’ New lesions on the basis of FDG-PET imaging can be 
identified according to the following algorithm:  
a. Negative FDG-PET at baseline with a positive FDG-PET at follow-up is 
a sign of PD based on a new lesion.  
b. No FDG-PET at baseline and a positive FDG-PET at follow-up:  
i. 
If the positive FDG-PET at follow-up corresponds to a new site of 
disease confirmed by CT, this is PD.  
ii. If the positive FDG-PET at follow-up is not confirmed as a new 
site of disease on CT at the same evaluation, additional follow-up 
CT scans (i.e., additional follow-up scans at least 4 weeks later) are 
needed to determine if there is truly progression occurring at that 
site. In this situation, the date of PD will be the date of the initial 
abnormal FDG-PET scan.  
Iii If the positive FDG-PET at follow-up corresponds to a pre-existing 
site of disease on CT that is not progressing on the basis of the 
anatomic images, it is not classified as PD.  
11.33 Measurement at Follow-up Evaluation:  
• 
There is only one follow up evaluation as part of the study (evaluation prior 
to surgery or after chemoradiation). Further follow up after surgical resection 
is as per institutional guidelines.  
• 
Histologic techniques could be used to differentiate between PR and CR in 
rare cases (e.g., residual lesions prior to surgical resection could represent 
fibrotic tissue)  
11.4 
Measurement of Effect  
11.41 Target Lesions & Target Lymph Nodes  
• 
Measurable lesions (as defined in Section 11.21) up to a maximum of 5 
lesions, representative of all involved organs, should be identified as “Target 
Lesions” and recorded and measured at baseline. These lesions can be non-
nodal or nodal (as defined in 11.21), where no more than 2 lesions are from 
the same organ and no more than 2 malignant nodal lesions are selected.  
Note: If fewer than 5 target lesions and target lymph nodes are identified 
(as there often will be), there is no reason to perform additional studies 
beyond those specified in the protocol to discover new lesions.  
• 
Target lesions and target lymph nodes should be selected on the basis of their 
size, be representative of all involved sites of disease, but in addition should 
be those that lend themselves to reproducible repeated measurements. It may 
be the case that, on occasion, the largest lesion (or malignant lymph node) 
does not lend itself to reproducible measurements in which circumstance the 
next largest lesion (or malignant lymph node) which can be measured 
reproducibly should be selected.  
• 
Baseline Sum of Dimensions (BSD): A sum of the longest diameter for all 
target lesions plus the sum of the short axis of all the target lymph nodes will 
be calculated and reported as the baseline sum of dimensions (BSD). The 

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BSD will be used as reference to further characterize any objective tumor 
response in the measurable dimension of the disease.  
• 
Post-Baseline Sum of the Dimensions (PBSD): A sum of the longest 
diameter for all target lesions plus the sum of the short axis of all the target 
lymph nodes will be calculated and reported as the post-baseline sum of 
dimensions (PBSD). If the radiologist is able to provide an actual measure 
for the target lesion (or target lymph node), that should be recorded, even if it 
is below 0.5 cm. If the target lesion (or target lymph node) is believed to be 
present and is faintly seen but too small to measure, a default value of 0.5 cm 
should be assigned. If it is the opinion of the radiologist that the target lesion 
or target lymph node has likely disappeared, the measurement should be 
recorded as 0 cm.  
• 
The minimum sum of the dimensions (MSD) is the minimum of the BSD and 
the PBSD.  
11.42 Non-Target Lesions & Non-Target Lymph Nodes  
Non-measurable sites of disease (Section 11.22) are classified as non- target 
lesions or non-target lymph nodes and should also be recorded at baseline. These 
lesions and lymph nodes should be followed in accord with Section 11.433. 
11.43 Response Criteria 
11.431 
All target lesions and target lymph nodes followed by CT/MRI/PET-
CT/ must be measured on re-evaluation at evaluation times specified in 
Section 11.1. Specifically, a change in objective status to either a PR or 
CR cannot be done without re-measuring target lesions and target 
lymph nodes.  
Note: Non-target lesions and non-target lymph nodes should be 
evaluated at each assessment, especially in the case of first response or 
confirmation of response.  
11.432 
Evaluation of Target Lesions  
• 
Complete Response (CR): All of the following must be true:  
a. Disappearance of all target lesions.  
b. Each target lymph node must have reduction in short axis 
to <1.0 cm.  
• 
Partial Response (PR): At least a 30% decrease in PBSD (sum of 
the longest diameter for all target lesions plus the sum of the short 
axis of all the target lymph nodes at current evaluation) taking as 
reference the BSD (see Section 11.41).  
• 
Progression (PD): At least one of the following must be true:  
a. At least one new malignant lesion, which also includes 
any lymph node that was normal at baseline (<1.0 cm short 
axis) and increased to ≥1.0 cm short axis during follow-up.  
b. At least a 20% increase in PBSD (sum of the longest 
diameter for all target lesions plus the sum of the short axis 
of all the target lymph nodes at current evaluation) taking as 
reference the MSD (Section 11.41). In addition, the PBSD 
must also demonstrate an absolute increase of at least 0.5 
cm from the MSD.  

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11.433 
Evaluation of Non-Target Lesions & Non-target Lymph Nodes  
• 
Complete Response (CR): All of the following must be true:  
a. Disappearance of all non-target lesions.  
b. Each non-target lymph node must have a reduction in 
short axis to <1.0 cm.  
• 
Non-CR/Non-PD: Persistence of one or more non-target lesions or 
non-target lymph nodes.  
• 
Progression (PD): At least one of the following must be true:  
a. At least one new malignant lesion, which also includes 
any lymph node that was normal at baseline (<1.0 cm short 
axis) and increased to ≥1.0 cm short axis during follow-up.  
b. Unequivocal progression of existing non-target lesions 
and non-target lymph nodes. (NOTE: Unequivocal 
progression should not normally trump target lesion and 
target lymph node status. It must be representative of 
overall disease status change.)  
c. See Section 11.32 for details in regards to the 
requirements for PD via FDG-PET imaging.  
11.44 Overall Objective Status  
The overall objective status for an evaluation is determined by combining the 
patient’s status on target lesions, target lymph nodes, non-target lesions, non-
target lymph nodes, and new disease as defined in the following tables:  
11.441 
For Patients with Measurable Disease  
Target Lesions & 
Target Lymph Nodes 
Non-Target Lesions & 
Non-Target Lymph Nodes 
New 
Sites of Disease 
Overall Objective 
Status 
CR 
CR 
No 
CR 
CR 
Non-CR/Non-PD 
No 
PR 
PR 
CR 
Non-CR/Non-PD 
No 
PR 
CR/PR 
Not All Evaluated* 
No 
PR** 
SD 
CR 
Non-CR/Non-PD 
Not All Evaluated* 
No 
SD 
Not all Evaluated 
CR 
Non-CR/Non-PD 
Not All Evaluated* 
No 
Not Evaluated (NE) 
PD 
Unequivocal PD 
CR 
Non-CR/Non-PD 
Not All Evaluated* 
Yes or No 
PD 
CR/PR/SD/PD/Not all 
Evaluated 
Unequivocal PD 
Yes or No 
PD 
CR/PR/SD/PD/Not all 
Evaluated 
CR 
Non-CR/Non-PD 
Not All Evaluated* 
Yes 
PD 
*See Section 11.431 
** NOTE: This study uses the protocol RECIST v1.1 template dated 2/16/2011. For data collection and 
analysis purposes the objective status changed from SD to PR in the protocol RECIST v1.1 template as of 
2/16/2011 and to match RECIST v1.1 requirements. 

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11.442 
For patients with Non-measurable disease Only 
Non-Target Lesions & 
Non-Target Lymph Nodes 
New  
Sites of Disease 
Overall  
Objective Status 
CR 
No 
CR 
Non-CR/Non-PD 
No 
Non-CR/Non-PD  
Not All Evaluated* 
No 
Not Evaluated (NE) 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
*See Section 11.431 
11.45 Symptomatic Deterioration  
Patients with global deterioration of health status requiring discontinuation of 
treatment without objective evidence of disease progression at that time, and not 
either related to study treatment or other medical conditions, should be reported 
as PD due to “symptomatic deterioration.” Every effort should be made to 
document the objective progression even after discontinuation of treatment due to 
symptomatic deterioration.  
11.5 
Treatment Evaluation after Completion of Surgery or Definitive Chemoradiation 
11.51 Definition of Recurrence  
The term “recurrence” is used if cancer returns either in the locoregional area of 
the primary tumor or at distant sites following R0 or R1 resection  
11.52 How Recurrence is Determined  
Recurrence is determined radiographically and biopsy could be performed at the 
discretion of treating physician except as detailed below or when CT findings are 
equivocal in the determination of the enrolling physician.  
Locoregional recurrence: Identified by a new soft-tissue mass in the operated 
thyroid bed or regional cervical lymph nodes. In some cases post-radiation 
changes may make it difficult to distinguish from early tumor progression. In 
cases in which the diagnosis is ambiguous, discussion with the PI should occur. 
Performance of tissue biopsy should be considered prior to assigning a diagnosis 
of locoregional recurrent disease. 
12.0 
Descriptive Factors  
12.1 
History of tobacco use: Yes vs. No 
If yes,  
Current tobacco user: Yes vs. No 
If yes 
Type: Smoking vs. smokeless tobacco 
If smoking: Number of pack years: ____ 
12.2 
AJCC 8 clinical staging: I vs II vs III 
12.3 
Clinical TNM staging (AJCC 8th Edition HPV-associated): specify T ___ N____ M____ 
12.4 
Planned treatment type: Surgery vs. chemo-radiation 

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13.0 
Treatment/Follow–up Decision at Evaluation of Patient  
13.1 
Continuation of treatment 
Patients who are CR, PR, or SD will continue treatment per protocol. 
13.2 
Recurrence/Progressive Disease (PD) 
Patients who develop PD or recurrence while in clinical follow-up will go to the survival 
follow-up phase. 
13.3 
Off protocol treatment 
Patients who go off protocol treatment for reasons other than PD will go to the survival 
followup/event-monitoring phase per Section 4.0. 
13.4 
Observation (Clinical Follow-up) 
If the patient has achieved CR, PR, or SD, the patient will proceed with surgery as 
indicated or definitive chemoradiation. Adjuvant therapy will be per the discretion of the 
treating team. Patients will be observed every 3 months for max of two years after 
surgery. Once patients have PD or go off treatment for other reasons, they’ll go to 
survival follow-up.  
13.5 
Duration of therapy for CR 
Patients who achieve a CR will still only receive the max of 2 cycles. After 2 cycles, the 
patient will proceed with surgery or chemoradiation. Patients will be observed after 
surgery or chemoradiation (see 13.4 above) every 3 months for 2 years or until PD and 
then they will go to survival follow-up.  
13.6 
Duration of therapy for PR or SD 
Patients who are in PR or SD will receive a maximum or total of 2 cycles. After 2 cycles, 
the patient will proceed with surgery or chemoradiation. After surgery or chemoradiation, 
they should be observed (see 13.4 above) for 6 months post-surgery or chemoradiation 
until PD and then they will go to survival follow-up/event monitoring. 
13.7 
Ineligible 
A patient is deemed ineligible if after registration, it is determined that at the time of 
registration, the patient did not satisfy each and every eligibility criteria for study entry. If 
the patient received treatment, the patient may continue treatment at the discretion of the 
physician as long as there are not safety concerns. The patient will continue in the Active 
Monitoring/Treatment phase of the study, as per section 4.0 of the protocol.  
• 
If the patient never received treatment, on-study material must be submitted. Survival 
Follow-up will be required per Section 4.0 of the protocol.  
13.8 
Major violation 
A patient is deemed a major violation, if protocol requirements regarding treatment in 
cycle 1 of the initial therapy are severely violated that evaluability for primary end point 
is questionable. If the patient received treatment, the patient may continue treatment at 
the discretion of the physician as long as there are not safety concerns. The patient will 
continue in the Active Monitoring/Treatment phase of the study, as per section 4.0 of the 
protocol. 
13.9 
Cancel 
A patient is deemed a cancel if he/she is removed from the study for any reason before 
any study treatment is given. On-study material and the End of Active Treatment/Cancel 
Notification Form must be submitted. No further data submission is necessary. 

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14.0 
Body Fluid Biospecimens 
14.1  
Summary Table of Research Blood and Body Fluid Specimens to be Collected for this Protocol 
Research (Section for more 
information) 
Specimen 
Purpose  
Mandatory 
or Optional 
Volume to 
collect per tube 
(# of tubes to 
be collected) 
Timepoint 1 
Timepoint 2 
Timepoint 3 
Timepoint 4 
Prior to 
treatment on 
C1D1  
(Baseline) 
Prior to 
treatment on 
C2D1 
(End of C1) 
End of C216 
Safety 
Follow Up17 
ctHPVDNA 
Section 14. 41 MC200710-C1 
Correlative 
Mandatory 
10mL (1) 
X  
X 10mL 
X 10mL 
X 10mL 
DNA 
Section 14.43  
Banking 
Mandatory 
varies 
X 4mL + 
10mL 
X 10mL 
X 10mL 
X 10mL 
PBMC analysis of immune 
biomarkers 
Section 14.42 MC200710-C2 
Correlative 
Mandatory 
10 mL (3) 
X 
X 
X 
X 
Immunogenic Markers Section 
14.42 
MC200710-C3 
Correlative 
Banking 
Mandatory 
10 mL (1) 
X 
X 
X 
X 
NOTE: See Lab Manual for additional information on collection, processing and shipping 
 
 
16 Prior to surgery for surgical patients and prior to chemo-radiation for chemo-radiation patients. 
17 For surgical patients first post-surgical visit (may be safety follow-up plus end of treatment plus observation); for chemo-radiation patients during Weeks 4-5 
assessments 

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14.2 
Collection and Processing  
See lab manual for details on collection and processing 
14.3 
Shipping and Handling 
14.31 Kits will be used for this study. 
14.311 Kits will be supplied by the study team and Naveris Inc.  
14.312 The kit contains supplies and instructions for collecting, processing, and 
shipping specimens. 
14.313 Naveris: Obtain kits by contacting Naveris (see Lab Manual). 
14.314 All specimens must be collected and shipped Monday – Friday ONLY. 
14.32 Shipping Specimens 
One tube per timepoint will be shipped to Naveris per lab manual. Naveris will 
supply the tubes and kits for this shipment. 
Three tubes to go to 
laboratory – page laboratory for 
expedited pickup per Protocol Resources. 
Remaining tubes to be processed/stored in BAP 
14.33 Handling Specimens 
See lab manual for details on specimen handling 
14.4 
Background and Methodology 
Correlative analyses will be performed on blood collected  
14.41 ctHPVDNA 
ctHPVDNA will be assessed prospectively at all timepoints using a previously 
validated multiplex ctHPVDNA panel including HPV type 16 (Routman, et al., 
2019). This ctHPVDNA assay has been previously characterized, with 
approximately 90% pretreatment sensitivity, and marked response to intervention 
including surgery and radiation therapy. ctHPVDNA will be reported at each 
timepoint as copies/mL. Detectable threshold for the purposes of this study will 
be 5 copies/mL or greater. A significant response to induction therapy will be 
considered decrease in absolute copies of ctHPVDNA ≥50% from baseline prior 
to surgery or definitive chemoradiation. Given increased shedding with cell kill 
documented in both oropharyngeal and anal cancer including with fractionated 
RT, an increase of ctHPVDNA at the interim timepoint after cycle 1 will not be 
considered progression. Patients with undetectable ctDNA will continue with 
blood draws for assessment. Patients with undetectable pretreatment ctDNA will 
be considered non-evaluable.  
14.42 Immunophenotyping 
Immunophenotyping will be used to characterize correlatives of response within 
and across patients. PBMCs will be analyzed to characterize specific CD8+ and 
CD4+ T cell populations of responders and non-responders by high flow 
cytometry, functional assays, and identification of HPV16-specific T cells. 
PBMCs will be processed per the BAP standard as above and frozen. 
14.43 Banking 
WBCs and plasma will be banked for future genomic analysis. Serum will be 
banked for future analyses. 
 

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15.0 
Drug Information 
15.1 
PDS0101 (R-DOTAP (Versamine®) + HPVmix) 
15.11 Background 
PDS0101 is a novel nanoparticle-based immunotherapy (therapeutic vaccine) 
developed to treat genital cancers such as anal, cervical, vulvar cancer etc. and 
their precancers (late-stage dysplasia/neoplasia), as well as head and neck 
cancers caused by infection with the human papilloma virus (HPV). PDS0101 is 
a subcutaneously administered therapy consisting of two vialed components 
mixed at the time of administration. The immunotherapy is composed of 
liposomal nanoparticles of the pure immunologically active R enantiomer of the 
cationic (positively charged) lipid DOTAP (dioleoyl-trimethylammonium 
propane) mixed with 6 lipidated antigenic peptides derived from the HPV-16 E6 
and E7 proteins. 
15.12 Formulation 
PDS0101 is a 2-vial formulation which is mixed 1:1 v/v just prior to 
administration. Active vials:  
• Vial #1: R-DOTAP (Versamine®) – 2 mg/mL, 6 mg/mL, and 20 mg/mL ± 10% 
concentrations in 280 mM sucrose/Sterile Water for Injection. Fill volume is 
1.8 mL. 
• Vial #2: HPVmix – 0.8 mg/mL per peptide ± 25% Peptide injectable 
formulation of 6 HPV-16 lipidated peptides in 280 mM sucrose and 20:80 
DMSO/Sterile Water for Injection. Fill volume is 0.6 mL.  
15.13 Preparation and storage 
PDS0101 (R-DOTAP (Versamine®) and HPVmix) is stored at -70 degrees 
Celsius ± 10 degrees Celsius. The two vial formulation should be thawed and 
mixed as outlined in the current PDS0101 Investigator’s Broochure and 
pharmacy manual provided by PDS Biotech. 
15.14 Administration 
The PDS0101 mixture (1.2 mL which contains overfill) is divided and 
administered as two subcutaneous injections of 0.5 mL in the upper anterior arm 
of the same arm. The two injections should be at least 6 cm apart for each 
vaccination. The first vaccination (two subcutaneous injections of 0.5 mL) should 
be given in the non-dominant arm. Each subsequent vaccination should be 
alternated between the non-dominant versus dominant arm. 
15.15 Pharmacokinetic information 
No pharmacokinetic testing in humans to date. 
15.16 Potential drug interactions 
None known to date. 
15.17 Known potential adverse events 
In Oncology patients (N= 15) receiving the combination of PDS0101 and 
pembrolizumab the following adverse events were observed. 
Very Common known potential adverse events >10% 
Injection site reactions (ISR): with or without swelling, pain, skin discoloration, 
or erythema. Fatigue; chills; hypertension; Pain in extremities; anxiety; nausea 

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Common known potential adverse events, ≥10%: None 
Uncommon known potential adverse events, 1% - 10%: 
Injection site reactions (ISR): fibrosis; site discomfort; site inflammation; site 
pruritus.  
Arthralgia, Insomnia, Tachycardia, Diarrhea, Lymphocyte count decreased, 
Rash, Headache 
The following adverse events were observed but deemed unrelated to the 
combination [PDS0101+pembrolizumab]: 
Hypotension, Lymphoedema, Peripheral ischemia, Pain in extremity, 
Compartment syndrome, Rhabdomyolysis, Bradycardia, Blood creatine 
phosphokinase increased, Acidosis, Hyperglycemia, Hyperhidrosis, Sepsis, 
Acute kidney injury, Oropharyngeal pain 
In pre-neoplastic patients (N=12) evaluated as healthy volunteers the following 
adverse events were observed: 
Very Common known potential adverse events >10% 
Injection site reactions (ISR): with or without swelling, pain, skin discoloration, 
site hemorrhage, induration, or erythema. Headache  
Common known potential adverse events, ≥10%: None 
Uncommon known potential adverse events, 1% - 10%: 
Injection site reactions: site papule, site nodule, site paresthesia, site 
inflammation. Site pruritus, site rash, site redness. 
Fatigue, Malaise, Pyrexia, Diarrhea, Nausea, Vomiting. Myalgia. Dizziness. 
Lethargy, and Insomnia. 
The adverse event assessments are similar whether subjects receive PDS0101 
monotherapy or in combination with pembrolizumab. 
15.18 Drug procurement: 
Drug will be provided free of charge by PDS Biotech 
Outdated or remaining drug is to be destroyed on-site as per procedures in place 
at each institution. 
15.19 Nursing guidelines 
15.191 
PDS0101 should be administered as two injections in the upper 
anterior of the same arm. They should be given approximately 6 cm 
apart. Subsequent injections should be administered in the opposite 
arm on a rotating basis.  
15.192 
Due to the early investigational nature of this agent not all side effects 
can be known at this time. Monitor patients for about one hour after 
first vaccine, and at least fifteen minutes after second dose and report 
any side effects to the study team. 
15.193 
The most common side effect in early studies was injection site 
reaction. This consisted of erythema, pain and swelling at the site.  

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15.194 
Gastrointestinal side effects have been noted including diarrhea, nausea 
and vomiting. Treat symptomatically and assess for effectiveness of 
intervention. 
15.195 
Fatigue, lethargy and malaise have been reported. Instruct patient in 
energy conserving lifestyle.  
15.196 
Patients have reported myalgia. Treat symptomatically and monitor for 
effectiveness. 
15.2 
Pembrolizumab (MK-3475, SCH 900475, Keytruda®) 
15.21 Background 
Pembrolizumab is a potent humanized IgG4 monoclonal antibody with high 
specificity of binding to the PD-1 receptor, thus inhibiting its interaction with 
PD-L1 and PD-L2. Based on preclinical in vitro data, pembrolizumab has high 
affinity and potent receptor blocking activity for PD-1. 
15.22 Formulation 
Pembrolizumab is available as a liquid 25 mg/mL, 100 mg/vial. 
15.23 Preparation and storage 
Vials should be stored in the refrigerator at temperatures between 2-8°C. 
Drug concentrate is further diluted with normal saline (or 5% dextrose in the 
concentration range of 1 to 10 mg/mL) in IV containers made of polyvinyl 
chloride (PVC) or non-PVC material. The infusion solution in the IV bag should 
be immediately administered. Diluted pembrolizumab solutions may be stored at 
room temperature for a cumulative period of up to 4 hours. This includes room 
temperature storage of admixture solutions in the IV bags and the duration of 
infusion. In addition, IV bags may be stored at 2-8°C for up to a cumulative time 
of 20 hours. This 24-hour total hold time from dilution may include up to 6 hours 
at room temperature 
15.24 Administration 
Pembrolizumab is administered by intravenous infusion over 30 minutes via a 
0.22 micron in-line filter. The final infusion volume must be between 1 and 10 
mg/mL. Maximum rate of infusion should not exceed 6.7 mL/minute through a 
peripheral or indwelling catheter. Flush the line with 0.9% NaCL following the 
completion of the infusion. 
15.25 Pharmacokinetic information 
a) Absorption – Because pembrolizumab is administered intravenously, it is 
immediately and completely bioavailable. Steady-state concentrations of 
pembrolizumab are reached by16 weeks of repeated dosing with a Q3W 
regimen, and the systemic accumulation is 2.1-fold. The peak concentration, 
trough concentration, and area under the plasma concentration versus time 
curve at steady state of pembrolizumab increased dose proportionally in the 
dose range of 2 to 10 mg/kg Q3W.  
b) Distribution – Pembrolizumab has a limited volume of distribution.  
c) Excretion – CL is approximately 23% lower after achieving maximal change 
at steady state compared with the first dose. The terminal elimination half-
life (t½) is estimated to be 22 days at steady state. 
d) Metabolism – Pembrolizumab is catabolized through non-specific pathways; 
metabolism does not contribute to its CL. 

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15.26 Potential Drug Interactions 
There are no known significant drug interactions. 
15.27 Known potential adverse events:  
Very common known potential adverse events, ≥10%: 
Skin and subcutaneous tissue disorders: Pruritus, skin rash 
Gastrointestinal disorders: Diarrhea, nausea, abdominal pain 
General disorders and administration site conditions: fatigue 
Common known potential adverse events, >10%: 
Blood and lymphatic system disorders: anemia 
Immune system disorders: infusion related reaction 
Endocrine disorders: hyperthyroidism, hypothyroidism 
Metabolism and nutrition disorders: decreased appetite 
Nervous system disorders: headache, dizziness, dysgeusia 
Respiratory, thoracic, and mediastinal disorders: pneumonitis, dyspnea, cough 
Gastrointestinal disorders: colitis, vomiting, constipation, dry mouth 
Skin and subcutaneous tissue disorders: severe skin reactions, vitiligo, dry skin, 
erythema 
Musculoskeletal and connective tissue disorders: arthralgia, myositis, 
musculoskeletal pain, arthritis, pain in extremity 
General disorders and administration site conditions: asthenia, edema, pyrexia, 
influenza like illness, chills 
Investigations: alanine aminotransferase increased, aspartate aminotransferase 
increased, blood alkaline phosphatase increased, blood creatinine increased 
Uncommon known potential adverse events, 1% - 10%: 
Infusion related reactions 
Blood and lymphatic system disorders: neutropenia, thrombocytopenia, 
leukopenia, lymphopenia, eosinophilia 
Endocrine disorders: hypophysitis, adrenal insufficiency, thyroiditis, 
hypopituitarism 
Metabolism and nutrition disorders: type I diabetes mellitus, hyponatremia, 
hypokalemia, hypocalcemia 
Psychiatric disorders: insomnia, confusional state 
Nervous system disorders: epilepsy, lethargy, peripheral neuropathy 
Eye disorders: uveitis, dry eye 
Cardiac disorders: myocarditis, atrial fibrillation 
Vascular disorders: hypertension 
Gastrointestinal disorders: pancreatitis 
Hepatobiliary disorders: hepatitis 
Skin and subcutaneous tissue disorders: lichenoid keratosis, psoriasis, alopecia, 
dermatitis, dermatitis acneiform, eczema, hair color changes, papule 
Musculoskeletal and connective tissue disorders: tenosynovitis 
Renal and urinary disorders: nephritis, acute kidney injury 
Investigations: blood bilirubin increased, amylase increased, hypercalcemia 
Rare known potential adverse events, <1% (Limited to important or life-
threatening): 
Blood and lymphatic system disorders: immune thrombocytopenic purpura, 
hemolytic anemia 
Immune system disorders: sarcoidosis 
Nervous system disorders: Guillain-Barre syndrome, myasthenic syndrome 

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Gastrointestinal disorders: small intestinal perforation 
Skin and subcutaneous tissue disorders: toxic epidermal necrolysis, Stevens-
Johnson syndrome, erythema nodosum 
The risk profile for pembrolizumab also includes two important potential risks: a) 
myasthenic syndrome, and b) an increased risk of severe complications (such as 
early severe graft versus host disease and veno-occlusive disease) of allogeneic 
transplant in patients with hematologic malignancies who have previously been 
treated with PD-1 inhibitors. 
15.28 Drug procurement 
Commercial supply will be purchased by the study. 
15.29 Nursing Guidelines 
15.291 
Pembrolizumab side effects vary greatly from those of traditional 
chemotherapy and can vary in severity from mild to life threatening. 
Instruct patients to report any side effects to the study team 
immediately. Side effects may be immediate or delayed up to months 
after discontinuation of therapy. Most side effects are reversible with 
prompt intervention of corticosteroids. 
15.292 
Diarrhea can be seen, however is less common than that seen with anti-
CTLA-4 agents. However, it can be severe, leading to colonic 
perforation. Instruct patients to report ANY increase in the number of 
stools and/or change in baseline, blood in the stool, abdominal pain to 
the study team immediately.  
15.293 
Rash/pruritis/dermatitis is seen. Patients should report any rash to the 
study team. Treat per section 9.0 and monitor for effectiveness.  
15.294 
Monitor LFTs closely as elevations in these levels could indicate early 
onset autoimmune hepatitis. Patients should also be instructed to report 
any jaundice, or right upper quadrant pain to the study team 
immediately. 
15.295 
Pneumonitis can be seen and may be mild (only seen on imaging) to 
severe. Patients should be instructed to report any SOB, dyspnea, 
cough, chest pain, etc. to the study team immediately. Patients 
reporting these symptoms should have a pulse ox checked and consider 
immediate imaging per the treating MD. 
15.296 
Endocrinopathies (including hypopituitarism, hypothyroidism, 
hypophysitis, and adrenal insufficiency) are seen with this agent. 
Patients may present only with the vague sense of fatigue and “not 
feeling well.” Additional symptoms may be that of nausea, sweating 
and decreased activity tolerance. Instruct patients to report these signs 
or symptoms immediately and obtain appropriate labs as ordered by 
MD. 
15.297 
Patients who are started on steroid therapy for any side effects of 
pembrolizumab toxicity should be instructed to take the steroids as 
ordered, and not to discontinue abruptly as symptoms may return and 
be severe. Patients may be on steroid therapy for weeks. Instruct 
patients to report any increase or change in side effects with any 
dosage decrease as patients may need a slower taper. 

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15.298 
Fatigue is common and may or may not be associated with immune-
related side effects. Assess patient’s fatigue level prior to each cycle of 
therapy and report any changes to the study team. 
15.299a Patients should avoid receiving live vaccines within 30 days of study 
drug administration or per other study guidelines.  
15.299b Patients who have undergone an allogenic bone marrow transplant, 
have an increased risk of severe complications including early GVHD, 
and veno-occlusive disease, if they have previously been treated with 
pembrolizumab 
15.299c Myocarditis has been reported and associated with pembrolizumab. 
Instruct patients to report chest pain, SOB, or dyspnea to study team 
immediately and/or seek emergency medical attention. 
15.299d Autoimmune hematologic disorders including ITP and hemolytic 
anemia have been reported. Monitor blood counts closely and report 
any abnormalities to the study team. 
15.299e Rare neurologic disorders including Guillain-Barre syndrome and 
myasthenia gravis have been reported. Instruct patients to report any 
neurologic symptoms including weakness, paresthesias or numbness, 
tingling to the study team immediately. 
 

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16.0 
Statistical Considerations and Methodology  
16.1 
Overview and Primary Endpoint Analysis: 
This pilot study will determine the initial clinical benefit of the PDS0101 vaccine alone 
(Arm A) and PDS0101 vaccine plus IV pembrolizumab (Arm B) for patients with high 
risk of HPV-OPSCC. The primary endpoint is to determine the pathologic and/or 
ctHPVDNA response rate in each arm separately, where pathologic response (pTR) is 
defined as necrosis, keratinous debris, giant cells/histiocytes as percentage of total tumor 
bed area (Uppaluri, Campbell, Egloff, & et al., 2020). Patients with a pTR-1 (10-49%) or 
greater will be considered pathologic responders. Each arm will be assessed separately. 
An observed response rate of at least 20% for either pathologic response or ctHPVDNA 
response ≥50% decrease from baseline) will be deemed worthy of further investigation 
for each arm. If the primary endpoint is negative, then secondary endpoints will be 
assessed to see if any of the treatment arms are promising enough for further study in this 
exploratory pilot study. All endpoints will be assessed. Secondary endpoints will consist 
of progression-free survival (PFS), overall survival (OS), objective response rate, and 
adverse events. These endpoints will be assessed in each cohort separately. In addition, 
this study will also assess a couple of translational endpoints as well. 
Note: 11% of patients may be unevaluable for the primary endpoint due to undetectable 
ctHPVDNA at baseline. These patients in the definitive chemo-radiation cohort will not 
be evaluated for the primary endpoint. All secondary endpoints, including adverse event 
reporting and correlative analyses, will be performed for these patients. 
16.11 Sample Size 
Study will enroll in a cohorts of 3 design, where the first 3 patients will be accrued 
to Arm A, then the next 3 to Arm B, then the next 3 to Arm A, etc. until we have 
18 patients enrolled. Then the study will enroll alternating arms with each patient 
until we have 10 patients per arm. We will continue to enroll up to 24 total 
patients (12 per arm) or until 10 evaluable patients per arm are enrolled. If we 
reach 10 evaluable patients in one arm but not the other, we will enroll exclusively 
to the incomplete arm for the remainder of the study, up to 24 patients maximum.  
16.12 Accrual Time and Study Duration 
The anticipated accrual rate is approximately 2 patients per month. Therefore, the 
accrual period for this pilot study is expected to be approximately 12 months. 
The final analysis can begin approximately 15 months after the trial begins, i.e., 
as soon as the last patient has completed surgery or definitive chemoradiation and 
all tissue has been evaluated for response. 
16.2 
Data and Safety Monitoring 
The Principal Investigator(s) and the study statistician will review the study at 
least twice a year to identify accrual, adverse event, and any endpoint problems 
that might be developing. The trial is monitored continually by the study team 
who are notified of every Grade 4 and 5 event in real time. The Mayo Clinic 
Cancer Center (MCCC) Data Safety Monitoring Board (DSMB) is responsible 
for reviewing accrual and safety data for this trial at least twice a year, based on 
reports provided by the MCCC Statistical Office. Any safety issues requiring 
protocol changes are communicated through protocol amendments. 
16.21 Adverse Event Stopping Rules 
Based on previous experience with this disease, we expect approximately 

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20% of patients to experience Grade 4+ adverse events.  
If at any time, 3 of the initial 10 patients or 30% of all patients (i.e., when 
accrual is greater than 10 patients), have experienced a Grade 3 or higher 
injection site reaction or infusion related reaction or any Grade 4 or 5 
adverse event (at least possibly related to the study treatment), accrual to 
the study will be suspended to allow for a full review of the data.  
Each Grade 5 event (death) will be reviewed on a case-by-case basis in a 
real time fashion to determine whether study accrual should be 
suspended.  
Study accrual will be suspended for: 
o Any Grade 5 event that is at least possibly related to the 
administration of the investigational product 
o Any Grade 5 event within 30 days of receiving investigational 
product that is at least possibly related to the administration of the 
investigational product 
o If two or more patients fail to proceed to planned surgery or chemo-
radiation due to disease progression or adverse events that prevent or 
delay surgical resection or chemo-radiation within the allotted 
timeline per protocol (>2 weeks or ≤8 weeks after the last dose of 
study drug) 
After consideration by the study team [i.e., Study Chair(s), Statistician, 
Operations Office, etc.] and consultation with representatives at the 
primary Institutional Review Board (IRB) affiliated with the Operations 
Office, and our MCCC DSMB, a decision will be made as to whether 
and how the study will proceed.  
16.3 
Analysis Plan: 
16.31 Primary Endpoint:  
The proportion of responses (pathologic response or ctHPVDNA responses done 
separately) will be estimated by the number of successes divided by the total 
number of evaluable patients. Ninety-five percent confidence intervals for the 
true success proportion will be calculated according to the exact binomial method 
for each arm separately.  
16.32 Definitions and Analyses of Secondary Endpoints (Note: These endpoints will be 
analyzed separately for each arm) 
16.321 
Progression-Free survival (PFS) is defined as the time from 
registration to the first of either disease progression or death from any 
cause. Patients who receive the study drug, but then never return for an 
evaluation will be censored on their last follow-up date. PFS will be 
estimated using the method of Kaplan-Meier. PFS rates at 12 and 24 
months will also be reported. 
16.322 
Overall survival (OS) is defined as the time from registration to death 
from any cause. OS will be estimated using the method of Kaplan-Meier. 
16.323 
The response rate will be estimated using RECIST 1.1 criteria. A tumor 
response is defined to be either a CR or PR noted up until surgery or 
definitive chemoradiation. All patients meeting the eligibility criteria 
who have signed a consent form and have begun treatment will be 

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evaluable for response. Patients who go off study early before having a 
tumor assessment performed will be considered a failure.  
16.33 Adverse Events 
All patients that have intitiated treatment will be considered evaluable for 
adverse event (AE) analyses. The maximum grade for each type of AE will be 
recorded for each patient, and frequency tables will be reviewed to determine AE 
patterns. AEs will be analyzed separately by arm.  
16.34 Translational Endpoints 
Determine the changes in tumor microenvironment (TME) with PDS0101 and 
PDS0101 ± pembrolizumab, assess circulating ctHPVDNA as a marker for tumor 
response, determine HPV16-specific T-cell response, and finally assess 
immunologic response utilizing multiplex flow cytometry. All of these 
translational endpoints are considered exploratory and hypothesis generating due 
to the small proposed sample size for this study with only 12 patients per arm. 
All analyses will be done separately for each arm. Associations of the categorical 
biomarkers with clinical data like response will be done via Fisher’s Exact tests. 
Continuous biomarker data will be associated with response using Wilcoxon 
Rank-Sum tests.  
16.35 Over Accrual:  
If more than the target number of patients are accrued, the additional patients will 
be included in final point estimates and confidence intervals as though they were 
accrued for the final analysis. 
16.4 
Inclusion of Women and Minorities 
16.41 Study Availability 
This study will be available to all eligible patients, regardless of gender, race, or 
ethnic origin. 
16.42 Differential effects 
There is no information currently available regarding differential effects of this 
regimen in subsets defined by gender, race, or ethnicity, and there is no reason to 
expect such differences to exist. Therefore, although the planned analysis will, as 
always, look for differences in treatment effect based on racial groupings, the 
sample size is not increased in order to provide additional power for subset 
analyses. 
 
 

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16.43 Area Population 
Based on prior studies involving similar disease sites, we expect about 20% of 
patients will be classified as minorities by race and around 50% will be women. 
Expected sizes (per study design) of racial by gender subsets are shown in the 
following table: 
Accrual Targets 
Ethnic Category 
Sex/Gender 
Females 
Males 
Total 
Hispanic or Latino 
2 
2 
4 
Not Hispanic or Latino 
10 
10 
20 
Ethnic Category: Total of all subjects 
12 
12 
24 
Racial Category 
American Indian or Alaskan Native 
1 
0 
1 
Asian 
0 
1 
1 
Black or African American 
1 
1 
2 
Native Hawaiian or other Pacific Islander 
1 
0 
1 
White 
9 
10 
19 
Racial Category: Total of all subjects 
12 
12 
24 
 
Ethnic 
Categories: 
Hispanic or Latino – a person of Cuban, Mexican, Puerto Rican, South or Central 
American, or other Spanish culture or origin, regardless of race. The term “Spanish 
origin” can also be used in addition to “Hispanic or Latino.” 
Not Hispanic or Latino 
Racial 
Categories: 
American Indian or Alaskan Native – a person having origins in any of the original 
peoples of North, Central, or South America, and who maintains tribal affiliations or 
community attachment. 
Asian – a person having origins in any of the original peoples of the Far East, 
Southeast Asia, or the Indian subcontinent including, for example, Cambodia, China, 
India, Japan, Korea, Malaysia, Pakistan, the Philippine Islands, Thailand, and 
Vietnam. (Note: Individuals from the Philippine Islands have been recorded as Pacific 
Islanders in previous data collection strategies.)  
Black or African American – a person having origins in any of the black racial 
groups of Africa. 
Native Hawaiian or other Pacific Islander – a person having origins in any of the 
original peoples of Hawaii, Guam, Samoa, or other Pacific Islands. 
White – a person having origins in any of the original peoples of Europe, the Middle 
East, or North Africa. 

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17.0 
Pathology Considerations/Tissue Biospecimens 
17.1  
Summary Table of Research Tissue Specimens to be Collected for this Protocol 
Research Study  
Specimen 
Purpose 
Mandatory 
or Optional 
Type of Tissue to 
Collect 
Archived tissue 
or biopsy 
At time of surgery 
or research 
biopsy18 
IHC for TILs and 
imaging mass 
cytometry 
☒ Correlative 
Mandatory 
Formalin fixed 
paraffin embedded 
(FFPE) 
X 
X 
TCR clonality and 
sequences, flow 
cytometry 
☒ Correlative 
Mandatory 
Frozen tissue 
X19 
X 
NOTE: See Lab Manual for additional information 
 
 
 
18 Biopsy is requested for chemoradiation patients 
19 If available 

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17.2 
Diagnostic Slides from Original and /or Recurrent Tissue 
Diagnostic slides from the time of surgical resection for the primary site and involved 
lymph nodes will be provided to Dr Joaquin Garcia or another pathologist specializing in 
Head and Neck Pathology, for review and characterization of pathologic response. Along 
with original diagnostic slides, include pathology reporting form, surgical pathology 
report and operative report. Pathologist will be blinded to study treatment arm. 
17.3 
Correlative Tissue Collection  
17.31 Tissue Kits will not be provided for this protocol. 
17.32 Paraffin Embedded Tissue 
Available tissue from diagnostic biopsy will stored for future correlative 
analyses. See Lab Manual for further information. 
17.33 Frozen Tissue 
At time of research biopsy 1-2 cores should be flash frozen. 
At the time of surgery, tissue from the primary site and up to 2 involved lymph 
nodes will also be frozen. See Lab Manual for further information. 
17.4 
Background and Methodology 
17.41 Immunohistochemistry, tumor infiltrating lymphocytes, and imaging mass 
cytometry 
We will quantify tumor infiltrating lymphocytes and compare responders and 
non-responders. We will determine spatial locations of T cells and other immune 
cells in tumor and lymph node tissues of both responders and non-responders 
using imaging mass cytometry, as well as at the primary tumor site in comparison 
to involved lymph nodes, noting differences by pathologic response.  
17.42 Frozen Tissue Analyses 
We will compare paired analysis of TCR clonality and sequences in tumor and 
peripheral samples. Additionally, we will utilize multi-parameter flow cytometry 
combined with single cell omics to characterize immune infiltrate and function of 
responders and non-responders. 
 
 
.

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18.0 
Records and Data Collection Procedures  
18.1 
Submission Timetable 
Data submission instructions for this study can be found in the Data Submission 
Schedule. 
18.2 
Survival Follow-up 
See Section 4.  
18.3 
CRF completion 
This study will use Medidata Rave® for remote data capture (rdc) of all study data. Data 
collection for this study will be done exclusively through the Medidata Rave® clinical 
data management system. Access to the trial in Rave is granted through the iMedidata 
application to all persons with the appropriate roles assigned in Regulatory Support 
System (RSS). To access Rave via iMedidata, the site user must have an active account 
and the appropriate Rave role (Rave CRA, Read-Only, Site Investigator) on the 
organization roster at the enrolling site. 
18.4 
Site responsibilities 
Each site will be responsible for ensuring that all materials contain the patient’s initials, 
MCCC registration number, and MCCC protocol number. Patient’s name must be 
removed. 
18.5 
Supporting documentation 
This study requires supporting documentation for diagnosis and progression prior to 
study entry, as well as for evidence of response to study therapy and progression after 
study therapy. These documents should be submitted within 14 days of registration (for 
prior to study entry materials) or within 14 days after the visit at which response or 
progression is determined. Pathology and operative reports from clinical and research 
biopsy as well as from surgery should be entered into Rave. 
Upload patient vaccine diaries into Rave when available. 
18.6 
Labeling of materials 
Each site will be responsible for ensuring that all materials contain the patient’s initials, 
MCCC registration number, and MCCC protocol number. Patient’s name must be 
removed. 
18.7 
Overdue lists 
A list of overdue forms and outstanding queries will be available in Rave through the 
Rave Task Summary. In addition to this, the Overdue Materials report is available on the 
Cancer Center Systems homepage. 
 

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19.0 
Budget 
19.1 
Costs charged to patient:  
Routine clinical care 
19.2 
Tests to be research funded: 
• 
Research biopsy 
• 
PDS0101 administration 
• 
Pembrolizumab administration 
• 
Collection, processing and storage of blood and tissue samples for future, unspecified 
research 
19.3 
Other budget concerns: 
• 
PDS Biotech will provide Mayo Clinic with funding to support the costs of running 
this study. 
• 
PDS Biotech will provide study drug PDS0101 and funding for pembrolizumab for 
use in this study 
 
 
 

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20.0 
References 
Ang, K. K., Harris, J., Wheeler, R., & et al. (2010). Human papillomavirus and survival of patients with 
oropharyngeal cancer. N Engl J Med, 363:24-35 PMID: 20530316. 
Burtness, B., Harrington, K. J., Greil, R., & et al. (2019). Pembrolizumab alone or with chemotherapy 
versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the 
head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet, 394: 1915-
1928 PMID: 31679945. 
Chang, W. J., & et al. (2016). Inflammation-related factors predicting prognosis of gastric cancer. World J 
Gastroenterol, 20(16):4586-96 PMID: 24782611. 
Dunn, G. P., Dunn, I. F., & Curry, W. T. (2007). Focus on TILs: Prognostic significance of tumor 
infiltrating lymphocytes in human glioma. Cancer Immun, 7:12 PMID: 17691714. 
Ferrarotto, R., Bell, D., Rubin, M. L., & et al. (2020). Impact of Neoadjuvant Durvalumab with or without 
Tremelimumab on CD8+ Tumor Lymphocyte Density, Safety, and Efficacy in Patients with 
Oropharynx Cancer: CIAO Trial Results. Clinical Cancer Research, DOI: 10.1158/1078-
0432.CCR-19-3977 Published July 2020. 
Guo, T., Rettig, E., & Fakhry, C. (2016). Understanding the impact of survival and human papillomavirus 
tumor status on timing of recurrence in oropharyngeal squamous cell carcinoma. Oral Oncol, 
52:97-103 PMID: 26589380. 
Ma, D. J., Price, K. A., Moore, E. J., & et al. (2019). Phase II Evaluation of Aggressive Dose De-
Escalation for Adjuvant Chemoradiotherapy in Human Papillomavirus-Associated Oropharynx 
Squamous Cell Carcinoma. J Clin Oncol, 37:1909-1918 PMID: 31163012. 
Preston, C. C., Maurer, M. J., Oberg, A. L., Visscher, D. W., Kalli, K. R., Hartmann, L. C., . . . et al. 
(2013). The ratios of CD8+ T cells to CD4+CD25+ FOXP3+ and FOXP3- T cells correlate with 
poor clinical outcome in human serous ovarian cancer. PLoS One, 8(11): e80063 PMID: 
24244610. 
Routman, D. M., Chera, B. S., Jethwa, K. R., Van Abel, K., Kumar, S., DeWees, T. A., . . . Ma, D. J. 
(2019). Detectable HPV ctDNA in Post-Operative Oropharyngeal Squamous Cell Carcinoma 
Patients is Associated With Progression. International Jorunal of Radiation Oncology, 
DOI:https://doi.org/10.1016/j.ijrobp.2019.08.033. 
Schoenfeld, J. D., Hanna, G. J., Jo, V. Y., & et al. (2020). Neoadjuvant Nivolumab or Nivolumab Plus 
Ipilimumab in Untreated Oral Cavity Squamous Cell Carcinoma: A Phase 2 Open-Label 
Randomized Clinical Trial. JAMA Oncol, 6:1563-1570 PMID: 32852531. 
Uppaluri, R., Campbell, K. M., Egloff, A. M., & et al. (2020). Neoadjuvant and Adjuvant Pembrolizumab 
in Resectable Locally Advanced, Human Papillomavirus–Unrelated Head and Neck Cancer: A 
Multicenter, Phase II Trial. Clinical Cancer Research, DOI: 10.1158/1078-0432.CCR-20-1695 
Published October 2020. 
Uppaluri, R., Dunn, G. P., & Lewis Jr, J. S. (2008). Focus on TILs : prognostic significance of tumor 
infiltrating lymphocytes in head and neck cancers. Cancer Immun, 8:16 PMID: 19053167. 
Weller, M. A., Ward, M. C., Berriochoa, C., & et al. (2017). Predictors of distant metastasis in human 
papillomavirus-associated oropharyngeal cancer. Head Neck, 39:940-946 PMID: 28188964. 
 
 

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Appendix I 
ECOG Performance Status 
 
ECOG PERFORMANCE STATUS* 
Grade ECOG 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out 
work of a light or sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work 
activities. Up and about more than 50% of waking hours 
3 
Capable of only limited selfcare, confined to bed or chair more than 50% of 
waking hours. 
4 
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or 
chair. 
5 
Dead 
*As published in Am. J. Clin. Oncol.: 
Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T., Carbone, P.P.: 
Toxicity And Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649-
655, 1982. 
The ECOG Performance Status is in the public domain therefore available for public use. To duplicate the 
scale, please cite the reference above and credit the Eastern Cooperative Oncology Group, Robert Comis 
M.D., Group Chair. 
 
 

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Appendix II 
Patient PDS0101 Vaccine Diary 
This document is provided separately per Mayo Clinic IRB requirement. 
 

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Appendix III Injection Site Reaction Gauge 
NOTE: Sample only – not to scale. (Will be printed on acetate) 
 
Example only. Please use the clear version provided by the study team to check vaccine site. 
 

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Appendix IV Suggested Contraception Options 
NOTE: Final decision for contraception method is between the provider and the patient. 
 
(1) practice abstinence† from heterosexual activity. 
OR  
(2) use (or have their partner use) acceptable contraception during heterosexual activity.  
Acceptable methods of contraception are‡:  
Single method (one of the following is acceptable):  
• intrauterine device (IUD)  
• vasectomy of a female subject’s male partner  
• contraceptive rod implanted into the skin  
Combination method (requires use of two of the following):  
• diaphragm with spermicide (cannot be used in conjunction with cervical 
cap/spermicide)  
• cervical cap with spermicide (nulliparous women only)  
• contraceptive sponge (nulliparous women only)  
• male condom or female condom (cannot be used together)  
• hormonal contraceptive: oral contraceptive pill (estrogen/progestin pill or progestin-
only pill), contraceptive skin patch, vaginal contraceptive ring, or subcutaneous 
contraceptive injection  
†Abstinence (relative to heterosexual activity) can be used as the sole method of 
contraception if it is consistently employed as the subject’s preferred and usual lifestyle 
and if considered acceptable by local regulatory agencies and ERCs/IRBs. Periodic 
abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation methods, etc.) and 
withdrawal are not acceptable methods of contraception.  
‡If a contraceptive method listed above is restricted by local regulations/guidelines, then 
it does not qualify as an acceptable method of contraception for patients participating at 
sites in this country/region.