A Phase Ib/II Clinical Trial of Nous-209 for Recurrent Neoantigen Immunogenicity and Cancer Immune Interception in Lynch Syndrome
Phase: PHASE1
Conditions: Colorectal Carcinoma, Lynch Syndrome
Sponsor: National Cancer Institute (NCI)

DCP Protocol MDA21-06-01 
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PROTOCOL TRACKING SHEET  
 
VERSION NUMBER 
VERSION DATE 
REASON FOR CHANGE 
(high-level) 
V5 
March 9, 2022 
Date of DCP Final Approval to 
open study: August 9, 2022 
V5.1 
June 26, 2023 
Added a study continuation 
phase (Cohort 2). Disapproved 
by DCP. 
V5.2 
August 18, 2023 
Added study continuation phase 
and incorporated all requested 
changes from DCP Consensus 
Review of Disapproved V5.1 
V5.3 
October 13, 2023 
Addressed requested revisions 
post-CIRB review of V5.2 
V5.4 
January 9, 2024 
Corrected the dose regimens to 
the nominal concentration of the 
vaccine in section 7.1.  
V5.5 
September 10, 2024 
We will randomize 28 
participants to Cohort 2 to reach 
24 evaluable participants in 
Cohort 2.   
 
V5.6 
February 19, 2025 
Replacing “gender” with “sex” 
in response to EO and 
investigator at University of 
Puerto Rico.  
 

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COVER PAGE 
DCP Protocol #: 
MDA21-06-01  
 
Local Protocol #: MDACC: 2022-0065; UPR: MDA21-06-01; COH: 22263; FCCC: 22-1009 
 
 
 
 
 
PROTOCOL TITLE 
 
A Phase Ib/II Clinical Trial of Nous-209 for Recurrent Neoantigen Immunogenicity and 
Cancer Immune Interception in Lynch Syndrome 
 
 
Lead Academic Organization (LAO) Name: iCAN-PREVENT: MD Anderson International Cancer 
Prevention Clinical Trial Consortium 
 
Name of LAO Principal  
       Eduardo Vilar Sanchez, MD, PhD 
Investigator: 
 
 
 
Chair Ad Interim, Department of Clinical Cancer Prevention 
 
 
 
 
 
1515 Holcombe Boulevard, Unit 1360 
Houston, TX 77030-4009 
Telephone: (713) 563-4743 
Fax: (713) 794-4403 
E-mail address: EVilar@mdanderson.org 
 
iCAN-PREVENT Consortium       Lana A. Vornik, MHA, MS 
Administrative Director: 
      Director, Research Planning and Development 
 
 
Department of Clinical Cancer Prevention 
 
 
University of Texas MD Anderson Cancer Center 
 
 
1515 Holcombe Boulevard, Unit 1360 
Houston, TX 77030-4009 
Telephone: (713) 792-9594 
Fax: (713) 745-4230 
 
 
E-mail address: lavornik@mdanderson.org 
  
Organization Name: 
 
 
University of Texas MD Anderson Cancer Center 
CTEP ID: TX035 
Protocol Co-Principal  
Eduardo Vilar-Sanchez, MD, PhD 
Investigator:  
Professor 
Department of Clinical Cancer Prevention 
1515 Holcombe Blvd, Unit 1360 
Houston, TX 77030 
Telephone: (713) 563-4743 
Fax: (713) 794-4403 
E-mail address: EVilar@mdanderson.org 
 
Protocol Co-Principal  
Jason A. Willis, MD, PhD  
Investigator:  
 
 
Assistant Professor 
Department of Gastrointestinal Medical Oncology 
1515 Holcombe Blvd, Unit 0426 
Houston, TX 77030 
Telephone: (713) 563-0038 
Fax: (713) 794-1873 
E-mail address: jason.willis@mdanderson.org 

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Organization:  
 
 
City of Hope Comprehensive Cancer Center 
CTEP ID: CA043 
Investigator: 
 
 
 
Gregory Idos MD, MS 
Associate Clinical Professor 
Department of Medicine 
1500 East Duarte Road 
Duarte, CA 91010 
Telephone: (626) 256-4673 
E-mail address: gidos@coh.org  
 
Organization:  
 
 
Fox Chase Cancer Center 
CTEP ID: PA086 
Investigator: 
 
 
 
Michael J Hall, MD, MS 
Professor and Chair, Department of Clinical Genetics  
333 Cottman Avenue 
Philadelphia, PA 19111 
 
 
 
 
 
Telephone: (215) 728-2861 
 
 
 
 
 
Fax: (787) 764-8365 
 
 
 
 
 
E-mail address: michael.hall@fccc.edu 
 
Organization:  
 
 
University of Puerto Rico, Medical Sciences Campus 
CTEP ID: PR008 
Investigator: 
 
 
 
Veroushka Ballester, MD, MS, AGAF 
Assistant Clinical Investigator 
Clinical and Translational Cancer Research Division 
University of Puerto Rico Comprehensive Cancer Center 
PO Box 363027 San Juan, PR 00936 
Telephone: 787-772-8300 x. 1217 
Email: vballester@cccupr.org  
 
 
 
Organization: 
 
University of Texas MD Anderson Cancer Center 
Statistician: 
 
J. Jack Lee, Ph.D. 
 
 
1515 Holcombe Boulevard, Unit 447 
Houston, TX 77230 
 
 
Telephone: (713) 794-4158 
 
 
Fax: (713) 563-4242 
 
E-mail address: jjlee@mdanderson.org  
 
Organization Name: 
National Cancer Institute, Division of Cancer Prevention 
Medical Monitor & 
Luz María Rodríguez, MD, FACS 
Scientific Lead: 
Gastrointestinal and Other Cancers Research Group 
9609 Medical Center Drive, Room: 5E228 
Rockville, MD 20850 
Phone: ( 240) 276-7039 
Fax: (240) 276-7848 
E-mail address: rodrigul@mail.nih.gov 
 
Nurse Consultant: 
Ellen Richmond, MS, GNP-BC 
 
 
 
Gastrointestinal and Other Cancers Research Group 
9609 Medical Center Drive, MSC-9782 

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Rockville, MD 20850 
Phone: ( 240) 276-7043 
Fax: (240) 276-7843 (with cover sheet, Attn: Ellen Richmond) 
E-mail address:: richmone@mail.nih.gov 
 
Scientific Lead: 
Asad Umar, DVM, PhD 
 
 
 
9609 Medical Center Drive, Room 5E226 
9609 Medical Center Drive, MSC-9782 
Rockville, MD 20850 
Phone: ( 240) 276-7038 
E-mail address: umara@mail.nih.gov 
 
 
IND Sponsor:  
NCI/Division of Cancer Prevention 
 
IND#  
 
 
 
Agent(s)/Supplier: 
Nous-209 vaccine composed of GAd20-209-FSP and MVA-209-FSP / NCI DCP 
 
 
Protocol Version Date: 02/19/2025 
 
Protocol Revision or   
Amendment #  
Version 5.6 

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SCHEMA 
A Phase Ib/II Clinical Trial of Nous-209 for Recurrent Neoantigen Immunogenicity and 
Cancer Immune Interception in Lynch Syndrome 
 
Schema for Cohort 1 
Individuals aged 18 years or older with Lynch Syndrome, as defined by: 
(a) germline mutation-positive Lynch Syndrome: carrier or obligate carrier (by pedigree) of a pathogenic germline mutation or 
likely pathogenic mutation in MMR genes (MLH1, MSH2/EPCAM, MSH6, or PMS2); or (b) germline mutation-negative 
Lynch Syndrome (“Lynch-like Syndrome”): personal history of a non-sporadic MMR-deficient premalignancy or malignancy 
associated with loss of MMR gene expression in the absence of somatic MLH1 hypermethylation and/or BRAF mutation, and 
germline MMR genetic testing showing either a variant of unknown significance, or mutation negative result, or had declined 
germline MMR genetic testing. 
p 
Participants have intact rectosigmoid; no active/recurrent malignancy; no cancer-directed treatment x 6 months; no other medical 
contraindications 
p
Consent / Registration 
(up to 60 potentially eligible participants will be consented and screened) 
p
Eligibility Confirmation 
Laboratory tests within acceptable limits and normal physical exam 
(up to 45 confirmed eligible participants) 
p 
Pre-Treatment Biomarker Acquisition 
(1) Tissue (collected via standard-of-care lower GI endoscopy [flexible sigmoidoscopy or colonoscopy]) with biopsies of polyps 
in the entire colon and grossly normal mucosa in the rectosigmoid 
(2) Blood 
p 
Intervention 
Duration 8 weeks 
Intramuscular vaccination with GAd20-209-FSPs (prime) at Week 0 and with MVA-209-FSPs (boost) at Week 8 
p 
Post-Treatment Biomarker Acquisition 
(1) Tissue (collected via standard-of-care lower GI endoscopy [flexible sigmoidoscopy or colonoscopy]) with biopsies of polyps 
in the entire colon and grossly normal mucosa in the rectosigmoid at Week 52 (12 months) post-vaccination 
(2) Blood at Weeks 3, 8, 9, 24, 52 
p 
Primary Endpoint(s) 
(1) Rates of grade 2/3 adverse events and symptom reactivity following vaccination with GAd20-209-FSPs (1 prime) 
and MVA-209-FSPs (1 boost) 
(2) Rate of immunogenicity following vaccination with GAd20-209-FSPs (1 prime) and MVA-209-FSPs (1 boost) 
Secondary Endpoint(s) 
(1) Changes in T cell immune profile and T cell receptor (TCR) repertoire in peripheral blood at Weeks 3, 9, 24, and 52 relative 
to baseline 
(2) Changes in TCR repertoire within histologically normal colorectal mucosa at Week 52 (Month 12) relative to baseline  
(3) Changes in the gene expression profile and TCR repertoire of tumor infiltrating lymphocytes (TIL) within colorectal 
adenomas at Week 52 and relative to baseline 
(4) T cell cytotoxicity against matched colorectal adenoma organoids derived from participants at Week 52 relative to baseline  
(5) Percentage change in the number of colorectal adenomas, advanced neoplasia, and/or carcinomas at Week 52 relative to 
baseline 
(6) Rate of LS-related carcinomas at Week 52 relative to baseline 
(7) Change in cfDNA detectability and mutation profile in the peripheral blood of participants with LS at Weeks 3, 9, 24, and 52 
relative to baseline 
(8) To correlate tobacco and alcohol consumption with the immune response to Nous-209 in trial participants. 
(9) To assess the MMR and/or MSI status of polyps (and adjacent normal mucosa as control) detected in the baseline and end-of-
the-study colonoscopy using different technologies such as immunohistochemistry, MSI analysis by PCR, or next-generation 
sequencing 

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SCHEMA 
A Phase Ib/II Clinical Trial of Nous-209 for Recurrent Neoantigen Immunogenicity and 
Cancer Immune Interception in Lynch Syndrome 
 
Schema for Cohort 2 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligible participants from Cohort 1 will be consented at 
week 52 
Randomization  
Arm A 
GAd20-209-FSP prime at Week 52 
followed by MVA-209-FSP boost at 
Week 60 
 (N=12 evaluable for Cohort 2) 
Arm B 
MVA-209-FSP boost at Week 52 
(N=12 evaluable for Cohort 2) 
Primary Endpoint(s) 
(1) Rates of grade 2/3 adverse events and symptom reactivity 
following revaccination with GAd20-209-FSPs (1 prime) 
And/or MVA-209-FSPs (1 boost) 
(2) Rate of immunogenicity following revaccination with GAd20-
209-FSPs (1 prime) and/or MVA-209-FSPs (1 boost) 
 

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TABLE OF CONTENTS 
PROTOCOL TRACKING SHEET ............................................................................................................... i
COVER PAGE.............................................................................................................................................. 1
SCHEMA ...................................................................................................................................................... 4
Schema for Cohort 1 ............................................................................................................................................... 4
Schema for Cohort 2 ............................................................................................................................................... 5
1.
OBJECTIVES ..................................................................................................................................... 9
1.1
Primary Objectives ...................................................................................................................................... 9
1.2
Secondary Objectives .................................................................................................................................. 9
2.
BACKGROUND ............................................................................................................................... 10
2.1
Lynch Syndrome ........................................................................................................................................ 10
2.2
Nous-209 Prime and Boost Vaccine .......................................................................................................... 11
2.3
Rationale .................................................................................................................................................... 15
3.
SUMMARY OF STUDY PLAN ...................................................................................................... 21
3.1
Study Design & Objectives ........................................................................................................................ 21
3.2
Study Population ........................................................................................................................................ 21
3.3
Interventions .............................................................................................................................................. 22
4.
PARTICIPANT SELECTION .......................................................................................................... 23
4.1
Inclusion Criteria for Participants in Cohort 1 ........................................................................................... 23
4.2
Inclusion Criteria for Participants in Cohort 2 ........................................................................................... 25
4.3
Exclusion Criteria ...................................................................................................................................... 25
4.4
Inclusion of Women and Minorities .......................................................................................................... 26
4.5 
Recruitment ............................................................................................................................................... 27
4.6 
Planned Accrual ......................................................................................................................................... 27
5.
REGISTRATION PROCEDURES ................................................................................................... 28
5.1
Investigator and Research Associate Registration with CTEP .................................................................. 28
6.
NCI CENTRAL INSTITUTIONAL REVIEW BOARD .................................................................. 29
7.
AGENT ADMINISTRATION .......................................................................................................... 29
7.1
Dose Regimen and Dose Groups ............................................................................................................... 29
7.2
Nous-209 Vaccine Administration ............................................................................................................ 30
7.3
Run-in Procedures ..................................................................................................................................... 31
7.4
Contraindications ....................................................................................................................................... 31
7.5
Concomitant Medications .......................................................................................................................... 31
7.6
Dose Modification ..................................................................................................................................... 31
7.7
Adherence/Compliance .............................................................................................................................. 32
8.
PHARMACEUTICAL INFORMATION ......................................................................................... 32
8.1
Nous-209 Vaccine ..................................................................................................................................... 32
8.2
Reported Adverse Events and Potential Risks ........................................................................................... 33
8.3 
Availability ................................................................................................................................................ 34
8.4
Agent Distribution ..................................................................................................................................... 34
8.5 
Agent Accountability ................................................................................................................................. 35
8.6
Packaging and Labeling ............................................................................................................................. 35
8.7
Storage ....................................................................................................................................................... 35
8.8
Registration/Randomization ...................................................................................................................... 35
8.9
Blinding and Unblinding Methods ............................................................................................................. 36
8.10 Agent Destruction/Disposal ....................................................................................................................... 36
9. 
CLINICAL EVALUATIONS AND PROCEDURES ...................................................................... 37
9.1
Schedule of Events .................................................................................................................................... 37
9.2
Baseline Testing/Pre-Study Evaluation ..................................................................................................... 39
9.3
Evaluation During Study Intervention for Cohort 1 .................................................................................. 41
9.4
Evaluation at Completion of Study Intervention for Cohort 1 ................................................................... 43
9.5
Post-intervention Follow-up Period for Cohort 1 ...................................................................................... 43
9.6
Evaluation During Study Intervention for Cohort 2 .................................................................................. 45
9.7
Methods for Clinical Procedures ............................................................................................................... 46

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10.  CRITERIA FOR EVALUATION AND ENDPOINT DEFINITION............................................... 47
10.1 Primary Endpoint ....................................................................................................................................... 47
10.2 Secondary Endpoints ................................................................................................................................. 48
10.3 Off-Agent Criteria ..................................................................................................................................... 49
10.4 Off-Study Criteria ...................................................................................................................................... 49
10.5 Study Termination ..................................................................................................................................... 49
11.
CORRELATIVE/SPECIAL STUDIES ............................................................................................ 49
11.1 Rationale for Methodology Selection ........................................................................................................ 49
11.2 Comparable Methods ................................................................................................................................. 51
12.
SPECIMEN MANAGEMENT ......................................................................................................... 51
12.1 Laboratories ............................................................................................................................................... 51
12.2 Collection and Handling Procedures ......................................................................................................... 52
12.3 Shipping Instructions ................................................................................................................................. 54
12.4 Tissue Banking .......................................................................................................................................... 57
13.
REPORTING ADVERSE EVENTS ................................................................................................. 57
13.1 Adverse Events .......................................................................................................................................... 58
13.2 Serious Adverse Events ............................................................................................................................. 60
14.
STUDY MONITORING ................................................................................................................... 63
14.1 Data Management ...................................................................................................................................... 63
14.2 Electronic Case Report Forms ................................................................................................................... 63
14.3 Source Documents ..................................................................................................................................... 63
14.4 Data and Safety Monitoring Plan ............................................................................................................... 63
14.5 Sponsor or FDA Monitoring ...................................................................................................................... 64
14.6 Record Retention ....................................................................................................................................... 64
14.7 Cooperative Research and Development Agreement (CRADA)/Clinical Trials Agreement (CTA) ......... 64
14.8    Genomic Data Sharing Plan ...................................................................................................................... 66
15.
STATISTICAL CONSIDERATIONS .............................................................................................. 66
15.1 Study Design/Description .......................................................................................................................... 66
15.2 Randomization/Stratification ..................................................................................................................... 66
15.3 Sample Size ............................................................................................................................................... 67
15.4 Primary Objective, Endpoint(s), Analysis Plan ......................................................................................... 67
15.5 Secondary Objectives, Endpoints, Analysis Plans ..................................................................................... 68
15.6 Reporting and Exclusions .......................................................................................................................... 69
15.7 Evaluation of Toxicity ............................................................................................................................... 69
15.8 Evaluation of Response ............................................................................................................................. 69
15.9 Interim Analysis ......................................................................................................................................... 70
15.10 Ancillary Studies ....................................................................................................................................... 71
16.
REGULATORY And ETHICAL CONSIDERATIONS .................................................................. 71
16.1 Required Documents ................................................................................................................................. 71
16.2 Informed Consent ...................................................................................................................................... 71
16.3 Collection of Regulatory Documents ......................................................................................................... 72
16.4 Other .......................................................................................................................................................... 72
17.  ROSTER MANAGEMENT .............................................................................................................. 72
18.
FINANCING, EXPENSES, AND/OR INSURANCE ...................................................................... 72
REFERENCES ........................................................................................................................................... 74
APPENDIX A 
PERFORMANCE STATUS CRITERIA .................................................................... 78
APPENDIX B ............................................................................................................................................. 79
ALCOHOL AND TOBACCO QUESTIONNAIRE INSTRUCTIONS ............................................................... 79
ALCOHOL ASSESSMENT-- BASELINE .......................................................................................................... 80
ALCOHOL ASSESSMENT - FOLLOW-UP ...................................................................................................... 83
TOBACCO ASSESSMENT – BASELINE ......................................................................................................... 85
TOBACCO ASSESSMENT - FOLLOW-UP ...................................................................................................... 89
NATIONAL AND LOCAL RESOURCES TO HELP WITH ALCOHOL ABUSE AND ALCOHOLISM ...... 92
NATIONAL AND LOCAL RESOURCES TO HELP WITH QUITTING SMOKING ...................................... 93

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APPENDIX C ............................................................................................................................................. 94
COVID-19 ASSESSMENT INSTRUCTIONS .................................................................................................... 94
CP-CT NET COVID-19 BASELINE ASSESSMENT ........................................................................................ 95
APPENDIX D ............................................................................................................................................. 98
PARTICIPANT CLINICAL TRIAL WALLET CARD ...................................................................................... 98
APPENDIX E ............................................................................................................................................. 99
PARTICIPANT BOOKLET FOR REPORTING INJECTION SITE REACTIONS ........................................... 99

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1. 
OBJECTIVES 
 
1.1 
Primary Objectives  
 
a) To evaluate the safety and tolerability of GAd20-209-FSPs (1 prime) and MVA-209-FSPs (1 
boost) vaccination when administered as a single agent (monotherapy) in participants with Lynch 
Syndrome (LS). 
 
b) To evaluate the neoantigen-specific immunogenicity of GAd20-209-FSPs (1 prime) and MVA-
209-FSPs (1 boost) vaccination when administered as a single agent (monotherapy) in 
participants with LS. 
 
c) To evaluate the neoantigen-specific immunogenicity of GAd20-209-FSP prime and MVA-209-
FSP boost or MVA-209-FSP boost alone when administered to previously-vaccinated 
immunogenic participants with LS. 
 
d) To evaluate the safety and tolerability of GAd20-209-FSP prime and MVA-209-FSP boost or 
MVA-209-FSP boost alone when administered to previously vaccinated immunogenic 
participants with LS. 
 
1.2 
Secondary Objectives  
 
a) To assess the effect of Nous-209 vaccination on T cell immune profile and T cell receptor (TCR) 
repertoire in the peripheral blood of participants with LS.  
 
b) To assess the effect of Nous-209 vaccination on TCR repertoire within histologically normal 
colorectal mucosa of participants with LS.  
 
c) To evaluate the effect of Nous-209 vaccination on tumor infiltrating lymphocyte (TIL) immune 
profile and TCR repertoire within colorectal adenomas in participants with LS.  
 
d) To assess the cytotoxicity of matched T cells on participant-derived colorectal adenoma 
organoids following Nous-209 vaccination in participants with LS. 
 
e) To evaluate the effect of Nous-209 vaccination on the burden of colorectal adenomas/advanced 
neoplasia/carcinoma in participants with LS. 
 
f) To assess the effect of Nous-209 vaccination on the burden of LS-related carcinomas in 
participants with LS.  
 
g) To evaluate the effect of Nous-209 vaccination on cell free DNA (cfDNA) mutation profiles and 
cfDNA burden in participants with LS.  
 
h) To correlate tobacco and alcohol consumption with the immune response to Nous-209 in trial 
participants.  
 
i) To assess the MMR and/or MSI status of polyps (and adjacent normal mucosa as control) detected 
in the baseline and end-of-the-study colonoscopy using different technologies such as 
immunohistochemistry, MSI analysis by PCR, or next-generation sequencing. 
 

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2. 
BACKGROUND 
 
2.1 
Lynch Syndrome 
 
Lynch Syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, affecting more 
than one million Americans (1). It is caused by deleterious germline mutations in one of four DNA 
mismatch repair (MMR) genes, with MLH1 and MSH2 mutations causing at least 50% of cases (2) 
conventionally detected using Clinical Laboratory Improvement Amendments (CLIA)-approved germline 
genetic testing. However, there is still a fraction of patients suspected to have Lynch Syndrome that do not 
have any detectable mutations in their germline testing despite of being diagnosed with MMR-deficient 
tumors with absence of somatic hypermethylation of the MLH1, V600E BRAF mutations, or double somatic 
events in one of the MMR genes (double somatic MMR mutations). This subpopulation of patients has 
been named in the literature as Lynch-like Syndrome and probably have large genomic re-arrangements 
that are not detectable with conventional genomic tests. In general, the lifetime CRC risk for LS mutation 
carriers is as high as 70%, depending on the series and the MMR gene that is responsible for LS (3-5). In 
individuals with LS, normal colorectal mucosa cells acquire somatic “second hit” mutations, thus becoming 
DNA mismatch repair deficient (dMMR). The MMR system repairs small insertion/deletion (indels) loops 
occurring in repetitive sequences known as microsatellites, which are widespread throughout the genome. 
Defects in MMR generate single-base mismatches and indels loops that result in ‘microsatellite instability’ 
(MSI) and associated frameshifts, whose open reading frames encode nonsense peptides. LS dMMR CRCs 
carry exceptionally high numbers of somatic 1-4 bp indels frameshifts and missense mutations (1). Elevated 
dMMR mutation rates cause some mutations to occur recurrently in tumors from different patients (shared 
mutations, shared frameshift peptides that become neoantigens). The greatly elevated mutation rates make 
dMMR CRC molecularly distinct from sporadic MMR-proficient (pMMR) CRC (6, 7). In summary, LS is 
a well-defined patient population with up to 70% lifetime CRC risk, and these hypermutant tumors are 
likely to benefit from immune-interception strategies. 
 
 
Abnormal tumor proteins are processed into short peptides (neoantigens) and presented on the cell 
surface complexed with major histocompatibility complex (MHC) class I. These frameshift peptides (FSP) 
can bind to T-cell receptors (TCRs) on cytotoxic CD8+ T-cells, thereby promoting interferon Ȗ (IFNȖ) 
secretion and cancer cell killing (8-10). Neoantigens are also presented in the context of MHC II at the cell 
surface of dendritic cells (DCs) where they activate CD4+ T-helper cells, which stimulate CD8+ T-cells, 
natural killer (NK) cells, CD68+ macrophages, and other immune cells to kill neoantigen-expressing cancer 
cells (11). In contrast, CD4+ CD25+ Foxp3+ regulatory T-cells (Tregs) inhibit CD8+ and CD4+ anti-
neoantigen immunity(11-13). Thus, activation of CD8+ and CD4+ T-cells recognizing neoantigens are 
important for adaptive immunity against tumors, and Tregs suppress the adaptive immune response. LS 
dMMR CRCs have extremely high numbers of neoantigens (including recurrent shared neoantigens that 
are repeatedly observed in different patient tumors) (14, 15). 
 

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Programmed 
cell 
death 
protein 1 (PD-1) is a receptor 
expressed 
on 
activated 
immune cells and following 
binding to its ligand PD-L1 
(CD274), promotes activated 
CD8+ 
and 
CD4+ 
T-cell 
apoptosis, T-cell exhaustion, 
and suppression of auto-
immunity (10, 16).  
 
Tumor 
cells 
and 
tumor-
associated 
macrophages 
commonly express PD-L1, 
which induces tumor immune 
tolerance. Anti-PD-1/PD-L1 
antibodies reverse T-cell exhaustion and reactivate anti-tumor immunity. Because of their high mutation 
rates, dMMR tumors are among the most responsive to PD-1/PD-L1 immune checkpoint inhibition (9, 17). 
However, PD-1/PD-L1 inhibitors also have significant rates of severe adverse events. These include 
autoimmunity-related lung, hepatic, skin, neuro, colon, and endocrine immune-related adverse events, 
lymphoma, and other toxicities, some of which may be fatal (18). Thus, while the risk: benefit ratio of PD-
1/PD-L1 blockade is acceptable for poor prognosis patients with metastatic tumors, it is unacceptable in the 
setting of healthy pre-symptomatic LS patients requiring cancer prevention, where the tolerance for side 
effects is low. PD-1/PD-L1 inhibitors do not, furthermore, have a clear dose response, which makes giving 
lower doses of these drugs for cancer prevention problematic (18). Therefore, new approaches with lower 
levels of toxicity are required for LS immune-interception such as preventive pre-cancer and tumor 
vaccines. 
 
2.2 
Nous-209 Prime and Boost Vaccine 
 
Genetic viral vaccines co-opt antigen processing and MHC presentation to activate T-cells and comprise 
another approach to neoantigen vaccination. Replication deficient adenoviral vectors expressing 
recombinant antigens may act as T-cell vaccines to induce potent CD8+ and CD4+ T-cell responses and 
protective immunity against multiple pathogens in pre-clinical and clinical studies (19-27). As reported in 
the New England Journal of Medicine, Nature Medicine, and Science Translational Medicine, adenoviral 
T-cell vaccination induces robust CD8+ and CD4+ T-cell responses and protective immunity against Ebola, 
Malaria, and other pathogens in both patients and mice (20, 25, 26, 28).  
 
Moreover, preclinical data recently published showed that immunization with Nouscom Great Ape 
Adenovirus (GAd) viral vector encoding neoantigens selected from murine tumor cell line was capable of 
inducing potent T-cell response (29). Prophylactic vaccination with GAd efficiently controls tumor growth 
in 100% of treated mice. In the setting of large established tumors, GAd vaccine can eradicate large tumors 
when combined with anti-PD1 or anti-PD-L1 and enhance the efficacy of such checkpoint inhibitors (29). 
Vaccination with viral vectors can induce host anti-vector immunity, thus limiting the efficacy of 
subsequent booster injections. The Nouscom approach employs sequential injections with immunologically 
unrelated viral vectors to circumvent this problem: (i) a priming infection with a recombinant Gad viral 
vector encoding a large number of predicted immunogenic neoantigens; (ii) a booster with a genetically 
unrelated virus, Modified Vaccinia Ankara virus (MVA), that encodes the same neoantigens, but with the 
neoantigens in a different sequential order so as to minimize potential immune response against junctional 
epitopes between neoantigens (20, 25, 26, 28) (Fig 2A). 
Fig 1. Expression levels of adaptive immunity genes in LS vs hereditary MMR 
proficient (pMMR) colon adenomas from FAP patients. Data are from RNAseq 
transcriptomes of 11 LS and 16 pMMR FAP colon adenomas. All P-values are adjusted 
for multiple comparisons. RPKM (Reads/Kb transcript/Million mapped reads; CD274 is PD-
L1). 

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Thus, this sequential vaccination strategy using two immunologically distinct viruses carrying the same 
antigens maximizes the predicted immune response, while minimizing host anti-viral vector immunity. 
Nouscom computationally predicted 209 recurrent FSP neoantigens in advanced dMMR malignancies from 
the TCGA data using colorectal, endometrial and gastric tumors according to the pipeline described in Fig 
2B (30). Then, four GAd (referred as GAd-209-FSP) and 4 MVA (MVA-209-FSP) recombinant viral vector 
pairs were constructed, each encoding 45-59 predicted immunogenic recurrent dMMR neoantigens for a 
total of 209 predicted FSPs (named Nous-209 vaccine). Details on the list of FSP included in the vaccine 
are included in Nous-209 Investigator Brochure. 
 
The selection of FSPs included in the Nous-209 vaccine was validated by using an independent cohort of 
samples of MSI CRC patients. The presence of vaccine-encoded mutations was confirmed in this cohort at 
the same frequencies observed in the TCGA dataset. Importantly, none of the FS mutations were present in 
the normal adjacent mucosa of patients with MSI, highlighting the anticipated safety profile of the vaccine 
(Fig 2C) (30).  
 
Next, as proof of principle, the immunogenicity of Nous-209 was evaluated in CB6F1 mice using 
heterologous prime/boost regimen according to the scheme depicted in Fig 2D. Mice were primed at week 
0 with GAd-209-FSP. Two weeks later, a group of animals was sacrificed to evaluate GAd-primed immune 
responses, whereas a second group was boosted with a mix of the MVA-209-FSP. FSP-specific T-cell 
responses post prime (week 2) and post MVA boost (week 3) were measured by IFN-gamma ELISpot on 
splenocytes re-stimulated with peptides covering the entire neoantigenic sequence encoded by Nous-209 
(Fig 2B, 2C). Priming with GAd-209-FSP elicited a strong T-cell–mediated immunity. Responses were 
efficiently boosted by MVA-209-FSP, with approximately overall 10,000 SFCs/106 splenocytes (Fig 2D). 
In summary, Great Apes Adenovirus (GAd) and Modified Vaccinia Ankara Virus (MVA) vector 
vaccination of dMMR neoantigens can induce potent T cell immune responses in mice. 
 
 

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Evidence from first-in-human clinical study of Nous-209 
The first-in-human (FIH) phase I multicenter, open-label study of Nous-209 (NCT04041310) was designed 
to evaluate its safety, tolerability, immunogenicity, and efficacy in combination with pembrolizumab – a 
programmed cell death receptor-1 (PD-1)-inhibitor – for patients with unresectable or metastatic dMMR 
CRC, gastric cancers, and gastro-esophageal junction (G-E junction) cancers. Nous-209 was administered 
intramuscularly as a prime (GAd-209-FSP) dose followed by three booster (MVA-209-FSP) doses each 
given 3 weeks apart (Fig 3). Pembrolizumab was administered concomitantly at standard doses according 
to FDA approved label and schedule.  
 
This study enrolled participants in two cohorts: a “low-dose” escalation cohort and a “high-dose” expansion 
cohort, with the goal of selecting the recommended phase 2 dose (R2PD) of Nous-209. The target “high-
dose” was pre-specified as follows: 
 
x 
GAd20-209-FSP polyvalent vaccine: 1.88 x1011 viral particles (vp), comprising a mixture of 
equal amounts of GAd20-209-FSP-A1; GAd20-209- FSP-A2; GAd20-209-FSP-A3 and GAd20-
209-FSP-A4.  
Fig 2. Recurrent LS patient neoantigen viral vaccine immunogenicity. A. Schematic of Nous-209 vaccine. NousCom 
dMMR vaccine is composed of 4 GAd and 4 MVA vector pairs, each coding for ~50 FSP neo-antigens for a total of 209. Each 
neo-antigen is indicated by a different colored box. Paired GAd and MVA inserts encode the same set of neoantigens in 
different orders to minimize potential boosting of junctional epitopes between neoantigens. The four vector pairs are pooled 
together. B Scheme to identify the 209 FSPs included in Nous-209 vaccine from TCGA database. C. Validation of FSPs 
selection in MSI patients. Number of FSMs in Nous-209 that were detected on Exomeseq of tumor and healthy tissue from an 
independent cohort of CRC MSI patients. D. Immunogenicity of Nous-209 vaccine in mice. Schematic of immunization 
schedules and animal groups used. Nous-209 immunogenicity was measured on splenocytes of vaccinated mice by IFNȖ 
ELISpot at 2 weeks post prime with the four GAd vectors (GAd-209-FSP) and one week post boost with the four MVA vectors 
(MVA-209-FSP). T-cell responses after prime and prime/boost are expressed as the sum of IFNȖ SFCs/106 splenocytes to the 
16 pools of synthetic peptides covering the entire sequence of 209 FSPs. MNR, mono-nucleotide repeat. GAd, Great Apes 
adenovirus. MVA, modified vaccinia Ankara virus. 

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x 
MVA-209-FSPs polyvalent vaccine: 1.65x108 infectious units (ifu), comprising a mixture of 
equal amounts of MVA-209-FSP-B1; MVA-209-FSP-B2; MVA-209-FSP-B3 and MVA-209-FSP-
B4. 
 
Accordingly, “low-dose” was defined as 1/10th of the “high-dose” (i.e., one log difference in vaccine 
concentration). The target “high dose” was pre-selected based on safety and immunogenicity data obtained 
in previous human clinical trials with similar vectors at dosages equivalent to those planned for the FIH 
study of Nous-209 (as summarized in the Investigator’s Brochure).  
 
 
 
Preliminary safety, immunogenicity, and efficacy results of the FIH study have been reported (31, 32). Most 
recently, data from 12 evaluable participants (3 in the dose escalation cohort, and 9 in the dose expansion 
cohort) were analyzed as of the reported cut-off date (32). Two participants with LS were among these 12 
evaluable participants. With a median follow-up of 20.5 months in dose escalation cohort and 9.4 months 
in the dose expansion cohort, no dose limiting toxicities, treatment-related deaths, treatment-related adverse 
events leading to discontinuation of treatment, or serious adverse events were observed. All adverse events 
related to either GAd20-209-FSP or MVA-209-FSP were grade 1 or 2 (see Section 8.2 for further details).  
 
Immunogenicity was assessed by ex vivo IFN-Ȗ ELISpot on peripheral blood mononuclear cells (PBMCs) 
stimulated with 16 pools of overlapping peptides covering the entire vaccine sequence (Fig 4). Across 10 
participants with evaluable pre- and post-vaccination PBMC samples, immune response was induced in 
67% of participants treated with low-dose FSP-209, and 100% of participants treated with high-dose FSP-
209. Vaccine-induced immune responses were potent, with a mean of ~1,500 IFN-Ȗ SFCs/million PBMCs 
at the peak of the immune response. Based on these data, the target high-dose was selected as the RP2D. 
 
 
 
Day
1 
22 
43 
64 
85 
106 
127 148 
169 
190 
736 
Fig 3. Overall schematic of vaccine 
administration and safety/efficacy 
assessments in the FIH Nous-209 study 
(NCT04041310). GAd, Great Apes 
adenovirus. MVA, modified vaccinia Ankara 
virus. a-PD1, anti-programmed cell death 
receptor-1. DLT, dose-limiting toxicity  
Fig 4. Evaluation of vaccine-induced immunogenicity in the FIH 
Nous-209 study (NCT04041310). Peak immunogenicity was assessed by 
ex vivo IFN-Ȗ ELISpot on pre- and post-treatment PBMC from 10 
evaluable participants using 16 pools of overlapping peptides covering the 
entire Nous-209 FSP sequence. The number of spot-forming cells (SFCs) 
per million PBMCs corresponding to the sum of the responses to the 
single pools are shown. Dot plot represents peak responses for each 
individual subject (compared with baseline pre-vaccination responses 
(post pembrolizumab). Lines represent the mean of immune response.     

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The FIH study also provided early insights into the temporal dynamics of Nous-209-induced immunity. 
Briefly, in the context of participants with metastatic dMMR/MSI-H cancer, we observed an expected 
contraction of T cell immune response beginning at 6 months post-vaccination (Fig 5). With the expectation 
of further decline over time, this finding supports the need for future studies to explore optimal Nous-209 
revaccination schedules in specific disease contexts.   
 
 
 
 
 
2.3 
Rationale 
 
Vaccine-based immune interception of LS premalignancies 
Vaccination represents an important strategy to enhance T-cell immunity against infections and selected 
tumors (33, 34). Neoantigens are the preferred target antigen for prophylactic cancer vaccines. Specifically, 
neoantigens derived from indels within coding genes give rise to FSP comprised of novel sequences that 
are not represented in the human normal proteome and which, therefore, represent the safest and most 
immunogenic class of neoantigens.  
 
In this context, the Vilar-Sanchez laboratory performed whole transcriptomic analysis of 11 adenomas from 
patients with LS and 16 MMR-proficient adenomas from patients with familial adenomatous polyposis 
(FAP). This work revealed that LS adenomas have higher transcript levels of CD4 (consistent with more 
infiltrating CD4+ T-cells), IFNȖ (more activated CD4+/CD8+), PD-L1 (CD274) and LAG3 than sporadic 
MMR-proficient colon adenomas (Fig 1) (35). This finding is consistent with elevated T-cell immune 
surveillance of LS adenoma neoantigens.  
 
Importantly, the immunogenicity of FSP was demonstrated in T stimulation experiments using blood 
mononuclear cells isolated both from healthy donors and MSI-H cancer patients (36). Given the 
observations that LS malignancies contain greatly elevated numbers of neoantigens and that pre-malignant 
lesions have a less immunosuppressive microenvironment than advanced cancers, we propose that 
vaccination against LS-associated neoantigens represents a compelling approach for enhancing immune 
surveillance for LS immunoprevention. Furthermore, based on pre-clinical and clinical evidence outlined 
above, we hypothesize that vaccination with Nous-209 will induce immunogenicity in T-cells against 
recurrent MMR-deficient neoantigens contained in the vaccine. 
 
Fig 5. Serial evaluation of Nous-209-induced immunogenicity 
in the FIH Nous-209 study (NCT04041310). Lines represent the 
mean ex vivo IFN-Ȗ ELISpot response to 16 peptide pools covering 
the entire Nous-209 sequence. 

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Therefore, we have developed this phase Ib/II study with the primary goal of determining the safety and 
immunogenicity of Nous-209 vaccination as an “off-the-shelf” immune-interception strategy in LS 
participants.  
 
The dose of Nous-209 to be evaluated in our trial is the RP2D (i.e., high dose) from the aforementioned 
FIH phase 1 study (NCT04041310). Our intent is to balance the safety and immunogenicity of GAd-209-
FSP MVA-209-FSP, which is supported by results of the initial safety and efficacy analysis summarized in 
Section 2.2 above. Although no vaccine-related SAEs have been reported with Nous-209 in the FIH clinical 
trial (NCT04041310) (31, 32), the AE profile could be different in patients with LS without active cancer, 
who are likely to be more immunocompetent than patients with advanced metastatic cancers. Furthermore, 
despite the immunosuppressive environment commonly associated with metastatic cancers, Nous-209 is 
highly immunogenic as defined by the development of T cell responses to at least one FSP pool (31, 32). 
However, in the healthy LS population, the native antigenic load might be different, thus affecting 
immunogenicity and efficacy. Therefore, the clinical efficacy of Nous-209 in a healthy LS carrier 
population warrants separate investigation. 
 
Importantly, our study also aims to evaluate optimal approaches for maintaining long-term immunogenicity 
in healthy LS participants following initial vaccination with the Nous-209 GAd/MVA series. Specifically, 
we have noted that revaccination at regular intervals is a common approach to promote long-lasting recall 
of immune response and protection in the context of infectious diseases. As a pertinent example, Capone et 
al. (37) have evaluated the safety/tolerability and efficacy of revaccination using Ad and MVA-based 
vectors against Hepatitis C Virus (HCV) among healthy individuals. The Ad and MVA vectors used in their 
study were closely related to Nous-209 and participants were revaccinated with additional doses of Ad 
(prime, n = 9) and/or MVA (boost, n = 14) at varying time intervals (range 8 to 92 weeks). Revaccination 
with either Ad and MVA was well tolerated regardless of the number of administrations, the order in which 
they were administered, or the time interval between administration (Fig 6). The AE profiles of participants 
who received a second cycle of Ad (prime) and/or MVA (boost) vaccination were similar to those observed 
following initial vaccination. In addition, no serious AEs were observed. Among evaluable participants, 
revaccination with Ad and/or MVA resulted in expansion of vaccine-induced, HCV-specific T cells (Fig 
7).  
 
While we acknowledge that these data are limited, they highlight the need for further evaluation of Nous-
209 revaccination with GAd/MVA (i.e., prime/boost) versus MVA (i.e., boost) only in the context of 
healthy LS participants, where the goal is to further expand antigen-specific memory T cell response 
through revaccination of previously-vaccinated participants. As a co-primary endpoint of our study, we 
have evaluated the rate of adverse events among participants who thus far have received initial vaccination 
with GAd-209-FSP (prime) and MVA-209-FSP (boost) as of October 3rd, 2023. A summary of the number 
of participants with their maximum grade event is shown in the table below.  
 
 
Maximum Grade 
# Participants 
 
 
 
GAd-209-FSP (prime) 
3 
1 
 
2 
5 
 
1 
6 
 
TOTAL # Participants with AE 
12 
 
 
 
MVA-209-FSP (boost) 
2 
2 
 
1 
5 
 
TOTAL # Participants with AE 
7 
 

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Details on the specific Adverse Events experienced by participants after first dose (so called ‘prime’) and 
second dose (‘boost’) are provided in the following Tables. Overall, the rates of AEs has been low with no 
unexpected adverse events. A total of 112 adverse events have been observed in 12 participants since 
vaccination.  
  
Summary of Adverse Events by Grade/Relationship 
 
Time 
Grade 
Relationship 
# Events 
 
 
 
 
Post-Prime 
3 
Definite 
1 
 
3 
Unlikely 
2 
 
 
GRADE 3 TOTALS 
3 
 
 
 
 
 
2 
Definite 
10 
 
2 
Probable 
5 
 
2 
Possible 
2 
 
2 
Unlikely 
4 
 
2 
Unrelated 
2 
 
 
GRADE 2 TOTALS 
23 
 
 
 
 
 
1 
Definite 
37 
 
1 
Probable 
17 
 
1 
Possible 
3 
 
1 
Unlikely 
7 
 
1 
Unrelated 
1 
 
 
GRADE 1 TOTALS 
65 
 
 
 
 
Post-Boost 
2 
Definite 
4 
 
2 
Possible 
1 
 
 
GRADE 2 TOTALS 
5 
 
 
 
 
 
1 
Definite 
6 
 
1 
Probable 
6 
 
1 
Possible 
2 
 
1 
Unrelated 
2 
 
 
GRADE 1 TOTALS 
16 
 
The following four participants had adverse events that were considered definitely related to vaccination. 
 
Participants Experiencing Adverse Events Definitely Related to Vaccination 
 
PID 
Registration Date Date_Prime Date_Booster CTCAE_Term 
Onset_Date 
Grade 
time 
1 
11/10/2022 11/15/2022 
01/13/2023 
Injection site reaction 
01/18/2023 
2 
Post Boost 
 
  
 
Flu like symptoms 
11/16/2022 
2 
Post Prime 
 
  
 
Headache 
11/16/2022 
2 
Post Prime 
 
  
 
Fatigue 
11/16/2022 
2 
Post Prime 
 
  
 
Fever 
11/16/2022 
2 
Post Prime 

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PID 
Registration Date Date_Prime Date_Booster CTCAE_Term 
Onset_Date 
Grade 
time 
 
  
 
Chills 
11/16/2022 
3 
Post Prime 
2 
12/30/2022 01/19/2023 
03/16/2023 
Myalgia 
01/20/2023 
2 
Post Prime 
 
  
 
Injection site reaction 
01/20/2023 
2 
Post Prime 
 
  
 
Injection site reaction 
01/21/2023 
2 
Post Prime 
 
  
 
Fatigue 
01/20/2023 
2 
Post Prime 
 
  
 
Musculoskeletal and connective tissue 
disorder - Other, specify 
01/20/2023 
2 
Post Prime 
3 
01/18/2023 01/18/2023 
03/10/2023 
Urticaria 
03/10/2023 
2 
Post Boost 
 
  
 
Nausea 
03/10/2023 
2 
Post Boost 
 
  
 
Pruritus 
03/10/2023 
2 
Post Boost 
4 
03/04/2023 03/17/2023 
05/19/2023 
Headache 
03/18/2023 
2 
Post Prime 
 
The following two tables below show maximum toxicity reported. Only those toxicities experienced while on 
the trial are presented. Should a participant experience the same adverse event but at different grades (say 
headache at grade 2, 3 and 4), the participant is counted only at the highest (maximum) grade experienced 
(grade 4 in this case) for that event.  
 
Summary of Adverse Events – Prime Vaccine 
 
Adverse Event 
Grade of Toxicity 
Total 
1 (Mild) 
2 (Moderate) 
3 (Severe) 
Anorexia 
0 
1 
0 
1 
Arthralgia 
1 
0 
0 
1 
Back pain 
0 
1 
0 
1 
Bloating 
0 
1 
0 
1 
Blurred vision 
1 
0 
0 
1 
Bruising 
1 
0 
0 
1 
Chills 
4 
0 
1 
5 
Diarrhea 
1 
0 
0 
1 
Dizziness 
0 
1 
0 
1 
Dyspnea 
1 
0 
0 
1 
Fatigue 
7 
3 
0 
10 
Fever 
6 
2 
0 
8 
Flu like symptoms 
0 
1 
0 
1 
Gastrointestinal disorders - Other, specify 
1 
0 
0 
1 
Headache 
6 
2 
1 
9 
Injection site reaction 
6 
1 
0 
7 
Muscle cramp 
0 
1 
0 
1 
Musculoskeletal and connective tissue disorder - Other, specify 
0 
1 
0 
1 
Myalgia 
5 
2 
1 
8 
Nausea 
4 
0 
0 
4 
Pain 
1 
0 
0 
1 
Pain of skin 
1 
0 
0 
1 
Palpitations 
1 
0 
0 
1 
Respiratory, thoracic and mediastinal disorders - Other, specify 
1 
0 
0 
1 
Sinusitis 
0 
1 
0 
1 

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Summary of Adverse Events – Boost Vaccine 
 
Adverse Event 
Grade of Toxicity 
Total 
1 (Mild) 
2 (Moderate) 
Arthralgia 
1 
0 
1 
Bruising 
1 
0 
1 
Fatigue 
2 
0 
2 
Headache 
1 
0 
1 
Infections and infestations - Other, specify 
1 
0 
1 
Injection site reaction 
2 
1 
3 
Musculoskeletal and connective tissue disorder - Other, specify 
1 
0 
1 
Myalgia 
2 
0 
2 
Nausea 
0 
1 
1 
Pain in extremity 
0 
1 
1 
Pain of skin 
1 
0 
1 
Pruritus 
0 
1 
1 
Respiratory, thoracic and mediastinal disorders - Other, specify 
1 
0 
1 
Urticaria 
0 
1 
1 
 
 
 
 
Fig 6. Reboosting with Ad and MVA 
is safe and well tolerated (Capone et 
al., Vaccines, 2020). The percentage 
of volunteers reporting an adverse 
event following 1st (1) or 2nd (2) 
vaccination with Ad (top) or MVA 
(bottom) against HCV. Severity 
moderate (grade1, green), mild (grade 
2, yellow), and severe (grade 3, red) 

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Our study will aim to have broad eligibility. Namely, we will not exclude participation of LS carriers on 
the basis of harboring specific MMR germline alterations, and neither will we exclude LS carriers with a 
prior personal history of premalignancy or malignancy. Nonetheless, it is important to acknowledge that 
the distinct biological and clinical features associated with right-sided versus left-sided colonic malignancy 
adds significant complexity to the development of effective immunoprevention strategies. Moreover, in LS 
carriers with a history of colorectal malignancy, primary treatment is likely to have included surgical 
resection by a variety of approaches depending on the anatomic location of the tumor (e.g., extended right 
or left hemicolectomy or partial colectomy, sigmoidectomy, or low anterior resection). To minimize the 
confounding effects of this biological and clinical heterogeneity, a subset of the secondary objectives in our 
study are focused on understanding the immunogenicity of Nous-209 vaccination at the level of the 
rectosigmoid colon (up to 25 cm from the anal verge), which is likely to be present in the majority of LS 
carriers even after primary treatment.  
 
Our study will be conducted within the context of the NCI CP-CTNet with at least 4 active academic 
Clinical Cancer Genetics Programs with a history of participation in major national and international 
clinical trials for hereditary cancer syndromes.  
 
As we explore the efficacy of vaccine-based immunoprevention strategies, it is notable that relatively few 
data exist regarding the prevalence and incidence rate of premalignant lesions in patients with LS. Based 
on results of the CAPP-2 study, which examined the prevalence of adenomas and hyperplastic polyps in 
mutation positive carriers of LS, approximately 10% of and 5% of LS patients presented with adenomatous 
polyps and hyperplastic polyps in their first colonoscopy in the CAPP-2 study, respectively. In addition, 
aspirin did not modify the development of adenomas in the CAPP-2 study but provided a reduction of CRC 
incidence of approximately 50% (IRR 0.56). 
 
Lastly, increasing evidence suggests that tobacco and alcohol use are risk factors in the development of 
intraepithelial neoplasia and cancer. In addition, tobacco and alcohol use may adversely affect agent 
intervention, for example by altering the safety profile or metabolism of a drug. Standardized assessments 
of tobacco and alcohol use during clinical trials will provide a better understanding the potential relationship 
Fig 7. Evaluation of Ad/MVA versus 
only MVA revaccination against HCV 
in healthy volunteers (Capone et al., 
Vaccines, 2020). The total ex vivo T 
cell response to the non-structural (NS) 
region of HCV encoded within the 
vaccine is shown over time (IFNȖ 
ELISpot; spot forming cells per 106 
PBMC). 

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between the use of these products and clinical endpoints or cancer prevention biomarkers. Therefore, this 
clinical trial will be including assessment of tobacco and alcohol use at baseline and at completion of the 
study follow-up period to determine the potential impact of tobacco and alcohol use on 1) treatment toxicity 
and symptom burden, and 2) the efficacy of treatment intervention.  
 
3. 
SUMMARY OF STUDY PLAN 
 
3.1 
Study Design & Objectives 
Our study is a phase Ib/II open-label, multicenter prevention study of Nous-209 vaccination as an immune-
interception agent in individuals with LS. The study will be performed in two parts: 
 
x 
Cohort 1 [initial vaccination] includes participants who have not previously received Nous-209 
(either as monotherapy or combination). All eligible participants in Cohort 1 will receive one cycle 
of Nous-209 prime-boost immunization.  
 
x 
Cohort 2 [revaccination] is comprised of eligible participants from Cohort 1 who received one 
complete cycle of Nous-209 prime-boost immunization and for whom peak vaccine-induced 
immune responses have been detected. Participants in Cohort 2 will be randomized to one of two 
revaccination schedules with Nous-209 prime and/or boost.  
 
Considering both Cohorts 1 and 2, the primary objectives of the study are to evaluate the safety, tolerability, 
and immunogenicity of GAd20-209-FSPs (1 prime) and MVA-209-FSPs (1 boost) vaccination when 
administered as a single agent (monotherapy) among participants with LS. The secondary objectives are to 
evaluate the effects of Nous-209 vaccination on a) T cell immune profile and T cell receptor (TCR) 
repertoire in peripheral blood; b) TCR repertoire within histologically normal colorectal mucosa; c) tumor 
infiltrating lymphocyte (TIL) immune profile and TCR repertoire within colorectal adenomas; d) 
cytotoxicity of T cells on matched participant-derived colorectal adenoma organoids; e) the burden of 
colorectal adenomas/advanced neoplasia/carcinoma; f) burden of LS-related carcinomas; g) cell free DNA 
(cfDNA) mutation profiles and cfDNA burden in participants with LS; h) to correlate tobacco and alcohol 
consumption with the immune response to Nous-209 in trial participants; and i) to assess the MMR and/or 
MSI status of polyps (and adjacent normal mucosa as control) detected in the baseline and end-of-the-study 
colonoscopy using different technologies such as immunohistochemistry, MSI analysis by PCR, or next-
generation sequencing.  
 
Considering Cohort 2, our additional co-primary objective is to ascertain an optimal revaccination schedule 
for Nous-209 by evaluating the safety, tolerability, and neoantigen-specific immunogenicity of GAd20-
209-FSP prime plus MVA-209-FSP boost or MVA-209-FSP boost alone when readministered to previously 
vaccinated participants with LS. 
 
3.2 
Study Population 
 
For Cohort 1 [initial vaccination], our study population is comprised of individuals aged 18 years or older 
with a diagnosis of LS as determined based on phenotypic and/or genetic criteria. Eligible participants will 
be those who a) have no active or recurrent invasive malignancy; b) must be at least 6 months from receipt 
of prior cancer-directed therapy, if any; and c) must have an intact rectosigmoid colon. With an estimated 
attrition rate of 20%, we will enroll a maximum of 45 participants to the study intervention in order to reach 
our target of 36 evaluable participants. To account for participants who may be deemed ineligible after 
consent, we may consent up to 60 individuals to achieve our target of 45 enrolled participants. 
 
For Cohort 2 [revaccination], our study population represents a subset of individuals who were enrolled 

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into Cohort 1. Specifically, we will be sequentially enrolling eligible participants who a) received a 
prime/boost vaccination cycle in Cohort 1; and b) for whom peak immunogenicity responses (Week 9 of 
Cohort 1) are proved by ELISPOT assay. We will enroll 28 participants to Cohort 2 with the goal of 
reaching 24 evaluable participants.  
 
3.3 
Interventions 
 
Cohort 1 [initial vaccination]: At Baseline, all participants will undergo standard-of-care (SOC) lower 
endoscopy (colonoscopy or flexible sigmoidoscopy) for screening, polyp removal, and research tissue 
collection. Participants will also have screening at baseline. Upon confirmation of eligibility, enrolled 
participants will receive Nous-209 vaccination according to the schedule as outlined in Fig 8. The initial 
(priming) vaccination (GAd20-209-FSPs) will be given on day 1 followed by booster (MVA-209-FSPs) at 
Week 8. Research blood samples will be collected for biomarker assays and AE monitoring on Day 1 (Visit 
1), Week 3, Week 8, Week 9, Month 6, and Month 12 (Week 52). All participants who will complete the 
study in Cohort 1 and who will not continue in Cohort 2 will undergo SOC lower endoscopy (colonoscopy 
or flexible sigmoidoscopy) with research tissue biopsies collected at Month 12.  
 
Cohort 2 [revaccination]: Eligible participants will undergo research blood collection at Month 12 (Week 
52) in accordance with study-related procedures for Cohort 1. Participants will then be randomly assigned 
(in a 1:1 ratio) to one of two revaccination schedules: 
 
x 
Arm A: GAd20-209-FSP prime and MVA-209-FSP boost 
x 
Arm B: MVA-209-FSP boost only 
 
As outlined in Fig 9, participants in Arm A will receive GAd20-209-FSP prime at Week 52, followed by 
MVA-209-FSP boost at Week 60. Participants in Arm B will receive MVA-209-FSP boost at Week 52. 
Research blood samples will be collected for biomarker assays at Weeks 52, 60 and 68. All participants in 
Cohort 2 will undergo SOC lower endoscopy (colonoscopy or flexible sigmoidoscopy) with research tissue 
biopsies collected at Week 68 instead of Week 52.  
Fig 8. Trial schema with basic procedures and timeline. Accrual duration: 18 mo accrual + 24 mo follow-up. Figure created with 
BioRender 

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4. 
PARTICIPANT SELECTION 
 
 
4.1 
Inclusion Criteria for Participants in Cohort 1 
 
4.1.1 
Participants must have a clinical diagnosis of Lynch Syndrome (LS) as defined by: 
 
a) Mutation-positive LS: documented carriers (or obligate carriers by pedigree) of a germline 
mutation in MMR genes (MLH1, MSH2/EPCAM, MSH6, or PMS2) that is deleterious/pathogenic 
or suspected to be deleterious/pathogenic (known or predicted to be detrimental/loss of function, 
respectively). The mutation must have been identified through a CLIA-approved laboratory setting 
or an equivalent international agency. Final determination of eligibility for any discordant results 
in pathogenicity of the mutation will be determined by the study investigator. A formal eligibility 
exception in those instances will not be required as long as approval by the overall study PI has 
been granted and documented. 
 
b) Mutation-negative LS (also known as “Lynch-like Syndrome” or “suspected Lynch 
Syndrome): individuals with both of the following: 
 
(i) 
 a personal history of a non-sporadic MMR-deficient premalignant lesion (i.e., colorectal 
polyp) or a non-sporadic MMR-deficient malignant tumor, where “non-sporadic MMR 
deficiency” is defined by (1) the loss of MLH1, MSH2, MSH6, or PMS2 expression by 
immunohistochemistry (IHC), or (2) the detection of MSI  by PCR or both, but no evidence 
of MLH1 promoter methylation in cases with loss of both MLH1 and PMS2, All testing 
must have been performed in accordance with local institutional guidelines in a CLIA-
approved setting. (Note: central confirmation of MMR expression status, MSI, MLH1 
promoter methylation or BRAF mutation is not required.); and 
 
(ii) 
 documented results of germline mutation testing performed in a CLIA-approved 
laboratory environment, demonstrating either a variant of unknown significance in MMR 
genes or the lack of a clinically significant variant in MMR genes; or, documentation that 
the individual declined to undergo germline MMR genetic testing. 
Fig 9. Trial schema for Cohort 2 [revaccination]. 

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4.1.2 
Participants must have no evidence of active or recurrent invasive cancer for 6 months prior to 
screening.  
 
4.1.3 
Participants must be at least 6 months from any prior cancer-directed treatment (such as surgical 
resection, chemotherapy, immunotherapy, hormonal therapy, or radiation). 
 
4.1.4 
Participants must have endoscopically accessible distal colon and/or rectal mucosa (i.e., 
participants must have at least part of the descending/sigmoid colon and/or rectum intact). 
 
4.1.5 
Participants must consent to standard of care surveillance with colonoscopy with biopsies every 12 
months. 
 
4.1.6 
Participants must consent to refrain from using aspirin or non-steroidal anti-inflammatory drugs 
(NSAIDs) or cyclooxygenase (COX) inhibitors for the duration of the trial, except for cardio-
preventive aspirin (<100 mg daily). Individuals taking such drugs may not be enrolled unless they 
are willing to stop the medications (and possibly change to alternative non-excluded medications 
to treat the same conditions) no less than 1 month prior to enrollment. Participants will discuss with 
their primary care provider/local provider about the discontinuation of such medication(s) and 
obtain approval prior to stopping any agent. 
 
4.1.7 
Age  18 years. Because no dosing or adverse event (AE) data are currently available on the use of 
Nous-209 in participants <18 years of age, children are excluded from this study but will be eligible 
for future pediatric trials, if applicable. 
 
4.1.8 
ECOG performance status 1 (Karnofsky 70%; see Appendix A) 
 
4.1.9 
Participants must have normal organ and marrow function as defined below: 
 
Hemoglobin 
>10 g/dL or Hematocrit > 30 % 
Leukocyte count 
3,500/microliter 
Platelet count 
100,000/microliter 
Absolute neutrophil count 
1,500/microliter 
estimated glomerular filtration rate (eGFR) 
[or creatinine clearance calculated using the 
Cockcroft-Gault equation] 
60 mL/min/1.73m2  
 
[mL/min, within institutional limits 
of normal] 
AST (SGOT)/ALT (SGPT) 
2 times the institutional upper 
limit of normal (ULN) 
Total bilirubin 
1.5 the ULN; participants with 
Gilbert’s disease may be enrolled 
with higher Total bilirubin if their 
Direct bilirubin is  1.5 times the 
ULN. 
 
4.1.10 Participants must consent to refrain from receiving any other type of vaccination during the first 10 
weeks of the trial. 
 

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4.1.11 Participants must consent to refrain from receiving adenoviral-based vaccines for the duration of 
the trial (including the period from week 9 to week 52). 
 
4.1.12 Willing and able to adhere to the prohibitions and restrictions specified in the final approved 
protocol. 
 
4.1.13 The effects of Nous-209 on the developing human fetus at the recommended therapeutic dose are 
unknown. For this reason, women of child-bearing potential and men must agree to use adequate 
contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the 
duration of study participation (12 months) and 6 months after end of study. Should a woman 
become pregnant or suspect she is pregnant while participating in this study, she should inform her 
study physician immediately. 
 
4.1.14 Ability to understand and the willingness to sign a written informed consent document (available 
for both English- and Spanish-speaking individuals). 
 
 
4.2 
Inclusion Criteria for Participants in Cohort 2 
 
4.2.1 
Participants must have been confirmed eligible and met all study inclusion criteria for participation 
in study Cohort 1.  
 
4.2.2 
Participants must have completed all baseline procedures and received a complete cycle of GAd20-
209 FSP (prime) and MVA-209-FSP (boost) vaccination per protocol for Cohort 1. 
 
4.2.3 
Participants must have undergone collection of research blood samples at Baseline (Week 0) and 
Week 9 for evaluation of the Nous-209-induced immunogenicity endpoint as specified for Cohort 
1. Only participants with evaluable and proved immunogenicity response at Week 9 are eligible for 
participation in Cohort 2.  
 
4.2.4 
Participants must consent to refrain from receiving any other type of vaccination during Weeks 52 
to 68 of the trial. 
 
4.2.5 
Participants must consent to refrain from receiving adenoviral-based vaccines for the duration of 
the trial (including the period from Week 52 to Week 68). 
 
4.2.6  Participants must consent to refrain from using aspirin or non-steroidal anti-inflammatory drugs 
(NSAIDs) or cyclooxygenase (COX) inhibitors for the duration of the cohort 2, except for cardio-
preventive aspirin (<100 mg daily). Individuals taking such drugs may not be enrolled unless they 
are willing to stop the medications (and possibly change to alternative non-excluded medications 
to treat the same conditions) no less than 1 month prior to enrollment. Participants will discuss 
with their primary care provider/local provider about the discontinuation of such medication(s) 
and obtain approval prior to stopping any agent. 
 
4.2.7 
Female participant must agree to a pregnancy test at week 52. 
 
 
4.3 
Exclusion Criteria  
Note:  Unless otherwise indicated, exclusion criteria are verified at entry into Cohort 1. 
 

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4.3.1 
Prior receipt of a recombinant adenoviral or MVA vaccine including COVID-19 Adenovirus 
vaccines within the previous 6 months. 
 
4.3.2 
Histologically-confirmed high-grade dysplasia or cancer on biopsy at screening. 
 
4.3.3 
Individuals with active malignancy (excluding non-melanoma skin cancer). 
 
4.3.4 
Any serious uncontrolled and/or unstable pre-existing medical disorder (aside from malignancy 
exception above), psychiatric disorder, or other conditions that could interfere with participant’s 
safety, obtaining informed consent, or compliance to the study procedures. 
 
4.3.5 
Active infection (acute and self-limited) or Human Immunodeficiency Virus (HIV), Hepatitis B 
virus (HBV), or Hepatitis C virus (HCV) infection. Participants with laboratory evidence of cleared 
HBV and HCV infection will be permitted. 
 
4.3.6 
History of organ allograft or other history of immunodeficiency.  
 
4.3.7 
Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically 
related to study drug, excipients, or to egg proteins. 
 
4.3.8 
Individuals with a condition requiring systemic treatment with either corticosteroids (>10 mg daily 
prednisone equivalents) or other immunosuppressive medications (such as infliximab, rituximab, 
adalimumab, tacrolimus) within 14 days of study drug administration. Inhaled or topical steroids 
and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence 
of active autoimmune disease. 
 
4.3.9 
Pregnant or breastfeeding or planning to become pregnant within 6 months after the end of study. 
Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment 
of the mother with Nous-209, breastfeeding should be discontinued if the mother is treated with 
Nous-209. 
 
4.3.10 Men attempting or planning to conceive children during the study or within 6 months after the end 
of the study. 
 
4.3.11 Participants may not be receiving any other Investigational Agents. 
 
4.3.12 Cohort 2 only: participants who experienced grade 3 or higher AE(s) attributed to study drug in 
Cohort 1, excluding reactogenicity events as defined in Section 13.1. 
 
 
4.4 
Inclusion of Women and Minorities 
 
Our study will include adult (age 18 years) men and women of all races and ethnic groups and who are 
deemed eligible. Children will not be recruited to the trial. Our recruitment strategies, including minority 
recruitment, will include identifying participants through The University of Texas MD Anderson Cancer 
Center Familial High-Risk Gastrointestinal Cancer Clinic, Houston, TX; University of Puerto Rico, San 
Juan, PR; Fox Chase Cancer Center, Philadelphia, PA; City of Hope National Medical Center, Duarte, CA. 
Our other sources of recruitment will involve working with the minority community and social network 
groups available at each accruing site within the US. We will advertise the study on minority and other 
national websites. Furthermore, our informed consent form will be available in both English and Spanish. 

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Site staff will be directed to pay special attention to the nature of any disadvantage that potential participants 
may have, and consider their respective unique needs and vulnerabilities. Consequently, potential 
participants will receive explanation of the costs of participating in the trial in detail. They will receive 
explanation the of trial and related procedures in lay language. In addition, when available, family members 
and caretakers will be in the consent discussion, and will be informed that the protocol allows assent and 
permits Legally Authorized Personnel. 
 
 
4.5  
Recruitment  
 
This multicenter protocol will be conducted at the following sites: UT MD Anderson Cancer Center, 
Houston, TX; Fox Chase Cancer Center, Philadelphia, PA; City of Hope National Medical Center, Duarte, 
CA; and University of Puerto Rico, San Juan, PR. Efforts will be made to enroll participants from diverse 
ethnic and socio-economic backgrounds. Prior to enrollment on the study, the physician and/or study 
personnel will discuss the study protocol in detail with the participant, including possible toxicities. The 
informed consent document will be reviewed by study personnel with the participant.  To facilitate accrual, 
information about the trial will be advertised, for example, on the websites of participating institutions and 
through social media channels. Recruitment and retention efforts will be evaluated routinely by site 
coordinators and study staff members. The study recruitment and retention plan will be modified as 
necessary to promote rapid accrual. Please refer to the study-specific Recruitment and Retention Plan for 
more details. 
 
4.6  
Planned Accrual 
 
Lynch syndrome has no known racial proclivity.   Previous studies have reported on only a modest number 
of African American and Hispanic families with Lynch syndrome.  Thus, we will project that the targeted 
number of participants from ethnic and racial subpopulations in our study will be proportionate to the 
prevalence distribution of the study cohort in the U.S. population. The planned enrollment estimates are 
shown below. 
 
 
DOMESTIC PLANNED ENROLLMENT REPORT 
Racial Categories 
Not Hispanic or 
Latino: 
Female 
Not Hispanic or 
Latino: 
Male 
Hispanic or 
Latino: 
 
Female 
Hispanic or 
Latino: 
 
Male 
 
Total 
American Indian/Alaska Native 
1 
0 
0 
0 
1 
Asian 
0 
1 
0 
0 
1 
Native Hawaiian or Other Pacific 
Islander 
0 
1 
0 
0 
1 
Black or African American 
2 
1 
0 
0 
3 
White  
16 
17 
2 
2 
37 
More Than One Race 
1 
1 
0 
0 
2 
Total 
20 
21 
2 
2 
45 
 
Note: The Planned Enrollment Report table has been revised with the protocol version dated 09/10/2024. The 
calculations have been adjusted to match the Black or African American enrollment projections to the ethnic and 
racial subpopulations of the States in which the study is conducted: California (5% Black or African American); 
Pennsylvania and Texas (12% of Black or African American); and Puerto Rico (17% of Black or African 
American). Given the historical barriers to Black or African American participant accrual to clinical trials (48), the 
goal was further adjusted to 3. 
 

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5. REGISTRATION PROCEDURES 
 
5.1 
Investigator and Research Associate Registration with CTEP 
 
Food and Drug Administration (FDA) regulations require IND sponsors to select qualified investigators.  
NCI policy requires all persons participating in any NCI-sponsored clinical trial to register and renew their 
registration annually which is done via the Registration and Credential Repository (RCR). 
 
To register, all individuals must obtain a Cancer Therapy Evaluation Program (CTEP) Identity and Access 
Management (IAM) account (https://ctepcore.nci.nih.gov/iam). In addition, persons with a registration type 
of Investigator (IVR), Non-Physician Investigator (NPIVR), or Associate Plus (AP) (i.e., clinical site staff 
requiring write access to Rave or acting as a primary site contact) must complete their annual registration 
using CTEP’s web-based Registration and Credential Repository (RCR) (https://ctepcore.nci.nih.gov/rcr). 
Documentation requirements per registration type are outlined in the table below. 
 
Documentation 
Required 
IVR 
(Investigator) 
 
 
NPIVR 
(Non-
physician 
Investigator) 
 
 
AP 
(Associate 
Plus) 
A 
(Associate) 
 
 
AB 
(Associate 
Basic) 
FDA Form 1572 
D 
D 
 
 
 
Financial Disclosure 
Form 
D 
D 
D 
 
 
NCI Biosketch 
(education, training, 
employment, license, and 
certification) 
D 
D 
D 
 
 
GCP training 
D 
D 
D 
 
 
CV (optional) 
D 
D 
D 
 
 
 
An active CTEP-IAM user account and appropriate RCR registration is required to participate in all CP-
CTNet clinical trials.   
 
All personnel directly involved in the performance of procedures required by the protocol and the collection 
of data should be registered in the RCR.  
 
Personnel associated with the five registration types include, but is not limited to, the following: 
 
x 
Investigator (IVR) — MD, DO, or international equivalent. 
x 
Non-Physician Investigator (NPIVR) — advanced practice providers (e.g., NP or PA) or graduate 
level researchers (e.g., PhD). 

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x 
Associate Plus (AP) — clinical site staff (e.g., RN or CRA) with data entry access to RAVE. Also 
includes site administrator, data administrator, and consenting person. Individuals with an auditing role 
should register as an AP. 
x 
Associate (A) — other clinical site staff involved in the conduct of NCI-sponsored trials.  
x 
Associate Basic (AB) — individuals (e.g., pharmaceutical company employees) with limited access to 
NCI-supported systems. 
In addition, the site-protocol Principal Investigator (PI) must meet the following criterion: 
x 
Active registration status 
x 
The IRB number of the CIRB (IRB of record) listed on their Form FDA 1572 
 
Additional information can be found on the CTEP website at 
https://ctep.cancer.gov/investigatorResources/default.htm. For questions, please contact the RCR Help 
Desk by email at RCRHelpDesk@nih.gov. 
 
 
6. NCI CENTRAL INSTITUTIONAL REVIEW BOARD 
 
The NIH policy on the Use of a Single Institutional Review Board for Multi-Site Research 
https://grants.nih.gov/grants/guide/notice-files/not-od-16-094.html became effective on January 25, 2018. 
In compliance with this policy, NCI Central IRB (NCI CIRB) is the sole IRB of record for all accruing sites 
conducting clinical trials through the CP-CTNet, all CP-CTNet U.S.-based sites must be members of the 
NCI Central Institutional Review Board (NCI CIRB), and utilize the Cancer Prevention and Control CIRB 
as their IRB of record. International sites should submit Research Ethics Board (REB) approval to the DCP 
Regulatory contractor following country-specific regulations. 
 
Signatory Institutions must submit a Study Specific Worksheet (SSW) to the CIRB via IRBManager to 
indicate their intent to open the study locally. The CIRB’s approval of the SSW is then communicated to 
the PIs at the Signatory Institution and the Regulatory Contractor. In order for the SSW approval to be 
processed, the Signatory Institution must inform which CIRB-approved institutions aligned with the 
Signatory Institution are participating in the study. 
 
Should changes to the study become necessary, protocol amendments will be submitted to the DCP PIO 
according to DCP Amendment Guidelines. The DCP-approved amended protocol must be approved by the 
CIRB prior to implementation. 
 
 
7. 
AGENT ADMINISTRATION 
 
The study agent will be administered on an outpatient basis. Reported AEs and potential risks are described 
in Section 8.2.  
 
 
7.1 
Dose Regimen and Dose Groups 
 
For Cohort 1 [initial vaccination], our study will be conducted as a single-arm, open-label, non-randomized 
intervention trial. As such, all eligible study participants in Cohort 1 will be assigned to a single treatment 
group and receive Nous-209 vaccination as follows: 
 

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x 
Week 0 (Day 1): GAd20-209-FSPs (prime)  
x 
Week 8: MVA-209-FSPs (boost) 
 
For Cohort 2 [revaccination], we will conduct an open-label, randomized intervention. 28 eligible 
participants in Cohort 2 will be randomly assigned to one of two treatment groups for revaccination (Arm 
A or B) as follows: 
 
Arm A: 
x 
Week 52: GAd20-209-FSPs (prime) 
x 
Week 60: MVA-209-FSPs (boost) 
 
Arm B: 
x 
Week 52: MVA-209-FSPs (boost) 
 
GAd20-209-FSP polyvalent vaccine comprises 4 replication-incompetent gorilla-derived Great Apes 
Adenoviruses (GAd20). GAd20-209-FSP polyvalent vaccine is formulated in A195 buffer at the nominal 
concentration of 2x1011 viral particles (vp)/mL. The vaccine is vialed in 3 mL Borosilicate Type 1 glass 
vials.  Each vial is used to prepare the vaccine dose for one participant. The vial is wasted after one 
participant dose preparation and not stored.  
 
MVA-209- FSP polyvalent vaccine comprises 4 attenuated, replication-defective orthopoxvirus, Modified 
Vaccinia virus Ankara (MVA). MVA-209-FSP polyvalent vaccine is formulated in MVA buffer at the 
nominal concentration of 2x108 infectious units (ifu)/mL. The vaccine is vialed in 3 mL Borosilicate Type 
1 glass vials. Each vial is used to prepare the vaccine dose for one participant. The vial is wasted after one 
participant dose preparation and not stored. 
 
Both vaccines must be administered as a single 1 mL-dose corresponding to the nominal concentration of 
2x1011 vp/mL for GAd20-209-FSP and 2x108 ifu/mL for MVA-209-FSP for intramuscular injection. 
 
GAd20-209-FSP and MVA-209-FSP are manufactured under Good Manufacturing Practice (GMP) 
conditions at Reithera GMP facility (Via di Castel Romano 100, 00128 Rome, Italy).  
 
 
7.2 
Nous-209 Vaccine Administration 
 
On the day of vaccination, GAd20-209-FSP (prime) and MVA-209-FSP (boost) vaccines will be allowed 
to thaw at room temperature and administered within 1 hour from thawing. Each vaccine will be 
administered intramuscularly over the deltoid region of the arm at the time points detailed in Section 9. The 
injection volume is 1 mL.  
 
The medical professional performing the procedure must wear gloves and appropriate eye protection. The 
2 vaccines (1 prime and 1 boost) will be administered each time on the contralateral arm compared to the 
previous administration. In the event that the investigator finds the injection location inappropriate (i.e., 
due to the loss of muscle mass of the deltoid region), then the vaccination can be performed by injection in 
the participant’s femoral quadriceps region.  
 
During the administration of the vaccines, appropriate medicines and resuscitation equipment must be 
immediately available for the management of anaphylaxis. In particular epinephrine and equipment for 
maintaining an airway should be available for immediate use. Following vaccination, participants must 
remain 1 hour in the unit for observation. The timing of 1 hour is considered adequate for the acute vaccine 

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reactions management [General Recommendations on Immunization: Recommendations of the Advisory 
Committee on Immunization Practices (ACIP) January 28, 2011].  
 
To minimize dissemination of the recombinant vectored vaccine virus into the environment, the inoculation 
site must be fully covered with an appropriate dressing immediately following immunization. This should 
absorb any virus that may leak out through the needle track. The dressing will be removed from the injection 
site and disposed as GMO waste, in accordance with the current standard US practice.  
 
 
7.3 
Run-in Procedures  
 
A placebo run-in phase will not be used in this study. 
 
 
7.4 
Contraindications 
 
x 
Participants should not be breast-feeding.   
x 
Women of child-bearing potential and men must agree to use adequate contraception (hormonal 
or barrier method of birth control; abstinence) prior to study entry, for the duration of study 
participation (12 months) and 6 months after end of study. Should a woman become pregnant or 
suspect she is pregnant while participating in this study, she should inform her study physician 
immediately. 
 
 
7.5 
Concomitant Medications 
 
All medications (prescription and over-the-counter), vitamin and mineral supplements, and/or herbs taken 
by the participant will be documented and will include: 1) start and stop date, dose and route of 
administration, and indication.  
 
Participants must refrain to receive any other type of vaccination during the first 10 weeks of the trial. In 
addition, participants must refrain from using aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) 
or cyclooxygenase (COX) inhibitors for the duration of the trial, except for cardio-preventive aspirin (<100 
mg daily) during the first 10 weeks of the trial. Individuals taking such drugs may not be enrolled unless 
they are willing to stop the medications (and possibly change to alternative non-excluded medications to 
treat the same conditions) no less than 1 month prior to enrollment. Participants will discuss with their 
primary care provider/local provider about the discontinuation of such medication(s) and obtain approval 
prior to stopping any agent. 
 
 
7.6 
Dose Modification 
 
Every effort must be made to administer the GAd20-209-FSP and MVA-209-FSP according to the protocol-
mandated schedule outlined in Section 9. Schedule modifications or dose reductions of GAd20-209-FSP 
and MVA-209-FSP are not permitted in individual participants.  
 
In the event of hypersensitivity reactions following the administration of GAd20-209-FSP and MVA-209-
FSP, the participant should be treated according to best medical practice. Acute Hypersensitivity Reactions 
including anaphylaxis may occur after vaccine injections, therefore appropriate resuscitation equipment 
should be available at the bedside and a physician readily available during the vaccine administration and 

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during the first hours after vaccination. All participants should be instructed to immediately report to the 
Investigator any delayed hypersensitivity reactions, which may manifest as: 
 
x 
Decreased oxygen saturations (<92%) on room air  
x 
Confusion  
x 
Lethargy  
x 
Hypotension  
x 
Pale or clammy skin  
x 
Cyanosis  
x 
Bronchospasm  
 
In the event of any such clinical findings and suspicion of a severe hypersensitivity reaction, either acute 
of delayed, participants must be immediately admitted to hospital for observation and monitoring. 
Participants who experience a severe hypersensitivity reaction following administration of GAd20-209-
FSP will not receive MVA-209-FSP.  
 
Exclusive of reactogenicity symptoms (defined in Section 13.1), participants who experience grade 2 
adverse events attributed to study drugs (GAd20-209-FSP and/or MVA-209-FSP) persisting > 48 hours or 
any grade 3 or higher adverse event attributed to study drugs following administration should receive no 
further doses.  
 
 
7.7 
Adherence/Compliance 
 
7.7.1 
Definition of Compliance 
 
Participants who receive at least the GAd20-209-FSP (prime) dose will be included in the evaluation of our 
safety-related endpoints. In addition, for Cohort 1, we will define compliance as receiving both the GAd20-
209-FSP (prime) and MVA-209-FSP (boost) vaccine administrations. 
 
In Cohort 2, participants who receive at least the GAd20-209-FSP (prime) dose in Arm A or MVA-209-
FSP (boost) in Arm B will be included in the evaluation of our safety-related endpoints. In addition, for 
Cohort 2, we will define compliance as receiving either both the GAd20-209-FSP (prime) and MVA-209-
FSP (boost) vaccine administrations in Arm A or MVA-209-FSP (boost) vaccine administrations in Arm 
B. 
 
7.7.2 
Monitoring of Compliance 
 
Adherence will be monitored during each study visit. Adherence will be measured by the proportion of 
missed appointments and drop-out rates. Participants will have a grace period of 7-14 days after the 
scheduled vaccination time. Adherence rates will be reported descriptively. 
 
For our biomarker-driven endpoints, we perform analyses in two levels: first, by including all participants, 
both compliant and non-compliant (i.e., intention-to-treat principle); and second, by including only 
participants who met the definition of compliance. 
 
 
8. 
PHARMACEUTICAL INFORMATION 
 
8.1 
Nous-209 Vaccine   

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Nous-209 is a neoantigen vaccine composed of two different products (GAd20-209-FSP and MVA-209-
FSP polyvalent vaccines) which are designed to be used in a heterologous prime/boost modality. The 
GAd20 and MVA viral vectors encode for a set of 209 FSPs identified following an analysis of 
dMMR/MSI-H CRC, gastric, G-E junction, and endometrial tumor sequences in the TCGA database.  
 
GAd20-209-FSP is a polyvalent vaccine.  It is manufactured under Good Manufacturing Practice (GMP) 
conditions at Reithera GMP facility (Via di Castel Romano 100, 00128 Rome, Italy). GAd20-209-FSP 
comprises 4 replication-incompetent gorilla-derived Great Apes Adenoviruses (GAd20).  The GAd20-209-
FSP polyvalent vaccine is formulated in A195 buffer (10 mM Tris, 75 mM NaCl, 1 mM MgCl2, 0.02% 
PS80, 5% sucrose, 0.1 mM EDTA, 10 mM Histidine, 0.5% ethanol, pH 7.4) at the dose of 2x1011 vp/mL. 
 
MVA-209-FSP is a polyvalent vaccine.  It is manufactured under Good Manufacturing Practice (GMP) 
conditions at Reithera GMP facility (Via di Castel Romano 100, 00128 Rome, Italy). MVA-209-FSP 
polyvalent vaccine comprises 4 attenuated, replication-defective orthopoxvirus, Modified Vaccinia virus 
Ankara (MVA). MVA-209-FSP polyvalent vaccine is formulated in MVA buffer (10 mM Tris, 140 mM 
NaCl, pH 7.7) at the dosage of 2x108 ifu/mL. The vaccine is vialed in 3 mL Borosilicate Type 1 glass vials. 
 
GAd20-209-FSP and MVA-209-FSP are each provided as a glass vial closed by a rubber stopper and sealed 
with an aluminum tear-off cap. Both vaccine products may be administered as a high-dose (1 mL) 
intramuscular injection formulated without preservative.  
 
Historically, the agent manufacturer used the actual concentrations of study agents, measured by qPCR, to 
define the doses of the initial lots produced. In keeping the industry best practices, the agent manufacturer 
currently uses the nominal concentrations for both GAd-209-FSP and MVA-209-FSP to define the doses 
after acquiring confidence on the qPCR acceptance range. Changes in the actual concentration within the 
acceptance range do not cause any difference in the safety and tolerability of the products, and therefore 
the nominal concertation is to be used to define subsequent lots. 
 
 
 
8.2 
Reported Adverse Events and Potential Risks 
 
The FIH phase I study of Nous-209 (NCT04041310) is designed to evaluate its safety, tolerability, 
immunogenicity, and efficacy in combination with pembrolizumab (anti-PD-1) for patients with 
unresectable or metastatic MMR-deficient CRC, gastric cancers, and gastro-esophageal junction (G-E 
junction) cancers. Although complete results of the FIH study are not yet reported, preliminary findings 
support the safety of Nous-209 (31, 32, 38). Participants were enrolled in two consecutive cohorts with one 
log difference in vaccine dose:  
 
x 
Low-dose (cohort A; dose-escalation): GAd20-209-FSP polyvalent (prime) vaccine at a dose of 
1.88 x1010 vp and MVA-209-FSPs polyvalent (boost) vaccine at a dose of 1.65x107 ifu 
x 
High-dose (cohort B; dose-expansion): GAd20-209-FSP polyvalent (prime) vaccine at a dose of 
1.88 x1011 vp and MVA-209-FSPs polyvalent (boost) vaccine at a dose of 1.65x108 ifu  
 
With a safety data cut-off of September 29th, 2021, no treatment-related deaths or treatment-related AEs 
leading to permanent discontinuation of treatments were observed among 12 evaluable participants (three 
in the low-dose cohort, and 9 in the high-dose cohort) (32). No DLTs were observed among the three 
participants in the low-dose cohort. 
 

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All AEs related to either GAd20-209-FSP or MVA-209-FSP were grade 1/2 and were comparable between 
both dose levels. These included injection site pain, fatigue, decreased appetite, and fever. AEs occurring 
on or after the date of GAd20-209-FSP administration were considered Treatment Emergent AEs (TEAEs). 
Among the 12 evaluable participants, 5 serious (grade 3/4) TEAEs were observed and included cellulitis, 
adenocarcinoma of colon, psychotic disorder, pulmonary embolism, and enteritis. None of the serious 
TEAEs were considered related to GAd-209-FSP or MVA-209-FSP per the Investigator and Sponsor’s 
assessment. 
 
Consistent with the above, several prior clinical studies using the GAd prime and MVA boost vector 
platform against viral pathogens have demonstrated its favorable safety profile (27, 28, 39-41). In one the 
largest studies performed to date, NCT01436357 was a phase I/II randomized, double-blind, placebo-
controlled trial evaluating the safety and efficacy of prime/boost vaccination in 548 healthy individuals at 
risk of HCV infection (42). Consistent with prior data, there were no vaccine-related serious adverse events 
identified in the study. 
 
Altogether, the most common reported vaccine-related adverse events are typically mild (grade 1 or 2) and 
manifest as local reaction and/or systemic reactions: 
 
x 
Local reactions: a local inflammatory reaction that can include redness, swelling, scaling, 
tenderness, or itching. 
x 
Systemic reactions:  flu-like symptoms, such as low-grade fever, chills, and malaise 
 
These reactions typically resolve within 7 days of vaccination. 
 
 
8.3  
Availability 
 
The GAd20-209-FSP (prime) and MVA-209-FSP (boost) vaccines are Investigational Agents supplied to 
investigators by the Division of Cancer Prevention (DCP), NCI.  
 
The GAd20-209-FSP (prime) and MVA-209-FSP (boost) vaccines are provided to the NCI under a Clinical 
Trials Agreement (CTA) between Nouscom (Agent Manufacturer) and the DCP, NCI (see §14.7). 
 
 
8.4 
Agent Distribution 
 
Agents will only be released by NCI, DCP after documentation of CIRB approval of the DCP-approved 
protocol and consent is provided to DCP and the collection of all Essential Documents is complete (see 
DCP website for description of Essential Documents).  
 
NCI, DCP-supplied agents may be requested by the Investigator (or his/her authorized designees) at each 
Organization. DCP guidelines require that the agent be shipped directly to the institution or site where the 
agent will be prepared and administered. DCP does not permit the transfer of agents between institutions   
(unless prior approval from DCP is obtained). DCP does not automatically ship agents; the site must make 
a request. Agents are requested by completing the DCP Clinical Drug Request form: 
https://prevention.cancer.gov/sites/default/files/uploads/clinical_trial/Investigational-Agent-
Request.docx (to include complete shipping contact information) and e-mailing the form to the DCP agent 
repository contractor:  
 
John Cookinham 

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MRIGlobal 
DCP Repository 
1222 Ozark Street 
North Kansas City, MO 64116 
Phone: (816) 360-3805 
E-mail: NCI.DCP@mriglobal.org 
 
 
8.5  
Agent Accountability 
 
The Investigator, or a responsible party designated by the Investigator, must maintain a careful record of 
the inventory and disposition of all agents received from DCP. The Investigator is required to maintain 
adequate records of receipt, dispensing and final disposition of study agent. This responsibility may be 
delegated to the study staff, institutional pharmacist or their designees. Include on receipt record from whom 
the agent was received and to whom study agent was shipped, date, quantity and batch or lot number. On 
dispensing record, note quantities and dates study agent was dispensed to and returned by each participant. 
The Investigator at each accruing site will be responsible for study agent accountability for participants. 
 
 
8.6 
Packaging and Labeling 
 
GAd20-209-FSP and MVA-209-FSP will be packaged by Nouscom, Inc. Labeling and distribution to the 
sites will be done by NCI, DCP or its authorized designee. 
 
 
8.7 
Storage 
 
The storage conditions are specified on the labels. Clinical supplies must be stored in a secure, limited-
access temperature controlled location. Receipt and dispensing of trial medication must be recorded by an 
authorized person at the study site. Clinical supplies may not be used for any purpose other than that stated 
in the protocol. 
 
Refer to the Pharmacy Manual for storage temperature and the Temperature Excursion policy and 
procedure(s).  The Pharmaceutical partner (if required), CP-CTNet LAO, the DCP agent repository 
contractor, DCP Medical Monitor and Nurse Consultant should be notified in the event of a Temperature 
Excursion. 
 
 
8.8 
Registration/Randomization 
This trial will use a web-based Registration/Randomization System, developed and maintained by the CP-
CTNet Data Management, Auditing, and Coordinating Center (DMACC). The Help Desk includes 
technical personnel and administrators of the registration programs at the Data Management Center in 
Amherst, NY, USA. The Help Desk is available round the clock 7 days per week, except for New Year's 
Eve, Memorial Day, Independence Day, Thanksgiving Day, and Christmas Day. 
Frontier Science Randomization Help Desk 
4033 Maple Rd, Amherst, NY 14226 USA 
Phone: +1 716 834 0900 Extension 7301 
Email:  UserSupport_CP-CTNet@frontierscience.org 
 

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Note: The Registration and Enrollment process is documented in the "Stars User Guide". 
 
Screening and Registration into the DMACC Stars System: 
To obtain a Screening ID, log into Stars and verify the participant is eligible for contact.  Once confirmed, 
a Screening ID will be assigned. Once informed consent has been signed, the participant can be registered 
into the DMACC Stars System. The Stars System will assign a Participant’s ID upon completion of the 
registration process.  
 
Enrollment: 
Participants will be assigned a Participant ID once the following has been accomplished: eligibility has 
been verified at the site level, eligibility has been confirmed by the site PI, and eligibility information has 
been entered into the Stars System web application. The Participant ID will be generated by the system and 
assigned to the participant.  The data from Stars will automatically transfer to Medidata Rave clinical data 
management system, which is the CP-CTNet database of record and subject to NCI and Food and Drug 
Administration (FDA) audits, within 5 minutes of entry into Stars.  
 
Recruitment Journaling and Clinical Study Data in Medidata Rave: 
The Affiliated Organizations will enter both Recruitment Journaling information and study data into the 
Medidata Rave.  
 
Screening/Registration/Enrollment into site-specific databases: 
The Medidata Rave is the database of record for the study. Registration and enrollment should occur per 
the procedures outlined above. If the site staff need to enter study data into site-specific electronic databases 
per their institutional requirements, they should do so in accordance with their institutional policies and 
procedures. 
 
Appropriate CRFs must be completed for any participant who signs an informed consent. If a consented 
participant is a screen failure and deemed ineligible, the following CRFs must be completed: 1) the 
Registration CRF with the eligibility box checked “no”, 3) the Inclusion and Exclusion CRFs showing why 
the participant is ineligible, 4) the Off-Study CRF, 5) the Adverse Event CRF, 6) the Concomitant 
Medication CRF and 7) the PI signoff form. If no Adverse Event and/or Concomitant Medications were 
assessed by the time the participant is deemed ineligible, the “NONE” box will be checked to complete 
both CRFs.  All participants who sign an informed consent must formally go off study. All participant 
registration information will be entered into Stars and Medidata Rave. If a participant experiences a serious 
adverse event during the screening process, an SAE form must be completed. 
 
 
8.9 
Blinding and Unblinding Methods 
 
No blinding will be utilized for this study.  
 
 
8.10 
Agent Destruction/Disposal 
 
DCP-supplied agents: at the completion of investigation, all unused study agent will be returned to NCI, 
DCP Repository according to the DCP “Guidelines for AGENT RETURNS” and using the DCP form 
“DCP Returned Agents List”.  
 

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9.  
CLINICAL EVALUATIONS AND PROCEDURES 
 
9.1 
Schedule of Events 
 
9.1.1 Schedule of Events for Cohort 1 
 
 
Study Schedule Footnotes 
1. 
Liver Function Panel: including serum AST/SGOT, serum ALT/SGPT, and serum total bilirubin. 
2. 
Hematology and Chemistry Laboratory Tests:  including CBC (complete blood count) with hemoglobin, leukocyte count, 
platelet count and differential (including absolute neutrophil count); serum creatinine; and serum electrolytes (sodium, 
potassium); prothrombin time (PT) / international normalized ration (INR), and partial thromboplastin time (PTT) 
3. 
Viral serology tests including: Hepatitis C Virus (HCV) antibody, Hepatitis B Virus (HBV) surface antigen (HBsAg), and 
Human Immunodeficiency Virus (HIV)-1/2 antibody. Counseling will be given prior to testing blood for these blood-borne 
viruses. 
Evaluation/ Procedure 
Baseline Testing / 
Pre-Study 
Evaluation 
 
Study Intervention 
Follow-up 
Evaluation/ Procedure 
Screening Visit / 
Eligibility / 
Registration / 
Enrollment 
[within < 30 days 
of Day 1] 
Week #: 
0 
[Day 1] 
0 
[Day 2-4] 
 
3 
(+/- 7 days) 
 
8 
(+/-7 days) 
 
9 
(+7 days) 
16 
(+/-14 days) 
24  
(+/-14 days) 
36 
(+/-14 days) 
 
52  
(+/- 14 
days) 
Study Visit 
#: 
1 
2 
3 
4 
5 
6 
7 
8 
 
99 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
Baseline Symptoms 
X 
 
 
 
 
 
 
 
 
 
 
Physical Exam / Vital 
Signs 
X 
 
 
 
 
 
 
 
 
 
 
Height & Weight 
X 
 
 
 
 
 
 
 
 
 
 
BMI 
X 
 
 
 
 
 
 
 
 
 
 
Liver Function Panel 
X1 
 
 
 
 
 
 
 
 
 
 
Hematology and 
Chemistry 
X2 
 
 
 
 
 
 
 
 
 
 
Anti-Hepatitis C Virus, 
Hepatitis B Virus, and 
HIV serology 
X3 
 
 
 
 
 
 
 
 
 
 
HLA typing 
X4 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test 
X5 
 
 
 
 
 
 
 
 
 
 
Confirm Eligibility 
X 
 
 
 
 
 
 
 
 
 
 
Registration 
X 
 
 
 
 
 
 
 
 
 
 
Lower GI endoscopy 
(flexible sigmoidoscopy or 
colonoscopy) with biopsies 
X6 
 
 
 
 
 
 
 
 
 
 
X6 
Research blood sample 
 
 
X 
 
X 
X 
X 
 
X 
 
X 
Concomitant Medications 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
GAd20-209-FSP (prime) 
administration 
 
 
X 
 
 
 
 
 
 
 
 
MVA-209-FSP (boost) 
administration 
 
 
 
 
 
X 
 
 
 
 
 
Adverse Events/Symptom 
Assessment7 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Telephone 
Contact/Telehealth Visit 
 
 
 
X 
 
 
 
X 
 
X 
 
Tobacco and Alcohol 
Assessment8 
 
 
X 
 
 
 
 
 
 
 
X 
COVID-19 Assessment8 
 
 
 
 
 
 
 
 
 
 
X 
Vaccine Report Card9  
 
 
X 
X 
 
X 
 
 
 
 
 

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4. 
Human Leukocyte Antigen genotyping.  The HLA genotyping test performed as part of “Baseline Testing/Pre-Study 
Evaluations” does not need to be repeated if the patient does not start the vaccine within 30 days of Day 1. The HLA report 
may be used at any time because the results will not change.  
5. 
In women of childbearing potential, a urine or serum pregnancy test must be done at Baseline as part of eligibility verification.  
a. 
If the pregnancy test result is positive at Baseline (any time before enrollment), the participant is a Screen 
Failure. 
b. 
If a pregnancy is discovered after Day 1, the vaccine will not be given. Take participant off-study, complete 
the Off-Study eCRFs, follow the pregnancy to term and complete the Outcome of Pregnancy CRF. 
6. 
If indicated, lower GI endoscopy may be performed as standard-of-care flexible sigmoidoscopy in those participants with total 
or subtotal colectomy; otherwise, complete colonoscopy is the standard of care procedure: 
a. 
Lower GI endoscopy may be performed within 60 days of Day 1. 
7. 
The Study staff should pay particular attention to the following potential events: abdominal pain, fever>100.4F, irregular heart 
rate/palpitations, hypotension, confusion, chest pain, shortness of breath, lightheadedness or dizziness, easy bruising/bleeding, 
and notify the study investigator(s) immediately if reported. 
8. 
The participants will be given the option to complete paper form questionnaires or complete the questionnaires 
electronically, either face to face with the study staff or remotely according to the participant’s preference. See Appendix B 
and Appendix C. 
9. 
Each participant will be asked to record symptom reactivity events daily in the Vaccine Report Card, from day 0 to day 6 
post vaccine. See Appendix E. 
 
ATTENTION COORDINATORS!  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
x If a participant is completing Cohort 1 and NOT moving on to Cohort 2, then 
the participant’s visit at Week 52 is their last visit and coordinators must 
perform all tests and procedures as outlined in § 9.1.1 Schedule of Events.  The 
lower GI endoscopy (flexible sigmoidoscopy or colonoscopy) with biopsies will 
be performed at Week 52 (+/- 14 days) if the participant is not continuing on for 
Cohort 2. 
x If the participant IS moving on to Cohort 2, then coordinators should start the 
participant’s Week 52 visit with the procedures noted in the § 9.1.2 Schedule of 
Events. For participants who continue to Cohort 2, the lower GI endoscopy 
(flexible sigmoidoscopy or colonoscopy) with biopsies will be performed at 
Week 68 (+/- 14 days) according to the Schedule of Events outlined in Section 
9.1.2.  

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9.1.2 Schedule of Events for Cohort 21 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Schedule Footnotes 
1. 
Only for participants who qualify for cohort 2.  
2. 
Participant must be consented before any study procedure is performed; participants who are screened 14 or more days after 
signing informed consent will need to be re-consented. 
3. 
In women of childbearing potential, a urine or serum pregnancy test must be done as part of eligibility verification for Cohort 
2 study.  
a. 
If a pregnancy is discovered at the Cohort 2 Screening Visit, the vaccine will not be given. Take participant off-
study, complete the Off-Study eCRFs, follow the pregnancy to term and complete the Outcome of Pregnancy 
CRF. 
4. 
Eligibility must be verified prior to randomization.  
5. 
If indicated, lower GI endoscopy may be performed as standard-of-care flexible sigmoidoscopy in those participants with total 
or subtotal colectomy; otherwise, complete colonoscopy is the standard of care procedure. 
6. 
The study staff should pay particular attention to the following potential events: abdominal pain, fever>100.4F, irregular heart 
rate/palpitations, hypotension, confusion, chest pain, shortness of breath, lightheadedness or dizziness, easy bruising/bleeding, 
and notify the study investigator(s) immediately if reported.  
7. 
The participants will be given the option to complete paper form questionnaires or complete the questionnaires 
electronically, either face to face with the study staff or remotely according to the participant’s preference. See Appendix B 
and Appendix C. 
8. 
Each participant will be asked to record symptom reactivity events daily in the Vaccine Report Card, from day 0 to day 6 
post vaccine. See Appendix E. 
 
 
9.2 
Baseline Testing/Pre-Study Evaluation 
 
Potentially eligible participants are identified through database/charts/clinic lists prior to Baseline Visit.  A 
letter will be mailed to all potentially eligible participants introducing the study to them. Alternatively, or 
Evaluation/ Procedure 
 
Study Intervention 
 
Week #: 
 
Screening Visit / 
week 52 (+/- 14 
days)1  
 
 
Week 60  
(+/-7 days) 
 
Week 68 
(+/-14 days) 
 
Study Visit #: 
9 
10 
11 
Informed Consent2 
X 
 
 
Physical Exam / Vital Signs 
X 
 
 
Height & Weight 
X 
 
 
Pregnancy Test3 
X 
 
 
Confirm Eligibility4 
X 
 
 
Randomization/stratification 
X 
 
 
Research blood sample 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
Lower GI endoscopy (flexible sigmoidoscopy 
or colonoscopy) with biopsies5 
 
 
X 
GAd20-209-FSP (prime) administration 
Arm A 
 
 
MVA-209-FSP (boost) administration 
Arm B 
Arm A 
 
Adverse Events/Symptom Assessment6 
X 
X 
X 
Telephone Contact/Telehealth Visit/ in-person 
visit. 
X 
X 
X 
Tobacco and Alcohol Assessment7 
X 
 
 
COVID-19 Assessment7  
 
X 
 
 
Vaccine Report Card8 
 
X 
X 
 

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in addition to the letter, a phone call from the study staff introducing the study may be made. 
 
Note: Receipt of a recombinant adenoviral or MVA vaccine including COVID-19 Adenovirus vaccines 
within 6 months of Baseline excludes individuals from study participation.  Participants must consent to 
refrain from receiving any other type of vaccination during the first 10 weeks of the trial (in Cohort 1) and 
weeks 52-68 of the trial (in Cohort 2).  Participants must consent to refrain from receiving adenoviral-based 
vaccines for the duration of the trial (including the period from week 9 to week 68). 
 
 
Screening Visit: Baseline Testing / Eligibility / Registration / Enrollment [<30 days of Day 1] 
 
The following procedures will be conducted at the Screening Visit which must occur within 30 days prior 
to Study Visit 1. Participants who are screened 30 or more days after signing the informed consent will 
need to be re-consented and have all screening procedures repeated to determine eligibility with the 
exception of the lower GI endoscopy, which will have a window of up to 60 days of Day 1; and that HLA 
typing does not have to be repeated if done outside the window of <30 days of Day 1.  
 
x 
Informed consent must be obtained prior to starting any further study procedures. 
x 
Registration: Once informed consent has been signed, participants will be registered into the 
DMACC Stars System. The DMACC Stars System will assign a participant’s ID upon completion 
of the registration process. Participants will also be registered into site-specific registry databases 
as applicable. 
x 
Medical history, to include a review of cancer history and previous medical history, previous 
surgery, chemotherapy, radiation, and other cancer-directed therapy history, family history and 
genetic diagnosis (including results of clinically-indicated genetic analysis to confirm the presence 
or absence of germline MMR gene mutation, if available), demographic information, including age 
and race. 
x 
Baseline symptom assessment will include: constipation, diarrhea, headache, dizziness, 
drowsiness, lightheadedness, vertigo, easy bruising/bleeding, gastrointestinal bleeding, 
hematemesis, hematochezia, melena, abdominal pain/cramping, heart burn, irregular heart 
rate/palpitations, chest pain, shortness of breath, and edema.  
x 
Use of concomitant medications will be collected, with particular attention to chemo-preventive 
use of non-steroidal anti-inflammatory drugs (NSAIDs), here defined as taking aspirin (>81 mg 
daily) or naproxen (>200 mg daily) more than 5 days per month; (2) pre- or probiotic supplement 
use; (3) antibiotic use; and (4) immunosuppressive drug use including (but not limited to) oral 
glucocorticoids. 
x 
Participants must consent to refrain from using aspirin or non-steroidal anti-inflammatory drugs 
(NSAIDs) or cyclooxygenase (COX) inhibitors for the duration of the trial, except for cardio-
preventive aspirin (<100 mg daily).  Individuals taking such drugs may not be enrolled unless they 
are willing to stop the medications (and possibly change to alternative non-excluded medications 
to treat the same conditions) no less than 1 month prior to enrolling.  Consultation with the 
participant’s primary care provider will be obtained prior to stopping any agent. 
x 
A physical examination including vital signs (temperature, blood pressure, heart rate, respiratory 
rate), height, weight, BMI. 
x 
Baseline laboratory evaluations include: complete blood count (including hemoglobin, leukocyte 
count, platelet count) with differential (including absolute neutrophil count); creatinine, electrolytes 
(including sodium, potassium), AST/SGOT, ALT/SGPT, bilirubin (total); viral serology (including 
HBV sAg, HCV antibody, HIV-1/2 antibody); HLA genotyping; coagulation panel (including 
PT/INR, PTT). Standard of care labs are acceptable for use to confirm eligibility if done within 30 
days of Study Visit 1.  The HLA genotyping test performed as part of “Baseline Testing/Pre-Study 

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Evaluations” does not need to be repeated if the patient does not start the vaccine within 30 days 
of Day 1. The HLA report may be used at any time because the results will not change.  
x 
Standard of care lower GI endoscopy (flexible sigmoidoscopy or colonoscopy) is performed to 
access the residual descending/sigmoid colon and/or rectum in a participant. (See Section 9.7 for 
details): 
o Lower GI endoscopy may be performed within 60 days of Day 1. 
o Visual counting of any polypoid lesion observed in the entire colon (colonoscopy) or 
rectosigmoid area (flexible sigmoidoscopy) should be done and recorded; 
 
If any abnormal mucosa/polypoid lesions were identified during endoscopy, 
standard procedures of clinical care of the local enrolling site should be followed 
for biopsy, tissue handling, and subsequent pathologic assessment of these lesions. 
 
Any abnormal mucosa/polypoid lesions tissue collected in the manner described 
above that may be residual after clinical care pathologic assessment will be 
collected and retained for research purposes (Refer to Section 12 for procedure for 
the collection of residual polyp tissue). 
o For research purposes, participants will undergo biopsy of grossly normal mucosa from the 
intact and accessible rectosigmoid (Refer to Section 12 for collection details). 
x 
For women of child-bearing potential, a urine or serum pregnancy test must be done at Baseline as 
part of eligibility verification. Results must be known prior to enrollment and initiation of study 
intervention. The urine pregnancy test must be done in the clinic. 
o If the pregnancy test result is positive at Baseline (any time before enrollment and initiation 
of study intervention), the participant is a Screen Failure. 
o If a pregnancy is discovered after Study Visit 1, vaccine will not be given. Take the 
participant off-study, complete the Off-Study CRFs, follow the pregnancy to term and 
complete the Outcome of Pregnancy CRF. 
x 
Confirm eligibility: At the completion of the screening period all baseline testing and pre-
evaluation procedures, eligibility must be confirmed. Only after eligibility is confirmed and 
eligibility CRF is entered into the web application, eligible participants will be scheduled for Study 
Visit 1. 
x 
All data will be captured on the appropriate CRFs. 
 
Notes: 
x 
Previously screened participants may be rescreened for enrollment in the study. Participants who are 
rescreened 30 days after signing the informed consent will need to be re-consented and have all 
screening procedures repeated to determined eligibility, with the exception of the lower GI endoscopy, 
which will have a window of up to 60 days of Day 1; and HLA typing does not have to be repeated if 
done outside the window of <30 days of Day 1. 
x 
Any screen failed participant based on medical history, physical exam or laboratory values will need to 
have a screen failure case report form completed. Information will be recorded on the appropriate 
CRF(s) up until the point at which the participant was found ineligible and screen failed. 
x 
For any participant who is deemed as screen failure, tissue samples collected at Baseline are to be saved 
for future use at the respective affiliated organization and shipped to Dr. Eduardo Vilar-Sanchez with 
the other specimens per the instructions in Section 12.3.  
 
 
9.3 
Evaluation During Study Intervention for Cohort 1 
 
Study Visit 1 (Start of Intervention): Week 0 (Day 1)  
x 
Study Visit 1 is an in-person visit. 
x 
Concomitant medication review. 

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x 
Research blood collection (75 mL) for immunogenicity and cfDNA studies (see Section 12 for 
details). 
x 
GAd20-209-FSP (prime) intramuscular injection (see Section 7 for details). 
x 
Review adverse events / symptom assessment. The study staff should pay particular attention to: 
abdominal pain, fever>100.4F, irregular heart rate/palpitations, hypotension, confusion, chest pain, 
shortness of breath, lightheadedness or dizziness, easy bruising/bleeding, and notify the study 
investigator(s) immediately if reported.  
x 
Tobacco and Alcohol Use Assessment questionnaires. The participants will be given the option to 
complete paper form questionnaires or complete the questionnaires electronically, either face to 
face with the study staff or remotely, according to the participant’s preference.  See Appendix B. 
Refer to Appendix B for resources for alcohol and tobacco quitting. These resources can be given 
to individuals if there is concern about alcohol or tobacco dependence. It is not expected that 
investigators will refer individuals for assistance or that they will undertake the care of individuals 
for alcohol or tobacco dependence. 
x 
Each participant will be asked to record symptom reactivity events daily in the Vaccine Report 
Card, from day 0 to day 6 post vaccine. See Appendix E. 
x 
All data will be captured on the appropriate CRFs, including the participant questionnaires. 
 
 
Study Visit 2 (Telephone/Telemedicine Contact): Week 0 (Days 2-4)  
x 
Study Visit 2 is a telephone/telemedicine visit. 
x 
Concomitant medication review. 
x 
Review adverse events / symptom assessment. The study staff should pay particular attention to: 
abdominal pain, fever>100.4F, irregular heart rate/palpitations, hypotension, confusion, chest pain, 
shortness of breath, lightheadedness or dizziness, easy bruising/bleeding, and notify the study 
investigator(s) immediately if reported.  
o If any AEs concerning to either the participant or the study staff are reported during the 
telephone contact, the participant will be scheduled for a clinic visit and evaluation, and 
the study investigator(s) will be notified in a timely fashion. 
o If no events concerning to either the participant or the study staff are reported that warrant 
a clinic visit, the participant will be scheduled for a subsequent study visit according to the 
calendar of events.  
o If any Grade 3-4 adverse events occur, the participants must be referred to the appropriate 
study physician.  
x 
The study staff will remind the participants to complete the VRC. See Appendix E. 
x 
All data will be captured on the appropriate eCRFs.  
 
Study Visit 3: Week 3 
x 
Study Visit 3 is an in-person visit. 
x 
Concomitant medication review. 
x 
Research blood collection (75 mL) for immunogenicity and cfDNA studies (see Section 12 for 
details). 
x 
Review adverse events / symptom assessment. The study staff should pay particular attention to: 
abdominal pain, fever>100.4F, irregular heart rate/palpitations, hypotension, confusion, chest pain, 
shortness of breath, lightheadedness or dizziness, easy bruising/bleeding, and notify the study 
investigator(s) immediately if reported.  
x 
All data will be captured on the appropriate eCRFs. 
 
Study Visit 4: Week 8  

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x 
Study Visit 4 is an in-person visit. 
x 
Concomitant medication review. 
x 
Research blood collection (75 mL) for immunogenicity and cfDNA studies (see Section 12 for 
details). 
x 
MVA-209-FSP (boost) intramuscular injection (see Section 7 for details). 
x 
Review adverse events / symptom assessment. The study staff should pay particular attention to: 
abdominal pain, fever>100.4F, irregular heart rate/palpitations, hypotension, confusion, chest pain, 
shortness of breath, lightheadedness or dizziness, easy bruising/bleeding, and notify the study 
investigator(s) immediately if reported.  
x 
The study staff will remind the participants to complete the VRC. See Appendix E. 
x 
All data will be captured on the appropriate eCRFs. 
 
 
9.4 
Evaluation at Completion of Study Intervention for Cohort 1 
 
Study Visit 5: Week 9  
x 
Study Visit 5 is an in-person visit. 
x 
Concomitant medication review. 
x 
Research blood collection (75 mL) for immunogenicity and cfDNA studies (see Section 12 for 
details). 
x 
Review adverse events / symptom assessment. The study staff should pay particular attention to: 
abdominal pain, fever>100.4F, irregular heart rate/palpitations, hypotension, confusion, chest pain, 
shortness of breath, lightheadedness or dizziness, easy bruising/bleeding, and notify the study 
investigator(s) immediately if reported.  
x 
All data will be captured on the appropriate eCRFs. 
 
 
9.5 
Post-intervention Follow-up Period for Cohort 1 
 
Study Visit 6: Week 16 (Month 4)  
x 
Study Visit 6 is a telephone/telemedicine visit. 
x 
Concomitant medication review. 
x 
Review adverse events / symptom assessment. The study staff should pay particular attention to: 
abdominal pain, fever>100.4F, irregular heart rate/palpitations, hypotension, confusion, chest pain, 
shortness of breath, lightheadedness or dizziness, easy bruising/bleeding, and notify the study 
investigator(s) immediately if reported.  
x 
All data will be captured on the appropriate eCRFs. 
 
Study Visit 7: Week 24 (Month 6)  
x 
Study Visit 7 is an in-person visit. 
x 
Concomitant medication review. 
x 
Research blood collection (75 mL) for immunogenicity and cfDNA studies (see Section 12 for 
details). 
x 
Review adverse events / symptom assessment. The study staff should pay particular attention to: 
abdominal pain, fever>100.4F, irregular heart rate/palpitations, hypotension, confusion, chest pain, 
shortness of breath, lightheadedness or dizziness, easy bruising/bleeding, and notify the study 
investigator(s) immediately if reported.  
x 
All data will be captured on the appropriate eCRFs. 
 

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Study Visit 8: Week 36 (Month 9)  
x 
Study Visit 8 is a telephone/telemedicine visit. 
x 
Concomitant medication review. 
x 
Review adverse events / symptom assessment. The study staff should pay particular attention to: 
abdominal pain, fever>100.4F, irregular heart rate/palpitations, hypotension, confusion, chest pain, 
shortness of breath, lightheadedness or dizziness, easy bruising/bleeding, and notify the study 
investigator(s) immediately if reported.  
x 
All data will be captured on the appropriate eCRFs. 
 
Note: a participant who, for any reason, received the first GAd20-209-FSP (prime) vaccination, but not the 
booster (MVA-209-FSPs), will be considered for a post-treatment lower GI endoscopy (flexible 
sigmoidoscopy or colonoscopy) and other study interventions listed under Study Visit 9 if the participant 
received GAd20-209-FSP (prime) vaccination not more than 15 months prior to the scheduled Study Visit 
9 procedures. 
 
 
Study Visit 9: Week 52 (Month 12)  
x 
For participants who complete Cohort 1 and do not continue in Cohort 2, all study procedures will 
complete according to the Schedule of Events outlined in Section 9.1.1. The lower GI endoscopy 
(flexible sigmoidoscopy or colonoscopy) with biopsies will be performed at Week 52 (+/- 14 days). 
For participants who continue to Cohort 2, the lower GI endoscopy (flexible sigmoidoscopy or 
colonoscopy) with biopsies will be performed at Week 68 (+/- 14 days) according to the Schedule 
of Events outlined in Section 9.1.2. 
x 
Study Visit 9 is an in-person visit. 
x 
Concomitant medication review. 
x 
Research blood collection (75 mL) for immunogenicity and cfDNA studies (see Section 12 for 
details). 
x 
Standard of care lower GI endoscopy (flexible sigmoidoscopy or colonoscopy) is performed to 
access the residual descending/sigmoid colon and/or rectum in a participant. (See Section 9.7 for 
details): 
o Visual counting of any polypoid lesion observed in the entire colon (colonoscopy) or 
rectosigmoid area (flexible sigmoidoscopy) should be done and recorded; 
 
If any abnormal mucosa/polypoid lesions were identified during endoscopy, 
standard procedures of clinical care of the local enrolling site should be followed 
for biopsy, tissue handling, and subsequent pathologic assessment of these lesions. 
 
Any abnormal mucosa/polypoid lesions tissue collected in the manner described 
above that may be residual after clinical care pathologic assessment will be 
collected and retained for research purposes (Refer to Section 12 for procedure for 
the collection of residual polyp tissue). 
o For research purposes, participants will undergo biopsy of grossly normal mucosa from the 
intact and accessible rectosigmoid (Refer to Section 12 for collection details). 
x 
Review adverse events / symptom assessment. The study staff should pay particular attention to: 
abdominal pain, fever>100.4F, irregular heart rate/palpitations, hypotension, confusion, chest pain, 
shortness of breath, lightheadedness or dizziness, easy bruising/bleeding, and notify the study 
investigator(s) immediately if reported.  
x 
Tobacco, Alcohol Use, and Covid-19 Assessment questionnaires. The participants will be given 
the option to complete paper form questionnaires or complete the questionnaires electronically, 
either face to face with the study staff or remotely, according to the participant’s preference. See 
Appendix B and Appendix C. 
x 
All data will be captured on the appropriate eCRFs. 

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9.6 
Evaluation During Study Intervention for Cohort 2 
 
Study Visit 9: Week 52 (Month 12)  
x 
Potentially eligible participants for Cohort 2 will be those who received a prime/boost vaccination 
cycle in Cohort 1 and for whom peak immunogenicity responses (Week 9 in Cohort 1) are proved 
by ELISPOT assay. Once such participants are identified, they will be notified that they are eligible 
for Cohort 2 of the study. A letter may be sent to them by mail, informing them of their eligibility 
for Cohort 2, alternatively, or in addition to the letter, a phone call from the Study Staff may be 
made, informing the participant of their eligibility for Cohort 2. 
x 
Informed consent must be obtained prior to starting any further study procedures. 
x 
Confirm eligibility: Once eligibility based on immunogenicity response has been verified, the 
pregnancy test has been verified negative and pre-evaluation procedures also confirm eligibility, 
the eligibility CRF should be entered into the web application and eligible participants will be 
randomized.  
x 
Randomization/stratification: Once registration is complete, eligibility has been confirmed and 
eligibility CRF is entered into the web application, participants will be assigned a randomization 
number pre-generated by the database. Participants will be randomized to receive either Arm A or 
Arm B.  
x 
Study Visit 9 is an in-person visit. 
x 
Gad20-209-FSP (prime) intramuscular injection for Arm A participants or MVA-209-FSP (boost) 
intramuscular injection for Arm B participants (see Section 7 for details). 
x 
Review adverse events / symptom assessment. The study staff should pay particular attention to: 
abdominal pain, fever>100.4F, irregular heart rate/palpitations, hypotension, confusion, chest pain, 
shortness of breath, lightheadedness or dizziness, easy bruising/bleeding, and notify the study 
investigator(s) immediately if reported. 
x 
A physical examination including vital signs (temperature, blood pressure, heart rate, respiratory 
rate), height, weight, BMI. 
x 
Concomitant medication review. 
x 
Research blood collection (75 mL) for immunogenicity and cfDNA studies (see Section 12 for 
details). 
x 
Tobacco, Alcohol Use, and Covid-19 Assessment questionnaires. The participants will be given 
the option to complete paper form questionnaires or complete the questionnaires electronically, 
either face to face with the study staff or remotely, according to the participant’s preference. See 
Appendix B and Appendix C.   
x 
Each participant will be asked to record symptom reactivity events daily in the Vaccine Report 
Card, from day 0 to day 6 post vaccine. See Appendix E.
x 
All data will be captured on the appropriate eCRFs. 
 
Study Visit 10: Week 60 (Month 15)  
x 
Study Visit 10 is an in-person visit. 
x 
Concomitant medication review. 
x 
Research blood collection (75 mL) for immunogenicity and cfDNA studies (see Section 12 for 
details). 
x 
MVA-209-FSP (boost) intramuscular injection for Arm A (see Section 7 for details). 
x 
Review adverse events / symptom assessment. The study staff should pay particular attention to: 
abdominal pain, fever>100.4F, irregular heart rate/palpitations, hypotension, confusion, chest pain, 
shortness of breath, lightheadedness or dizziness, easy bruising/bleeding, and notify the study 
investigator(s) immediately if reported.  

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x 
The study staff will remind the participants to complete the VRC. See Appendix D. 
x 
All data will be captured on the appropriate eCRFs. 
 
Study Visit 11: Week 68 (Month 17)  
x 
Study Visit 11 is an in-person visit. 
x 
Concomitant medication review. 
x 
Research blood collection (75 mL) for immunogenicity and cfDNA studies (see Section 12 for 
details). 
x 
Review adverse events / symptom assessment. The study staff should pay particular attention to: 
abdominal pain, fever>100.4F, irregular heart rate/palpitations, hypotension, confusion, chest pain, 
shortness of breath, lightheadedness or dizziness, easy bruising/bleeding, and notify the study 
investigator(s) immediately if reported.  
x 
Standard of care lower GI endoscopy (flexible sigmoidoscopy or colonoscopy) is performed to 
access the residual descending/sigmoid colon and/or rectum in a participant. (See Section 9.7 for 
details): 
o Visual counting of any polypoid lesion observed in the entire colon (colonoscopy) or 
rectosigmoid area (flexible sigmoidoscopy) should be done and recorded; 
 
If any abnormal mucosa/polypoid lesions were identified during endoscopy, 
standard procedures of clinical care of the local enrolling site should be followed 
for biopsy, tissue handling, and subsequent pathologic assessment of these lesions. 
 
Any abnormal mucosa/polypoid lesions tissue collected in the manner described 
above that may be residual after clinical care pathologic assessment will be 
collected and retained for research purposes (Refer to Section 12 for procedure for 
the collection of residual polyp tissue). 
x 
All data will be captured on the appropriate eCRFs. 
 
 
9.7 
Methods for Clinical Procedures 
 
Lower GI endoscopy (flexible sigmoidoscopy or colonoscopy) with biopsies: 
1. Standard of care lower GI endoscopy (flexible sigmoidoscopy or colonoscopy) is performed to 
access the residual descending/sigmoid colon and/or rectum in a participant. 
2. Bowel preparation: all patients will undergo an oral bowel prep. No prep should be taken per rectum 
(i.e., enema or suppository) due to possible rectal mucosal trauma and possible associated changes 
in prostaglandin levels.  Dietary instructions prior to this procedure are according to the standard 
of care at the local site/provider, but typically include NPO except for medications after midnight.   
3. For patients undergoing colonoscopy, sedation is customary. For patients undergoing flexible 
sigmoidoscopy, sedation is optional.  
4. The flexible endoscopy equipment to be utilized is per the standard of care and/or physician 
preference at the local site.  There is no requirement for magnification, narrow-band imaging, dye 
spray or any other advanced equipment. 
5. Patient is placed in lateral decubitus position. The flexible endoscope is advanced via the anus 
and/or an end ostomy as applicable and traversed proximally until accessible mucosa of the 
descending/sigmoid colon and/or rectum is visualized.   
6. Any polypoid lesion visualized on the mucosa of study interest in the entire colon should be visually 
counted and recorded.   
7. The actual tissue of abnormalities or polypoid lesions visualized on the mucosa anywhere within 
the colorectum should be handled according to the standard of care at the local site in terms of 
endoscopic tattoo, biopsy, handling, and clinical care pathologic assessment. Any such tissue 

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collected in the manner above that may be residual after clinical care pathologic assessment will be 
collected and retained for research purposes. 
8. For research purposes, a total of up to 10 biopsies of grossly normal mucosa from the rectosigmoid 
colon (up to 25 cm from the anal verge) will be obtained using jumbo biopsy forceps (Radial Jaw 
4, 2.8mm bite size and 3.2mm working channel diameter) by opening and pressing the biopsy 
forceps perpendicular to the mucosal surface with mild pressure. Each biopsy is taken 
approximately 1 cm or more from other biopsy sites within the rectosigmoid colon that had no 
visual appearance of trauma or recent biopsy.  Endoscopists are encouraged to maintain as much 
consistency as possible in the biopsy depth into the mucosa.   
9. All samples are processed according to procedures specified in Section 12. 
 
 
10.  
CRITERIA FOR EVALUATION AND ENDPOINT DEFINITION 
 
10.1 
Primary Endpoint 
 
The primary endpoints of our study are: 
 
a) Rates of grade 2/3 adverse events and symptom reactivity following vaccination with GAd20-209-
FSPs (1 prime) and MVA-209-FSPs (1 boost): Each participant will be asked to record symptom 
reactivity events daily on a memory aid (Vaccine Report Card, Appendix E). Participants will 
record temperature and the presence and intensity of post-vaccination reactogenicity events, 
including pain at injection site, muscle aches, chills, headache, nausea, feeling tired, underarm pain, 
underarm swelling, warmth at vaccination site, itchiness at vaccination site, change in appetite, 
joint pain, and any other symptoms they might be experiencing after vaccination. Erythema and 
induration at the vaccination site will be measured in millimeters. Any symptoms still present 8 
days after initiation will continue to be followed by participant memory aid notations until 8 days 
after symptom resolution. Participants will also be asked to record any medications taken and any 
emergency room or physician visits (other than routine check-ups). The memory aid will be 
reviewed with each participant at subsequent clinic visits. 
 
b) Rate of immunogenicity following vaccination with GAd20-209-FSPs (1 prime) and MVA-209-
FSPs (1 boost) (Cohort 1): Immunogenicity will be defined as reactivity to at least 1 of 16 synthetic 
FSP pools using an enzyme-linked immune absorbent spot (ELISpot) assay. For each participant, 
the endpoint will be evaluated at baseline and at Week 9 (following vaccination with MVA-209-
FSP). In the case of detection of reactivity pools at baseline, an increase of at least 80% of the pre-
existing reactivity will be considered as a positive response to the vaccine. This methodology has 
been used in the evaluation of immunogenicity in the FIH clinical trial presented in section 2.2 of 
this protocol. 
 
c) Rate of immunogenicity following revaccination with GAd20-209-FSPs (1 prime) and MVA-209-
FSPs (1 boost) or MVA-209-FSP (1 boost) alone (Cohort 2): Immunogenicity will be defined as 
reactivity to at least 1 of 16 synthetic FSP pools using an enzyme-linked immune absorbent spot 
(ELISpot) assay. For each participant in Cohort 2, the endpoint will be evaluated at Week 52 and 
at 8 Weeks after the last boost with MVA-209-FSP, corresponding to Week 68 and Week 60, for 
arm A and B, respectively. This methodology has been used in the evaluation of immunogenicity 
in the FIH clinical trial presented in section 2.2 of this protocol. 
 
d) Rates of grade 2/3 adverse events and symptom reactivity following revaccination with GAd20-
209-FSPs (1 prime) and MVA-209-FSPs (1 boost) or MVA-209-FSPs (1 boost) alone (Cohort 2): 

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Each participant will be asked to record symptom reactivity events daily on a memory aid (Vaccine 
Report Card, Appendix E). Participants will record temperature and the presence and intensity of 
post-vaccination reactogenicity events, including pain at injection site, muscle aches, chills, 
headache, nausea, feeling tired, underarm pain, underarm swelling, warmth at vaccination site, 
itchiness at vaccination site, change in appetite, joint pain, and any other symptoms they might be 
experiencing after vaccination. Erythema and induration at the vaccination site will be measured in 
millimeters. Any symptoms still present 8 days after initiation will continue to be followed by 
participant memory aid notations until 8 days after symptom resolution. Participants will also be 
asked to record any medications taken and any emergency room or physician visits (other than 
routine check-ups). The memory aid will be reviewed with each participant at subsequent clinic 
visits. 
 
 
10.2 
Secondary Endpoints 
 
Our secondary endpoints include the following: 
 
a) Changes in T cell immune profile and T cell receptor (TCR) repertoire in the peripheral blood of 
participants with LS at Weeks 3, 9, 24 (Month 6), and 52 (Month 12) relative to baseline following 
vaccination with GAd20-209-FSPs (1 prime) and MVA-209-FSPs (1 boost). 
 
b) Changes in TCR repertoire within histologically normal colorectal mucosa of participants with LS 
at Week 52 (Month12) relative to baseline following vaccination with GAd20-209-FSPs (1 prime) 
and MVA-209-FSPs (1 boost). 
 
c) Changes in the gene expression profile and TCR repertoire of tumor infiltrating lymphocytes (TIL) 
within colorectal adenomas of participants with LS at Week 52 (Month 12) relative to baseline 
following vaccination with GAd20-209-FSPs (1 prime) and MVA-209-FSPs (1 boost). 
 
d) T cell cytotoxicity against matched colorectal adenoma organoids derived from participants with 
LS at Week 52 (Month 12) relative to following vaccination with GAd20-209-FSPs (1 prime) and 
MVA-209-FSPs (1 boost). 
 
e) Percentage change in the number of colorectal adenomas, advanced neoplasia, and/or carcinomas 
in participants with LS at Week 52 (Month 12) relative to baseline following vaccination with 
GAd20-209-FSPs (1 prime) and MVA-209-FSPs (1 boost). 
 
f) Rate of LS-related carcinomas at Week (Month 12) relative to baseline following vaccination with 
GAd20-209-FSPs (1 prime) and MVA-209-FSPs (1 boost). 
 
g) Change in cfDNA detectability and mutation profile in the peripheral blood of participants with LS 
at Weeks 3, 9, 24 (Month 6), and 52 (Month 12) relative to baseline following vaccination with 
GAd20-209-FSPs (1 prime) and MVA-209-FSPs (1 boost). 
 
h) To correlate tobacco and alcohol consumption with the immune response to Nous-209 in trial 
participants. 
 
i) To assess the MMR and/or MSI status of polyps (and adjacent normal mucosa as control) detected 
in the baseline and end-of-the-study colonoscopy using different technologies such as 
immunohistochemistry, MSI analysis by PCR, or next-generation sequencing. 
 

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This protocol will retain residual tissue biopsies of adenomatous polyps and normal mucosa in participants 
with LS to determine future candidate biomarkers measured by genomic and transcriptomic platforms after 
the samples have been processed for standard pathologic evaluation. 
 
 
10.3 
Off-Agent Criteria  
 
Participants may stop taking study agent for the following reasons: completed the protocol-prescribed 
intervention, AE or serious adverse event (SAE), inadequate agent supply, noncompliance, concomitant 
medications, medical contraindication, or development of gastrointestinal or other malignancy. Participants 
will continue to be followed, if possible, for safety reasons and in order to collect endpoint data according 
to the schedule of events.  
 
 
10.4 
Off-Study Criteria 
 
Participants may go ‘off-study’ for the following reasons: the protocol intervention and any protocol-
required follow-up period is completed, AE/SAE, lost to follow-up, non-compliance, concomitant 
medication, medical contraindication, withdraw consent, death, determination of ineligibility (including 
screen failure), pregnancy, or physician decision to take the participant off study. 
 
Participants found to be ineligible during the screening phase and after signing the Informed Consent 
document and assigning the PID number, will be considered “screen failures”.  Such participants will be 
taken off study and the appropriate end of study CRFs will be completed for these participants. In cases of 
early termination, when possible, participants will be asked to return to the clinic site prior to going off 
study for an early termination visit according to the Schedule of Events. A detailed description can be found 
in Section 8.8. 
 
 
10.5 
Study Termination 
 
NCI, DCP as the study sponsor has the right to discontinue the study at any time.  
 
 
11. 
CORRELATIVE/SPECIAL STUDIES 
 
To evaluate the effect of Nous-209 vaccination on our biomarker endpoints, this study will collect and 
process samples of peripheral blood, normal rectosigmoid tissue, and adenomatous (polyp) tissue for all 
eligible participants. Details regarding the planned methodology are provided in the accompanying 
Pharmacokinetic and Biomarker Methods Development Report. 
 
11.1 
Rationale for Methodology Selection 
 
11.1.1 Rationale for Blood Analyses 
We will collect 75 mL of blood from each participant at Visit 1 (Day 1), Week 3, Week 8, Week 9, Week 
24 (Month 6), and Week 52 (Month 12) [during Cohort 1] and at Weeks 60 and 68 [during Cohort 2] in 
order to perform the laboratory correlates outlined below and in the accompanying Biomarker Methods 
Development Report. The correlates will support our primary and secondary objectives to evaluate both the 
temporal and spatial dynamics of neoantigen FSP immunogenicity following vaccination with Nous-209. 
 

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Quantification of immunogenicity: The primary assay to monitor vaccine-induced immunogenicity is the 
ex-vivo IFN-Ȗ ELISpot. 60 mL of blood will be collected in green vacutainer at pre-prime at Visit 1 (Day 
1), post-prime (Week 3), pre-boost (Week 8), post-boost (Week 9) vaccination and then at Months 6 and 
12 visits [during Cohort 1] and at Weeks 60 and 68 [during Cohort 2] will be drawn. Peripheral blood cell 
monocytes (PBMCs) will be isolated and viably frozen using standard protocols. PBMCs will be thawed 
and placed in microplate wells pre-coated with anti-human IFN-Ȗ antibody. PBMC will be cultured with 
antigen peptides for 16-20 hours, resulting in the re-stimulation of the precursor cells and secretion of IFN-
Ȗ. The assay will measure the number IFNȖ-secreting cells from frozen PBMC obtained before and after 
each vaccination (prime and boosts) and at all defined time points in the study will be compared. ELISpot 
activity will be measured using a central ELISpot reader following SOPs. For the purpose of the primary 
endpoint within Cohort 1, PBMCs collected on Visit 1 (Day 1) and post-boost (Week 9) will be used to 
establish immunogenicity, which will be defined as an increase in the number of spot-forming cells of at 
least 80% compared to the baseline in at least one of the 16 peptide pools. Similarly, within Cohort 2, 
PMBCs collected on Week 52 and at 8 Weeks after the last boost with MVA-209-FSP (corresponding to 
Week 68 and Week 60, for arm A and B, respectively) will be used to evaluate immunogenicity following 
prime-boost or boost-alone. Immunogenicity results obtained from ELISPOTs will be put into the context 
of the specific HLA alleles present in each of the participants to verify antigen presentation. 
 
Characterization of T cell receptor (TCR) repertoire in peripheral blood.  For participants in Cohort 
1, 5 mL will be collected in EDTA vacutainer at Visit 1 (Day 1), post-prime (Week 3), pre-boost (Week 8), 
post-boost vaccination (Week 9), months 6 and 12. For participants in Cohort 2, samples will also be 
collected at Weeks 52, 60, and 68. Blood will be aliquoted into cryovials tubes and stored in -80°C. For the 
analysis, frozen blood will be thawed and DNA from CD3+ T cells will be analyzed using ImmunoSeq 
Deep (Adaptive) to assess and quantify the T cell repertoire. 
 
Quantification and characterization of cfDNA in peripheral blood.  10 mL blood will be collected in 
Streck BCT isolation tubes for plasma. Total cell-free DNA (cfDNA) will be purified using standard 
isolation protocols for the time points described in the ELISPOT section. Sequencing reads will be aligned 
using different methodologies such as MS_Mutect (43) and others, and cfDNA MSI fraction will be 
delineated using MSI-Sensor and other methodologies (44-46).   
 
11.1.2 Rationale for Rectosigmoid Tissue Sampling 
At Baseline and Month 12 (or Week 68 for Cohort 2), we will obtain up to a total of 10 jumbo random 
biopsies of macroscopically normal tissue in the visualized rectosigmoid colon. We will collect an 
additional 1-2 biopsies from polyps larger than 10 mm in size. Further details regarding the collection of 
biopsies are provided in Sections 9.2 and 9.6. Our planned usage for the tissue samples is outlined in Table 
1 below. After standard processing, all clinical and research biopsies will be read at each site by an 
experienced gastrointestinal pathologist. Standard reporting criteria for adenomatous and non-adenomatous 
polyps, advanced adenomas and carcinoma will be used. Microscopic inflammation will be reported 
according to established criteria. 
 
Table 1. Planned use of tissue biopsies 
Biopsy # 
Tissue type 
Planned use 
Biopsy 1 (Formalin-fixed) 
Normal 
Histological evaluations and tissue markers 
Biopsy 2-3 (RNALater) 
Normal 
mRNA for transcriptomic analysis 
Biopsy 4 (Flash frozen) 
Normal 
For future studies 
Biopsy 5-10 (Fresh)*/Flash 
frozen 
Normal 
T cell isolation 
Biopsy 11-12 (Fresh)*/Flash 
frozen 
Adenoma** 
T cell isolation 

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*The fresh biopsies will be collected in MD Anderson participants only; and only when feasible due to timing of 
procedure/experimental conditions. The rest of the trial sites will be collecting these samples as flash frozen.  
** only to be collected in participants with polyps > 10 mm 
 
11.1.3 Rationale for Rectosigmoid Tissue Analyses 
T cell TCR repertoire analysis in T cells of normal mucosa and adenomas. Biopsies of normal 
colorectal mucosa and adenomas will be taken during pre-vaccination and post-vaccination colonoscopies 
(baseline, month 12). Lamina propria CD3+ T cells will be isolated using CD3 magnetic bead sorting. 
Autologous PBMCs will be infected with a non-GAd, non-MVA viral vector carrying as insert the 209 
neoantigens or insert-less viral vector control and used as antigen presenting cells. ELISPOT will be 
performed and also DNA from CD3+ T cells will be isolated and analyzed using ImmunoSeq Deep 
(Adaptive) to assess and quantify the T cell repertoire. 
 
11.2 
Comparable Methods 
 
The co-primary and secondary objectives of our study are to provide novel insights regarding the 
immunogenicity effect of Nous-209 vaccination within normal and pre-malignant intestinal tissue of 
individuals with LS. To achieve this aim, we will apply validated high-throughput genomic and 
transcriptomic profiling methods such as ELISPOT and ImmunoSeq. Although the context of these 
methods is unique to our study, similar methods have been applied in prior and on-going studies of GAd 
and MVA prime/boost vaccination, including NCT04041310. We anticipate that our results will be 
comparable to genomics datasets derived from pre-clinical mouse models of LS, as discussed above in 
section 2.3.  
 
 
12. 
SPECIMEN MANAGEMENT  
 
12.1 
Laboratories 
 
12.1.1 Tissue Samples 
 
Normal rectosigmoid mucosa 
 
Biopsy 1 
Histopathology and tissue markers 
 
Eduardo Vilar-Sanchez, M.D., Ph.D. 
MD Anderson Cancer Center 
Biopsy 2, 3: RNALater 
mRNA for genomic analysis 
Eduardo Vilar-Sanchez, M.D., Ph.D. 
MD Anderson Cancer Center 
Biopsy 4: Flash frozen 
Future studies (biorepository) 
Eduardo Vilar-Sanchez, M.D., Ph.D. 
MD Anderson Cancer Center 
Biopsy 5-10: Fresh*/Flash Frozen 
T cell isolation/TCR sequencing 
Eduardo Vilar-Sanchez, M.D., Ph.D. 
MD Anderson Cancer Center 
Colon polyp 
 
Biopsy 11-12: Fresh*/Flash Frozen 
T cell isolation/TCR sequencing 
Eduardo Vilar-Sanchez, M.D., Ph.D. 
MD Anderson Cancer Center 
*The fresh biopsies will be collected in MD Anderson participants only; and only when feasible due to timing of 
procedure/experimental conditions. The rest of the trial sites will be collecting those samples as flash frozen.  
 
12.1.2 Blood Samples 
 
Whole blood 
Eduardo Vilar-Sanchez, M.D., Ph.D. 
MD Anderson Cancer Center 

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PBMCs 
 
Central Laboratory (Nouscom, s.r.l.)  
Italy  
 
 
Plasma 
cfDNA 
Eduardo Vilar-Sanchez, M.D., Ph.D. 
MD Anderson Cancer Center 
 
 
 
12.1.3 Abnormal mucosa/polypoid lesions tissue 
 
Abnormal mucosa/polypoid lesions tissue 
Future studies  
Eduardo Vilar-Sanchez, M.D., Ph.D. 
MD Anderson Cancer Center 
 
 
 
12.2 
Collection and Handling Procedures 
 
Random, blinded, unique ID numbers will be assigned to specimens at baseline and post-treatment and will 
be distributed with the PID number.  All specimens will be labeled with the unique specimen number 
(XXXX), date (MM-DD-YY) and product code (N) using a permanent, waterproof marker.  All efforts will 
be made to keep laboratories blinded from distinguishing participant information and visit point but will be 
kept available in a password protected log at each site to indicate which specimen number belongs to which 
participant and at what visit.  Shipped specimens will be tracked by the shipping company per routine. 
 
12.2.1 Fresh Tissue 
Rectosigmoid colon mucosa biopsy techniques have been described in Section 9.2 and 9.6. The types of 
assays planned for each of the tissue biopsy specimens are listed in Table 1, Section 11.  
 
12.2.1.1 Normal rectosigmoid colon mucosa 
 
Biopsy 1: Histopathology and tissue markers 
Collected at Baseline and Study Visit 9 for Cohort 1 participants (who do not proceed to Cohort 2) or at 
Baseline and Study Visit 11 (for participants who continue on to participate in Cohort 2).  Normal 
rectosigmoid colon mucosa biopsy 1 will be processed following standard pathological procedures to 
obtain a formalin-fixed paraffin-embedded block of the biopsy. The block will be sent to the Vilar Lab at 
MD Anderson to prepare an H&E slide for pathology evaluation and verification of the normal status of 
the mucosa. The rest of the block will be used to determine the type and number of immune and 
mesenchymal cells changes after exposure to Nous-209. Paraffin blocks obtained from Biopsy 1 will be 
used to create a TMA and assessed by different multiplex technologies.  
 
Biopsy 2, 3: RNALater 
mRNA for genomic analysis collected at Baseline and Study Visit 9 for Cohort 1 participants (who do not 
proceed to Cohort 2) or at Baseline and Study Visit 11 (for participants who continue on to participate in 
Cohort 2). Normal rectosigmoid colon mucosa biopsies 2 and 3 will be kept in RNALater for mRNA 
extraction and sequencing studies. Immediately upon removal from participant, the tissue should be 
rinsed in sterile phosphate buffered saline (PBS).  Using tissue collection tool, place each biopsy in (1) 
prefilled cryovial. Store in a secure 4 °C refrigerator (range of 4-6 °C) for a minimum of 24 hours and up 
to 7 days. Remove the cryovials from the refrigerator and place them in a secure -80 degree Celsius 
freezer (range -70 °C to  -80 °C). 
 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–53– 
February 3, 2025 
Biopsy 4: Flash Frozen 
Future studies (biorepository) collected at Baseline and Study Visit 9 for Cohort 1 participants (who do 
not proceed to Cohort 2) or at Baseline and Study Visit 11 (for participants who continue on to participate 
in Cohort 2). Normal rectosigmoid colon mucosa will be flash frozen in liquid nitrogen.  Immediately 
upon removal from participant, colonic tissue should be rinsed in sterile PBS. All fecal material should be 
removed from the sample during this process. The biopsies will be placed in cryovials, then placed in 
liquid nitrogen or on dry ice. Store at a temperature of -80 °C. Biopsies 4 will be retained for those cases 
in which any of the previous techniques fail to render adequate results due to lack of sufficient amounts of 
tissue or for future genomic and transcriptomic studies. 
 
Biopsy 5 – 10: Fresh/Flash Frozen 
T cell isolation/TCR sequencing collected at Baseline and Study Visit 9 for Cohort 1 participants (who do 
not proceed to Cohort 2) or at Baseline and Study Visit 11 (for participants who continue on to participate 
in Cohort 2). Fresh biopsies will be collected in MD Anderson participants only; and only when feasible 
due to timing of procedures/experimental conditions. The rest of the trial sites will be collecting these 
samples as flash frozen.  Normal rectosigmoid colon mucosa biopsies 5 through 10 will be plunged into a 
50 mL tube containing ice-cold sterile PBS, immediately upon removal. The tissue will then be minced 
with a sterile scalpel inside a petri dish containing collagenase dissociation solution (DS). The dissected-
tissue solution will be incubated at 37qC for 1.5 hours to activate the enzymatic digestion by collagenase. 
Then, the digested solution will be serially filtered using 70 Pm and 40 Pm filters to obtain a single-cell 
suspension, which will be washed with PBS and resuspended in PBS with 0.04% BSA. CD3+ TILs will be 
isolated from the single-cell suspension using the REAlease® CD3 (TIL) MicroBead Kit (Milteny Biotec, 
cat#130-121-152). DNA extraction will be performed from the sorted CD3+ TILs using the QIAamp DNA 
Micro kit. With the DNA, we will perform capture, amplification, and sequencing of the CDR3 region from 
the TCRȕ variable (V), diversity (D) and joining (J) segments using the ImmunoSEQ TCRB Assay by 
Adaptive Biotechnologies, Inc (Seattle, WA). (edited)  
 
12.2.1.2 Colon polyp 
 
Biopsy 11, 12: Fresh/Flash Frozen 
T cell isolation/TCR sequencing collected at Baseline and Study Visit 9 for Cohort 1 participants (who do 
not proceed to Cohort 2) or at Baseline and Study Visit 11 (for participants who continue on to participate 
in Cohort 2). Fresh biopsies will be collected in MD Anderson participants only; and only when feasible 
due to timing of procedures/experimental conditions.  The rest of the trial sites will be collecting these 
samples as flash frozen. Colon polyp biopsies 11 and 12 will be plunged into a 50 mL tube containing ice-
cold sterile PBS, immediately upon removal. The tissue will then be minced with a sterile scalpel inside a 
petri dish containing collagenase dissociation solution (DS). The dissected-tissue solution will be incubated 
at 37qC for 1.5 hours to activate the enzymatic digestion by collagenase. Then, the digested solution will 
be serially filtered using 70 Pm and 40 Pm filters to obtain a single-cell suspension, which will be washed 
with PBS and resuspended in PBS with 0.04% BSA. CD3+ TILs will be isolated from the single-cell 
suspension using the REAlease® CD3 (TIL) MicroBead Kit (Milteny Biotec, cat#130-121-152). DNA 
extraction will be performed from the sorted CD3+ TILs using the QIAamp DNA Micro kit. With the DNA, 
we will perform capture, amplification, and sequencing of the CDR3 region from the TCRȕ variable (V), 
diversity (D) and joining (J) segments using the ImmunoSEQ TCRB Assay by Adaptive Biotechnologies, 
Inc (Seattle, WA). (edited)  
 
12.2.2 Blood samples 
 
PBMC, plasma, and frozen blood  

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–54– 
February 3, 2025 
Collected at Study Visits 1, 3-5, 7, and 9 in Cohort 1 and at Visits 9, 10 and 11 in Cohort 2. Heparinized 
whole blood will be collected and timely processed to collect PBMCs according to established protocols. 
For preservation until analysis, PBMCs will be mixed in 1:1 ratio with a specialized media in 10% 
DMSO, slowly cooled at 1°C/min and stored in the vapor phase of liquid nitrogen in backed up freezers at 
a temperature of -132°C for preservation until analysis. For plasma, blood will be collected using streck 
tube. Centrifuge upon collection into cryovial tubes and quickly frozen at -80°C. Whole blood collected 
in EDTA tube will be aliquoted into cryovial tubes and frozen at -80 °C until shipment.   
 
12.2.3 Formalin-Fixed Paraffin-Embedded Tissue 
Collected at Baseline and Study Visits 9 for Cohort 1 participants (who do not proceed to Cohort 2) or at 
Baseline and Study Visit 11 (for participants who continue on to participate in Cohort 2). If any abnormal 
mucosa/polypoid lesions were identified during Baseline and/or Study Visit 9 and/or Study Visit 11 [for 
participants in Cohort 2], standard procedures of clinical care of the local enrolling site should be followed 
for biopsy, tissue handling, and subsequent pathologic assessment of these lesions. This process involves 
the preservation of tissues in formalin-fixed paraffin-embedded blocks. Any abnormal mucosa/polypoid 
lesions tissue that may be residual after clinical care pathologic assessment should be collected and retained 
for research purposes.  Residual tissue at every study site after standard pathology assessment will be 
shipped to Dr. Vilar-Sanchez’s laboratory at MD Anderson Cancer Center per shipping instructions 
provided below. 
 
12.3 
Shipping Instructions 
 
The following table describes packaging, carrier requirements, when specimens may be shipped, and name, 
address, and telephone number of the person to whom the specimens are being sent.  
 
Table 2. Overview of specimen shipment specifications and destinations 
Biomarker/ 
Procedure 
Laboratory 
Type of 
specimen 
Packaging 
requirements 
Batching 
Allowed 
(Yes/No) 
Contact person, 
address and telephone 
number to whom 
specimens are being 
sent  
Normal 
rectosigmoid colon 
mucosa biopsies #5-
10 
 
Colon polyp 
biopsies #11 and 12 
 
Eduardo 
Vilar-
Sanchez 
Tissue (flash 
frozen) 
Dry ice / 
Diagnostic Goods 
Label 
 
Yes 
Vilar-Sanchez Lab 
UT – MD Anderson 
Cancer Center 
6767 Bertner St. 
BSRB, S7.8414 
Houston, TX 77030  
United States 
P: (713) 563-9840 / 
Ext. 7-2170 
F: (713) 834-6397 
Email: 
evilar@mdanderson.org 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–55– 
February 3, 2025 
Normal 
rectosigmoid colon 
mucosa biopsies #5-
10 
 
Colon polyp 
biopsies #11 and 12 
 
Note: MD Anderson 
site only. 
Eduardo 
Vilar-
Sanchez 
Tissue (fresh, 
refrigerated) 
Refrigerated 
(range of 4-6 °C) 
/ Diagnostic 
Goods Label 
No 
Vilar-Sanchez Lab 
UT – MD Anderson 
Cancer Center 
6767 Bertner St. 
BSRB, S7.8414 
Houston, TX 77030  
United States 
P: (713) 563-9840 / 
Ext. 7-2170 
F: (713) 834-6397 
Email: 
evilar@mdanderson.org 
 
 
 
 
 
 
Normal 
rectosigmoid colon 
mucosa biopsy #4 
 
 
Eduardo 
Vilar-
Sanchez 
Tissue (flash 
frozen)  
Dry ice / 
Diagnostic Goods 
Label 
Yes 
Vilar-Sanchez Lab 
UT – MD Anderson 
Cancer Center 
6767 Bertner St. 
BSRB, S7.8414 
Houston, TX 77030  
United States 
P: (713) 563-9840 / 
Ext. 7-2170 
F: (713) 834-6397 
Email: 
evilar@mdanderson.org 
 
 
 
 
 
 
Normal 
rectosigmoid 
mucosa biopsies #2 
and 3 
 
Eduardo 
Vilar-
Sanchez 
Tissue 
(RNALater) 
Dry ice / 
Diagnostic Goods 
Label 
Yes 
Vilar-Sanchez Lab 
UT – MD Anderson 
Cancer Center 
6767 Bertner St. 
BSRB, S7.8414 
Houston, TX 77030  
United States 
P: (713) 563-9840 / 
Ext. 7-2170 
F: (713) 834-6397 
Email: 
evilar@mdanderson.org 
 
 
 
 
 
 
Any abnormal 
mucosa/polypoid 
lesions tissue that 
may be residual 
after clinical care 
pathologic 
assessment  
Eduardo 
Vilar-
Sanchez 
Formalin-Fixed 
Paraffin-
Embedded 
Diagnostic Goods 
Label 
Yes 
Vilar-Sanchez Lab 
UT – MD Anderson 
Cancer Center 
6767 Bertner St. 
BSRB, S7.8414 
Houston, TX 77030  
United States 
P: (713) 563-9840 / 
Ext. 7-2170 
F: (713) 834-6397 
Email: 
evilar@mdanderson.org 
 
 
 
 
 
 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–56– 
February 3, 2025 
Frozen blood 
Eduardo 
Vilar-
Sanchez 
Blood  
Dry ice / 
Diagnostic Goods 
Label 
Yes 
Vilar-Sanchez Lab 
UT – MD Anderson 
Cancer Center 
6767 Bertner St. 
BSRB, S7.8414 
Houston, TX 77030  
United States 
P: (713) 563-9840 / 
Ext. 7-2170 
F: (713) 834-6397 
Email: 
evilar@mdanderson.org 
PBMCs  
 
Claudia 
Massimi 
 
 
PBMCs  
aliquots 
 
Liquid 
Nitrogen/Diagnos
tic Goods Label 
 
Yes 
Central Lab. 
Nouscom srl  
Via di Castel Romano 
100 Rome, 00128 IT 
Claudia Massimi 0039 
0699775303  
  
Plasma 
Eduardo 
Vilar-
Sanchez 
Plasma 
Dry ice / 
Diagnostic Goods 
Label 
Yes 
Vilar-Sanchez Lab 
UT – MD Anderson 
Cancer Center 
6767 Bertner St. 
BSRB, S7.8414 
Houston, TX 77030  
United States 
P: (713) 563-9840 / 
Ext. 7-2170 
F: (713) 834-6397 
Email: 
evilar@mdanderson.org 
 
Shipping frequency: 
x 
Batched specimens: Unless otherwise specified in Table 2 above, specimens will be shipped in 
batches. Each batch must be sent with overnight delivery. For shipping frequency refer to the study 
lab manual.  
 
Instructions for shipping to MD Anderson Cancer Center (Dr. Vilar-Sanchez): 
x 
Unless otherwise specified in Section 12.2 and Table 2 above, all samples (either tissue or blood) 
must be kept frozen (-80 °C or below) after preparation and until shipment is initiated. 
x 
Wrap the frozen samples in bundles or place samples in a storage box. Then place in a plastic 
freezer bag. 
x 
Shipping containers should be insulated and filled with enough dry ice to prevent specimens from 
thawing.  The shipping labels should be affixed firmly to the outside of each container. 
x 
Plasma must be kept frozen (-80°C or below) after preparation and until shipment is initiated. 
x 
All samples must be shipped in accordance with local biohazard requirements. Please refer to 
your institutional policy for biohazard labeling and packaging for shipment of hazardous and 
infectious human samples.  Place dry ice around the bundles or the storage box.  Include enough 
dry ice to ensure the dry ice does not evaporate before shipment is delivered.  
x 
Ship via overnight express (i.e., FedEx, UPS).  Do not ship on Thursday, Friday or the day prior 
to a public holiday. 
 
Instructions for shipping to Central laboratory – Nouscom, s.r.l. (Attention to: Claudia Massimi): 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–57– 
February 3, 2025 
x 
MD Anderson will schedule the shipments for all the sites upon agreement with the Central lab. 
x 
PBMC must be kept frozen (-80°C) for less than a week. For long term storage (more than a 
week) please store in liquid nitrogen until shipment is initiated.  
x 
Shipping containers should be insulated and filled with enough liquid nitrogen to prevent 
specimens from thawing.  The shipping labels should be affixed firmly to the outside of each 
container. 
x 
All samples must be shipped in accordance with local biohazard requirements. Please refer to 
your institutional policy for biohazard labeling and packaging for shipment of hazardous and 
infectious human samples. If shipping in dry ice, include enough to ensure it does not evaporate 
before shipment is delivered.  
x 
Ship via World Courier. 
 
Include a copy of the corresponding case report form (CRF) matching each specimen being shipped. Before 
placing in the shipping container, put the CRFs in a plastic bag for protection. Sample shipment should be 
made to the address provided in Table 2. 
 
All specimens will be shipped in accordance with the International Air Transport Association (IATA) 
Dangerous Goods Regulations.  The study staff from each site will be responsible for shipping specimens 
to the appropriate laboratory listed in Table 2. 
 
 
12.4 
Tissue Banking 
 
The NCI reserves the right to require the transfer of biologic specimens and data, or true copies of such 
data, acquired from research supported under this award to an eligible third party. This transfer can occur 
in order to preserve the specimens and data and/or to continue the research. Third parties supported under 
this award must be informed of this right.   
 
 
13. 
REPORTING ADVERSE EVENTS  
 
DEFINITION: An adverse event (AE) means any untoward medical occurrence associated with the use of 
a drug in humans, whether or not the untoward occurrence is considered drug related. Thus, an AE can 
include any unfavorable sign (e.g., an abnormal laboratory finding), symptom, or clinical outcome 
temporally associated with the use of a test drug, active control, or placebo, regardless of whether the event 
is thought to be related to the drug. An AE can arise with the use of a drug or biologic (e.g., use for a 
purpose other than FDA-approved indication or in combination with another drug) and with any route of 
administration, formulation, or dose, including an overdose. 
 
Please note that all abnormal clinical laboratory values that are determined to be of clinical significance 
based on a physician’s assessment are to be reported as AEs. A clinically significant lab value is one that 
indicates a new disease process, an exacerbation or worsening of an existing condition, or requires further 
action(s) to be taken. Those labs determined to be of no clinical significance or of unknown clinical 
significance (per the physician’s assessment) should not be reported as AEs. Any lab value of unknown 
clinical significance should continue to be investigated/followed-up further for a final determination, if 
possible. 
(See 
the 
DCP 
Baseline 
and 
Adverse 
Event 
Reporting 
Guidelines 
[https://prevention.cancer.gov/clinical-trials/clinical-trials-management/cp-ctnet-instructions-forms] 
for 
more detail on reporting abnormal clinical laboratory values.) 
 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–58– 
February 3, 2025 
A list of AEs that have occurred or might occur can be found in §8.2 Reported Adverse Events and Potential 
Risks, as well as the Investigator’s Brochure or package insert.  
 
 
13.1 
Adverse Events 
 
13.1.1 Reportable AEs 
All AEs that occur after the informed consent is signed and baseline assessments are collected, must be 
recorded on the AE CRF whether or not related to study agent. 
 
13.1.2 AE Data Elements 
The following data elements are required for AE reporting: 
x 
AE verbatim term 
x 
NCI Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) AE term 
(MedDRA lowest level term) 
x 
CTCAE (MedDRA) System Organ Class (SOC) 
x 
Event onset date and event ended date 
x 
Treatment assignment code (TAC) at time of AE onset 
x 
Severity grade 
x 
Attribution to study agent (relatedness) 
x 
Whether or not the event was reported as a SAE 
x 
Whether or not the participant dropped due to the event 
x 
Outcome of the event 
 
13.1.3  Severity of AEs 
 
 
 
13.1.3.1 Identify the AE using CTCAE v5.0.  
The CTCAE provides descriptive terminology (MedDRA lowest level term) and a severity grading scale 
for each AE listed. A copy of the CTCAE can be found at:  
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm 
 
AE severity will be assessed according to the grade associated with the CTCAE term. AEs that do not have 
a corresponding CTCAE term will be assessed according to the general guidelines for grading used in the 
CTCAE v5.0. as shown in Table 3 below.  
 
Table 3. CTCAE v5.0 general severity guidelines:  
Grade 
Severity 
Description  
1 
Mild 
Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated. 
2 
Moderate 
Moderate; minimal, local or noninvasive intervention indicated; 
limiting age-appropriate instrumental activities of daily living 
(ADL)*. 
3 
Severe 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; 
disabling; limiting self-care ADL**. 
4 
Life-threatening 
Life-threatening consequences; urgent intervention indicated. 
5 
Fatal 
Death related to AE. 
   

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–59– 
February 3, 2025 
*Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc. 
**Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, taking 
medications, and not bedridden. 
 
13.1.3.2 Injection site reactions and systemic reactogenicity symptoms 
Injection site reactions and systemic reactogenicity symptoms, both subsets of all AEs, may occur up to 7 
days after administration of study drugs (GAd20-209-FSP and/or MVA-209-FSP). Such events will also 
be reported by use of a participant-completed Vaccine Report Card (Appendix E), captured on a separate 
CRF, and reported to NCI, DCP. The following guidelines will be used to evaluate injection site reactions 
and reactogenicity symptoms, the onset of which is within 7 days after administration of study drugs 
(GAd20-209-FSP and/or MVA-209-FSP):  
 
Table 4. Injection Site Reaction and Systemic Reactogenicity Grading 
  
Mild (Grade 1)  
Moderate (Grade 2)  
Severe (Grade 3)  
Potentially Life Threatening 
(Grade 4)  
Injection Site Reactions 
Pain  
Does not interfere 
with activity  
Repeated use of non-
narcotic pain reliever 
> 24 hours or 
interferes with 
activity  
Any use of narcotic pain 
reliever or prevents 
daily activity  
Emergency room (ER) visit or 
hospitalization  
Tenderness  
Mild discomfort 
to touch  
Discomfort with 
movement  
Significant discomfort 
at rest  
ER visit or hospitalization  
Erythema/ Redness 
2.5 – 5 cm  
5.1 – 10 cm  
> 10 cm  
Necrosis or exfoliative 
dermatitis  
Induration/ Swelling  
2.5 – 5 cm and 
does not interfere 
with activity  
5.1 – 10 cm or 
interferes with 
activity  
> 10 cm or prevents 
daily activity  
Necrosis  
Itching 
Mild or localized; 
topical 
intervention 
indicated 
Widespread and 
intermittent; 
skin changes from 
scratching; oral 
intervention indicated; 
limiting instrumental 
ADL 
Widespread and 
constant; 
limiting self care ADL 
or sleep; 
systemic corticosteroid 
or 
immunosuppressive 
therapy 
indicated 
 
Bruising 
Localized or in a 
dependent 
area 
Generalized 
 
 
Systemic Reactogenicity Symptoms 
Fever 
100.4qF – 102.2qF 
102.3qF – 104.0qF 
> 104.0qF 
 
Chills 
Mild sensation of 
cold; 
shivering; 
chattering of teeth 
Moderate tremor of 
the 
entire body; narcotics 
indicated 
Severe or prolonged, 
not 
responsive to narcotics 
 
Malaise  
Uneasiness or lack 
of well 
being 
Uneasiness or lack of 
well 
being limiting 
instrumental 
Uneasiness or lack of 
well 
being limiting self-care 
ADL 
 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–60– 
February 3, 2025 
  
Mild (Grade 1)  
Moderate (Grade 2)  
Severe (Grade 3)  
Potentially Life Threatening 
(Grade 4)  
ADL 
Fatigue 
Fatigue relieved 
by rest 
Fatigue not relieved 
by rest; 
limiting instrumental 
ADL 
Fatigue not relieved by 
rest, 
limiting self care ADL 
 
Muscle aches/myalgia 
Mild pain 
Moderate pain; 
limiting 
instrumental ADL 
Severe pain; limiting 
self care 
ADL 
 
Headache 
Mild pain 
Moderate pain; 
limiting 
instrumental ADL 
Severe pain; limiting 
self care 
ADL 
 
Nausea 
Loss of appetite 
without 
alteration in eating 
habits 
Oral intake decreased 
without 
significant weight 
loss, 
dehydration or 
malnutrition   
Inadequate oral caloric 
or 
fluid intake; tube 
feeding, 
TPN, or hospitalization 
indicated 
 
Vomiting 
Intervention not 
indicated 
Outpatient IV 
hydration; 
medical intervention 
indicated 
tube feeding, 
TPN, or hospitalization 
indicated 
 
Anorexia 
Loss of appetite 
without 
alteration in eating 
habits 
Oral intake altered 
without 
significant weight loss 
or 
malnutrition; oral 
nutritional 
supplements indicated 
Associated with 
significant 
weight loss or 
malnutrition 
(e.g., inadequate oral 
caloric 
and/or fluid intake) 
 
Joint pain/arthralgia 
Mild pain 
Moderate pain; 
limiting 
instrumental ADL 
Severe pain; limiting 
self care 
ADL 
 
 
 
13.1.4 Assessment of relationship of AE to treatment 
The possibility that the AE is related to study agent will be classified as one of the following: unrelated, 
unlikely, possible, probable, definite. Criteria for these classifications are provided in DCP’s Serious 
Adverse Event Report Form: Instructions for Completion and Submission 
(https://prevention.cancer.gov/clinical-trials/clinical-trials-management/cp-ctnet-instructions-
forms). 
 
13.1.5 Follow-up of AEs 
All AEs, including laboratory abnormalities that in the opinion of the investigator are clinically significant, 
will be followed according to good medical practices and documented as such.  
 
13.1.6 Collection of AEs 
AEs will be collected for each participant for a maximum of 52 weeks (12 months) after the receipt of the 
GAd prime vaccination.  
 
 
13.2 
Serious Adverse Events  

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–61– 
February 3, 2025 
 
13.2.1 Definition 
Regulations at 21 CFR §312.32 define an SAE as any untoward medical occurrence that at any dose has 
one or more of the following outcomes: 
 
• 
Death 
• 
A life-threatening AE  
(According to FDA safety guidelines, an AE is considered life-threatening if in the view of 
either the investigator or sponsor, its occurrence places the subject at immediate risk of death. 
It does not include an event that, had it occurred in a more severe form, might have caused 
death. Example: An allergic reaction resulting in angioedema of the larynx, allergic 
bronchospasm or anaphylaxis is considered life-threatening; however, an allergic reaction 
resulting only in a localized rash is not life-threatening.)   
     • 
In patient hospitalization or prolongation of existing hospitalization  
(NCI, DCP uses admission or stay (including emergency room) equal to or greater than 24 hours 
as the definition of hospitalization. Exceptions are hospitalization for treatment of a pre-existing 
condition [unless the condition increased in severity on study], outpatient surgery, 
planned/elective procedures, and procedures described in the protocol [e.g., pharmacokinetic 
sampling, surgery] even if the hospital stay is of the described length; however, it does include 
events resulting from any of these that fulfill other serious outcome criteria, e.g., prolongation of 
hospitalization or life-threatening.) 
• 
A persistent or significant incapacity or substantial disruption of the ability to conduct normal life 
functions 
• 
A congenital anomaly or birth defect 
• 
Important medical events that may not be immediately life-threatening or result in death 
or hospitalization should also be considered serious when, based upon appropriate 
medical judgment, they may jeopardize the Participant and may require intervention to 
prevent one of the other outcomes listed above. 
 
13.2.2 Reporting SAEs to DCP 
 
13.2.2.1 The accruing LAO and all Affiliated Organizations (AOs) will report SAEs on the DCP SAE 
Report Form as described in DMACC’s CP-CTNet SOP 02-01, found at  CP-CTNet SOP 02-01 
Reporting Serious Adverse Events (cp-ctnet-dmacc.org) and DCP’s Serious Adverse Event 
Report Form: Instructions for Completion and Submission found at 
https://prevention.cancer.gov/clinical-trials/clinical-trials-management/cp-ctnet-instructions-
forms.  
 
13.2.2.2 Contact the DCP Medical Monitor, Protocol PI, and DCP Regulatory Contractor’s Safety 
Department within 24 hours of knowledge of the event. Contact via email is preferred, but phone 
contact is acceptable.  
 
 
NCI DCP Medical Monitor: 
Luz María Rodríguez, MD, FACS  
National Cancer Institute  
Division of Cancer Prevention 
Gastrointestinal and Other Cancers Research Group 
9609 Medical Center Drive, Room: 5E228 
Rockville, MD 20850 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–62– 
February 3, 2025 
Phone: 240-276-7039 
Fax: 240-276-7848 
E-mail address: rodrigul@mail.nih.gov 
 
The contact information for the DCP Regulatory Contractor’s Safety Department is: phone: 650-691-4400 
x133; email: safety@ccsainc.com). 
 
Include the following information when contacting both the DCP Medical Monitor and the DCP 
Regulatory Contractor’s Safety Department: 
x 
Participant ID 
x 
Date and time of SAE onset 
x 
Date and time the accruing LAO or AO was notified about the SAE by the study participant or 
other person(s) 
x 
Name of person reporting the SAE 
x 
Call back phone number and email address 
x 
Accruing LAO or AO at which the subject is enrolled 
x 
DCP protocol number 
x 
Title of protocol 
x 
Suspected drugs (if any) 
x 
Description of the SAE, including attribution to the Investigational Agent 
 
13.2.2.3 
The accruing LAO and AOs will email written SAE reports to the DCP Medical Monitor, 
Protocol PI, LAO Coordinator, and the DCP Regulatory Contractor’s Safety Department within 48 hours 
of learning of the event using the Word SAE Report Form.    
  
13.2.2.4 
The DCP Medical Monitor and the DCP Regulatory Contractor will determine which SAEs 
require submission to FDA or the manufacturer as expedited safety reports. 
 
13.2.2.5 
The accruing LAO and AOs will comply with applicable regulatory requirements related 
to reporting SAEs to the CIRB and local IRB/IEC as applicable. Specifically, if an SAE meets the definition 
of an unanticipated problem (UP; i.e., requires expedited reporting to FDA or the manufacturer as a safety 
report [serious, unexpected, and related to a study agent]), then it needs to be reported to the CIRB by the 
Signatory Institution PI at the accruing LAO or AO where the SAE occurred (see SOP 02-02 Reporting 
Protocol Deviations for more information). In addition to CIRB requirements, UPs must be reported to the 
accruing LAO’s or AO’s local IRB per local requirements. 
 
13.2.3 Follow-up of SAE 
Accruing LAO or AO staff should send follow-up reports as requested when additional information is 
available. Additional information should be entered on the DCP SAE Report Form in the appropriate 
format. Follow-up information should be sent to the DCP Medical Monitor, Protocol PI, LAO Coordinator, 
and DCP Regulatory Contractor’s Safety Department as soon as available. SAEs related to the study agent 
will be followed until resolved.  
 
Furthermore, to minimize the number of study participants exposed to a potentially unacceptable risk, study 
treatment and enrollment will be paused pending a comprehensive safety evaluation by the DCP Medical 
Monitor, DSMB, and/or IRB/IEC when any of the following death events occur:  
 
x 
Any death at least possibly related to the study treatment 
x 
Any death within 30 days of receiving the study treatment unless clearly due to disease progression 
 

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14. 
STUDY MONITORING 
 
14.1 
Data Management 
 
This study will report clinical data using Medidata RAVE, a cloud–based clinical trials data management 
system managed by the DMACC. RAVE will be the database of record for the protocol and subject to NCI 
and FDA audit. All RAVE users will be trained to use the system and will comply with the instructions in 
the guidelines provided to the LAO by the DMACC as well as applicable regulatory requirements such as 
21 CFR; Part 11. Data management procedures for this protocol will adhere to the Data Management Plan 
(DMP) on file at the DCP for this study. 
 
 
14.2 
Electronic Case Report Forms 
 
The System Variable and Attribute Report (SVAR) template will be used to create the study-specific eCRFs 
or SVAR workbook. The SVAR template contains NCI Common Data Elements (CDEs) to facilitate data 
collection and analysis across studies. The SVAR template will be modified to capture the unique data 
elements of each protocol and prepare a protocol-specific SVAR workbook. NCI CDEs, where available, 
shall be used for the initial SVAR workbooks and all subsequent workbook modifications. The DCP 
approved SVAR will be used to create the electronic CRF (e-CRF) screens in the Medidata RAVE 
application.  Site staff will enter data into the e-CRFs in Medidata RAVE. SVAR amendments, if needed, 
will be submitted to the DCP Protocol Information Office for review and approval prior to deployment in 
Medidata RAVE.  Approved changes will be programmed into the Medidata RAVE database by DMACC. 
Study questionnaires will be collected electronically using the REDCap system.  
 
 
14.3 
Source Documents 
 
Source documentation will include only those documents containing original forms of data, including clinic 
charts, shadow files, hospital charts, and physician notes.  Data recorded directly on the CRFs designated 
as source documents (i.e., no prior written or electronic record of data) will be considered source data.  All 
other data recorded on the CRFs will not be considered source documentation. 
 
 
14.4 
Data and Safety Monitoring Plan 
 
NIH and NCI policy requires a Data and Safety Monitoring Plan (DSMP) to document the institution’s 
procedures to ensure safety of participants, validity of data, and the appropriate termination of studies for 
which significant benefits or risks have been uncovered or when it appears that the trials cannot be 
concluded successfully.  
 
The Data and Safety Monitoring Plan for the iCAN-PREVENT Consortium is on file at the DCP.  This 
study will be monitored yearly by the MDACC Data and Safety Monitoring Board (DSMB), the data and 
safety monitoring board of record for this study.   The DSMB reports to the President, or his designee, as 
the on-campus representative of The University of Texas Board of Regents. It oversees the data and patient 
safety issues for randomized clinical trials that originate at MD Anderson; that are coordinated or analyzed 
by MD Anderson and are not being monitored by any other DSMB; or have been designated as requiring 
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are to ensure that patients' rights pertaining to participation in a research study are protected, and that 
patients' interests are prioritized over the interests of the scientific investigation. Responsibilities include: 
(a) Review interim analyses of outcome data (prepared by the study statistician or other responsible 
person at the time points defined in the study) approved by the IRB and additional time points 
as determined by the DSMB, and to recommend, if necessary, whether the study needs to be 
changed or terminated based on these analyses; 
(b) Determine whether, and to whom, outcome results should be released prior to the reporting of 
study results; 
(c) Review interim toxicity data and efficacy of treatment; 
(d) Review major research modifications proposed by the investigator or appropriate study 
committee prior to implementation (e.g., termination, dropping an arm based on toxicity results 
from the study or results of other studies, increasing target sample size). 
 
To minimize the number of study participants exposed to a potentially unacceptable risk, study treatment 
and enrollment will be paused pending a comprehensive safety evaluation by the DSMB, DCP Medical 
Monitor, and/or IRB/IEC when any of the following death events occur:  
 
• 
Any death at least possibly related to the study treatment 
• 
Any death within 30 days of receiving the study treatment unless clearly due to disease progression 
 
Refer to the Data and Safety Monitoring Plan for the iCAN-PREVENT Consortium on file at the DCP for 
further details. 
 
 
14.5 
Sponsor or FDA Monitoring  
 
The NCI, DCP (or their designee), pharmaceutical collaborator (or their designee), or FDA may 
monitor/audit various aspects of the study. These monitors will be given access to facilities, databases, 
supplies and records to review and verify data pertinent to the study.  
 
 
14.6 
Record Retention 
 
Clinical records for all participants, including eCRFs, all source documentation (containing evidence of 
study eligibility, history and physical findings, laboratory data, results of consultations, etc.), as well as 
CIRB records and other regulatory documentation will be retained by the Investigator in a secure storage 
facility in compliance with Health Insurance Portability and Accountability Act (HIPAA), Office of Human 
Research Protections (OHRP), Food and Drug Administration (FDA) regulations and guidances, and 
NCI/DCP requirements, unless the standard at the site is more stringent. The records for all studies 
performed under an IND will be maintained, at a minimum, for two years after the approval of a New Drug 
Application (NDA). For NCI/DCP, records will be retained for at least three years after the completion of 
the research. NCI will be notified prior to the planned destruction of any materials. The records should be 
accessible for inspection and copying by authorized persons of the Food and Drug Administration. If the 
study is done outside of the United States, applicable regulatory requirements for the specific country 
participating in the study also apply. 
 
 
14.7 
Cooperative Research and Development Agreement (CRADA)/Clinical Trials Agreement 
(CTA) 
 

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The agent supplied by DCP, NCI used in this protocol, is provided to the NCI under a Collaborative 
Agreement (CTA) between the Pharmaceutical Company (Nouscom) (hereinafter referred to as 
Collaborator) and the NCI Division of Cancer Prevention. Therefore, the following obligations/guidelines, 
in addition to the provisions in the “Intellectual Property Option to Collaborator” contained within the terms 
of award, apply to the use of Agent in this study: 
 
14.7.1 Agent(s) may not be used for any purpose outside the scope of this protocol, nor can Agent(s) be 
transferred or licensed to any party not participating in the clinical study. Collaborator(s) data for Agent(s) 
are confidential and proprietary to Collaborator(s) and shall be maintained as such by the investigators. The 
protocol documents for studies utilizing Investigational Agents contain confidential information and should 
not be shared or distributed without the permission of the NCI. If a Participant participating on the study or 
participant’s family member requests a copy of this protocol, the individual should sign a confidentiality 
agreement. A suitable model agreement can be downloaded from the DCP website. 
 
14.7.2 For a clinical protocol where there is an Investigational Agent used in combination with (an) other 
Investigational Agent(s), each the subject of different collaborative agreements, the access to and use of 
data by each Collaborator shall be as follows (data pertaining to such combination use shall hereinafter be 
referred to as "Multi-party Data”). 
 
14.7.3 NCI must provide all Collaborators with prior written notice regarding the existence and nature of 
any agreements governing their collaboration with NIH, the design of the proposed combination protocol, 
and the existence of any obligations that would tend to restrict NCI's participation in the proposed 
combination protocol. 
 
14.7.4 Each Collaborator shall agree to permit use of the Multi-Party Data from the clinical trial by any 
other Collaborator solely to the extent necessary to allow said other Collaborator to develop, obtain 
regulatory approval, or commercialize its own Investigational Agent. 
 
14.7.5 Any Collaborator having the right to use the Multi-Party Data from these trials must agree in writing 
prior to the commencement of the trials that it will use the Multi-Party Data solely for development, 
regulatory approval, and commercialization of its own Investigational Agent. 
 
14.7.6 Clinical Trial Data and Results and Raw Data developed under a collaborative agreement will be 
made available exclusively to Collaborator(s), the NCI, and the FDA, as appropriate. All data made 
available will comply with HIPAA regulations. 
 
14.7.7 When a Collaborator wishes to initiate a data request, the request should first be sent to the NCI, 
who will then notify the appropriate investigators of Collaborator's wish to contact them. 
 
14.7.8 Any manuscripts reporting the results of this clinical trial must be provided to DCP for immediate 
delivery to Collaborator(s) for advisory review and comment prior to submission for publication. 
Collaborator(s) will have 30 days (or as specified in the CTA) from the date of receipt for review. 
Collaborator shall have the right to request that publication be delayed for up to an additional 30 days in 
order to ensure that Collaborator’s confidential and proprietary data, in addition to Collaborator(s)’s 
intellectual property rights, are protected. Copies of abstracts must be provided to DCP for forwarding to 
Collaborator(s) for courtesy review as soon as possible and preferably at least three days prior to 
submission, but in any case, prior to presentation at the meeting or publication in the proceedings. Press 
releases and other media presentations must also be forwarded to DCP prior to release. Copies of any 
manuscript, abstract, and/or press release/ media presentation should be sent to the Protocol Information 
Office at NCI_DCP_PIO@mail.nih.gov.  
 
 
 
 

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The Protocol Information Office will forward manuscripts to the DCP Project Officer for distribution to the 
Collaborator(s). No publication, manuscript or other form of public disclosure shall contain any of 
Collaborator’s confidential/proprietary information. 
 
14.8    Genomic Data Sharing Plan 
 
Data produced through this protocol will be shared in a manner consistent with data-sharing under the NIH 
Genomic Data Sharing Policy (NOT-OD-14-124). Several of the exploratory endpoints will generate 
genome-wide RNA sequencing, single-cell sequencing and TCR sequencing data. Interpretation of 
transcriptomic results, single-cell sequencing and TCR sequencing results, including minimal phenotype 
information needed to reproduce the primary analysis – such as associated phenotype data (e.g., clinical 
information), exposure data, relevant metadata, and descriptive information (e.g., protocols or 
methodologies used) – will be shared with the public and the scientific community. Individual-level 
phenotype data will include, at a minimum: sex, race, weight, height, and age. We will submit the 
sequencing and phenotype data after it has been cleaned and processed (i.e., once the QA/QC is complete 
and the analytical dataset is finalized). The data repository to be used will be Gene Expression Omnibus 
(GEO) or equivalents. Data will be made available with unrestricted access. We understand that following 
data submission, the data may be held for a period not to exceed six months. Following this period of 
exclusivity, or at the time of publication (whichever comes first), the data will be available for secondary 
research access without restrictions on publication (i.e., there will be no publication embargo). Data will be 
made available for general research use. 
 
 
15. 
STATISTICAL CONSIDERATIONS 
 
15.1 
Study Design/Description 
 
Ours is a phase Ib/II open-label study to evaluate the safety and immunogenicity of Nous-209 monotherapy 
as an immune-interception agent for participants with LS. The study will be conducted in two cohorts: 
Cohort 1 (initial vaccination, single-arm, non-randomized) and Cohort 2 (revaccination, randomized into 
two arms, Arm A and Arm B). Both chart review and the electronic database search will be applied to 
identify the potentially eligible participants diagnosed with LS who are undergoing standard-of-care lower 
GI endoscopy. Eligible and consenting participants will receive GAd20-209-FSP (prime) and/or MVA-
209-FSP (boost) vaccination. Serial tissue biopsies and blood specimens will be collected for biomarker 
analyses.  
 
For Cohort 1, we will apply Simon’s minimax two-stage design and the response rate (i.e., the 
immunogenicity induction rate) defined by number of participants with immunogenicity among all 
participants treated will be estimated accordingly (Simon, 1989).  
 
Cohort 2 will only open conditional on the trial continuing to Stage 2, with at least 16 participants having 
achieved immune response by Week 9.  
 
 
15.2 
Randomization/Stratification  
 
For Cohort 1 of our study, there is no planned randomization or stratification.  
 
For Cohort 2, all eligible participants will be randomized (1:1 ratio) to one of two intervention arms 
(revaccination schedules) as specified in Section 7.1. Furthermore, we will apply stratification according to 

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the level of peak vaccine-induced immune response measured at Week 9 per protocol under participation 
in Cohort 1. We will define “good responders” as those individuals with an overall T cell response (sum of 
T cell responses against the 16 peptide pools covering the vaccine sequence) that is equal to or above the 
median value calculated on 16 or more participants with evaluable response at Week 9 prior to randomizing 
the first participant in Cohort 2. We will further define “intermediate responders” as those individuals with 
an overall T cell response that is less than the median value calculated on 16 or more participants with 
evaluable response at Week 9 prior to randomizing the first participant in Cohort 2.  
 
 
15.3 
Sample Size 
 
For Cohort 1, we plan to consent up to 60 individuals with the goal of enrolling 45 eligible participants to 
the study intervention [initial vaccination]. For Cohort 2, we plan to randomize 28 eligible participants from 
Cohort 1 to reach 24 evaluable participants in Cohort 2 (12 evaluable per treatment arm).  It is expected 
that up to 15% of samples (4 samples) may not be evaluable, thus, our goal is to randomize 28 participants 
and reach 24 evaluable. We expect the total study duration to be approx. four years, to include 
approximately two years of accrual, one year to complete of all participant interventions, and approximately 
one year for biomarker and statistical analyses. 
 
 
15.4 
Primary Objective, Endpoint(s), Analysis Plan 
 
The co-primary objectives of our study are to evaluate the safety/tolerability and immunogenicity of Nous-
209 vaccination in healthy individuals with LS. Accordingly, our primary safety/tolerability endpoints will 
be the rates of grade 2/3 and symptom reactivity following initial vaccination with GAd20-209-FSPs 
(prime) and MVA-209-FSPs (boost) in Cohort 1, and following revaccination with GAd20-209-FSPs 
(prime) and/or MVA-209-FSPs (boost) in Cohort 2. For participants in Cohort 1, our primary 
immunogenicity endpoint will be the rate of reactivity to at least 1 of 16 synthetic FSP pools using the 
ELISpot assay. Our immunogenicity endpoint will be evaluated at Baseline and Week 9 (i.e., following the 
MVA-209-FSP boost vaccination). For participants in Cohort 2, our immunogenicity endpoint will be 
evaluated at Week 52 and at 8 weeks after the last boost with MVA-209-FSP, corresponding to Week 68 
and Week 60, for arm A and B, respectively.  
 
Cohort 1 
For Cohort 1, we expect that the enrollment of 45 participants will provide 36 evaluable LS participants 
for this clinical trial. The trial will be conducted using the Simon’s minimax two-stage design, where the 
response rate (i.e., the immunogenicity induction rate) is defined by number of participants with 
immunogenicity among all participants treated (Simon, 1989). It is assumed that this vaccination regimen 
will elicit an immune response in at least 75% of the vaccinated participants (target response rate of 75%) 
based on previously published data indicating that all LS/MSI-H patients exhibited specific T-cell responses 
to at least one frameshift neoantigen peptides using ELISpot analysis after in vitro re-stimulation (36). 
Finally, we considered a response rate of 55% or lower as a failure, thus the hypothesis being rejected. 
 
We have applied the Simon’s two-stage minimax design assuming that the probability of accepting a “bad” 
vaccine (i.e., response rated55%) is 0.05 and the probability of rejecting a “good” vaccine (i.e., response 
rate t75%) is 0.20. In the first stage, 24 LS participants will be enrolled and accrual will be halted to fully 
evaluate immunogenicity in these patients; if 15 or fewer participants respond to the vaccine (i.e., with 
immunogenicity), the trial will be stopped and the vaccine will be declared as ineffective. If there are 16 or 
more responses, additional participants will be enrolled in the study to reach a total of 36 evaluable LS 
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immunogenicity is less than or equal to 24 and will be accepted otherwise. The operating characteristics of 
the trial are given as follows. If the true response rate is 0.55 the probability of stopping the trial early is 
83% and the expected sample size is 26.  
 
As stated in Section 3.2, we assume an estimated attrition rate of 20%. Therefore, for Cohort 1, we plan to 
enroll a maximum of 45 participants in order to reach 36 evaluable LS participants for our co-primary 
endpoint of immunogenicity. Every effort will be made to minimize the attrition rate including but not 
limited to careful screening of eligibility criteria, close contact with patients after enrollment to monitor the 
adverse events, email/phone reminders of the follow-up visits.  
 
Cohort 2 
For Cohort 2, our aim is to establish an optimal Nous-209 revaccination schedule to ensure proper boosting 
of immune responses following initial vaccination (Cohort 1). We will evaluate the median overall T cell 
response detected at 8 weeks after the last boost with MVA-209-FSP (Week 68 and Week 60, for arm A 
and B, respectively) separately for both treatment arms. We will compare the fold increase in median overall 
T cell response (relative to Week 52, baseline for assessment of immunogenicity to re-vaccination in 
participants to Cohort #2) between treatment arms. The treatment arm associated with the highest fold 
increase in immune response will be considered the optimal schedule.. Previous studies in human shown 
still significant levels of T cell response detected at 4 weeks post-boost in participants vaccinated with 
similar Ad and MVA vaccines/regimen (47). 
 
Cohorts 1 and 2 
To address the potential missing data, we could apply multiple imputations as the secondary analysis. For 
example, under the missing at random assumption, imputations of the missing outcome variable can be 
achieved by regressing the outcome variable on medical demographic variables such as age, sex, race, BMI, 
and adverse event rate, etc. In addition, controlled multiple imputation procedures could be applied to 
combine pattern-mixture modeling with multiple imputation to provide a practical platform for sensitivity 
analysis to address the potential biased caused by treatment related dropouts. 
 
Descriptive statistics such as mean, median, standard deviation (sd), frequency and range, as well as graphic 
presentations (e.g., boxplot) will be used to assess the distribution of all study-related variable of interest 
(e.g., medical and demographics variables) and report the data when appropriate.  The rate of 
immunogenicity induced by Nous-209 will be reported along with its 95% exact (Clopper-Pearson) 
confidence interval. Immunogenicity will be defined as a significant increase in ELISpot activity comparing 
pre- and post-vaccination IFNJT cell numbers. Changes from baseline will assessed using a paired t-test or 
the Wilcoxon signed-rank test, if more appropriate. 
 
If underlying distributional assumptions are not met, nonparametric tests (e.g., Wilcoxon signed rank test) 
and/or data transformation (e.g., logarithm) may be applied when appropriate. Time to event (e.g., time to 
adenoma) will be estimated by Kaplan-Meier method; log-rank test may be applied to evaluate the 
difference in time-to-event outcomes between different prognostic groups of participants (e.g., 
immunogenic vs non-immunogenic participants). Cox proportional hazards regression, when possible, will 
be employed to further evaluate the effects of important covariates on time-to-event outcomes while 
adjusting for clinical and demographic characteristics of interest (e.g., age, sex, BMI, tobacco use, etc.). 
Other statistical methods, when appropriate, may be utilized.   
 
 
15.5 
Secondary Objectives, Endpoints, Analysis Plans 
 

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The secondary objectives of our study are to evaluate the effects of Nous-209 vaccination on a) T cell 
immune profile and T cell receptor (TCR) repertoire in peripheral blood; b) TCR repertoire within 
histologically normal colorectal mucosa; c) tumor infiltrating lymphocyte (TIL) immune profile and TCR 
repertoire within colorectal adenomas; d) cytotoxicity of T cells on matched participant-derived colorectal 
adenoma organoids; e) the burden of colorectal adenomas/advanced neoplasia/carcinoma; f) burden of LS-
related carcinomas; g) cell free DNA (cfDNA) mutation profiles and cfDNA burden in participants with 
LS; h) to correlate tobacco and alcohol consumption with the immune response to Nous-209 in trial 
participants; and i) assess the MMR and/or MSI status of polyps (and adjacent normal mucosa as control) 
detected in the baseline and end-of-the-study colonoscopy using different technologies such as 
immunohistochemistry, MSI analysis by PCR, or next-generation sequencing.  
 
 
We will use two-sample t-test and general linear models for the comparison of continuous secondary 
endpoints (e.g., number of adenomas and advanced adenomas) among different groups of participants [e.g., 
participants displaying immunogenicity (immunogenic) vs. those without immunogenicity (non-
immunogenic)]. One-sample binomial tests and one-sample t-tests will be utilized to assess the proportion 
and mean of specific outcomes of interest in this group of participants, respectively (e.g., proportion of 
adenomas, advanced adenomas and colorectal carcinomas, and mean sum of the maximum diameters of 
neoplasms). The occurrence of a neoplasm defined in three categories (adenoma, advanced adenoma, and 
CRC) will be compared to historical cohorts (e.g., CAPP-2 study placebo cohort). 
 
Other analyses may be employed when appropriate. 
 
 
15.6 
Reporting and Exclusions 
 
Regular clinical visits will be applied to monitor study participants during the intervention period. The non-
compliance rates will be computed for both study cohorts. Complete case analysis will be performed as our 
primary analysis method in this phase Ib/II study. Multiple imputations will be applied whenever 
appropriate.      
 
 
15.7 
Evaluation of Toxicity 
 
All enrolled participants will be considered evaluable for our toxicity and tolerability endpoints. We will 
describe the toxicity profile with respect to the types, attribution, and grade of toxicities.  
 
 
15.8 
Evaluation of Response 
 
For our co-primary endpoint of immunogenicity following initial vaccination (Cohort 1), all enrolled 
participants who receive the MVA-209-FSP (boost) vaccine at Week 8 and undergo research blood 
collection at Week 9 will be considered evaluable, if the quality of collected PBMC allows measurement 
of immunogenicity. For our co-primary endpoint of immunogenicity following revaccination (Cohort 2), 
all enrolled participants who receive the MVA-209-FSP (boost) vaccine at Week 52 (in Arm B) or at Week 
60 (in Arm A) and undergo research blood collection at 8 weeks post last MVA boost vaccine (Week 68 
and Week 60, for arm A and B, respectively), will be considered evaluable, if the quality of collected PBMC 
allows measurement of immunogenicity.  
 

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For our secondary endpoints, all participants (with the possible exception of those who did not receive at 
least the GAd-209-FSP (prime) vaccine at Week 0) will be considered evaluable. Sub-analyses may be 
performed on the subsets of participants, excluding those for whom major protocol deviations have been 
identified (e.g., early death due to other reasons, early discontinuation of intervention, major protocol 
violations, etc.). However, sub-analyses may not serve as the basis for drawing conclusions concerning 
efficacy, and the reasons for excluding participants from the analysis should be clearly reported. For all 
measurements of response, the 95% confidence intervals should also be provided. 
 
 
15.9 
Interim Analysis 
 
A Bayesian toxicity monitoring approach will be applied in this study. Expected local toxicities are 
erythema, swelling, pruritus, warmth and local pain and systemic toxicities are fever, arthralgia, myalgia, 
malaise, fatigue, abdominal pain, headache and nausea. Unacceptable toxicity is defined as any treatment 
related Adverse Event (AE) of grade 3 or higher including any death at least possibly related to the study 
treatment or any death within 30 days of receiving the study treatment unless clearly due to disease 
progression. Participants enrolled only in Cohort 1 will be monitored for AEs up to Week 52 (Month 12) 
visit.  Participants enrolled in Cohort 1 and continuing in Cohort 2 will be monitored for AEs up to Week 
68 visit using the same boundaries, including the AEs during the first 30 days of receiving the first and 
second study treatment, cumulatively. We will not include Grade 3 symptom reactogenicity towards the 
definition of AE as specified earlier as Section 13 Table 4. AEs following immunization will be considered 
following the guidance of the WHO and include: fatal or life-threatening adverse reactions, neuritis, 
convulsion, anaphylaxis, syncope, encephalitis, thrombocytopenia, vasculitis, Guillain-Barré syndrome and 
Bell’s palsy.  
 
We will consider the vaccination regimen unsafe if it results in an unacceptable toxicity rate of 30% or 
greater with 70% or higher probability. With a beta prior probability of toxicity with parameters (0.3, 0.7), 
consideration to stop the trial will be guided according to the stopping boundaries in Table 5. The operating 
characteristics for these stopping rules are summarized in Table 6. The boundaries and operating 
characteristics were generated using Bayesian Toxicity Monitoring, developed by the department of 
Biostatistics (https://ibl.mdanderson.org/BTM/). 
 
 
 
 
 
 
 
Considering both 
Simon’s two-stage 
design and toxicity 
monitoring 
and 
assuming 
independence 
between response 
and 
toxicity, 
operating characteristics indicate that the trial has a 99.6% chance of stopping early if the true toxicity rate 
is 50% when the true response rate is 55%. On the other hand, if the true response rate is 75% when the 
true toxicity rate is 10%, we will have an 13.7% chance of stopping the trial early. 
 
Table 5. Stopping 
boundaries for toxicity 
monitoring 
 
Table 6. Operating characteristics for the 
stopping rules for toxicity 
Cohort 
Stop if number of 
Toxicity t 
 
True 
Toxicity 
Rate 
Probability 
of Early 
Termination 
Average No. 
of 
Participants 
Treated 
6 
3 
 
0.1 
0.018 
35.5 
12 
5 
 
0.2 
0.155 
31.9 
18 
7 
 
0.3 
0.490 
24.1 
24 
9 
 
0.4 
0.832 
15.4 
30 
11 
 
0.5 
0.975 
9.9 
36 
13 
 
0.6 
0.999 
7.4 

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Furthermore, as noted in Section 14.4, study treatment and enrollment will be paused pending a 
comprehensive safety evaluation by the DCP Medical Monitor and DSMB when any of the following death 
events occur:  
 
x 
Any death at least possibly related to the study treatment 
x 
Any death within 30 days of receiving the study treatment unless clearly due to disease progression 
 
 
15.10 Ancillary Studies 
 
No ancillary studies are planned. 
  
 
16. 
REGULATORY AND ETHICAL CONSIDERATIONS 
 
16.1 
Required Documents 
 
Besides the regulatory information that will be entered into the Registration and Credential Repository (see 
Section 5.1), the following documents are also required: 
 
16.1.1 Documentation of Federalwide Assurance (FWA) number for the LAO and all Affiliate 
Organizations. 
 
16.1.2 Signed Investigator’s Brochure/Package Insert acknowledgement form 
 
16.1.3 Delegation of Tasks Log form for the Lead Accruing Organization and all Accruing Sites signed by 
the Principal Investigator for each site and initialed by all study personnel listed on the form.  
 
 
16.2 
Informed Consent 
 
All potential study participants will go through the Informed Consent process. The informed consent 
process may be conducted either in person or electronically (remotely). Electronic informed consent may 
be used to either supplement or replace paper based informed consent processes in order to best address 
the participant’s need. Electronic means relating to technology having electrical, digital, magnetic, 
wireless, optical, electromagnetic, or similar capabilities; electronic informed consent process may be 
conducted via telephone or video conferencing, for example. 
 
All potential study participants will be given a copy of the CIRB-approved Informed Consent to review. 
The Informed Consent may be provided on paper or electronically. The investigator will explain all aspects 
of the study in lay language and answer all questions regarding the study. If the participant decides to 
participate in the study, he/she will be asked to sign and date the Informed Consent document. The signature 
may be provided on paper or electronically. The study agent(s) will not be released to a participant who has 
not signed the Informed Consent document. Individuals who refuse to participate or who withdraw from 
the study will be treated without prejudice. 
 
Participants must be provided the option to allow the use of blood samples, other body fluids, and tissues 
obtained during testing, operative procedures, or other standard medical practices for further research 
purposes. If applicable, statement of this option should be included within the informed consent document.  
 

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Prior to study initiation, the informed consent document must be reviewed and approved by NCI, DCP, and 
the NCI CIRB. The NCI CIRB approves a model consent for each protocol. Each Signatory Institution 
inserts their CIRB-approved institutional boilerplate language into the model consent to create the CIRB-
approved consent. If the model informed consent document is amended, Signatory Institutions must use the 
revised model informed consent document and insert their CIRB-approved institutional boilerplate 
language at the time the change becomes active.  
 
The NCI CIRB is the IRB of record and is the only IRB authorized to approve changes to the protocol or 
informed consent document. Institutions may require additional oversight that involves the local IRB, but 
the local IRB is not responsible for any regulatorily-required IRB actions.  
 
16.3 
Collection of Regulatory Documents 
 
Regulatory documents will be collected by the DCP regulatory contractor and reviewed for completeness 
and accuracy.  
 
 
16.4 
Other 
This trial will be conducted in compliance with the protocol, the International Conference on 
Harmonisation’s (ICH) Good Clinical Practice (GCP) guidelines, and the applicable regulatory 
requirements. 
17.  
ROSTER MANAGEMENT 
 
The LAO is responsible for establishing, maintaining, and monitoring all its members that participate in 
CP-CTNet studies. The LAO must have a “real-time,” comprehensive, consolidated roster of all its 
members with their relevant Cancer Therapy Evaluation Program (CTEP) institution codes, associated 
investigators, and research staff. This roster information is used for determining compliance with 
monitoring requirements. 
The LAO’s organizational rosters will be managed by the CP-CTNet Roster Management 
System 
website 
(https://applications.prevention.cancer.gov/cp-ctnet) 
Requests 
to 
add 
memberships to a roster will be done via this website. All requests require that the 
following documents be uploaded: 
x 
Consortium Letter of Commitment
x 
Site Letter of Commitment
x 
CV/NIH Biosketch 
 
 
18. 
FINANCING, EXPENSES, AND/OR INSURANCE 
 
Participants will not be responsible for non-standard of care costs of this study. Study agent will be provided 
at no cost to the participant. There will be compensation for additional expenses associated with study visits, 
such as additional travel expenses, time missed from work or other expenses.  The amount of compensation 
will be $50 provided at the time of study initiation (the first endoscopic procedure) and at the time of the 
study visits at Weeks 3, 8, 9, 24 and 52 (in Cohort 1), and additionally at Weeks 60 and 68 (in Cohort 2).  
The participants will also receive parking compensation for in person study related visits (at those centers 
where parking fees are charged).  If, as a result of participation in this study, an individual experiences 
injury from known or unknown risks of the research procedures as described in the informed consent, 

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immediate medical care and treatment, including hospitalization, if necessary, will be available.  No 
monetary compensation is available for the costs of medical treatment for an injury, thus, the participant 
will be responsible for the costs of such medical treatment, either directly or through their medical insurance 
and/or other forms of medical coverage. 
 
 
 

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adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge. Nature 
medicine. 2014;20(10):1126-9. doi: 10.1038/nm.3702. PubMed PMID: 25194571. 
21. 
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immunogenicity of DNA vaccines encoding Ebolavirus and Marburgvirus wild-type glycoproteins in a 
phase I clinical trial. J Infect Dis. 2015;211(4):549-57. doi: 10.1093/infdis/jiu511. PubMed PMID: 
25225676; PubMed Central PMCID: PMC4318920. 
22. 
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determines adenoviral vaccine potency independent of IFN and STING signaling. J Clin Invest. 
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23. 
Quinn KM, Da Costa A, Yamamoto A, Berry D, Lindsay RW, Darrah PA, et al. Comparative 
analysis of the magnitude, quality, phenotype, and protective capacity of simian immunodeficiency virus 
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vector immunization. J Immunol. 2013;190(6):2720-35. doi: 10.4049/jimmunol.1202861. PubMed 
PMID: 23390298; PubMed Central PMCID: PMC3594325. 
24. 
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defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults. 
Vaccine. 2010;29(2):304-13. doi: 10.1016/j.vaccine.2010.10.037. PubMed PMID: 21034824. 
25. 
Ewer K, Rampling T, Venkatraman N, Bowyer G, Wright D, Lambe T, et al. A Monovalent 
Chimpanzee Adenovirus Ebola Vaccine Boosted with MVA. N Engl J Med. 2016;374(17):1635-46. doi: 
10.1056/NEJMoa1411627. PubMed PMID: 25629663. 
26. 
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derived from a large collection of simian adenoviruses induce potent cellular immunity across multiple 
species. Sci Transl Med. 2012;4(115):115ra2. doi: 10.1126/scitranslmed.3002925. PubMed PMID: 
22218691; PubMed Central PMCID: PMC3627206. 
27. 
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vaccines induce broad and sustained T cell responses to HCV in man. Sci Transl Med. 
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28. 
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vaccine strategy based on chimpanzee adenoviral and MVA vectors that primes, boosts, and sustains 
functional HCV-specific T cell memory. Sci Transl Med. 2014;6(261):261ra153. Epub 2014/11/08. doi: 
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29. 
D'Alise AM, Leoni G, Cotugno G, Troise F, Langone F, Fichera I, et al. Adenoviral vaccine 

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targeting multiple neoantigens as strategy to eradicate large tumors combined with checkpoint blockade. 
Nat Commun. 2019;10(1):2688. Epub 2019/06/21. doi: 10.1038/s41467-019-10594-2. PubMed PMID: 
31217437; PubMed Central PMCID: PMC6584502. 
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32690723. 
31. 
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APPENDIX A  PERFORMANCE STATUS CRITERIA 
 
ECOG Performance Status Scale 
Grade 
Descriptions 
0 
Normal activity. Fully active, able to carry on all 
pre-disease performance without restriction. 
1 
Symptoms, but ambulatory. Restricted in 
physically strenuous activity, but ambulatory and 
able to carry out work of a light or sedentary 
nature (e.g., light housework, office work). 
2 
In bed <50% of the time. Ambulatory and 
capable of all self-care, but unable to carry out 
any work activities. Up and about more than 50% 
of waking hours. 
3 
In bed >50% of the time. Capable of only limited 
self-care, confined to bed or chair more than 50% 
of waking hours. 
4 
100% bedridden. Completely disabled. Cannot 
carry on any self-care. Totally confined to bed or 
chair. 
5 
Dead. 
 
Karnofsky Performance Scale 
Percent 
Description 
100 
Normal, no complaints, no evidence of 
disease. 
90 
Able to carry on normal activity; minor signs 
or symptoms of disease. 
80 
Normal activity with effort; some signs or 
symptoms of disease. 
70 
Cares for self, unable to carry on normal 
activity or to do active work. 
60 
Requires occasional assistance, but is able to 
care for most of his/her needs. 
50 
Requires considerable assistance and frequent 
medical care. 
40 
Disabled, requires special care and assistance. 
30 
Severely disabled, hospitalization indicated. 
Death not imminent. 
20 
Very sick, hospitalization indicated. Death not 
imminent. 
10 
Moribund, fatal processes progressing rapidly. 
0 
Dead. 
 
 
 

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APPENDIX B 
 
ALCOHOL AND TOBACCO QUESTIONNAIRE INSTRUCTIONS 
 
x 
Data collection will be required for all CP-CTNet studies. 
o Data will be collected at baseline and end of every study. Data may also be collected at 
follow-up visits as determined by each protocol. If you wish to collect additional information 
beyond these core elements, you may certainly do so. However, all studies need to collect the 
basic elements in the attached eCRFs.  
o The eCRFs will be completed by the Site Staff or participant at the time of the designated 
visit. 
x 
Data will be submitted as part of the final clinical data set. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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ALCOHOL ASSESSMENT-- BASELINE 
 
REGISTERING 
INSTITUTION  
 
_________________________________ 
PARTICIPANT ID 
 
______________________ 
VISIT TYPE 
 
__________________________ 
VISIT DATE 
(MM/DD/YYYY) 
___ ___ / ___ ___ / ___ ___ ___ ___ 
 
Instructions: 
For the following questions about drinking alcoholic beverages, a drink means a 12 oz. 
beer, a 5 oz. glass of wine, or one and a half ounces of liquor.  
When a number is requested in the response, please enter a whole number (i.e., “4”) and 
not a range or fraction of a number.  
 
1. In your entire life, have you had at least 12 drinks of any kind of alcoholic beverage?  
 
 Yes 
 No (End) 
 Refused (End) 
 Don’t know/Not sure 
 
2. In the past 12 months, on average, how often did you drink any type of alcoholic beverage?  
 
________ (Enter the number of days you drank based on the timeframe checked below.  
Enter 0 if you never drank and skip to Question 6.)  
 Week  
 Month 
 Year 
 Refused 
 Don’t know/Not sure 
 
3. In the past 12 months, on those days that you drank alcoholic beverages, on average, how many 
drinks   
did you have per day?  
________ (Enter the average number of drinks per day)  
 
 Refused 
 Don’t know/Not sure 
 
4. In the past 12 months, on how many days did you have 5 or more drinks of any alcoholic 
beverage?  
 
_________ (Enter the number of days you had 5 or more drinks, or enter 0 if none.) 
 
 Refused 
 Don’t know/Not sure 

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5. Was there ever a time or times in your life when you drank 5 or more drinks of any kind of 
alcoholic beverage almost every day?  
 
 Yes 
 No  
 Refused 
 Don’t know/Not sure 
 
6. If you do not currently drink alcoholic beverages, but did in the past, how long has it been 
since 
you last drank regularly?  
 
 Within the past month (0 to 1 month ago) 
 Between 1 and 3 months (1 to 3 months ago) 
 Between 3 and 6 months (3 to 6 months ago) 
 Between 6 and 12 months (6 to 12 months ago) 
 Between 1 and 5 years (1 to 5 years ago) 
 Between 5 and 15 years (5 to 15 years ago) 
 More than 15 years ago  
 Don’t know/Not sure 
 Never drank regularly 
 
7. At the heaviest point, either now or in the past, on the days when you drank, about how many 
drinks did you drink a day on the average?  
 
__________ (Enter the number of drinks a day) 
  
 Refused 
 Don’t know/Not sure 
 
8. How many years have you been drinking (or did drink) regularly?  
 
______ years 
 
 Refused 
 Don’t know/Not sure  
 
9. At what age did you begin drinking regularly?  
 
______ years of age 
 
 
 Refused 
 Don’t know/Not sure  

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10. What type(s) of alcohol do you drink? (Mark ALL that apply) 
 
 Wine 
 Liquor 
 Beer 
 Wine cool 
 
 
CRF completed by (check one):  
Study participant  _____    
Study site staff      _____     Staff name (optional)  ____________________________ 
Date __ __ / __ __ / __ __ __ __ 
                  (MM/DD/YYYY) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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ALCOHOL ASSESSMENT - FOLLOW-UP 
 
 
REGISTERING INSTITUTION  
 
_________________________________ 
PARTICIPANT ID 
 
______________________ 
VISIT TYPE 
 
__________________________ 
VISIT DATE 
(MM/DD/YYYY) 
___ ___ / ___ ___ / ___ ___ ___ ___ 
 
Instructions: 
 
For the following questions about drinking alcoholic beverages, a drink means a 12 oz. 
beer, a 5 oz. glass of wine, or one and a half ounces of liquor.  
When a number is requested in the response, please enter a whole number (i.e., “4”) and 
not a range or fraction of a number. 
 
1. During the past 30 days, did you drink any alcoholic beverages?  
 
 Yes 
 No (End) 
 Refused (End) 
 Don’t know/Not sure 
 
2. During the past 30 days, how many days per week or per month did you drink any alcoholic 
beverages, on the average?  
 
________ (Enter number of days you drank based on the timeframe checked below.  Enter 0 
if you did not drink.)  
 
 Week  
 Month 
 Refused 
 Don’t know/Not sure 
 
3. On the days when you drank, on average, about how many drinks did you have?  
 
________ (Enter the average number of drinks you had per day.) 
 
 Refused 
 Don’t know/Not sure 
 
4. In the past 30 days, on how many days did you have 5 or more drinks per day?  
 
_____________ (Enter the number of days you had 5 or more drinks, or enter 0 if none.)  
 
 Refused 

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 Do not know/Not sure 
 
 
CRF completed by (check one):  
Study participant  _____    
Study site staff      _____     Staff name (optional)  ____________________________ 
Date __ __ / __ __ / __ __ __ __ 
                  (MM/DD/YYYY) 
 
 
 
 
 
 
 
 
 
 

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TOBACCO ASSESSMENT – BASELINE 
 
REGISTERING INSTITUTION  
 
_________________________________ 
PARTICIPANT ID 
 
______________________ 
VISIT TYPE 
 
__________________________ 
VISIT DATE 
(MM/DD/YYYY) 
___ ___ / ___ ___ / ___ ___ ___ ___ 
 
Instructions:  
When a number is requested in the response, please enter a whole number (i.e., “4”) and 
not a range or fraction of a number.  
 
Section A. Basic Cigarette Use Information 
 
1. Have you smoked at least 100 cigarettes (5 packs = 100 cigarettes) in your entire life? 
 
Yes  
 
 No ĺ Skip to Section B 
 Don’t know/Not sure ĺ Skip to Section B 
 
2. How old were you when you first smoked a cigarette (even one or two puffs)? 
 
_______ Years old 
 
 
3. How old were you when you first began smoking cigarettes regularly?   
 
_______ Years old 
 
  Check here if you have never smoked cigarettes regularly. 
 
4. How many total years have you smoked (or did you smoke) cigarettes? Do not count any time 
you may have stayed off cigarettes. 
 
______ Years (If you smoked less than one year, write “1.”) 
 
 
5. On average when you have smoked, about how many cigarettes do you (or did you) smoke a 
day? (A pack usually has 20 cigarettes in it).  
 
_____ Number of cigarettes per day 
 
6. Do you NOW smoke cigarettes?  
 
 Everyday 
 Some days 
 Not at all ĺ Skip to question 8 
 
 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–86– 
February 3, 2025 
7.  How soon after you wake up do you smoke your first cigarette?  
 
  Within 30 minutes 
  After 30 minutes 
 
8. How long has it been since you last smoked a cigarette (even one or two puffs)?  
 
First check which one of the following choices applies to you. Then, if applicable, write a 
number on the line 
for how many days, weeks, months, or years it has been since your last cigarette. 
 
 I smoked a cigarette today (at least one puff) 
 1-7 days ĺ Number of days since last cigarette  ________ 
 Less than 1 month ĺ Number of weeks since last cigarette  _________ 
 Less than 1 year ĺ Number of months since last cigarette  __________ 
 More than 1 year ĺ Number of years since last cigarette  ___________ 
 Don’t know/Don’t remember 
 
Section B. Use of Other Forms of Tobacco 
 
9.  Have you ever used other forms of tobacco, not including cigarettes? 
  
 Yes  
 No ĺ Skip to Section C 
 
10. How often do you/did you use other forms of tobacco?  
 
 Every day ĺ Number of times per day  ________ 
 Some days ĺ Number of days _______ per 
 Week 
 Month 
Year 
 
11. Which of the following products have you ever used regularly? 
 Check all that apply  
 
 Cigarettes 
 E-cigarettes or other electronic nicotine delivery system 
 Traditional cigars, cigarillos or filtered cigars 
 Pipes 
 Waterpipe 
 Hookah 
 Clove cigarettes or kreteks 
 Bidis  
 Smokeless tobacco, like dip, chew, or snuff 
 Snus 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–87– 
February 3, 2025 
 Paan with tobacco, gutka, zarda, khaini 
 Other, Please specify:__________________________ 
12.  If you do not currently use other forms of tobacco, but did in the past, how long has it been  
since you last used other forms of tobacco regularly?  
 
 Within the past month (0 to 1 month ago) 
 Between 1 and 3 months (1 to 3 months ago) 
 Between 3 and 6 months (3 to 6 months ago) 
 Between 6 and 12 months (6 to 12 months ago) 
 Between 1 and 5 years (1 to 5 years ago) 
 Between 5 and 15 years (5 to 15 years ago) 
 More than 15 years ago 
 Don’t know/Not sure 
 Never used other forms of tobacco regularly 
 
Section C. Second-Hand Smoke Exposure 
 
13. Are you currently living with a smoker?   
 
Yes 
 
 No  
 
14. In the past 30 days, have you lived in a place where other people smoked cigarettes indoors?  
 
Yes 
 
 No  
 
15. In the past 30 days, have you worked in a place where other people smoked cigarettes 
indoors? 
 
Yes 
 
 No  
 
16. Thinking of all your childhood and adult years, have you ever lived in a place where other 
people smoked cigarettes indoors? 
 
 
 Yes 
In total, for about how many years?_______ If less than 1, write “1.”   
 No  
 
17. Thinking of all the years you have worked, have you ever worked in a place where other 
people smoked cigarettes indoors?   
 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–88– 
February 3, 2025 
Yes 
ĺ In total, for about how many years?_______ If less than 1, write “1.”    
 No 
 
 
CRF completed by (check one):  
Study participant  _____    
Study site staff      _____     Staff name (optional)  ____________________________ 
Date __ __ / __ __ / __ __ __ __ 
                  (MM/DD/YYYY) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–89– 
February 3, 2025 
TOBACCO ASSESSMENT - FOLLOW-UP 
 
REGISTERING INSTITUTION 
 
_________________________________ 
PARTICIPANT ID 
 
______________________ 
VISIT TYPE 
 
__________________________ 
VISIT DATE 
(MM/DD/YYYY) 
___ ___ / ___ ___ / ___ ___ ___ ___ 
 
Instructions:  
When a number is requested in the response, please enter a whole number (i.e., “4”) and 
not a range or fraction of a number.  
 
1. Do you NOW smoke cigarettes?  
 
 Everyday 
 Some days 
 Not at all ĺ Skip to Question 3. 
 Never smoked ĺ Skip to Question 4 
 
 
2. On average, when you smoked, about how many cigarettes do you (or did you) smoke a day? 
(A pack usually has 20 cigarettes in it).     
 
_____ Number of cigarettes per day 
 
3. How long has it been since you last smoked a cigarette (even one or two puffs)?    
 
First check which one of the following choices applies to you. Then, if applicable, write a 
whole number on the line for how many days, weeks, months, or years it has been since your 
last cigarette. 
 
 I smoked a cigarette today (at least one puff) 
 1-7 days ĺ Number of days since last cigarette ________ 
 Less than 1 month ĺ Number of weeks since last cigarette _________ 
 Less than 1 year ĺ Number of months since last cigarette __________ 
 More than 1 year ĺ Number of years since last cigarette ___________ 
 Don’t know/Don’t remember 
 
4. Since your last visit, have you used other forms of tobacco, not including cigarettes?  
 
 Yes 
  No (End) 
 
5. How often do you/did you use other forms of tobacco?  
 
 Every day ĺ Number of times per day ________ 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–90– 
February 3, 2025 
 Some days ĺ Number of days _______ per 
 Week 
 Month 
Year 
6. Since your last visit, which of the following products have you used?  Check all that apply 
 
 Cigarettes 
 E-cigarettes or other electronic nicotine delivery system 
 Traditional cigars, cigarillos or filtered cigars 
 Pipes 
 Waterpipe 
 Hookah 
 Clove cigarettes or kreteks 
 Bidis  
 Smokeless tobacco, like dip, chew, or snuff 
 Snus 
 Paan with tobacco, gutka, zarda, khaini 
 Other, 
Specify____________________________________________________________________ 
 
7. If you do not currently use other forms of tobacco, but did in the past, how long has it been 
since you last used other forms of tobacco regularly?  
 
 Within the past month (0 to 1 month ago) 
 Between 1 and 3 months (1 to 3 months ago) 
 Between 3 and 6 months (3 to 6 months ago) 
 Between 6 and 12 months (6 to 12 months ago) 
 Between 1 and 5 years (1 to 5 years ago) 
 Between 5 and 15 years (5 to 15 years ago) 
 More than 15 years ago 
 Don’t know/Not sure 
 Never used other forms of tobacco regularly 
 
The following instructions pertain to questions 8 - 10.  During each of the following time frames, 
please indicate whether you smoked cigarettes every day, some days, or not at all. 
 
8.  During study treatment 
 
 Smoked every day 
 Smoked some days 
 Did not smoke at all 
 Don’t know/not sure 
 Not applicable  
 
 
 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–91– 
February 3, 2025 
9.  After the end of study treatment 
 
 
 Smoked every day 
 Smoked some days 
 Did not smoke at all 
 Don’t know/not sure 
 Not applicable (I have not completed the study treatment)  
 
10. Since your last visit to this clinic 
 
 
 Smoked every day 
 Smoked some days 
 Did not smoke at all 
 Don’t know/not sure 
 
 
CRF completed by (check one):  
Study participant  _____    
Study site staff      _____     Staff name (optional)  ____________________________ 
Date __ __ / __ __ / __ __ __ __ 
                  (MM/DD/YYYY) 
 
 
 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–92– 
February 3, 2025 
 
NATIONAL AND LOCAL RESOURCES TO HELP WITH ALCOHOL ABUSE AND 
ALCOHOLISM 
 
NIAAA’s online guide Treatment for Alcohol Problems: Finding and Getting Help is written 
for individuals, and their family and friends, who are looking for options to address alcohol 
problems. It is intended as a resource to understand what treatment choices are available and 
what to consider when selecting among them. 
https://pubs.niaaa.nih.gov/publications/treatment/treatment.htm 
Other resources: 
National Institute on Alcohol Abuse and Alcoholism www.niaaa.nih.gov  
301–443–3860  
National Institute on Drug Abuse www.nida.nih.gov  
301–443–1124  
National Clearinghouse for Alcohol and Drug Information www.samhsa.gov  
1–800–729–6686  
Substance Abuse Treatment Facility Locator www.findtreatment.samhsa.gov  
1–800–662–HELP  
Alcoholics Anonymous (AA) www.aa.org  
212–870–3400 or check your local phone directory under “Alcoholism”  
Moderation Management www.moderation.org 
212–871–0974  
Secular Organizations for Sobriety www.sossobriety.org  
323–666–4295  
SMART Recovery www.smartrecovery.org  
440–951–5357  
Women for Sobriety www.womenforsobriety.org  
215–536–8026  
Al-Anon Family Groups www.al-anon.alateen.org  
1–888–425–2666 for meetings  
Adult Children of Alcoholics  www.adultchildren.org 
310–534–1815  
 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–93– 
February 3, 2025 
NATIONAL AND LOCAL RESOURCES TO HELP WITH QUITTING SMOKING 
NCI’s Smokefree.gov offers science-driven tools, information, and support that has helped 
smokers quit. You will find state and national resources, free materials, and quitting advice from 
NCI. 
Smokefree.gov was established by the Tobacco Control Research Branch of NCI, a component 
of the National Institutes of Health, in collaboration with the Centers for Disease Control and 
Prevention and other organizations. 
Publications available from the Smokefree.gov Web site include the following: 
x 
Clearing the Air: Quit Smoking Today for smokers interested in quitting. 
x 
Clear Horizons for smokers over age 50. 
x 
Staying Smoke-Free for Good for smokers who have recently quit. 
x 
Smoke-free for women, including pregnant women. 
x 
Smoke-free information in Spanish 
x 
Pathways to Freedom: Winning the Fight Against Tobacco for African American 
smokers. 
NCI’s Smoking Quitline at 1–877–44U–QUIT (1–877–448–7848) offers a wide range of 
services, including individualized counseling, printed information, referrals to other resources, 
and recorded messages. Smoking cessation counselors are available to answer smoking-related 
questions in English or Spanish, Monday through Friday, 8:00 a.m. to 8:00 p.m., Eastern time. 
Smoking cessation counselors are also available through LiveHelp, an online instant messaging 
service. LiveHelp is available Monday through Friday, 8:00 a.m. to 11:00 p.m., Eastern time. 
Your state has a toll-free telephone quitline. Call 1–800–QUIT–NOW (1–800–784–8669) to get 
one-on-one help with quitting, support and coping strategies, and referrals to resources and local 
cessation programs. The toll-free number routes callers to state-run quitlines, which provide free 
cessation assistance and resource information to all tobacco users in the United States. This 
initiative was created by the Department of Health and Human Services. For more information 
about quitlines, speak to an expert on the Smokefree.gov Web site. 
 
 
 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–94– 
February 3, 2025 
APPENDIX C 
 
COVID-19 ASSESSMENT INSTRUCTIONS 
 
 
x 
Data collection will be required for all CP-CTNet studies. 
o Data will be collected end of every study. All studies need to collect the elements in the 
attached eCRFs.  
o The eCRFs will be completed by the Site Staff or participant at the time of the designated 
visit. 
x 
Data will be submitted as part of the final clinical data set. 
 
 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–95– 
February 3, 2025 
CP-CT NET COVID-19 BASELINE ASSESSMENT 
 
REGISTERING 
INSTITUTION  
 
_________________________________ 
PARTICIPANT 
ID 
 
______________________ 
VISIT TYPE 
 
__________________________ 
VISIT DATE 
(MM/DD/YYYY) 
___ ___ / ___ ___ / ___ 
___ ___ ___ 
 
Instructions: 
The following information is being collected for all Cancer Prevention Clinical Trials 
Network (CP-CTNet) studies. Only information from before study entry should be 
reported on this form. 
 
Have you ever had a COVID-19 test?  
 Yes 
 No  
 
If Yes, have you ever received a positive test result? 
 
 Yes 
 No  
 Prefer not to answer 
 
      Date of latest positive test: _ _ /  _ _ / _ _ _ _ 
      If positive, were you symptomatic? 
 
 
 Yes 
      
 No  
 
Have you received a COVID-19 vaccine? 
 
 Yes 
 No  
 Prefer not to answer 
 
If Yes, which vaccine did you receive for your first dose? 
 
 Moderna 
 Pfizer - BioNTech  
 Johnson & Johnson 
 AstraZeneca 
 Other 
 
If Other, specify: ______________________________ 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–96– 
February 3, 2025 
 
Date of first vaccine dose: _ _ /  _ _ / _ _ _ _ 
 
Have you received a second vaccine dose? 
 
 Yes 
 No  
 
If Yes, date of second vaccine dose:  _ _ /  _ _ / _ _ _ _ 
 
      If No, provide reason: 
 
             
 Not yet due 
 
 Second dose not required  
 
 Other 
 
If Other, specify: ______________________________ 
 
Have you received a booster dose? 
 
 Yes 
 No  
 
1. Date of first booster dose: _ _ /  _ _ / _ _ _ _ 
 
Which vaccine did you receive? 
 
 Moderna 
 Pfizer - BioNTech  
 Johnson & Johnson 
 AstraZeneca 
 Other 
 
            If Other, specify: ______________________________ 
 
2. Date of second booster dose: _ _ /  _ _ / _ _ _ _ 
 
Which vaccine did you receive? 
 
 Moderna 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–97– 
February 3, 2025 
 Pfizer - BioNTech  
 Johnson & Johnson 
 AstraZeneca 
 Other 
 
            If Other, specify: ______________________________ 
 
 
Comments: 
______________________________________________________________________________
______________________________________________________________________________ 
 
 
CRF completed by (check one):  
Study participant  _____    
Study site staff      _____     Staff name (optional)  ____________________________ 
Date __ __ / __ __ / __ __ __ __ 
                  (MM/DD/YYYY) 
 
 
 
 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–98– 
February 3, 2025 
 
 
 
APPENDIX D 
 
PARTICIPANT CLINICAL TRIAL WALLET CARD 
 
 
 

CLINICALTRIALWALLETCARD
Showthiscardtoallofyour
healthcareprovidersandkeep
itwithyouincaseyougoto
theemergencyroom.
ParticipantName:     
Diagnosis/Condition:     
StudyDoctor:     
StudyDoctorPhone#:     
NCITrial#:     
StudyDrug(S):     
GAd20Ͳ209ͲFSPpolyvalent
vaccine;
MVAͲ209ͲFSPpolyvalentvaccine



Formoreinformation:1Ͳ800Ͳ4ͲCANCER
cancer.gov|clinicaltrials.gov
 
 
 
 
 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–99– 
February 3, 2025 
APPENDIX E 
 
PARTICIPANT BOOKLET FOR REPORTING INJECTION SITE REACTIONS 
 

VaccineReportCard



ParticipantIDNumber:__________________________________________

InjectionAdministrationDate:____________________________________



NotetoParticipant:Ifyouhaveanyquestionsorproblems,pleasecontactyourstudystaff.

Name:_______________________________________________________

Telephone:___________________________________________________

Email(optional):_______________________________________________




Participantsignature____________________________________________

Datereportcardreturnedtothestudystaff:_________________________






DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–100– 
February 3, 2025 
GeneralInstructions

Temperature:Takeyourtemperatureorallyaroundthesametimeeachevening,usingthe
thermometerprovided,andrecorditinthespaceprovided.Alsorecordthetimeatwhichyoutook
yourtemperature.Ifyourecentlydrankveryhotorcoldliquids,wait15minutesbeforetakingyour
temperature.

InjectionSiteSymptoms:

Painanditching

Somepeopleexperiencepainintheareawheretheywereinjected.Somepeoplemayalsoexperience
itchingintheareawheretheywereinjected.Bypainwemeanthattheplacewhereyouwereinjected
hurtsevenwhenitisn’ttouched.

Ifyouexperiencepainoritchingattheinjectionsite,usethefollowingcategoriestodescribehow
severethesesymptomswere.Ifyoudon’texperienceoneormoreofthesesymptoms,marktheNONE
box.

x 
Mild
Ionlyhadalittlediscomfort.Icouldstillusemyarmlikealways.

x 
Moderate
Inoticedthediscomfortanddidn’tusemyarmasmuchasusual.
IusedoverͲtheͲcounterpainmedicationstorelievethediscomfort.

x 
Severe
Ireallynoticedthediscomfort.ItkeptmefromdoingsomethingIwantedor
hadtodo.OverͲthecounterpainmedicationsdidn’twork.

x 
LifeͲthreatening
Ihadtogotothehospitaloremergencyroom.Ifthishappens,pleaseletyour
studyteamknowrightaway.

Redness,swelling,andbruising

Somepeopleexperienceredness,swelling,orbruisingintheareawheretheywereinjected.Ifyou
experienceredness,swelling,orbruising,measuretheareausingthemeasuringtoolyouwereprovided,
andrecordthemeasurementinthespaceprovided.

Tomeasuretheareaofredness,swelling,orbruising,pleasedothefollowing:
1. Placethemeasuringtoolovertheareawhereyouwereinjected,
withthedotoverthecenterofthearea.
2. Selectthecirclewherethelongestpartoftheareatouchestheline.
3. Iftheareaisbetweentwocircles,selectthelargercircle.
Forexample,theareashowntotherightmeasures3centimeters(cm)
becauseitistouchingthe3cmline.




DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–101– 
February 3, 2025 
GeneralandOtherSymptomsandMedications

Ifyouhaveadditionalsymptomsthatarenotlisted,orifyousoughtmedicalcareforanyreasonfroma
healthcareprovider(e.g.,doctor’soffice,emergencyroom),orifyoutookanymedications,these
shouldbelistedinthespacesprovided.PleasedesignateanysymptomsasMild,Moderate,orSevere.

x 
MildͲ 
Ionlyhadminordiscomfort.Iwentaboutmyusualactivities.

x 
Moderate
Inoticedthesymptom.ItbotheredmeenoughthatIdidn’tdoasmuchasI
usuallydo.IusedoverͲtheͲcounterpainmedicationstorelievethediscomfort.

x 
Severe
Ireallynoticedthesymptom.ItkeptmefromdoingsomethingIwantedorhad
todo.OverͲthecounterpainmedicationsdidn’twork.

x 
Lifethreatening
Ihadtogotothehospitaloremergencyroom.Ifthishappens,pleaseletyour
studyteamknowrightaway.






DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–102– 
February 3, 2025 
Day0:TheEveningoftheInjectionDate:_____/_____/_____
Sometimeduringtheeveningonthedayyouwereinjected,fillouttheinformationbelow.Theitemson
thispagerefertothetimebetweenwhenyouwereinjectedand11:59p.m.oftoday(Day0).Ifanyof
theinformationchangesafteryoufilloutthispagebutbefore11:59p.m.tonight,makeanynecessary
changesbelow.
 
Temperature
EveningTemp.:___________oCoroF(circleone)
TimeTaken:____________AMorPM(circleone)
 
 
GeneralSymptoms
Ifyouexperienceanyofthesesymptoms,marktheboxthatdescribestheworstthesymptomwasuntil
11:59p.m.tonight(Day0).SeeGeneralInstructionsonpage2formoreinformation.
Symptom
None
Mild
Moderate
Severe
Life
Threatening
Unusuallytired/feelingunwell





Muscleaches





Headache





Nauseaorvomiting





Jointpain





 
 
InjectionSiteSymptoms
Ifyouexperienceaninjectionsitesymptom,marktheboxthatdescribestheworstthesymptomwas
until11:59p.m.tonight(Day0).SeeGeneralInstructionsonpage2formoreinformation.
Symptom
None
Mild
Moderate
Severe
Life
Threatening
Pain





Itching







Redness,Swelling,orBruising
None
ProvideMaximumMeasurement
Redness

____cmatthelongestpart
Swelling

____cmatthelongestpart
Bruising

____cmatthelongestpart
 
 
 
 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–103– 
February 3, 2025 
OtherSymptoms

Ifyouexperiencesymptomsotherthantheonesyou’vealreadydescribed,writetheminthespace
belowaccordingtotheGeneralInstructionsonpage2.
Didyouexperienceanyothersymptoms?
Yes
No

SymptomorMedicalEvent
Mild
Moderate
Severe
Life
Threatening




















 
Didyoutakeanymedications?
Yes
No
Ifyes,pleaselistoutthename(s)anddosage(s)below:
_____________________________________________________________________________________
_____________________________________________________________________________________
_____________________________________________________________________________________
_______________






DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–104– 
February 3, 2025 
Day1:TheDayaftertheInjectionDate:_____/_____/_____
Theitemsonthispagerefertothetimebetweenmidnightoflastnightand11:59p.m.today(Day1).If
any of the information changes after you fill out this page but before 11:59 p.m. tonight make any
necessarychangesbelow.
 
Temperature
EveningTemp.:___________oCoroF(circleone)
TimeTaken:____________AMorPM(circleone)


GeneralSymptoms
Ifyouexperienceanyofthesesymptoms,marktheboxthatdescribestheworstthesymptomwasuntil
11:59p.m.tonight(Day1).SeeGeneralInstructionsonpage2formoreinformation.
Symptom
None
Mild
Moderate
Severe
Life
Threatening
Unusuallytired/feelingunwell





Muscleaches





Headache





Nauseaorvomiting





Jointpain





 
 
InjectionSiteSymptoms
Ifyouexperienceaninjectionsitesymptom,marktheboxthatdescribestheworstthesymptomwas
until11:59p.m.tonight(Day1).SeeGeneralInstructionsonpage2formoreinformation.
Symptom
None
Mild
Moderate
Severe
Life
Threatening
Pain





Itching







Redness,Swelling,orBruising
None
ProvideMaximumMeasurement
Redness

____cmatthelongestpart
Swelling

____cmatthelongestpart
Bruising

____cmatthelongestpart
 
 
 
 
 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–105– 
February 3, 2025 
OtherSymptoms

Ifyouexperiencesymptomsotherthantheonesyou’vealreadydescribed,writetheminthespace
belowaccordingtotheGeneralInstructionsonpage2.
Didyouexperienceanyothersymptoms?
Yes
No

SymptomorMedicalEvent
Mild
Moderate
Severe
Life
Threatening




















 
Didyoutakeanymedications?
Yes
No
Ifyes,pleaselistoutthename(s)anddosage(s)below:
_____________________________________________________________________________________
_____________________________________________________________________________________
_____________________________________________________________________________________
_______________



DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–106– 
February 3, 2025 
Day2:TwoDaysaftertheInjectionDate:_____/_____/_____
Theitemsonthispagerefertothetimebetweenmidnightoflastnightand11:59p.m.today(Day2).If
any of the information changes after you fill out this page but before 11:59 p.m. tonight make any
necessarychangesbelow.
 
 
Temperature
EveningTemp.:___________oCoroF(circleone)
TimeTaken:____________AMorPM(circleone)


GeneralSymptoms
Ifyouexperienceanyofthesesymptoms,marktheboxthatdescribestheworstthesymptomwasuntil
11:59p.m.tonight(Day2).SeeGeneralInstructionsonpage2formoreinformation.
Symptom
None
Mild
Moderate
Severe
Life
Threatening
Unusuallytired/feelingunwell





Muscleaches





Headache





Nauseaorvomiting





Jointpain





 
 
InjectionSiteSymptoms
Ifyouexperienceaninjectionsitesymptom,marktheboxthatdescribestheworstthesymptomwas
until11:59p.m.tonight(Day2).SeeGeneralInstructionsonpage2formoreinformation.
Symptom
None
Mild
Moderate
Severe
Life
Threatening
Pain





Itching







Redness,Swelling,orBruising
None
ProvideMaximumMeasurement
Redness

____cmatthelongestpart
Swelling

____cmatthelongestpart
Bruising

____cmatthelongestpart
 
 
 
 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–107– 
February 3, 2025 
OtherSymptoms

Ifyouexperiencesymptomsotherthantheonesyou’vealreadydescribed,writetheminthespace
belowaccordingtotheGeneralInstructionsonpage2.
Didyouexperienceanyothersymptoms?
Yes
No

SymptomorMedicalEvent
Mild
Moderate
Severe
Life
Threatening




















 
Didyoutakeanymedications?
Yes
No
Ifyes,pleaselistoutthename(s)anddosage(s)below:
_____________________________________________________________________________________
_____________________________________________________________________________________
_____________________________________________________________________________________
_______________





DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–108– 
February 3, 2025 
Day3:ThreeDaysaftertheInjectionDate:_____/_____/_____
Theitemsonthispagerefertothetimebetweenmidnightoflastnightand11:59p.m.today(Day3).If
any of the information changes after you fill out this page but before 11:59 p.m. tonight make any
necessarychangesbelow.
 
 
Temperature
EveningTemp.:___________oCoroF(circleone)
TimeTaken:____________AMorPM(circleone)


GeneralSymptoms
Ifyouexperienceanyofthesesymptoms,marktheboxthatdescribestheworstthesymptomwasuntil
11:59p.m.tonight(Day3).SeeGeneralInstructionsonpage2formoreinformation.
Symptom
None
Mild
Moderate
Severe
Life
Threatening
Unusuallytired/feelingunwell





Muscleaches





Headache





Nauseaorvomiting





Jointpain





 
 
InjectionSiteSymptoms
Ifyouexperienceaninjectionsitesymptom,marktheboxthatdescribestheworstthesymptomwas
until11:59p.m.tonight(Day3).SeeGeneralInstructionsonpage2formoreinformation.
Symptom
None
Mild
Moderate
Severe
Life
Threatening
Pain





Itching







Redness,Swelling,orBruising
None
ProvideMaximumMeasurement
Redness

____cmatthelongestpart
Swelling

____cmatthelongestpart
Bruising

____cmatthelongestpart
 
 
 
 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–109– 
February 3, 2025 
OtherSymptoms

Ifyouexperiencesymptomsotherthantheonesyou’vealreadydescribed,writetheminthespace
belowaccordingtotheGeneralInstructionsonpage2.
Didyouexperienceanyothersymptoms?
Yes
No

SymptomorMedicalEvent
Mild
Moderate
Severe
Life
Threatening




















 
Didyoutakeanymedications?
Yes
No
Ifyes,pleaselistoutthename(s)anddosage(s)below:
_____________________________________________________________________________________
_____________________________________________________________________________________
_____________________________________________________________________________________
_______________
 



DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–110– 
February 3, 2025 
Day4:FourDaysaftertheInjectionDate:_____/_____/_____
Theitemsonthispagerefertothetimebetweenmidnightoflastnightand11:59p.m.today(Day4).If
any of the information changes after you fill out this page but before 11:59 p.m. tonight make any
necessarychangesbelow.
 
 
Temperature
EveningTemp.:___________oCoroF(circleone)
TimeTaken:____________AMorPM(circleone)


GeneralSymptoms
Ifyouexperienceanyofthesesymptoms,marktheboxthatdescribestheworstthesymptomwasuntil
11:59p.m.tonight(Day4).SeeGeneralInstructionsonpage2formoreinformation.
Symptom
None
Mild
Moderate
Severe
Life
Threatening
Unusuallytired/feelingunwell





Muscleaches





Headache





Nauseaorvomiting





Jointpain





 
 
InjectionSiteSymptoms
Ifyouexperienceaninjectionsitesymptom,marktheboxthatdescribestheworstthesymptomwas
until11:59p.m.tonight(Day4).SeeGeneralInstructionsonpage2formoreinformation.
Symptom
None
Mild
Moderate
Severe
Life
Threatening
Pain





Itching







Redness,Swelling,orBruising
None
ProvideMaximumMeasurement
Redness

____cmatthelongestpart
Swelling

____cmatthelongestpart
Bruising

____cmatthelongestpart
 
 
 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–111– 
February 3, 2025 
OtherSymptoms

Ifyouexperiencesymptomsotherthantheonesyou’vealreadydescribed,writetheminthespace
belowaccordingtotheGeneralInstructionsonpage2.
Didyouexperienceanyothersymptoms?
Yes
No

SymptomorMedicalEvent
Mild
Moderate
Severe
Life
Threatening




















 
Didyoutakeanymedications?
Yes
No
Ifyes,pleaselistoutthename(s)anddosage(s)below:
_____________________________________________________________________________________
_____________________________________________________________________________________
_____________________________________________________________________________________
_______________
 
 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–112– 
February 3, 2025 
Day5:FiveDaysaftertheInjectionDate:_____/_____/_____
Theitemsonthispagerefertothetimebetweenmidnightoflastnightand11:59p.m.today(Day5).If
any of the information changes after you fill out this page but before 11:59 p.m. tonight make any
necessarychangesbelow.
 
 
Temperature
EveningTemp.:___________oCoroF(circleone)
TimeTaken:____________AMorPM(circleone)


GeneralSymptoms
Ifyouexperienceanyofthesesymptoms,marktheboxthatdescribestheworstthesymptomwasuntil
11:59p.m.tonight(Day5).SeeGeneralInstructionsonpage2formoreinformation.
Symptom
None
Mild
Moderate
Severe
Life
Threatening
Unusuallytired/feelingunwell





Muscleaches





Headache





Nauseaorvomiting





Jointpain





 
 
InjectionSiteSymptoms
Ifyouexperienceaninjectionsitesymptom,marktheboxthatdescribestheworstthesymptomwas
until11:59p.m.tonight(Day5).SeeGeneralInstructionsonpage2formoreinformation.
Symptom
None
Mild
Moderate
Severe
Life
Threatening
Pain





Itching







Redness,Swelling,orBruising
None
ProvideMaximumMeasurement
Redness

____cmatthelongestpart
Swelling

____cmatthelongestpart
Bruising

____cmatthelongestpart
 



DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–113– 
February 3, 2025 
OtherSymptoms

Ifyouexperiencesymptomsotherthantheonesyou’vealreadydescribed,writetheminthespace
belowaccordingtotheGeneralInstructionsonpage2.
Didyouexperienceanyothersymptoms?
Yes
No

SymptomorMedicalEvent
Mild
Moderate
Severe
Life
Threatening




















 
Didyoutakeanymedications?
Yes
No
Ifyes,pleaselistoutthename(s)anddosage(s)below:
_____________________________________________________________________________________
_____________________________________________________________________________________
_____________________________________________________________________________________
_______________





DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–114– 
February 3, 2025 
Day6:SixDaysaftertheInjectionDate:_____/_____/_____
Theitemsonthispagerefertothetimebetweenmidnightoflastnightand11:59p.m.today(Day6).If
any of the information changes after you fill out this page but before 11:59 p.m. tonight make any
necessarychangesbelow.
 
 
Temperature
EveningTemp.:___________oCoroF(circleone)
TimeTaken:____________AMorPM(circleone)


GeneralSymptoms
Ifyouexperienceanyofthesesymptoms,marktheboxthatdescribestheworstthesymptomwasuntil
11:59p.m.tonight(Day6).SeeGeneralInstructionsonpage2formoreinformation.
Symptom
None
Mild
Moderate
Severe
Life
Threatening
Unusuallytired/feelingunwell





Muscleaches





Headache





Nauseaorvomiting





Jointpain





 
 
InjectionSiteSymptoms
Ifyouexperienceaninjectionsitesymptom,marktheboxthatdescribestheworstthesymptomwas
until11:59p.m.tonight(Day6).SeeGeneralInstructionsonpage2formoreinformation.
Symptom
None
Mild
Moderate
Severe
Life
Threatening
Pain





Itching







Redness,Swelling,orBruising
None
ProvideMaximumMeasurement
Redness

____cmatthelongestpart
Swelling

____cmatthelongestpart
Bruising

____cmatthelongestpart
 
 
 
 

DCP Protocol MDA21-06-01 
Protocol Version 5.6, dated 02/19/2025 
 
DCP Protocol Template Version 17 
–115– 
February 3, 2025 
OtherSymptoms

Ifyouexperiencesymptomsotherthantheonesyou’vealreadydescribed,writetheminthespace
belowaccordingtotheGeneralInstructionsonpage2.
Didyouexperienceanyothersymptoms?
Yes
No

SymptomorMedicalEvent
Mild
Moderate
Severe
Life
Threatening




















 
Didyoutakeanymedications?
Yes
No
Ifyes,pleaselistoutthename(s)anddosage(s)below:
_____________________________________________________________________________________
_____________________________________________________________________________________
_____________________________________________________________________________________