Phase I/II Trial Investigating the Safety, Tolerability, Pharmacokinetics, Immune and Clinical Activity of SX-682 in Combination With BinTrafusp Alfa (M7824 or TGF-beta "Trap"/PD-L1) With CV301 TRICOM in Advanced Solid Tumors (STAT)
Phase: PHASE1
Conditions: Metastatic Cancer, Solid Tumors
Sponsor: National Cancer Institute (NCI)

Abbreviated Title: STAT Trial 
Version Date: 08/17/2022 
 
1 
Abbreviated Title: STAT Trial 
NIH Protocol # 20C0155 
Version Date: 08/17/2022 
NCT # NCT04574583 
IBC # RD-20-IV-09  
Title: Phase I/II Trial Investigating the Safety, Tolerability, Pharmacokinetics, Immune and 
Clinical Activity of SX-682 in Combination with BinTrafusp Alfa (M7824 or TGF-β 
“Trap”/PD-L1) with CV301 TRICOM in Advanced Solid Tumors (STAT). 
 
NIH Principal Investigator: 
 
James Gulley, MD, PhD  
Genitourinary Malignancies Branch (GMB)  
Center for Cancer Research (CCR) 
National Cancer Institute (NCI) 
 
 
 
 
  
 
 
Drug Name: 
SX-682 
Bintrafusp alfa 
(M7824) 
 
MVA-BN-
CV301 
FPV-CV301 
IND Number: 
21166  
Sponsor: 
CCR, NCI 
 
Manufacturer: 
Syntrix 
EMD Serono 
Bavarian 
Nordic 
Bavarian 
Nordic 
Supplier: 
Syntrix 
EMD Serono 
Bavarian 
Nordic 
Bavarian 
Nordic 
 
Commercial Agents: None 

Abbreviated Title: STAT Trial 
Version Date: 08/17/2022 
 
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PRÉCIS  
Background: 
• Combination immunotherapy approaches are being actively explored to further improve 
responses, enhance clinical benefit, and overcome resistance to PD(L)-1 agents in cancer 
participants.  
• Interleukin-8 (IL-8) is a pro-inflammatory chemokine produced by various cell types. 
Overexpression of IL-8 and/or its receptors CXCR1 and CXCR2, is commonly seen in 
many human cancers including breast, cervical, melanoma and prostate.  
• SX-682 is an oral, small molecule inhibitor of the CXCR1/2 chemokine receptors that are 
believed involved in MDSC-recruitment to tumor and other pro-tumoral mechanisms.  
• Bintrafusp alfa (M7824 or MSB0011359C) is a bifunctional protein composed of the 
extracellular domain of the TGF-βRII receptor (TGF-β “trap”) fused to a human IgG1. 
Preclinical data shows bintrafusp alfa treatment increases T-cell trafficking, antigen-
specific CD8+ T-cell lysis and NK cell activation. 
• CV301 is a poxviral-based vaccine comprised of recombinant Modified vaccinia Ankara 
(MVA-BN-CV301, prime) and recombinant fowlpox (FPV-CV301, boost). CV301 
contains transgenes encoding two (2) tumor-associated antigens (TAA), mucin 1 (MUC1) 
and carcinoembryonic antigen (CEA), as well as three costimulatory molecules (B7.1, 
ICAM-1 and LFA-3, designated TRICOM). A recent phase 1 clinical trial demonstrated 
that antigen-specific T cells to MUC1 and CEA, as well as to a cascade antigen, 
brachyury, were generated in most participants.  
• Preclinical studies performed in LTIB with SX-682, M7824 and a CEA-based vaccine 
showed a significant reduction in tumor growth as well as a significant increase in tumor 
infiltration with CD4+ and CD8+ T cells. 
Objectives: 
• Arm 1 (Sequential Dose Escalation):  
 To evaluate the safety and tolerability of single agent SX-682. 
 To determine the MTD of SX-682 followed by M7824 and CV301 vaccines in 
participants with advanced or metastatic solid tumors. If the MTD is not reached 
the study will be focused to describe the safety and tolerability of SX-682 
followed by M7824 and CV301 vaccines. 
• Arm 2 (Combination Dose Escalation):  
 To determine the recommended phase 2 dose (RP2D) of SX-682 with M7824 and 
CV301 vaccines in participants with advanced or metastatic solid tumors. If the 
MTD is not reached the study will be focused to describe the safety and 
tolerability of the drug combination. 
• Arm 3 (Expansion): 

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 To evaluate preliminary efficacy based on Objective Response Rate (ORR), in 
each disease cohort separately. 
Eligibility: 
• Age > 18 years old 
• Arms 1 and 2 (Dose-Escalation Cohort): Subjects with cytologically or histologically 
confirmed locally advanced or metastatic solid tumors.  
• Arm 3 (Expansion Cohorts): 
o TNBC: Subjects with cytologically or histologically confirmed locally advanced 
or metastatic Triple Negative Breast Cancer that has progressed on at least one 
prior treatment in the advanced or in the metastatic setting.  
o HPV negative HNSCC: Subjects with cytologically or histologically confirmed 
locally advanced or metastatic, HPV negative head and neck squamous cell 
cancer (p16 negative for oropharyngeal) that has progressed on at least one prior 
treatment involving a platinum drug or cetuximab in advanced or in the metastatic 
setting.  
• Prior first line systemic therapy is required unless there is no standard treatment 
available, the participant cannot tolerate standard first line treatment, or the participant 
declines standard treatment after appropriate counseling has been provided.  
• ECOG performance status of 0 to 1 
• Adequate renal, hepatic, and hematologic function 
• Subjects in Arms 1 and 2 may have disease that is measurable or non-measurable but 
evaluable disease (e.g. present on bone scan, rising tumor markers, non-measurable by 
RECIST but visible on CT scan). Participants with third space fluid (for example pleural 
effusions) as only site of disease will not be eligible. Subjects in Arm 3 must have 
measurable disease according to RECIST 1.1 
Design: 
• Arm 1 is a phase I, open-label, 3+3 sequential dose escalation trial with short term, 2-
week SX-682 monotherapy lead-in followed by treatment with M7824 and CV301 
vaccine series in advanced solid tumors (Q2W dosing schedule) for the duration of 
treatment. 
• Arm 2 is a phase I, open-label, 3+3 combination dose escalation trial with short term SX-
682 monotherapy lead in followed by SX-682 combination with M7824 and CV301 
vaccine series in advanced solid tumors (Q2W dosing schedule). Each enrolled 
participant will receive SX-682 as monotherapy for 2 weeks then will receive SX-682, 
M7824 and CV301 for the duration of treatment 
• Arm 3 has two expansion cohorts. Following identification of the MTD or R2PD for the 
combination of SX-682, M7824 and CV301 vaccine, disease-specific phase 2 expansion 
cohorts will open in 1) advanced/metastatic triple negative breast cancer and 2) 
advanced/metastatic, platinum-refractory HPV negative head and neck squamous cell 
carcinoma. 

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TABLE OF CONTENTS  
PRÉCIS ........................................................................................................................................... 2 
TABLE OF CONTENTS ................................................................................................................ 4 
STATEMENT OF COMPLIANCE ................................................................................................ 7 
1. 
INTRODUCTION .................................................................................................................. 8 
1.1 
Study Objectives .............................................................................................................. 8 
1.2 
Background and Rationale ............................................................................................... 9 
2 
ELIGBILITY ASSESSMENT AND ENROLLMENT ........................................................ 39 
2.1 
Eligibility Criteria .......................................................................................................... 39 
2.2 
Screening Evaluation ...................................................................................................... 42 
2.3 
Participant Registration And Status Update Procedures ................................................ 44 
2.4 
Baseline Evaluation ........................................................................................................ 45 
3 
STUDY IMPLEMENTATION ............................................................................................ 45 
3.1 
Study Design .................................................................................................................. 45 
3.2 
Study Stopping rules ...................................................................................................... 52 
3.3 
Drug Administration ...................................................................................................... 53 
3.4 
Dose Modifications ........................................................................................................ 54 
3.5 
Study Calendar ............................................................................................................... 68 
3.6 
Cost and Compensation .................................................................................................. 77 
3.7 
Criteria for Removal from Protocol Therapy and Off Study Criteria ............................ 77 
4 
Concomitant Therapy............................................................................................................ 78 
4.1 
The Following Treatments Should not be Administered During the Trial: ................... 78 
5 
CORRELATIVE STUDIES FOR RESEARCH ................................................................... 79 
5.1 
Samples .......................................................................................................................... 79 
5.2 
Correlative Studies for Research/Pharmacokinetic Studies ........................................... 80 
5.3 
Samples for Genetic/Genomic Analysis ........................................................................ 83 
5.4 
Sample Storage, Tracking and Disposition .................................................................... 84 
6 
DATA COLLECTION AND EVALUATION ..................................................................... 88 
6.1 
Data Collection ............................................................................................................... 88 
6.2 
Data Sharing Plans ......................................................................................................... 89 
6.3 
Response Criteria ........................................................................................................... 89 
7 
NIH REPORTING REQUIREMENTS / DATA AND SAFETY MONITORING PLAN .. 96 

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7.1 
Definitions ...................................................................................................................... 96 
7.2 
OHSRP Office of Compliance and Training / IRB Reporting ....................................... 96 
7.3 
NCI Clinical Director Reporting .................................................................................... 96 
7.4 
Institutional Biosafety Committee (IBC) Reporting Criteria ......................................... 96 
7.5 
NIH Required Data and Safety Monitoring Plan ........................................................... 98 
8 
SPONSOR PROTOCOL/SAFETY REPORTING ............................................................... 98 
8.1 
Definitions ...................................................................................................................... 98 
8.2 
Assessment of Safety Events ........................................................................................ 100 
8.3 
Reporting of Serious Adverse Events .......................................................................... 100 
8.4 
Waiver of expedited reporting to CCR ........................................................................ 101 
8.5 
Safety Reporting Criteria to the Pharmaceutical Collaborators ................................... 101 
8.6 
Reporting Pregnancy .................................................................................................... 101 
8.7 
Regulatory Reporting for Studies Conducted Under CCR-Sponsored IND ................ 102 
8.8 
Sponsor Protocol Non-Adherence Reporting ............................................................... 102 
9 
CLINICAL MONITORING ............................................................................................... 102 
10 STATISTICAL CONSIDERATIONS................................................................................ 103 
10.1 
Statistical Hypothesis ............................................................................................... 103 
10.2 
Sample Size Determination ...................................................................................... 104 
10.3 
Populations for Analyses .......................................................................................... 105 
10.4 
Statistical Analyses ................................................................................................... 106 
11 Collaborative Agreements .................................................................................................. 107 
11.1 
Cooperative Research and Development Agreement (CRADA) ............................. 107 
12 HUMAN SUBJECTS PROTECTIONS ............................................................................. 108 
12.1 
Rationale for Subject Selection ................................................................................ 108 
12.2 
Participation of Children .......................................................................................... 108 
12.3 
Participation of Subjects Unable to Give Consent ................................................... 108 
12.4 
Risk/Benefit Assessment for All Participants .......................................................... 108 
12.5 
Consent Process and Documentation ....................................................................... 111 
13 REGULATORY AND OPERATIONAL CONSIDERATIONS ....................................... 112 
13.1 
Study Discontinuation and Closure .......................................................................... 112 
13.2 
Quality Assurance and Quality Control.................................................................... 112 
13.3 
Conflict of Interest Policy......................................................................................... 112 
13.4 
Confidentiality and Privacy ...................................................................................... 113 

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14 PHARMACEUTICAL INFORMATION ........................................................................... 113 
14.1 
SX-682 (IND#21166) ............................................................................................... 113 
14.2 
M7824 (IND#21166) ................................................................................................ 114 
14.3 
CV301 (IND#21166) ................................................................................................ 115 
15 REFERENCES ................................................................................................................... 117 
16 Appendices .......................................................................................................................... 124 
16.1 
Appendix A-Performance Status Criteria ................................................................. 124 
16.2 
Appendix B: Drugs Known to Significantly Prolong the Qtc* ................................ 125 
16.3 
Appendix C Participant’s Medication Diary ________________________ ........... 127 
 

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STATEMENT OF COMPLIANCE 
The trial will be carried out in accordance with International Conference on Harmonisation Good 
Clinical Practice (ICH GCP) and the following:  
• United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 
CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812)  
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training. 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the Institutional Review Board (IRB) for review and approval. Approval of both 
the protocol and the consent form must be obtained before any participant is enrolled. Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study. In addition, all changes to the consent form will be IRB-approved; an 
IRB determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form. 

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1. INTRODUCTION 
1.1 
STUDY OBJECTIVES 
1.1.1 Primary Objectives: 
• Arm 1 (Sequential Dose Escalation):  
 To evaluate the safety and tolerability of single agent SX-682. 
 To determine the MTD of SX-682 followed by M7824 and CV301 vaccines in 
participants with advanced or metastatic solid tumors. If the MTD is not reached 
the study will be focused to describe the safety and tolerability of SX-682 
followed by M7824 and CV301 vaccines. 
• Arm 2 (Combination Dose Escalation):  
 To determine the RP2D of SX-682 with M7824 and CV301 vaccines in 
participants with advanced or metastatic solid tumors. If the MTD is not reached 
the study will be focused to describe the safety and tolerability of the drug 
combination. 
• Arm 3 (Expansion): 
 To evaluate preliminary efficacy based on objective response rate (ORR), in each 
disease cohort separately. 
1.1.2 Secondary Objectives: 
• Arms 1 and 2 (Dose Escalations):  
 To characterize the PK/PD profile of SX-682 as a single agent and in 
combination. 
• All Arms:  
 To evaluate preliminary efficacy: disease control rate (DCR; CR+PR+SD) and 
progression-free survival (PFS) using RECIST1.1. 
1.1.3 Exploratory Objectives (may be performed on selected participants if there are adequate 
samples.): 
• All Arms: 
 To evaluate the effect on immune cell subsets and soluble factors in peripheral 
blood. 
 To evaluate the effect on cytokine levels (IL-8, IL-6 and others) in peripheral 
blood. 
 To evaluate the effect on T cell clonality in peripheral blood and tumor samples. 
 To evaluate the effect on antigen-specific T cells responses to CEA, MUC1 and 
the cascade antigen brachyury in peripheral blood. 
 To evaluate the effect on antigen-specific T cell responses to CEA, MUC1 and the 
cascade antigen brachyury in tumor biopsies. 

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2 
ELIGBILITY ASSESSMENT AND ENROLLMENT 
2.1 
ELIGIBILITY CRITERIA 
2.1.1 Inclusion Criteria  
• Participants must have histologically or cytologically confirmed: 
 Metastatic or locally advanced, Solid tumor (Cohort 1) 
OR 
 Metastatic or locally recurrent, non-resectable Triple Negative Breast Cancer (TNBC), 
defined as ER < 10%, PR < 10% per immunohistochemistry (IHC) and HER 2 negative. 
HER2 negative or unamplified breast cancer is defined as IHC 0 or 1+ or IHC 2+ with 
FISH average HER2 copy number < 4.0 signals per cell or HER2/CEP17 < 2.0 with 
average HER2 copy number < 4.0 signals per cell.[89] HER2 testing must have been 
performed in a laboratory accredited by the College of American Pathology (CAP) or 
another accrediting entity (Cohort 2). 
OR 
 Metastatic or locally recurrent, non-resectable p16 negative Head and Neck Squamous 
Cell Cancer (HNSCC). Oropharyngeal tumors must be negative for p16 overexpression 
by IHC per ASCO/CAP guidelines and in a CAP accredited lab.[90] All other head and 
neck malignancies do not require p16 testing (Cohort 3). 
• Participants must have histologically or cytologically confirmed metastatic or locally 
advanced disease. Historical reports from a CAP accredited lab are acceptable.  
• Subjects in Arms 1 and 2 may have disease that is measurable or non-measurable but 
evaluable disease (e.g. present on bone scan, rising tumor markers, non-measurable by 
RECIST but visible on CT scan). Participants with third space fluid (for example pleural 
effusions) as only site of disease will not be eligible. Subjects in Arm 3 must have 
measurable disease according to RECIST 1.1See Section 6.3.1 for the evaluation of 
measurable disease.  
• Participants must  
 have received at least one prior systemic therapy for metastatic or locally advanced 
disease, unless there is no standard treatment available, 
OR 
 not tolerate standard first line treatment,  
OR 
 decline standard treatment after appropriate counseling has been provided.  
Note: Participants in Arm 3, Cohort 3 who have PD-L1 positive TNBC must have progressed on 
atezolizumab + nab-paclitaxel. Participants in Arm 3, Cohort 3 (p16 negative HNSCC) must 
have progressed on or been intolerant to a regimen involving a platinum drug or cetuximab 
monotherapy.  
• Age >18 years. 

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• ECOG performance status 0 or 1 (Appendix A). 
• Participants must have adequate organ and marrow function as defined below:  
 Absolute neutrophil count (ANC) >1,500/mcL 
 Platelets >100,000/mcL 
 Hemoglobin > 9 g/dL without a blood transfusion in the 14 days prior to enrollment.  
 Total bilirubin < 1.5X upper limit of normal (ULN) OR in subjects with Gilbert’s 
Syndrome, a total bilirubin < 3.0 x ULN  
 AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal OR in subjects with 
known liver metastasis, AST/ALT < 3.0 X ULN 
 An estimated creatinine clearance (CrCl) > 60 mL/min/1.73 m2 using the Cockroft-Gault 
calculation (https://www.kidney.org/professionals/KDOQI/gfr_calculatorCoc). 
• The effects of immunotherapies on the developing human fetus are unknown. For this reason 
and because immunotherapy agents as well as other therapeutic agents used in this trial are 
known to be teratogenic, women of child-bearing potential and men must agree to use 
adequate contraception (hormonal or barrier method of birth control; abstinence) at the time 
of study entry, for the duration of study treatment and up to 6 months after the last dose of 
the study drug (s). Should a woman become pregnant or suspect she is pregnant while she or 
her partner is participating in this study, she should inform her treating physician 
immediately.  
• Participants with well-controlled HIV infection are eligible for trial as long as: 
 On an effective anti-retroviral therapy (ART) > 4 weeks and with evidence of viral 
suppression defined as HIV viral load < 400 copies/mL at enrollment  
 CD4+ count > 200 cells/µL at enrollment  
• No reported opportunistic infections within 6 months prior to enrollment except for the 
following which will be allowed: 
o Esophageal candidiasis treated within last 6 months or currently improving with 
antifungal treatment 
o Oral and/or genital HSV treated within last 6 months or currently improving with 
antiviral treatment  
o Mycobacterium avium infection in last 6 months or that has been treated for at least 1 
month. 
• Immunomodulating drugs must be discontinued at least 1 weeks prior to enrollment for 
recent short course use (≤ 14 days) or discontinued at least 4 weeks prior to enrollment for 
long term use (> 14 days). 
• Participants must have a received their last treatment > 4 weeks or 5 half-lives of the last 
treatment drug, whichever is shorter before starting on trial. 
• Participants with known history of hepatitis B (HBV) infection are eligible for trial as long as 
the HBV viral load is undetectable.  

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• Participants with known history of hepatitis C (HCV) infection must have been treated and 
cured (viral load is undetectable). For participants with HCV infection who are currently on 
treatment, they are eligible if they have an undetectable or unquantifiable HCV RNA 12 
weeks or longer after definitive treatment completion. 
• Subjects must be able to understand and be willing to sign a written informed consent 
document. 
2.1.2 Exclusion Criteria 
• Participants who are receiving any other investigational agents. 
• Participants with active brain metastases or central nervous system metastasis (less than 28 
days out from definitive radiotherapy or surgery of brain metastasis) are excluded from this 
clinical trial. However, participants with treated brain metastasis are eligible if there is no 
magnetic resonance imaging (MRI) evidence of progression for 6 weeks after treatment is 
complete and the MRI within 28 days prior to enrollment. Participants requiring 
immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalent) 
for palliation are excluded. Participants with evidence of intratumoral or peritumoral brain 
metastasis hemorrhage on screening imaging are also excluded unless the hemorrhage of 
brain metastases is grade < 1 and has been stable on two consecutive imaging scans.  
• History of allergic reactions attributed to compounds of similar chemical or biologic 
composition to any of study drugs 
• Steroid use or active autoimmune disease that might deteriorate when receiving an 
immunostimulatory agent with the exception of:  
 Diabetes type I, eczema, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid disease or 
other mild autoimmune disorder not requiring immunosuppressive treatment; 
 Participants requiring hormone replacement with corticosteroid are eligible if the 
steroids are administered only for the purpose of adrenal insufficiency and at doses of 
<10 mg of prednisone or equivalent per day; 
 Administration of steroids for other conditions through a route known to result in a 
minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) is 
acceptable; 
 Participants on physiologic doses of systemic intravenous or oral corticosteroid 
therapy (≤ the equivalent of prednisone 10 mg/day.  
 The use of corticosteroids as premedication for contrast-enhanced studies which is 
allowed prior to enrollment. 
• Participants with a history of serious intercurrent chronic or acute illness, such as cardiac or 
pulmonary disease, hepatic disease, bleeding diathesis or recent (within 3 months) clinically 
significant bleeding events or other illness considered by the Investigator as high risk for 
investigational drug treatment. 
• History of second malignancy within 3 years of enrollment except for the following: 
adequately treated localized skin cancer, ductal carcinoma in situ, cervical carcinoma in situ, 
superficial bladder cancer or other localized malignancy which has been adequately treated.  

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• Receipt of any organ transplantation requiring ongoing immunosuppression including 
allogenic stem-cell transplant.  
• Participants with bone metastases who have initiated denosumab or a bisphosphonate therapy 
within 28 days prior to enrollment. Continuation of prior therapy is allowed.  
• Participants who have a QTcf interval > 475 msec or > 480 msec with a BBB on screening 
electrocardiogram.  
• Participants with a personal or family history of long-QT syndrome or are on a concomitant 
drug that is known to cause significant QTc prolongation within 2 weeks or 5 half-lives 
(whichever is shorter) of enrollment (see Appendix B for list of drugs) 
• Participants with heart failure (New York Heart Association [NYHA] class III or IV) or 
cerebrovascular accident within one year or acute myocardial infarction within one year. 
• Participants unwilling to accept blood products or blood transfusions as medically indicated. 
As there is a risk of severe bleeding with M7824, participants must be willing to receive 
blood transfusions if medically necessary for their own safety 
• Any other condition, which would, in the opinion of the Principal Investigator indicated the 
subject is a poor candidate for the clinical trial or would jeopardize the subject or the 
integrity of the data obtained. 
• Pregnant women are excluded from this study because study drugs potential for teratogenic 
or abortifacient effects are unknown. Because there is an unknown but potential risk for 
adverse events in nursing infants secondary to treatment of the mother with study drugs, 
breastfeeding should be discontinued if the mother is treated with study drugs. 
2.1.3 Recruitment Strategies 
This protocol may be abstracted into a plain language announcement posted on NIH websites, 
including www.clinicaltrials.gov and the CCR website, and on NIH social media forums. 
Outside providers and colleagues may directly refer participants for screening into this study. 
2.2 
SCREENING EVALUATION 
2.2.1 Screening activities performed prior to obtaining informed consent 
Minimal risk activities that may be performed before the subject has signed a consent include the 
following:  
• Email, written, in person or telephone communications with prospective subjects  
• Review of existing medical records to include H&P, laboratory studies, etc.  
• Review of existing MRI, x-ray, or CT images 
• Review of existing photographs or videosReview of existing pathology specimens/reports 
from a specimen obtained for diagnostic purposes. 
2.2.2 Screening activities performed after a consent for screening has been signed 
The following activities will be performed only after the subject has signed the study consent OR 
the consent for study #01-C-0129 (provided the procedure is permitted on the study) on which 
screening activities will be performed. Assessments performed at outside facilities or on another 

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NIH protocol within the timeframes below may also be used to determine eligibility once a 
participant has signed the consent. 
All screening tests and procedures must be performed within 28 days prior to initiation of study 
therapy, unless otherwise specified:  
• Complete medical history and physical examination (including weight, height, vital 
signs, and ECOG performance status). 
• CT of chest, abdomen and pelvis with contrast (preferred)  
• A brain CT  
• Clinical laboratory tests (within 16 days prior to enrollment) 
− Biochemical Profile: sodium, potassium, chloride magnesium, phosphorus,  
bicarbonate, calcium, glucose, BUN, creatinine, ALT, AST, alkaline phosphatase, 
total protein, albumin, and total and direct bilirubin,. 
− Hematology: complete blood count (CBC) with differential and platelets 
− CD4 (if clinically indicated) 
− TSH, free T4, lipase, amylase 
− Lymphocyte panel (TBNK) 
− Coagulation panel: PT, INR, PTT 
− Urinalysis 
− Serum pregnancy test (β-HCG) for females of childbearing-potential and women 
< 12 months since the onset of menopause (within 7 days prior to enrollment).  
− HBV, HCV (or HCV viral load if recently completed treatment for HCV), HIV 
viral load by PCR (within 3 months prior to enrollment). 
• Electrocardiogram (EKG) in triplicate 
• Histologic or cytologic confirmation of tumor disease (at any time point prior to 
enrollment). Confirmation of tumor histology in NCI Laboratory of Pathology 
(archival tumor samples will be requested; if unavailable, the subject may choose to 
undergo fresh biopsy). Pathological confirmation of diagnosis of cancer in the 
Laboratory of Pathology at NIH Clinical Center or Walter Reed National Military 
Medical Center at Bethesda. However, if no pathologic specimen is available or if 
participants arrived with a diagnosis from Walter Reed National Military Medical 
Center at Bethesda, patients may enroll with a pathologist’s report showing a 
histologic diagnosis of metastatic cancer, TNBC or HPV negative HNSCC in a 
College of American Pathologists (CAP) accredited laboratory and a clinical course 
consistent with the disease. If there is no available tumor sample or pathology report 
from a CAP accredited lab, a biopsy will be performed to confirm the diagnosis in a 
CAP accredited lab. 
• Documentation of Immunohistochemistry (IHC) confirmation of Triple Negative 
Breast Cancer (TNBC), defined as ER < 10%, PR < 10% and HER2 negative. HER2 

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negative or unamplified breast cancer is defined by IHC and FISH HER2 testing. 
FISH must have been performed in a laboratory accredited by the College of 
American Pathology (CAP) or another accrediting entity (Arm 3, Cohort 2 only) (at 
any time point prior to initiation of study therapy) 
• Documentation of IHC confirmation of HPV negative, oropharyngeal tumor is 
defined by negative p16 overexpression in the tumor (Arm 3, Cohort 3 only) (at any 
time point prior to initiation of study therapy). Other head and neck malignancies do 
not require p16 testing. 
2.3 
PARTICIPANT REGISTRATION AND STATUS UPDATE PROCEDURES 
Registration and status updates (e.g., when a participant is taken off protocol therapy and when a 
participant is taken off-study) will take place per CCR SOP ADCR-2, CCR Participant 
Registration & Status Updates found  at: 
https://ccrod.cancer.gov/confluence/pages/viewpage.action?pageId=73203825. 
2.3.1 Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical trial but are 
not subsequently assigned to the study intervention or entered in the study. A minimal set of 
screen failure information is required to ensure transparent reporting of screen failure 
participants, to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements and to respond to queries from regulatory authorities. Minimal information 
includes demography, screen failure details, eligibility criteria, and any serious adverse event 
(SAE). 
Individuals who do not meet the criteria for participation in this trial (screen failure) because of a 
lab abnormality or temporary condition may be rescreened.. 
2.3.2 Treatment Assignment Procedures (for registration purpose only): 
Cohorts 
Number Name 
Description 
1 
Phase 1: Solid Tumor  
Participants with any solid tumor enrolled to SX-682 
escalation dose levels 
2 
Phase 2: TNBC Expansion 
Participants with Triple Negative Breast Cancer 
enrolled at the RP2D of SX-682 in combination with 
M7824 and CV301 
3 
Phase 2: HPV-HNSCC 
Expansion 
Participants with HPV negative Head and Neck 
Cancer enrolled at the RP2D of SX-682 in 
combination with M7824 and CV301 
Arms 
Number Name 
Description 
1 
Sequential Dose Escalation 
Escalating doses of SX-682 for 2 weeks THEN 
M7824 + CV301  

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Number Name 
Description 
2 
Combination Dose 
Escalation  
Escalating doses of SX-682 for 2 weeks THEN 
Escalating doses of SX-682 + M7824 + CV301  
3 
Disease-Specific Expansion  RP2D of SX-682 + M7824 + CV301  
Participants in Cohort 1 will be sequentially assigned to Arms 1 and 2.  
Participants in Cohorts 2 and 3 will be assigned to Arm 3. 
2.4 
BASELINE EVALUATION 
Tests done at screening do not need to be repeated on baseline if performed in designated time 
frame prior to start of study treatment 
Within 7 days prior to first dose of any study drug: 
• Physical exam including height, weight, ECOG performance status and vital signs.  
• Concomitant Medications and Baseline Signs and Symptoms evaluation. 
• EKG 
• Serum pregnancy test (β-HCG) for females of childbearing-potential and women 
< 12 months since the onset of natural menopause (i.e., amenorrhea not induced by 
chemotherapy or other medication). 
• Biochemical Profile: sodium, potassium, chloride, magnesium, phosphorus,  
bicarbonate, calcium, glucose, BUN, creatinine, ALT, AST, alkaline phosphatase, 
total protein, albumin, and total and direct bilirubin. 
• TSH, free T4, lipase, amylase 
• Hematology: CBC with differential and platelets. Lymphocyte panel (TBNK)  
• Coagulation panel: PT, INR, and PTT 
• Urinalysis 
• Flexible clinic-based pharyngolaryngoscopy to evaluate the airway for safety and for 
mucosal involvement (if clinically indicated in participants with head and neck 
cancers) 
• Collection of archival tumor samples for research if available (any time prior to 
treatment). 
• Optional tumor biopsy for research purposes. 
3 
STUDY IMPLEMENTATION 
3.1 
STUDY DESIGN  
This is an open label Phase I/II trial, consisting of a safety run-in phase I (Arms 1 and 2) and an 
expansion phase II, disease-specific cohorts (Arm 3). 
In Arm 1 the safety and MTD dose of short term (2 weeks) SX-682 monotherapy lead-in 
following by treatment with M7824 and CV301 will be determined in participants with solid 

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tumors (Schema 1). An evaluation of DLTs (eDLTs) will occur at the completion of each dose 
level and will be done prior to enrolling on the next dose level.  
In Arm 2 the safety, MTD/RP2D of continuing treatment of SX-682 in combination with M7824 
and CV301 will be determined in participants with solid tumors (Schema 2). An evaluation of 
DLTs (eDLTs) will occur at the completion of each dose level and will be done prior to enrolling 
on the next dose level. 
During Arm 3 expansion cohorts, when RP2D of SX-682 in combination with M7824 and 
CV301 is estimated, we will proceed with enrollment to Cohorts 2 (participants with triple 
negative breast cancer) and Cohort 3 (participants with HPV negative head and neck cancer) to 
evaluate efficacy of the SX-682 in combination with M7824 and CV301 (Schema 3).  
SX-682 will be self-administered by the participant orally twice daily according to designated 
Dose Level ( Table 4). 
Administration of M7824 will be at a flat dose of 1,200 mg every 2 weeks by IV. Participants 
will receive M7824 treatment every 14 (-1/+3) days. 
CV301 will be administered at a flat dose for both the prime and booster vaccines. The priming 
MVA-BN-CV301 is delivered as four subcutaneous injections of 4x108 infectious units 
(Inf.U)/0.5 mL every 14 days for 2 doses (Cycle 1, Day 1 and Cycle 1, Day 15). FPV-CV301 is 
given subcutaneously at 1×109Inf.U/0.5 mL every 4 weeks starting on Cycle 2 Day 1 x 4 cycles 
then on Day 1 of every 3 cycles (every 12 weeks) for up to 1 year on trial. Participants will 
receive CV301 as scheduled (-1/+3) days. 
Subjects on all arms will receive combined treatment with study drugs for up to 2 years (BN-
CV301 will be administered for up to 1 year on trial; M7824 and SX-682 will be administered 
for up to 2 years on trial). Furthermore, after 2 years on treatment with M7824 and/or SX-682, 
the PI can discuss an additional treatment period with CRADA partners as long as in the opinion 
of the PI the participant continues to gain clinic benefit and is tolerating the drug regimen. 
Disease progression should be confirmed with a subsequent scan 4 to 8 weeks later prior to 
removing a participant from study therapy, unless the participant is clinically progressing or is no 
longer gaining benefit in the opinion of the investigator. Subjects with evidence of disease 
progression can remain on treatment beyond radiographic progression if in the opinion of the 
investigator the subject is benefiting from treatment. For complete list of off treatment criteria, 
see Section 3.7.2. 
Patients may undergo up to three optional biopsies for research purposes only: at baseline, at first 
restaging (+/- 1 week) and at time of progression. 
 

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Schema 1. Cohort 1, Arm 1 
 

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Schema 2. Cohort 1, Arm 2. Combination Dose Escalation Cohort. 
 
3.1.1 Dose Limiting Toxicity 
Dose-limiting toxicity (DLT) will be defined as any one of the following adverse events (AEs), 
as defined by CTCAE v5.0, possibly attributable to study drugs by the Investigator, that occur 
within 28 days after the start of study therapy: 
• Any Grade 4 AEs, except for: 
o  laboratory values that are determined to not be clinically significant or single 
laboratory valued that resolve to Grade ≤ 1 or baseline grade within 7 days with 
adequate medical management. 
o adverse drug reaction which in the opinion of the investigator is not clinically 
relevant or can be medically managed with minimal risk to the participant (e.g. 
placement of a pleural catheter for recurrent inflammatory pleural effusions) 
• Average QTcf ≥ 501 msec or > 60 msec change from baseline (Grade 3) 
• Any Grade 3 AEs except for any of the following: 
o Grade 3 flu-like symptoms or fever, as well as associated symptoms of fatigue, 
headaches, nausea, emesis which can be controlled with conservative medical 
management.  
o Tumor flare phenomenon defined as local pain, irritation, or rash localized at sites 
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o Any Grade ≥ 3 drug-related amylase or lipase abnormality that is not associated 
with symptoms or clinical manifestations of pancreatitis.  
o Grade 3 Hgb decrease (< 8.0 g/dL) that is clinically manageable with blood 
transfusions or erythroid growth factor use does not require treatment 
discontinuation.  
o Keratoacanthoma and squamous cell carcinoma of the skin.  
o Any endocrinopathy that can be medically managed with hormone replacement 
o Grade 3 neutropenia without fever 
o Since the safety profile of M7824 is well characterized (see IB), a single grade 3 
adverse event known to be associated with M7824, as per IB section 6.2.6 will not 
be considered a DLT. 
 Additionally, M7824 has a known potential to cause bleeding, with a rate 
of grade 3 bleeding events as high as 15.3% [92].  Therefore a grade 3 
bleeding event will not be considered a DLT. 
o Any grade 3 adverse drug reaction which in the opinion of the investigator is not 
clinically relevant or can be medically managed with minimal risk to the 
participant (e.g. placement of a pleural catheter for recurrent inflammatory pleural 
effusions) 
• Any grade 3 or higher adverse event or unexpected toxicities due to the combination of 
therapies that would not be expected with individual agents alone, will be considered a 
DLT. 
3.1.2 Dose Escalation Common Rules 
Starting dose of SX-682 will be 25 mg by mouth twice daily (50 mg total daily dose). 
The first 3 participants enrolled on a given dose level of Arms 1 and 2 will be observed for DLT. 
If no DLT in those 3 participants, the next dose level will open. If DLT(s) occur, seeTable 5. 
There will be an interval of at least 28 days between enrolling the last participant on a given dose 
level and enrolling a participant on the next dose level in Arms 1 and 2, in order to assess for 
DLTs.  
Subjects who do not complete the DLT observation period for reasons other than a DLT will be 
replaced and not included in the evaluation. 
Participants will be eligible for the DLT evaluation if at least ≥85 percent of SX-682 scheduled 
doses were taken and 100% of scheduled doses of M7824 or CV301 were administered within 
the DLT period. 
In case of DLT, DLT will be documented and participant, per PI discretion, may continue study 
treatment if toxicity could be managed by interruption of the dose of study treatment or dose 
reductions (See section 3.4). Participant, once having DLT, will not be used for DLT evaluation 
on another dose level if treated on a lower dose level.  
Any of the trial drugs may be discontinued for toxicity per the discretion of the primary 
investigator if is it felt that the toxicity can be directly linked to a specific drug or drugs. Per PI 

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discretion participant can continue treatment with 2 other drugs. However, if 2 drugs or more 
must be discontinued, the participant will be taken off treatment. 
3.1.3 Sequential Dose Escalation (Arm 1) 
In Arm 1 participants will receive SX-682 as monotherapy for 2 weeks during the lead-in (Days -
14L to -1L) and then continue treatment with M7824 and CV301 starting Cycle 1, Day 1.  
The dose escalation will start from dose level 1 and continue until dose level 3 (Table 4) in 
sequential order using a standard 3+3 design (Table 5). Aside from looking at DLTs within a 
given dose level, the total number of DLTs will also be evaluated among the initial 3DLs in Arm 
1 to guide further safety assessments.  If there are 0 DLTs reported in the initial 3 DLs 
(minimum of 12 participants) in Arm 1, then Arm 2 can open as depicted in Schema 2 with 
starting at DL2. If there is 1 or more DLTs identified among all the participants in the first 3 
DLs, enrollment in Arm 1 will continue with the next participants being enrolled on DL4 then 
DL5, using a 3+3 design in order to determine the maximally tolerated dose (MTD) before 
proceeding to Arm 2, DL 1.  
Dose escalation will proceed in groups of 3–6 participants. The MTD is the dose level at which 
no more than 1 of up to 6 participants experience DLT during 28 days of treatment, and the dose 
below that at which at least 2 (of ≤6) participants have DLT as a result of the drug. 
 
Table 4: Dose levels of SX-682 
 
 
Dose Escalation Schedule 
 
Dose Level 
Dose of SX-682  
Total SX-682 daily 
dose 
Level 1 
25 mg by mouth twice daily  
50 mg 
Level 2 
50 mg by mouth twice daily 
100 mg 
Level 3 
100 mg by mouth twice daily 
200 mg 
Level 4 
200 mg by mouth twice daily 
400 mg 
Level 5 
400 mg by mouth twice daily 
800 mg 
SX-682 is dispensed as a 25mg tablet. M7824 and CV301 will be given at fixed doses.  

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Table 5. Escalation Decision Rules 
 
Number of Participants 
with DLT 
at a Given Dose Level 
Escalation Decision Rule* 
0 out of 3 
Enter up to 3 participants at the next dose level 
> 2 
Dose escalation will be stopped. This dose level will 
be declared the maximally administered dose 
(highest dose administered). Up to three (3) 
additional participants will be entered at the next 
lowest dose level if only 3 participants were treated 
previously at that dose. 
1 out of 3 
Enter up to 3 more participants at this dose level. 
• If 0 of these 3 participants experience DLT, 
proceed to the next dose level. 
• If 1 or more of this group suffer DLT, then dose 
escalation is stopped, and this dose is declared 
the maximally administered dose. UP to three (3) 
additional participants will be entered at the next 
lowest dose level if only 3 participants were 
treated previously at that dose. 
<1 out of 6 at highest dose 
level below the maximally 
administered dose 
This is the MTD and is generally the recommended 
phase 2 dose. At least 6 participants must be entered 
at the recommended phase 2 dose. 
 
3.1.4 Combination Dose Escalation (Arm 2) 
In Arm 2 participants will receive SX-682 as monotherapy for the lead-in (Days -14L to -1L) and 
then will continue treatment with SX-682 combined with M7824 and CV301 starting on Cycle 1 
Day 1. 
If 6 participants have been treated in Arm 1 at dose level 3 without DLT during DLT period, the 
dose escalation of SX-682 will start from dose level 2 and continue until dose level 5 (Table 4) 
in sequential order using a standard 3+3 design (Table 5). 
If there was 1 or more DLT in Arm 1 at dose level 1 through 3 during DLT period, the dose 
escalation of SX-682 will start from dose level 1 and continue until dose level 5 (Table 4) in 
sequential order using a standard 3+3 design (Table 5). 
If in Arm 1 dose level 1 or 2 are estimated as MTD, we will submit an amendment with 
justification for study continuation.  
Dose escalation will proceed in groups of 3–6 participants. The MTD is the dose level at which 
no more than 1 of up to 6 participants experience DLT during 28 days of treatment, and the dose 
below that at which at least 2 (of ≤6) participants have DLT as a result of the drug. The RP2D 
may not necessarily be the same as the MTD.  

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3.1.5 Expansion Cohorts (Arm 3, Cohorts 2 and 3) 
The safety, tolerability and efficacy evaluation of combination will continue with the RP2D of 
SX-682, M7824 and CV301 found during the dose escalation cohort (Arms 1 and 2). The dose of 
SX-682 used in combination with M7824 and CV301 in Arm 3 cannot exceed the highest 
tolerable dose for SX-682 monotherapy as determined in Arms 1 and 2. 
Enrollment into the expansion cohorts can commence after the RP2D has been determined (after 
the 6th participant on relevant dose level completes the DLT evaluation period). For performance 
of the expansion cohorts, see Schema 3 
Schema 3 Expansion Cohorts in Triple Negative Breast Cancer and HPV negative HNSCC 
  
 
3.2 
STUDY STOPPING RULES 
For safety reasons, enrollment will be temporarily halted until an expedited safety report has 
been evaluated by the investigators, IND sponsor, and submitted to the FDA for either of the 
following events attributable to treatment regimen occurring within 30 days of receiving 
investigational agent:  
• One occurrence of grade 5 toxicity  
• Two occurrences of grade 4 toxicity 
• Grade 3 or higher toxicities that occur at a higher rate than expected for each individual 
agent in the combination.  

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3.3 
DRUG ADMINISTRATION 
3.3.1 General Dosing Rules: 
Except where stated otherwise in the study calendar a window of -1/+ 3 days for every two 
weeks M7824 dosing and/or study calendar a window of -1/+ 3 days for the scheduled CV301 
dosing is allowed in the event of scheduling issues (i.e. holiday, bad weather or other scheduling 
issues). Any dose that cannot be accommodated within this window will be skipped and the dose 
not made up. Similar drug administrations should not be given less than 11 days from one 
another.  
The preferred order of drug administration in the day hospital is CV301, then M7824 
administration; when possible, administer the vaccine within 60 minutes prior to the M7824 
administration; however, the exact timing of vaccine administration is flexible. 
3.3.2 SX-682  
SX-682 will be given orally at designated dose twice a day every day. SX-682 is available as a 
25 mg and a 100 mg tablet. If necessary, the 100 mg tablets can be cut in half using a pill splitter; 
the tablets are pre-scored for this purpose. The tablets are not to be crushed, chewed, or dissolved 
before swallowing.  
SX-682 should be taken at approximately the same times each day. Participants should take SX-
682 with water once in the morning (suggested between 6-9 am) and once in the evening 
(suggested between 6-9 pm). For two hours before and one hour after the dose, the participant’s 
diet should be limited to clear liquids only (no solid foods). Doses should be taken within 2 hours 
of the scheduled time.  
In case of a missed dose (more than 2 hours late) or vomiting after taking SX-682, participants 
will be instructed not to make up the missed dose. 
Up to 15% of scheduled doses of SX-682 can be missed per cycle unless directed by PI/AI to 
hold additional doses of SX-682 during a planned cycle.  
Participants will complete and return Participant’s Diary (Appendix C), which will be reviewed 
by research staff at the end of each cycle. 
3.3.3 CV301 Vaccines  
Participants will be primed with MVA-BN-CV301 twice during Cycle 1 (Days 1 and 15), 
followed by booster vaccines with FPV-CV301 on Day 1 of subsequent cycles (every 4 weeks) x 
4 cycles  (Cycle 2 through Cycle 5) then on Day 1 of every 3 cycles (Cycles 8 and Cycle 11).  
A single dose of MVA-BN-CV301 is given as four subcutaneous injections with each of these 
injections containing 4x108 Inf.U/0.5ml. Each injection will be given in a different arm or leg. 
A dose of FPV-CV301 is given as one subcutaneous injection with each injection containing 
1x109 Inf.U/0.5ml. For participant comfort, it is generally preferred if FPV-CV301 is 
administered in the upper arm; however, the vaccine can be given in any extremity. 
3.3.4 M7824  
Subjects will be scheduled to receive M7824 at a flat dose of 1,200 mg IV on Days 1 and 15 of 
each cycle.  

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Subjects will receive M7824 via IV infusion over 1 hour (-10 minutes / +20 minutes, that is, over 
50 to 80 minutes) once every 2 weeks. Infusion rate may be adjusted in the event of certain 
adverse events as described in section 3.4.4. M7824 can be administered through a central line 
(preexisting) or a peripheral IV. A 0.2 micron in-line filter is required for administration of 
M7824. The preference is for M7824 to be given via peripheral line. However, if the research 
team documents that the main material of the port is titanium, M7824 can be administered via 
mediport. It is the responsibility of the research team to confirm and document this in CRIS. 
Once documented, the ordering physician can change the route of administration to mediport. 
Please refer to the pharmacy manual for a list of acceptable materials known to be compatible 
with M7824. 
In order to mitigate potential infusion-related reactions, premedication with an antihistamine and 
with acetaminophen (for example, 25-50 mg diphenhydramine and 500-650 mg acetaminophen) 
within approximately 30 to 60 minutes prior to dosing of M7824 is optional and at the discretion 
of the Investigator. Steroids as premedication are not permitted. 
3.4 
DOSE MODIFICATIONS 
3.4.1 General Rules  
When, at the beginning of a treatment week, treatment delay related to one of study drugs is 
indicated, treatment with other drugs should not be delayed.  
If, in the opinion of the investigator, a toxicity is considered to be due solely to one drug, the 
dose of other drugs does not require modification. 
Any of the trial drugs may be held for toxicity per the discretion of the primary investigator if is 
it felt that the toxicity can be directly linked to a specific drug. For AEs that are attributed to a 
study drug, a study drug may be held or reduced (only SX-682 can be reduced) when in the 
opinion of the investigator doing so will minimize the risks to the participant and maximize 
clinic benefit (e.g., in the event of observed tumor reduction but also intolerable ADRs at the full 
dose).  
If one drug is discontinued during first year of treatment, a participant may per PI discretion 
continue treatment with 2 other drugs. However, if 2 drugs must be discontinued, the participant 
will be taken off treatment. If one drug is discontinued during second year of treatment, a 
participant may per PI discretion continue treatment with the other drug. 
For non-medical logistical reasons, unrelated acute illnesses, or palliative radiation, dosing with 
any drug can be delayed up to 2 months. Where at all possible, dosing should be restarted to keep 
in line with the original treatment schedule. 
For AEs that are unrelated to the study drugs, study drug(s) may be held for up to 2 months at the 
discretion of the PI. 
Any dose that would have occurred within this window will be skipped and the dose not made 
up. 
If a participant on trial continues to gain benefit from treatment with one or more of the trial 
drugs at the two-year mark, the investigator can discuss with the CRADA partners the possibility 
of continuing the participant on treatment with the assigned trial drugs for an additional specified 
period of time. 

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In case of Grade 3 and Grade 4 AEs not study drug related, the study treatment may be 
interrupted based on the Investigator assessment and the subject will be medically treated for the 
event. 
If the AE reduces to a lower tolerable grade the study treatment might be resumed in the 
subsequent week. If the AE remains the same despite the medical treatment until the next 
treatment (second cycle after the AE occurred) a consideration of a possible extension of the 
dose interruption for up to 1 additional cycle or a permanent withdrawal from the study treatment 
should be considered. 
If upon the resumed study treatment, the subject experiences the same AE, permanent 
withdrawal from the study treatment should be considered. 
Grade 3 and 4 laboratory abnormalities that do not have clinical significance and are not related 
to study drugs do not require dose interruption. 
3.4.2 SX-682 
If any SX-682 related AE observed is grade > 2 (except for electrolyte abnormalities that can be 
easily replenished or other lab abnormalities that have no clinical consequence or can be easily 
medically managed with minimal risk to the participant), treatment should be delayed by 1 week 
(except for hyperbilirubinemia where drug will be held for grade 2) – and up to 4 consecutive 
weeks. If, with a delay of up to 4 weeks, the treatment related AE resolves, then SX-682 can be 
resumed at the same dose level or at a lower dose level per the PI discretion. 
If, after 4 weeks of delay, all treatment related AEs have still not resolved (to grade ≤ 1), then 
any further treatment with SX-682 should be delayed until AEs are resolved (to grade ≤ 1), and 
then reduced by one dose level at the time of reinitiating.  
3.4.3 CV301 
Dose delays or dose omissions of CV301 vaccines are allowed per PI discretion. There are no 
dose reductions for the CV301 vaccines.  
3.4.4 M7824 
Dose delays or dose omissions of M7824 are allowed per PI discretion. There are no dose 
reductions for M7824.  
3.4.4.1 Adverse Drug Reactions (ADRs) Requiring Treatment Discontinuation  
All adverse events in this trial will be graded using the NCI Common Terminology Criteria for 
Adverse Events (CTCAE) version 5.0. 
Any Grade 4 ADRs require permanent treatment discontinuation except for any of the 
following: 
• Single laboratory values out of normal range that do not have any clinical correlate and 
resolve to Grade ≤ 1 or Baseline grade within 7 days with adequate medical management.  
• Grade 4 symptomatic endocrinopathies (e.g., thyroiditis or hypophysitis), treatment 
should be delayed, and treatment started according to best medical judgement based on 
the most updated professional guidelines (NCCN, EMSO, SITC, etc.). Following the 
initiation of appropriate medical therapy for the endocrinopathy, treatment can be 
resumed per PI discretion.  

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• Asymptomatic lab abnormalities (Grade 3 or 4) as described below in the Grade 3 ADR 
section.  
• Grade 4 non-tumor bleeding will not require permanent treatment discontinuation if an 
alternative explanation for the bleeding is identified. If no alternative explanation is 
identified, treatment must be permanently discontinued.  
Any Grade 3 ADRs require treatment temporary discontinuation except for any of the 
following:  
• Transient (≤ 48 hours) Grade 3 flu-like symptoms or fever, which is controlled with medical 
management. 
• Transient (≤ 48 hours) Grade 3 fatigue, local reactions, headache, nausea, emesis that is 
controlled with medical management.  
• Tumor flare phenomenon defined as local pain, irritation, or rash localized at sites of known 
or suspected tumor. 
• Any single Grade ≥ 3 drug-related transaminase, alkaline phosphatase, or bilirubin 
abnormality with no other associated laboratory (or other) abnormality that is not associated 
with symptoms or clinical manifestations of hepatitis. If the liver function abnormality not 
associated with symptoms or clinical manifestations of hepatitis has not resolved to Grade ≤ 1 
within the subsequent 2 cycles (56 days), the subject should permanently discontinue 
treatment with M7824.  
• Any single Grade ≥ 3 drug-related amylase or lipase abnormality with no other associated 
laboratory (or other) abnormality that is not associated with symptoms or clinical 
manifestations of pancreatitis. If the amylase or lipase abnormality not associated with 
symptoms or clinical manifestations of pancreatitis has not resolved to Grade ≤ 1 within the 
subsequent 2 cycles (56 days), the subject should permanently discontinue treatment with 
M7824.  
• Grade 3 Hgb decrease (< 8.0 g/dL) that is clinically manageable with blood transfusions or 
erythroid growth factor use does not require treatment discontinuation.  
• Increases in Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 3 that 
resolves to ≤ 2 by Day 1 of the next cycle (infusions should not be given if the ECOG PS is 
≥ 3 on the day of M7824 administration and should be delayed until ECOG PS ≤ 2). 
• Keratoacanthoma and squamous cell carcinoma of the skin. Any suspicious skin lesion should 
be biopsied for confirmation of diagnosis and be surgically removed as indicated by 
dermatologist and a dermatological consult obtained.  
• Grade 3 non-tumor bleeding requiring intervention or hospitalization. Study treatment must 
be permanently discontinued unless an alternative explanation can be identified. In the case of 
alternative explanations for the Grade 3 bleeding event, study treatment should be held until 
recovery to at least Grade 1.  
• Other infusion reactions and immune-related ADRs, see NCCN guidelines for the 
management of immune related adverse events (Table 6). NCCN guidelines are merely 

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57 
suggestions based on current knowledge; however, given this is an evolving field, 
investigators are encouraged to consult professional guidelines.  
o In addition to NCCN guidelines, the following recommendations should be 
considered when managing irAEs: 
• Permanent treatment discontinuation is required in case of immune-related 
Grade 4 rash/inflammatory dermatitis, nephritis, autoimmune hemolytic 
anemia, 
hemolytic 
uremic 
syndrome, 
aplastic 
anemia, 
immune 
thrombocytopenia, 
acquired 
thrombotic 
thrombocytopenic 
purpura 
inflammatory arthritis, myositis and polymyalgia-like syndrome.  
 
• For Grade 4 immune-related lymphopenia, permanent treatment 
discontinuation will be required, if lymphopenia is considered immune-
related in nature, no clear alternative explanation exists for the event, and 
it does not resolve within 14 days. Permanent treatment discontinuation is 
not required when the AE is manifested by a single laboratory value out of 
normal range without any clinical correlates. In this case, treatment should 
be held until the etiology is determined. If the event is not considered 
immune-related and resolves to Grade ≤ 1, restarting treatment may be 
considered.  
 
• For Grade 1 immune-related pneumonitis: continue treatment. If clinically 
indicated, monitor participants weekly or more frequently as needed with 
history, physical examination and pulse oximetry. If symptoms appear 
and/or changes in the physical exam are noted, treat as Grade 2.  
 
•  For myositis requiring management with rituximab, treatment should be 
discontinued.  
 
• For Grade 3 or 4 endocrinopathies: withhold until clinically stable or 
permanently discontinue depending on severity.  
 
• For hepatitis with no tumor involvement of the liver: withhold if total 
bilirubin increases to more than 1.5 and up to 3 times ULN, permanently 
discontinue if more than 3 times ULN  
 
• Hepatitis with tumor involvement of the liver: permanently discontinue if 
total bilirubin increases to more than 3 times ULN.  
3.4.4.2 Infusion-related Reactions 
Signs and symptoms usually develop during or shortly after drug infusion and generally resolve 
completely within 48 hours after completion of infusion. These possible IRR are identified based 
on a list of MedDRA PTs and divided into reactions versus signs and symptoms. 

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• An IRR should be considered when onset is on the day of infusion (during or after the 
infusion) or the day after the infusion (irrespective of resolution date) for any infusion related 
reaction, drug hypersensitivity, anaphylactic reaction, hypersensitivity and/or Type 1 
hypersensitivity. 
• Signs and symptoms of infusion related reactions and hypersensitivity/allergic reactions 
should be considered when onset is on the day of infusion (during or after the infusion) and 
resolved completely with the end date within 2 days after onset. Signs and symptoms may 
include but not limited to: fever, chills or shaking, rigors, flushing, hypotension, wheezing, 
pruritus, rash and hypoxemia, shortness of breath, back or neck pain, facial swelling, 
dizziness, feeling of passing out. 
Infusion-related reactions and hypersensitivity reactions (Grades 1 to 4) should be handled 
according to the best medical judgement based on the most updated professional guidelines 
(NCCN, ESMO, SITC, etc.). Guidelines provided in Table 6 are merely suggestions based on 
current knowledge; however, given this is an evolving field, investigators are encouraged to 
consult the most updated professional guidelines. 
Table 6: Treatment Modifications for Symptoms of Infusion-related Reactions  
NCI-CTCAE Grade 
Treatment Modification for M7824 
Grade 1 – mild 
Mild transient reaction; infusion interruption 
not indicated; intervention not indicated. 
Consider decreasing the infusion rate of the 
particular agent by 50% and monitoring 
closely for any worsening. 
 
Grade 2 – moderate 
Therapy or infusion interruption indicated but 
responds promptly to symptomatic treatment 
(e.g., antihistamines, NSAIDs, narcotics, i.e. 
fluids); prophylactic medications indicated for 
≤ 24 hours. 
Consider temporarily discontinuing infusion 
of the particular agent. 
Consider resuming infusion of the particular 
agent at 50% of previous rate once infusion 
related reaction has resolved or decreased to 
at least Grade 1 in severity and monitor 
closely for any worsening. 
Grade 3 or Grade 4 – severe or life-
threatening 
Grade 3: Prolonged (e.g., not rapidly 
responsive to symptomatic medication and/or 
brief interruption of infusion); hospitalization 
indicated for clinical sequelae. 
Grade 4: Life-threatening consequences; 
urgent intervention indicated. 
Stop the infusion immediately and disconnect 
infusion tubing from the subject. 
For grade 3 events: Consider withdrawing 
immediately 
from 
treatment 
with 
that 
particular agent and not offering any further 
treatment with that agent based upon if the 
clinical condition can be safely managed. 
For grade 4 events: Withdraw immediately 
from treatment and do not offer further 
treatment with that agent.  
 
If the infusion rate of M7824 has been decreased by 50% or interrupted due to an infusion 
reaction, keep it decreased for the next scheduled infusion. If no infusion reaction is observed in 
the next scheduled infusion, the infusion rate may be returned to baseline at the subsequent 
infusions based on investigator’s medical judgment.  

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condition can be safely managed; 
Consider 
1.0 to 2.0 mg/kg/day 
prednisone or equivalent 
Consider adding prophylactic 
antibiotics for opportunistic infections  
Specialty consult as appropriate 
month. 
Grade 4  
 
Permanently discontinue M7824; 
Consider 
1.0 to 2.0 mg/kg/day 
prednisone or equivalent and/or other 
immunosuppressant as needed 
Consider adding prophylactic 
antibiotics for opportunistic infections  
Consider specialty consult as 
appropriate 
If improves to Grade ≤ 1:  
Consider tapering steroids over at least 1 month 
Requirement for 10 mg per day 
or greater prednisone or 
equivalent for more than 12 
weeks for reasons other than 
hormonal replacement for 
adrenal insufficiency 
 
Persistent Grade 2 or 3 irAE 
lasting 12 weeks or longer 
Consider permanently discontinuing 
M7824  
Consider specialty consult as 
appropriate  
 
 
3.4.4.4.1 Rash with Hyperkeratosis / Keratoacanthoma / Squamous Cell Carcinoma of the Skin 
Dermatological consults will be requested on a case-by-case basis as needed with potential 
biopsy of suspicious skin lesions.  
3.4.4.4.2 Suggested Evaluation of Suspected Bleeding or Hemorrhage Events and Treatment 
Modification  
For anemia or hemorrhage events assessed as treatment-related, items queried may include but 
are not limited to detailed relevant past medical and treatment history, bruising tendency, history 
of blood transfusions and/or dependency, and a request for an updated participant history 
including details such as concomitant medications, all laboratory data, updated dosing 
information and recent tumor evaluation scans.  
In this protocol, anemia may be due to M7824 (documented in 29% of patients based on pooled 
safety analysis set from a total of 765 participants, refer to IBv7) and/or SX-682. For M7824 
anemia is an AESI and important identified risk (see Investigators’ Brochure). Notably, there are 
many reasons for hemorrhage and/or anemia in patients with advanced cancer, and Hb level of at 
least 9 g/dL is required for this study. A thorough investigation of new anemia cases of 
unspecified etiology is recommended: 
• Participants must enter the study with Hgb values at least 9 g/dL and baseline anemia 
evaluation is conducted per recommendations below.  
• Consider hematology consult for severe and or refractory anemias.  

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• All relevant hematologic testing for treatment related anemias should be done prior to blood 
transfusion, if clinically feasible. 
• Transfusion should be performed at the discretion of the investigator, based on clinical 
assessment and considered when participant experiences significant anemia.  
• Guidance for evaluation of baseline anemia or suspected treatment-related anemias is 
provided below. Investigators may consider the following laboratory evaluations in 
participants with anemia.  
o Hb and CBC with differential (e.g. MCV, RDW, ANC, hematocrit, reticulocytes 
counts) 
o Peripheral blood smear for cell morphological assessment 
o Complete metabolic panel including liver panel-LFTs, bilirubin, LDH, renal function, 
and serum folate, B12 values and other chemistries 
o Coagulation factors (PT, PTT, INR) 
o Urinalysis including culture 
o Iron panel (TIBC, ferritin, Fe) 
• Discuss further management with Principal Investigator for clinically significant treatment 
related anemias.  
Multiple protocols using M7824, several mucosal bleeding events ranging from low grade 
gingival bleeding and epistaxis to more serious hemoptysis, GI bleeding and hematuria have 
been observed. Some of these events can be attributed to bleeding events related to cancer 
directly and others bleeding events can be attributed to an inflammatory process (e.g. colitis) 
which is a known toxicity of anti-PD-L1 agents including M7824. However, there remains the 
possibility that M7824 may increase the overall risk of bleeding in ways that may not be directly 
related to direct tumor bleeding or inflammatory bleeding events described with checkpoint 
inhibitors like M7824. However, there is no evidence of a negative effect on coagulation or 
platelet number or function. It is hypothesized that this possible increased mucosal bleeding risk 
may be due to the known mucoprotective effects of TGFβ. Accordingly, participants will be 
closely monitored for mucosal bleeding (e.g., gum bleeding, nose bleeds, coughing up blood, 
blood in their urine, or blood in the stool).  

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5 MVA-BN-CV301 will be given on days 1 and 15 of Cycle 1. FPV-CV301 will be given Day 1 of Cycles 2 through 5 then Day 1 of 
Cycle 8 and Cycle 11. Can be -1/+3 days due to holidays, inclement weather, conflicts, or similar reasons except where explicitly 
noted elsewhere. CV301 administrations should not be given less than 11 days apart. See Table 8  
 
6 EOT – End of treatment visit: Where feasible, on the day of or within 30 days of the decision to discontinue treatment prematurely 
before completion of one year of treatment. Does not need to be completed if drug is withheld after one year of treatment. Research 
labs will be collected if feasible. Participants continuing to experience toxicity at the off-treatment visit will be contacted for 
additional assessments until the toxicity has resolved or is deemed irreversible. Participants must remain on the study to have 
additional assessments completed 
7 30 days (+/- 7 days) after last treatment. If subjects are not willing to come to NIH to FU visit, they will be contacted by phone to 
assess adverse events. Does not need to be repeated if EOT performed within this time frame.  
8 Participants who are taken off treatment for reasons other than disease progression, will be invited for optional imaging studies every 
3 months (+/- 2 weeks) until they experience PD in order to assess PFS. If participants unable to come, participants will be followed 
by phone or email and outside images will be requested. Participants who opt out of these scans will have their data censored in data 
analysis at the time they become unfollowable for PFS. After progression and 30 days Safety Follow up visit, participants will be 
followed by phone or email for long-term clinical outcomes, and further tumor therapy every year for 2 years.  
9 EKGs will be done in triplicate on screening, before SX-682 administration at baseline and then every two weeks until cycle 6, at 
EOT and at the safety FU visit.  
10 Biochemical profile: sodium, potassium, magnesium, phosphorus, chloride, bicarbonate, calcium, glucose, BUN, creatinine, ALT, 
AST, alkaline phosphatase, total protein, albumin, and total and direct bilirubin.  
11 Performed every 8 weeks: Lymphocyte panel (TBNK), TSH, Free T4, lipase, amylase, urinalysis, PT/PTT/INR, unless there is a 
clinical concern that warrants evaluation on a more frequent basis 
12 For women of childbearing potential at screening and baseline serum pregnancy test must be performed, but on day 1 of each cycle 
and EOT, urine pregnancy test can also be used. 
13 In Arms 1 and 2, the first restaging will occur 6 weeks after starting treatment (+/- 1 week) and then every eight weeks (+/- 1 week). 
In Arm 3, restaging will occur every eight weeks (+/- 1 week). In the event of a PR or CR tumor imaging assessments may be 
performed every 3 months (+/- 2 weeks) at the discretion of the investigator. Tumor assessment should be continued beyond end of 
treatment in participants who have not experienced PD until they experience PD in order to assess PFS. In addition to a baseline scan, 
confirmatory scans can also be obtained 4 to 8 weeks following initial documentation of objective response per the discretion of the 
primary investigator. MRI of chest, abdomen and pelvis (if participant has contradiction to CT). 
14 Brain CT/MRI if there is a history of prior CNS metastasis or there is a concern for CNS involvement. 
15 Optional biopsies at baseline and as close as logistically feasible to first imaging restaging (+/- 1 week if possible). Optional biopsy 
also at time of progression. In addition, tissue collected during unscheduled procedures may also be collected for research purposes. 

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Cycle 
(Day)  
Time 
SX-682 
M7824 
Immune and Other Analyses 
  
  
PK 
PK 
ADA Soluble Factors 
Immune phenotyping/ 
RNA analysis, 
Antigen-specific 
response, T-cell 
clonality 
CTCs 
 
30 
minutes 
X 
 
 
Cycle 1 (1) predose 
X 
X 
X 
X 
X 
X 
  
End 
of 
Infusion 
(EOI) 
X 
X 
 
 
 
Cycle 
1 
(15) 
 
X 
 
 
X 
X 
Cycle 2 (1) predose 
X 
 
 
X 
X 
X 
Cycle 
3 
(1)** 
predose 
X 
X** X** X 
X 
EOT 
 
X 
X 
X 
X 
 
*Lead-In, Day -14L labs only for Cohort 1, Arm 1 (Sequential Dose Escalation).  
**The last M7824 PK/ADA timepoint should be Cycle 3, Day 1 predose or EOT, whichever comes first.  
 
Table 10: Arm 2 Research Blood Draws 
Cycle 
(Day)  
Time 
SX-682 
M7824 
Immune and Other Analyses 
  
  
PK 
PK 
ADA 
Soluble Factors 
Immune phenotyping/ RNA 
analysis, Antigen-specific 
response, T-cell clonality 
CTCs 

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Cycle (Day) Time 
Immune and Other Analyses 
  
  
Soluble 
Factors 
Immune 
phenotyping/ RNA 
analysis, Antigen-
specific response,        
T-cell clonality 
CfDNA 
CTCs 
Cycle 1 (1) 
predose 
X 
X 
X 
X 
Cycle 1 (15) predose 
X 
X 
X 
Cycle 2 (1) 
predose 
X 
X 
X 
X 
Cycle 3 (1) 
predose 
X 
X 
X 
EOT 
 
X 
X 
X 
 

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3.6 
COST AND COMPENSATION 
3.6.1 Costs 
NIH does not bill health insurance companies or participants for any research or related clinical 
care that participants receive at the NIH Clinical Center. If some tests and procedures performed 
outside the NIH Clinical Center, participants may have to pay for these costs if they are not 
covered by insurance company. Medicines that are not part of the study treatment will not be 
provided or paid for by the NIH Clinical Center. 
3.6.2 Compensation 
There will no compensation provided in this study.  
3.6.3 Reimbursement  
The NCI will cover the costs of some expenses associated with protocol participation.  Some of 
these costs may be paid directly by the NIH and some may be reimbursed to the 
participant/guardian as appropriate.  The amount and form of these payments are determined by 
the NCI Travel and Lodging Reimbursement Policy. 
3.7 
CRITERIA FOR REMOVAL FROM PROTOCOL THERAPY AND OFF STUDY CRITERIA 
Prior to removal from study, efforts must be made to have all subjects complete a safety visit 
approximately 30 days (+/- 7 days) following the last dose of study therapy. 
3.7.1 Criteria for Removal from Protocol Therapy 
• Participant request to be withdrawn from active therapy 
• Confirmed clinical or radiographic progression of disease except when the investigator 
feels the subject is still benefiting from treatment. NOTE: treatment may be continued 
despite progression according to RECIST 1.1 at any time if: 
 There are no new or concerning symptoms. 
 There is no decrease in ECOG PS. 
 The Investigator does not consider it necessary to administer a salvage therapy. 
• Unacceptable Toxicity as described in sections 3.3  
• Investigator discretion 
• Positive pregnancy test 
• Need to use restricted medication, section 4.1 
• Completion of 2 years of therapy unless the PI feels that the participant continues to gain 
benefit from two or more of the trial drugs and discusses continuing on trial with the 
CRADA partners for an additional specified period of time.  
3.7.2 Off -Study Criteria 
• Completion of 2 years follow-up period after confirmed disease progression  
• PI decision to end the study 
• Participant lost to follow up 

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• Investigator discretion 
• Death 
• Participant request to be withdrawn from the study 
• Screen Failure 
3.7.3 Lost to Follow-up 
A participant will be considered lost to follow-up if he or she fails to return for 3 consecutive 
scheduled visits and is unable to be contacted by the study site staff.  
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site will attempt to contact the participant and reschedule the missed visit and 
counsel the participant on the importance of maintaining the assigned visit schedule and 
ascertain if the participant wishes to and/or should continue in the study. 
• Before a participant is deemed lost to follow-up, the investigator or designee will make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, an IRB approved certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented in 
the participant’s medical record or study file.  
• Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
4 
CONCOMITANT THERAPY 
For this protocol, a prescription medication is defined as a medication that can be prescribed only 
by a properly authorized/licensed clinician. Medications to be reported in the Case Report Form 
(CRF) are concomitant prescription medications, over-the-counter medications and supplements. 
Any medications (other than those excluded by the clinical trial protocol) that are considered 
necessary to protect subject welfare or alleviate symptoms and will not interfere with the trial 
medications may be given at the Investigator’s discretion. 
Palliative radiotherapy delivered in a normal organ-spearing technique may be administered 
during the trial. The assessment of PD will not be based on the necessity for palliative 
radiotherapy.  
4.1 
THE FOLLOWING TREATMENTS SHOULD NOT BE ADMINISTERED DURING THE TRIAL: 
• Other immunotherapies or immunosuppressive drugs for example, chemotherapy or 
systemic corticosteroids except for prophylaxis or treatment of allergic reactions, 
endocrine replacement therapy at low dose prednisone [≤ 10 mg daily] or equivalent, for 
the treatment of irAEs, or for short courses (≤ 14 days) as appropriate medical therapy for 
unrelated medical conditions (e.g. asthma). Steroids with no or minimal systemic effect 
(topical, inhalation) are allowed. 
• Prophylactic use of corticosteroids for infusion related reactions. Corticosteroid 
administration prior to CT scans in participants with intravenous contrast allergy is 
allowed. 

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• QTc prolonging drugs: The drug-drug interactions of SX-682 in humans have not yet 
been determined. However, due to its in vitro inhibition of hERG, concomitant dosing of 
SX0682 with drugs known to have a clinically significant prolongation the QT interval 
(See Appendix B), such as pimozide and thioridazine, should be avoided until further 
human EKG data is gathered. Drugs that may conditionally prolong QTc that are not 
included in Appendix B, maybe be used with caution after reviewing the risks/benefits 
and potential alternative options. QTc prolonging agents are not prohibited in participants 
no longer receiving SX-682. 
• In vitro studies indicate SX-682 inhibits CYP2C8. Medications that are substrates of this 
enzyme may have altered metabolism when administered concurrently with SX-682. 
CYP2C8 substrates will be evaluated on a case-by-case basis prior to concurrent use with 
SX-682. Updated drug-information resources should be consulted   
(e.g. https://drug-interactions.medicine.iu.edu/MainTable.aspx). 
• Any live vaccine therapies for the prevention of infectious disease. Administration of 
inactivated vaccines is allowed (for example, inactivated influenza vaccines). Locally 
approved COVID vaccines are permitted.  
• Systemic anticancer treatment other than the investigational agents in this trial except for 
disease specific appropriate hormonal therapies (e.g., ADT for prostate cancer, anti-
estrogen for breast cancer, somatostatin analogue for neuroendocrine cancer). 
• All anticoagulation drugs will be reviewed by the investigator to determine the potential 
for interactions or potential safety concerns with the investigational agents. Any 
anticoagulation agent deemed to have a potentially clinically significant interaction with 
the investigational agent(s) by the investigator should not be administered while on the 
clinical trial.  
• All herbal supplements will be reviewed by the investigator to determine the potential for 
herbal interactions or potential safety concerns with the investigational agents. Any 
herbal supplement deemed to have a potentially clinically significant interaction with the 
investigational agent(s) by the investigator should not be administered while on the 
clinical trial. 
5 
CORRELATIVE STUDIES FOR RESEARCH 
Biospecimens will be evaluated to help identify the effect of the study dugs on the immune 
response before and after treatment, to gain insight into potential biomarkers, and help improve 
the administered therapy. 
5.1 
SAMPLES 
5.1.1 Tumor Samples 
Where available, archival tumor samples will be requested. 
Optional biopsies may be performed as per Study Calendar 3.5. Attempts will be made to obtain 
up to six cores (18G or 20G preferred) or direct biopsies with biopsy forceps if safe and feasible. 
These tumor core biopsies will be obtained percutaneously by interventional radiology as long as 
considered minimal procedural risk. Direct biopsies with biopsy forceps will be obtained by 
Otolaryngology as long as considered minimal procedural risk. Two 3-millimeter punch biopsies 

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5.2.4 ADA 
Serum samples may be analyzed by a validated electrochemiluminescence immunoassay 
(ECLA) to detect the presence of anti-M7824. Samples that screen positive will be subsequently 
tested in a confirmatory assay. Those confirmed positive will be titered for a quasi-quantitative 
result. Samples may be further tested in qualified or validated immunogenicity characterization 
methods. The investigation will be done by Syntrix and EMD Serono for analysis under existing 
CRADAs with these companies. 
5.2.5 Analyses of Tumor Tissue for Immune Markers  
Biopsy samples may be used to study immune infiltration as well as PD-L1 status within the 
tumor microenvironment pre vs. post treatment by IHC and/or multiplex immunofluorescence. 
Biopsies may be subjected to dissociation and analysis by flow cytometry to determine immune 
infiltration. Tumor infiltrating lymphocytes may be cultured from biopsies for assessment of T 
cell clonality and antigen specificity. 
Tumor samples will be sent to the Laboratory of Pathology at NIH for disease evaluation; 
remaining samples will be used for research. 
5.2.5.1 Antigen-specific T cell responses to CEA, MUC1 and the cascade antigen brachyury in 
tumor biopsies. 
Tumor infiltrating lymphocytes (TIL) may be cultured from tumor fragments in standard T cell 
media with high dose recombinant human IL-2 (6000 U/mL). CD8 and CD4 TIL will be purified 
from cultured TIL using pan T cell negative magnetic selection. B cells will be sorted from 
PBMC using negative magnetic isolation and will be expanded using flt3-expressing 3T3 cells 
and IL-7. Expanded B cells will serve as autologous antigen presenting cells for coincubation 
assays. B cells will be electroporated with full length capped and tailed mRNA encoding for 
MUC1, CEA or the cascade antigen brachyury. Autologous B cells loaded with mRNA will be 
co-incubated with TIL cultured from tumor fragments (2:1 APC: T cell ratio) and IFNg 
production will be measured by ELISA. 
5.3 
SAMPLES FOR GENETIC/GENOMIC ANALYSIS 
5.3.1 RNA and T-cell Receptor Clonality Analysis of Blood and Tumor Tissue 
RNA expression and T-cell receptor clonality analysis may be done on the peripheral blood as 
well as archived tumor tissue or optional biopsies to help further evaluate changes in immune 
response and RNA expression levels with treatment as well as to determine tumor and infiltrating 
lymphocyte characteristics which may be predictive of response to treatment. In addition, these 
analyses will also be used to gauge resistance mechanisms and additional targets for future 
therapy. Digital Spatial Profiling (DSP) including RNA in situ hybridization may also be 
performed on tissue for spatially resolved high plex profiling of RNA and protein targets. De-
identified, coded samples may be analyzed for RNA expression levels and DSP using the 
Nanostring platform and T-cell receptor clonality using the ImmunoSeq platform (LTIB and NCI 
Frederick Genomic Core Facility).  
NCI Fredrick Genomic Core Facility:  
Leidos Biomedical Research, Inc:  
  

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participant confidentiality. Using a computerized inventory system and a backup hardcopy 
process, all specimen collection and processing steps will be documented, and the specific 
location of each specimen will be tracked. Each new specimen collected will be assigned a 
unique barcode identifier that can be linked to the original specimen collected and other relevant 
information within the inventory system. Specimen labels will indicate protocol number, order in 
which the participant enrolled on the trial, type of sample, as appropriate. The inventory process 
contains other security provisions sufficient to safeguard participant privacy and confidentiality. 
Access to the inventory system and associated documents is restricted to appropriate individuals. 
Requests to use specimens stored in the repository must be approved by the trial Principal 
Investigator. SOPs ensure that any changes in informed consent made by a participant and 
relayed to the trial Principal Investigator will be reflected in the inventory system to ensure that 
specimens are destroyed as appropriate. All laboratory personnel are trained to adhere to SOPs 
and are monitored for high-quality performance. Samples are stored in labeled boxes in secured 
freezers (i.e., -80°C, liquid nitrogen or other, as appropriate) according to stability requirements. 
These freezers are located in the 
 
5.4.6 Protocol Completion/Sample Destruction 
All specimens obtained in the protocol are used as defined in the protocol. Any specimens that 
are remaining at the completion of the protocol will be stored in the conditions described in 
sections above. The study will remain open so long as sample or data analysis continues. 
Samples from consenting subjects will be stored until they are no longer of scientific value or if a 
subject withdraws consent for their continued use, at which time they will be destroyed.  
The PI will record any loss or unanticipated destruction of samples as a deviation. Reports will 
be per the requirements of section 7.2. 
If the participant withdraws consent the participant’s data will be excluded from future 
distributions, but data that have already been distributed for approved research use will not be 
able to be retrieved. 
6 
DATA COLLECTION AND EVALUATION  
6.1 
DATA COLLECTION 
The PI will be responsible for overseeing entry of data into a 21 CFR Part 11-compliant data 
capture system provided by the NCI CCR and ensuring data accuracy, consistency and 
timeliness. The principal investigator, associate investigators/research nurses and/or a contracted 
data manager will assist with the data management efforts. Primary and final analyzed data will 
have identifiers so that research data can be attributed to an individual human subject participant. 
All adverse events, including clinically significant abnormal findings on laboratory evaluations, 
regardless of severity, will be followed until return to baseline or stabilization of event. 
Document AEs from the administration of the first study intervention through 30 after the study 
agent (s) was/were last administered. Beyond 30 days after the last intervention, only adverse 
events which are serious and related to the study intervention need to be recorded. 
An abnormal laboratory value will be recorded in the database as an AE only if the laboratory 
abnormality is characterized by any of the following: 
• 
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• 
Is associated with clinical signs or symptoms  
• 
Requires treatment or any other therapeutic intervention 
• 
Is associated with death or another serious adverse event, including hospitalization.  
• 
Is judged by the Investigator to be of significant clinical impact 
If any abnormal laboratory result is considered clinically significant, the investigator will provide 
details about the action taken with respect to the test drug and about the participant’s outcome. 
Adverse Events of grade 1 will not be collected. 
End of study procedures: Data will be stored according to HHS, FDA regulations and NIH 
Intramural Records Retention Schedule as applicable.  
Loss or destruction of data: Should we become aware that a major breech in our plan to protect 
subject confidentiality and trial data has occurred, his will be reported expeditiously per 
requirements in section 7.2.1 
6.2 
DATA SHARING PLANS 
6.2.1 Human Data Sharing Plan 
The PI will share coded linked human data generated in this research for future research  
− in a NIH-funded or approved public repository clinicaltrials.gov and dbGaP 
− in BTRIS  
− in publication and/or public presentations 
− with approved outside collaborators under appropriate agreements 
− at the time of publication or shortly thereafter. 
6.2.2 Genomic Data Sharing Plan 
Unlinked genomic data will be deposited in public genomic databases such as dbGaP in 
compliance with the NIH Genomic Data Sharing Policy. 
6.3 
RESPONSE CRITERIA  
For the purposes of this study, participants should be re-evaluated for response according to 
schedule in the Study Calendar, section 3.5.  
In the event of a PR or CR tumor imaging assessments may be performed every 3 months (+/- 2 
weeks) at the discretion of the investigator. In addition to a baseline scan, confirmatory scans can 
also be obtained 4 to 8 weeks following initial documentation of objective response per the 
discretion of the primary investigator. 
The preferred method of disease assessment is CT with contrast. If CT with contrast is 
contraindicated, CT of the chest without contrast and MRI scan of the abdomen/pelvis is 
preferred. Additional assessment of tumor response may include the following evaluations; 
nuclear bone scan for subjects with known/suspected bone lesions; and CT or MRI scan of the 
brain (only as clinically warranted based on symptoms/findings). 
Brain CT / MRI scan should be performed, if clinically indicated by development of new specific 
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designate 1 or more of the following measures of tumor status to follow for determining response: 
CT or MRI images of primary and / or metastatic tumor masses, physical examination findings, 
and the results of other assessments. All available images collected during the trial period will be 
considered. The most appropriate measures to evaluate the tumor status of a subject should be 
used. The measure(s) to be chosen for sequential evaluation during the trial have to correspond to 
the measures used to document the progressive tumor status that qualifies the subject for 
enrollment. 
Progressive disease should be confirmed by imaging 4 to 8 weeks (preferably at 4 weeks, but not 
more than 8 weeks) after progression has been diagnosed according to RECIST 1.1. before the 
participant is removed from treatment [93]. If progression is based on the occurrence of a new 
lesion in an area not scanned at Baseline, a further on-study scan 4 to 8 weeks later should be 
considered before performing the 28-Day Safety Follow-up visit. 
Tumor responses to treatment will be assigned based on the evaluation of the response of target, 
non-target, and new lesions according to RECIST 1.1 (all measurements should be recorded in 
metric notation). 
To assess objective response, the tumor burden at baseline will be estimated and used for 
comparison with subsequent measurements. At baseline, tumor lesions will be categorized in 
target and non-target lesions according to RECIST 1.1. 
Results for these evaluations will be recorded with as much specificity as possible so that pre and 
post-treatment results will provide the best opportunity for evaluating tumor response. 
The Investigator may perform scans in addition to a scheduled trial scan for medical reasons or if 
the Investigator suspects PD. 
iRECIST will also be used for exploratory endpoints (See section 6.3.3) 
For the primary endpoint antitumor activity will be evaluated with target and/or non-target 
lesions according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. [93]. 
Palliative radiotherapy delivered in a normal organ-spearing technique may be administered 
during this trial. The assessment of PD will not be based on the necessity for palliative 
radiotherapy. 
If a target lesion is radiated during the course of treatment, this target lesion will no longer be 
considered a measurable lesion and will be removed from the target lesion sum moving forward 
as is recommended in RECISTv1.1.  
6.3.1 Disease Parameters 
Measurable disease: Measurable lesions are defined as those that can be accurately measured in 
at least one dimension (longest diameter to be recorded) as:  
• By chest x-ray: >20 mm;  
• By CT scan:  
o Scan slice thickness 5 mm or under: as >10 mm 
o Scan slice thickness >5 mm: double the slice thickness  
• With calipers on clinical exam: >10 mm. 

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All tumor measurements must be recorded in millimeters (or decimal fractions of centimeters). 
Tumor lesions that are situated in a previously irradiated area may be considered measurable if 
there is demonstrated progression in the radiated lesion prior to starting on the trial.  
Malignant lymph nodes. To be considered pathologically enlarged and measurable, a lymph node 
must be >15 mm in short axis when assessed by CT scan (CT scan slice thickness recommended 
to be no greater than 5 mm). At baseline and in follow-up, only the short axis will be measured 
and followed. 
Non-measurable disease. All other lesions (or sites of disease), including small lesions (longest 
diameter <10 mm or pathological lymph nodes with ≥10 to <15 mm short axis), are considered 
non-measurable disease. Bone lesions, leptomeningeal disease, ascites, pleural/pericardial 
effusions, lymphangitis cutis/pulmonitis, inflammatory breast disease, and abdominal masses 
(not followed by CT or MRI), are considered as non-measurable. 
Note: Cystic lesions that meet the criteria for radiographically defined simple cysts should not be 
considered as malignant lesions (neither measurable nor non-measurable) since they are, by 
definition, simple cysts. 
‘Cystic lesions’ thought to represent cystic metastases can be considered as measurable lesions, 
if they meet the definition of measurability described above. However, if non-cystic lesions are 
present in the same participant, these are preferred for selection as target lesions. 
Target lesions. All measurable lesions up to a maximum of 2 lesions per organ and 5 lesions in 
total, representative of all involved organs, should be identified as target lesions and recorded 
and measured at baseline. Target lesions should be selected on the basis of their size (lesions 
with the longest diameter), be representative of all involved organs, but in addition should be 
those that lend themselves to reproducible repeated measurements. It may be the case that, on 
occasion, the largest lesion does not lend itself to reproducible measurement in which 
circumstance the next largest lesion which can be measured reproducibly should be selected. A 
sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target 
lesions will be calculated and reported as the baseline sum diameters. If lymph nodes are to be 
included in the sum, then only the short axis is added into the sum. The baseline sum diameters 
will be used as reference to further characterize any objective tumor regression in the measurable 
dimension of the disease. 
Non-target lesions. All other lesions (or sites of disease) including any measurable lesions over 
and above the 5 target lesions should be identified as non-target lesions and should also be 
recorded at baseline. Measurements of these lesions are not required, but the presence, absence, 
or in rare cases unequivocal progression of each should be noted throughout follow-up.  
6.3.2 Methods for Evaluation of Measurable Disease 
All measurements should be taken and recorded in metric notation using a ruler or calipers. All 
baseline evaluations should be performed as closely as possible to the beginning of treatment and 
never more than 4 weeks before the beginning of the treatment. 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up. Imaging-based evaluation is 
preferred to evaluation by clinical examination unless the lesion(s) being followed cannot be 
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Clinical lesions: Clinical lesions will only be considered measurable when they are superficial 
(e.g., skin nodules and palpable lymph nodes) and ≥10 mm diameter as assessed using calipers 
(e.g., skin nodules). In the case of skin lesions, documentation by color photography, including a 
ruler to estimate the size of the lesion, is recommended.  
Chest x-ray: Lesions on chest x-ray are not acceptable as measurable lesions.  
Conventional CT and MRI: This guideline has defined measurability of lesions on CT scan based 
on the assumption that CT slice thickness is 5 mm or less. If CT scans have slice thickness 
greater than 5 mm, the minimum size for a measurable lesion should be twice the slice thickness. 
MRI is also acceptable in certain situations (e.g. for body scans). 
Use of MRI remains a complex issue. MRI has excellent contrast, spatial, and temporal 
resolution; however, there are many image acquisition variables involved in MRI, which greatly 
impact image quality, lesion conspicuity, and measurement. Furthermore, the availability of MRI 
is variable globally. As with CT, if an MRI is performed, the technical specifications of the 
scanning sequences used should be optimized for the evaluation of the type and site of disease. 
Furthermore, as with CT, the modality used at follow-up should be the same as was used at 
baseline and the lesions should be measured/assessed on the same pulse sequence. It is beyond 
the scope of the RECIST guidelines to prescribe specific MRI pulse sequence parameters for all 
scanners, body parts, and diseases. Ideally, the same type of scanner should be used and the 
image acquisition protocol should be followed as closely as possible to prior scans. Body scans 
should be performed with breath-hold scanning techniques, if possible. 
PET-CT: At present, the low dose or attenuation correction CT portion of a combined PET-CT is 
not always of optimal diagnostic CT quality for use with RECIST measurements. However, if 
the site can document that the CT performed as part of a PET-CT is of identical diagnostic 
quality to a diagnostic CT (with IV and oral contrast), then the CT portion of the PET-CT can be 
used for RECIST measurements and can be used interchangeably with conventional CT in 
accurately measuring cancer lesions over time. Note, however, that the PET portion of the CT 
introduces additional data which may bias an investigator if it is not routinely or serially 
performed. 
Ultrasound: Ultrasound is not useful in assessment of lesion size and should not be used as a 
method of measurement. Ultrasound examinations cannot be reproduced in their entirety for 
independent review at a later date and, because they are operator dependent, it cannot be 
guaranteed that the same technique and measurements will be taken from one assessment to the 
next. If new lesions are identified by ultrasound in the course of the study, confirmation by CT or 
MRI is advised. If there is concern about radiation exposure at CT, MRI may be used instead of 
CT in selected instances. 
Endoscopy, Laparoscopy: The utilization of these techniques for objective tumor evaluation is 
not advised. However, such techniques may be useful to confirm complete pathological response 
when biopsies are obtained or to determine relapse in trials where recurrence following complete 
response (CR) or surgical resection is an endpoint. 
Tumor markers: Tumor markers alone cannot be used to assess response. If markers are initially 
above the upper normal limit, they must normalize for a participant to be considered in complete 
clinical response. Specific guidelines for both CA-125 response (in recurrent ovarian cancer) and 
PSA response (in recurrent prostate cancer) have been published. [94-96] In addition, the 

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Gynecologic Cancer Intergroup has developed CA-125 progression criteria which are to be 
integrated with objective tumor assessment for use in first-line trials in ovarian cancer.[97]  
Cytology, Histology: These techniques can be used to differentiate between partial responses 
(PR) and complete responses (CR) in rare cases (e.g., residual lesions in tumor types, such as 
germ cell tumors, where known residual benign tumors can remain). 
The cytological confirmation of the neoplastic origin of any effusion that appears or worsens 
during treatment when the measurable tumor has met criteria for response or stable disease is 
mandatory to differentiate between response or stable disease (an effusion may be a side effect of 
the treatment) and progressive disease. 
FDG-PET: While FDG-PET response assessments need additional study, it is sometimes 
reasonable to incorporate the use of FDG-PET scanning to complement CT scanning in 
assessment of progression (particularly possible 'new' disease). New lesions on the basis of FDG-
PET imaging can be identified according to the following algorithm:  
a. Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of 
PD based on a new lesion. 
b. No FDG-PET at baseline and a positive FDG-PET at follow-up: If the positive FDG-
PET at follow-up corresponds to a new site of disease confirmed by CT, this is PD. If 
the positive FDG-PET at follow-up is not confirmed as a new site of disease on CT, 
additional follow-up CT scans are needed to determine if there is truly progression 
occurring at that site (if so, the date of PD will be the date of the initial abnormal 
FDG-PET scan). If the positive FDG-PET at follow-up corresponds to a pre-existing 
site of disease on CT that is not progressing on the basis of the anatomic images, this 
is not PD. 
c. FDG-PET may be used to upgrade a response to a CR in a manner similar to a biopsy 
in cases where a residual radiographic abnormality is thought to represent fibrosis or 
scarring. The use of FDG-PET in this circumstance should be prospectively described 
in the protocol and supported by disease-specific medical literature for the indication. 
However, it must be acknowledged that both approaches may lead to false positive 
CR due to limitations of FDG-PET and biopsy resolution/sensitivity. 
Note: A ‘positive’ FDG-PET scan lesion means one which is FDG avid with an uptake greater 
than twice that of the surrounding tissue on the attenuation corrected image. 
Evaluation of Target Lesions 
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to <10 mm. 
Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, 
taking as reference the baseline sum of diameters. 
Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that is the 
smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an 
absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also 
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Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum of diameters while on study. 
Evaluation of Non-Target Lesions 
Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor 
marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). 
Note: If tumor markers are initially above the upper normal limit, they must normalize for a 
participant to be considered in complete clinical response. 
Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance of tumor 
marker level above the normal limits. 
Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal 
progression of existing non-target lesions. Unequivocal progression should not normally trump 
target lesion status. It must be representative of overall disease status change, not a single lesion 
increase. 
Although a clear progression of “non-target” lesions only is exceptional, the opinion of the 
treating physician should prevail in such circumstances, and the progression status should be 
confirmed at a later time by the review panel (or Principal Investigator). 
Evaluation of Best Overall Response 
The best overall response is the best response recorded from the start of the treatment until 
disease progression/recurrence (taking as reference for progressive disease the smallest 
measurements recorded since the treatment started). The participant's best response assignment 
will depend on the achievement of both measurement and confirmation criteria. 
Table 12. Response Criteria for Participants with Measurable Disease (i.e., Target Disease) 
 
Target 
Lesions 
Non-Target 
Lesions 
New 
Lesions 
Overall 
Response 
Best Overall Response when 
Confirmation is Required* 
CR 
CR 
No 
CR 
> 4 to 8 wks. Confirmation** 
CR 
Non-
CR/Non-PD 
No 
PR 
>4 to 8 wks. Confirmation** 
CR 
Not 
evaluated 
No 
PR 
PR 
Non-
CR/Non-
PD/not 
evaluated 
No 
PR 
SD 
Non-
CR/Non-
PD/not 
evaluated 
No 
SD 
Documented at least once >4 
wks. from baseline** 
PD 
Any 
Yes or 
No 
PD 
no prior SD, PR or CR 
Any 
PD*** 
Yes or 
No 
PD 

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Any 
Any 
Yes 
PD 
* 
See RECIST 1.1 manuscript for further details on what is evidence of a 
new lesion. 
** 
Only for non-randomized trials with response as primary endpoint. 
*** 
In exceptional circumstances, unequivocal progression in non-target 
lesions may be accepted as disease progression. 
Note: Participants with a global deterioration of health status requiring 
discontinuation of treatment without objective evidence of disease progression at 
that time should be reported as “symptomatic deterioration.” Every effort should 
be made to document the objective progression even after discontinuation of 
treatment. 
 
For Participants with Non-Measurable Disease (i.e., Non-Target Disease) 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/non-PD* 
Not all evaluated 
No 
not evaluated 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
* ‘Non-CR/non-PD’ is preferred over ‘stable disease’ for non-target disease since 
SD is increasingly used as an endpoint for assessment of efficacy in some trials 
so to assign this category when no lesions can be measured is not advised 
 
6.3.3 iRECIST 
As an exploratory endpoint antitumor activity will also be evaluated according to iRECIST.[98] 
Using iRECIST criteria the following will be incorporated into the assessment: 
• An increase in the sum of target lesions of more than 20%, unequivocal increase in the 
non-target lesions or new lesions result in iUPD (unconfirmed progression disease); 
iUPD can be assigned multiple ties as long as iCPD (confirmed progressive disease) is 
not confirmed at the next assessment.  
•  Progression is confirmed in the target lesion category if the next imaging assessment 
after iUPD (4-8 weeks later) confirms a further increase in sum of measures of target 
disease from iUPD, with an increase of at least 5mm. Progression is confirmed in the 
non-target lesion category if subsequent imaging, done every 4-8 weeks after iUPD 
shows a further unequivocal increase in non-target lesions. Progression is confirmed in 
the new lesions category if at next assessment additional new lesions appear or an 
increase in the size of previously seen new lesions is seen (>5 mm for sum of new target 
lesion).  
However, the criteria for iCPD (after iUPD) are not considered to have been met if complete 
response, partial response or stable disease criteria (compared with baseline and as defined by 
RECIST 1.1) are met at the next assessment after iUPD. The status is reset (unlike RECIST 1.1, 
in which any progression precludes later complete response, partial response, or stable disease). 
iCR, iPR, or iSD should then be assigned; and if no change is detected, then the timepoint 
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6.3.4 Duration of Response 
Duration of overall response: The duration of overall response is measured from the time 
measurement criteria are met for CR or PR (whichever is first recorded) until the first date that 
recurrent or progressive disease is objectively documented. 
Duration of stable disease: Stable disease is measured from the start of the treatment until the 
criteria for progression are met.  
6.3.5 Progression-Free Survival (PFS)  
PFS is defined as the duration of time from start of treatment to time of progression or death, 
whichever occurs first 
7 
NIH REPORTING REQUIREMENTS / DATA AND SAFETY MONITORING PLAN 
7.1 
DEFINITIONS 
Please refer to definitions provided in Policy 801: Reporting Research Events found at: 
https://irbo.nih.gov/confluence/pages/viewpage.action?pageId=36241835#Policies&Guidance-
800Series-ComplianceandResearchEventReportingRequirements. 
7.2 
OHSRP OFFICE OF COMPLIANCE AND TRAINING / IRB REPORTING 
7.2.1 Expedited Reporting 
Please refer to the reporting requirements in Policy 801: Reporting Research Events and Policy 
802 Non-Compliance Human Subjects Research found at: 
https://irbo.nih.gov/confluence/pages/viewpage.action?pageId=36241835#Policies&Guidance-
800Series-ComplianceandResearchEventReportingRequirements.  
Note: Only IND Safety Reports that meet the definition of an unanticipated problem will need to 
be reported per these policies. 
7.2.2 IRB Requirements for PI Reporting at Continuing Review 
Please refer to the reporting requirements in Policy 801: Reporting Research Events found at: 
https://irbo.nih.gov/confluence/pages/viewpage.action?pageId=36241835#Policies&Guidance-
800Series-ComplianceandResearchEventReportingRequirements. 
7.3 
NCI CLINICAL DIRECTOR REPORTING  
Problems expeditiously reported to the OHSRP in the NIH eIRB system will also be reported to 
the NCI Clinical Director/designee; therefore, a separate submission for these reports is not 
necessary. 
In addition to those reports, all deaths that occur within 30 days after receiving a research 
intervention should be reported via email unless they are due to progressive disease.   
To report these deaths, please send an email describing the circumstances of the death t  
 
7.4 
INSTITUTIONAL BIOSAFETY COMMITTEE (IBC) REPORTING CRITERIA 
7.4.1 Serious Adverse Event Reports to IBC 
The Principal Investigator (or delegate) will notify IBC of any unexpected fatal or life-
threatening experience associated with the use of CV301 vaccines as soon as possible but in no 

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event later than 7 calendar days of initial receipt of the information. Serious adverse events that 
are unexpected and associated with the use of the CV301 vaccines, but are not fatal or life-
threatening, must be reported to the NIH IBC as soon as possible, but not later than 15 calendar 
days after the investigator’s initial receipt of the information. Adverse events may be reported by 
using the FDA Form 3500a. 
7.4.2 Annual Reports to IBC 
Within 60 days after the one-year anniversary of the date on which the IBC approved the initial 
protocol, and after each subsequent anniversary until the trial is completed, the Principal 
Investigator (or delegate) shall submit the information described below. Alternatively, the IRB 
continuing review report can be sent to the IBC in lieu of a separate report. Please include the 
IBC protocol number on the report. 
7.4.3 Clinical Trial Information  
A brief summary of the status of the trial in progress or completed during the previous year. The 
summary is required to include the following information:  
• the title and purpose of the trial  
• clinical site 
• the Principal Investigator 
• clinical protocol identifiers;  
• participant population (such as disease indication and general age group, e.g., adult or 
pediatric);  
• the total number of participants planned for inclusion in the trial; the number entered into 
the trial to date whose participation in the trial was completed; and the number who 
dropped out of the trial with a brief description of the reasons  
• the status of the trial, e.g., open to accrual of subjects, closed but data collection ongoing, 
or fully completed,  
• if the trial has been completed, a brief description of any study results.  
7.4.4 Progress Report and Data Analysis  
Information obtained during the previous year's clinical and non-clinical investigations, 
including:  
• a narrative or tabular summary showing the most frequent and most serious adverse 
experiences by body system 
• a summary of all serious adverse events submitted during the past year 
• a summary of serious adverse events that were expected or considered to have causes not 
associated with the use of the gene transfer product such as disease progression or 
concurrent medications 
• if any deaths have occurred, the number of participants who died during participation in 
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a brief description of any information obtained that is pertinent to an understanding of the gene 
transfer product’s actions, including, for example, information about dose-response, information 
from controlled trials, and information about bioavailability. 
7.5 
NIH REQUIRED DATA AND SAFETY MONITORING PLAN 
7.5.1 Principal Investigator/Research Team  
The clinical research team will meet on a weekly basis when participants are being actively 
treated on the trial to discuss each participant. Decisions about dose level enrollment and dose 
escalation will be made based on the toxicity data from prior participants. Evaluation of DLTs 
(eDLTs; Schema 1 and 2) will occur after all participants are enrolled on a given dose level.  
All data will be collected in a timely manner and reviewed by the principal investigator or a lead 
associate investigator. Events meeting requirements for expedited reporting as described in 
section 7.2.1 will be submitted within the appropriate timelines.  
The principal investigator will review adverse event and response data on each participant to 
ensure safety and data accuracy. The principal investigator will personally conduct or supervise 
the investigation and provide appropriate delegation of responsibilities to other members of the 
research staff. 
7.5.2 Data Safety Monitoring Board (DSMB) 
The DSMB is an independent group of at least 3 experts that monitors participant safety and 
advises The Sponsor. DSMB members will be separate and independent of study staff 
participating in this trial and should not have scientific, financial, or other conflicts of interest 
related to this trial. The DSMB will consist of members with appropriate expertise to contribute 
to the interpretation of data from this trial. A quorum will consist of a simple majority. 
The DSMB will review cumulative safety data from this trial at least annually. 
The DSMB will meet when trial halting criteria (see Section 3.2) are met, or as requested by the 
sponsor or PI. 
The DSMB will have a final review meeting at the end of the study. 
Procedures for DSMB reviews/meetings will be defined in the DSMB charter. The DSMB will 
review applicable data, including, but not limited to, enrollment, demographics, dosing data, 
clinical laboratory data, and safety data, at scheduled timepoints during this trial as defined in the 
DSMB charter. The DSMB will review blinded aggregate data in the open session of the DSMB 
meetings. 
Additional data may be requested by the DSMB, and interim statistical reports may be generated 
as deemed necessary and appropriate by the Sponsor. As an outcome of each review/meeting, the 
DSMB will make a recommendation as to the advisability of proceeding with study product 
administration, and to continue, modify, or terminate this trial.  
 
8 
SPONSOR PROTOCOL/SAFETY REPORTING 
8.1 
DEFINITIONS 
8.1.1 Adverse Event  
Any untoward medical occurrence in a participant or clinical investigation subject administered a 
pharmaceutical product and which does not necessarily have a causal relationship with this 
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(including an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of a medicinal (investigational) product, whether or not related to the medicinal 
(investigational) product (ICH E6 (R2)) 
8.1.2 Serious Adverse Event (SAE) 
An adverse event or suspected adverse reaction is considered serious if in the view of the 
investigator or the sponsor, it results in any of the following: 
• 
Death, 
• 
A life-threatening adverse event (see section 8.1.3) 
• 
Inpatient hospitalization or prolongation of existing hospitalization: 
o A hospitalization/admission that is pre-planned (i.e., elective or scheduled surgery 
arranged prior to the start of the study), a planned hospitalization for pre-existing 
condition, or a procedure required by the protocol, without a serious deterioration in 
health, is not considered a serious adverse event. 
o A hospitalization/admission that is solely driven by non-medical reasons (e.g., 
hospitalization for participant convenience) is not considered a serious adverse event.  
o Emergency room visits or stays in observation units that do not result in admission to 
the hospital would not be considered a serious adverse event. The reason for seeking 
medical care should be evaluated for meeting one of the other serious criteria 
• 
Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• 
A congenital anomaly/birth defect. 
• 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse drug experience when, based upon 
appropriate medical judgment, they may jeopardize the patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in this definition. 
8.1.3 Life-threatening  
An adverse event or suspected adverse reaction is considered "life-threatening" if, in the view of 
either the investigator or sponsor, its occurrence places the patient or subject at immediate risk of 
death. It does not include an adverse event or suspected adverse reaction that, had it occurred in a 
more severe form, might have caused death. (21CFR312.32) 
8.1.4 Severity 
The severity of each Adverse Event will be assessed utilizing the CTCAE version 5.0. 
8.1.5 Relationship to Study Product 
All AEs will have their relationship to study product assessed using the terms: related or not 
related.  
• Related – There is a reasonable possibility that the study product caused the adverse 
event. Reasonable possibility means that there is evidence to suggest a causal relationship 
between the study product and the adverse event. 

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• Not Related – There is not a reasonable possibility that the administration of the study 
product caused the event. 
8.1.6 Adverse Events of Special Interest (AESI) 
An adverse event of special interest (AESI) is one of scientific and medical interest specific to 
understanding of the Investigational Product(s) and may require close monitoring and rapid 
communication by the investigator to the sponsor. An AESI may be serious or non-serious. The 
rapid reporting of AESIs assessed as severe allows ongoing surveillance of these events to 
characterize and understand them in association with the use of these investigational products.  
Only AESIs that match the definition of SAE will be reported within 7 days from the knowledge 
of event. Other non-SAE AESIs do not need to be reported to OSRO but only collected in the 
clinical database. 
The adverse events related to mucosal bleeding, regardless of site, will be collected as an AESI 
to enable evaluation of potential risk factors, such as site/past radiation/associated infection at 
site/recent instrumentation and other variables such as time to onset, exposure history, grade of 
bleeding, anatomical sites, etc. can be collected. 
 
8.2 
ASSESSMENT OF SAFETY EVENTS 
AE information collected will include event description, date of onset, assessment of severity 
and relationship to study product and alternate etiology (if not related to study product), date of 
resolution of the event, seriousness and outcome. The assessment of severity and relationship to 
the study product will be done only by those with the training and authority to make a diagnosis 
and listed on the Form FDA 1572 as the site principal investigator or sub-investigator. AEs 
occurring during the collection and reporting period will be documented appropriately regardless 
of relationship. AEs will be followed through resolution. 
SAEs will be: 
• 
Assessed for severity and relationship to study product and alternate etiology (if not 
related to study product) by a licensed study physician listed on the Form FDA 1572 as 
the site principal investigator or sub-investigator. 
• 
Recorded on the appropriate SAE report form, the medical record and captured in the 
clinical database. 
• 
Followed through resolution by a licensed study physician listed on the Form FDA 1572 
as the site principal investigator or sub-investigator. 
For timeframe of recording adverse events, please refer to section 6.1. All serious adverse events 
recorded from the time of first investigational product administration must be reported to the 
Sponsor with the exception of any listed in section 8.4. 
8.3 
REPORTING OF SERIOUS ADVERSE EVENTS 
Any AE that meets a protocol-defined serious criteria or meets the definition of Adverse Event 
of Special Interest that require expedited reporting must be submitted immediately (within 24 
hours of awareness) to OSRO Safety using the CCR SAE report form. Any exceptions to the 
expedited reporting requirements are found in section 8.4 
All SAE reporting must include the elements described in 8.2. 

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Pregnancy of the participant’s partner is not considered to be an AE. However, the outcome of 
all pregnancies occurring from the date of the first dose until 6 months after the last dose should, 
if possible, be followed up and documented. Pregnant partners may be offered the opportunity to 
participate in an institutional pregnancy registry protocol (e.g., the NIH IRP pregnancy registry 
study) to provide data about the outcome of the pregnancy for safety reporting purposes. 
8.7 
REGULATORY REPORTING FOR STUDIES CONDUCTED UNDER CCR-SPONSORED IND 
Following notification from the investigator, CCR, the IND sponsor, will report any suspected 
adverse reaction that is both serious and unexpected. CCR will report an AE as a suspected 
adverse reaction only if there is evidence to suggest a causal relationship between the study 
product and the adverse event. CCR will notify FDA and all participating investigators (i.e., all 
investigators to whom the sponsor is providing drug under its INDs or under any investigator’s 
IND) in an IND safety report of potential serious risks from clinical trials or any other source, as 
soon as possible, in accordance to 21 CFR Part 312.32.  
All serious events will be reported to the FDA at least annually in a summary format. 
8.8 
SPONSOR PROTOCOL DEVIATION REPORTING 
A Protocol Deviation is defined as any non-compliance with the clinical trial Protocol, Manual 
of Operational Procedures (MOP) and other Sponsor approved study related documents, GCP, or 
protocol-specific procedural requirements on the part of the participant, the Investigator, or the 
study site staff inclusive of site personnel performing procedures or providing services in support 
of the clinical trial. 
It is the responsibility of the study Staff to document any protocol deviation identified by the 
Staff or the site Monitor in the CCR Protocol Deviation Tracking System (PDTS) online 
application. The entries into the PDTS online application should be timely, complete, and 
maintained per CCR PDTS user requirements.   
In addition, any deviation to the protocol should be documented in the participant’s source 
records and reported to the reviewing IRB per their guidelines. OSRO required protocol 
deviation reporting is consistent with E6(R2) GCP: Integrated Addendum to ICH E6(R1): 4.5 
Compliance with Protocol; 5.18.3 (a), and 5.20 Noncompliance; and ICH E3 16.2.2 Protocol 
deviations. 
9 
CLINICAL MONITORING  
Clinical site monitoring is conducted to ensure: 
• that the rights of the participants are protected; 
• that the study is implemented per the approved protocol, Good Clinical Practice and 
standard operating procedures; and 
• the quality and integrity of study data and data collection methods are maintained.  
Monitoring for this study will be performed by NCI CCR Office of Sponsor and Regulatory 
Oversight (OSRO) Sponsor and Regulatory Oversight Support (SROS) Services contractor. 
Clinical site monitoring activities will be based on OSRO standards, FDA Guidance E6(R2) 
Good Clinical Practice: Integrated Addendum to ICH E6(R1) March 2018, and applicable 
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Details of clinical site monitoring will be documented in a Clinical Monitoring Plan (CMP) 
developed by OSRO. CMPs will be protocol-specific, risk-based and tailored to address human 
subject protections and integrity of the study data. OSRO will determine the intensity and 
frequency of monitoring based on several factors, including study type, phase, risk, complexity, 
expected enrollment rate, and any unique attributes of the study and the site. The Sponsor will 
conduct a periodic review of the CMP to confirm the plan's continued appropriateness. A change 
to the protocol, significant or pervasive non-compliance with GCP, or the protocol may trigger 
CMP updates. 
OSRO SROS Monitoring visits and related activities will be conducted throughout the life cycle 
of each protocol. The first activity is before the study starts to conduct a Site Assessment Visit 
(SAV) (as warranted), followed by a Site Initiation Visit (SIV), Interim Monitoring Visit(s) 
(IMVs), and a study Close-Out Visit (COV). 
Some monitoring activities may be performed remotely, while others will occur at the study 
site(s). Monitoring visit reports will describe visit activities, observations, and associated action 
items or follow-up required for resolution of any issues, discrepancies, or deviations. Monitoring 
reports will be distributed to the study PI, NCI CCR QA, CCR Protocol Support Office, 
coordinating center (if applicable), and the Sponsor regulatory file. 
The site Monitor will inform the study team of any deviations observed during monitoring visits. 
If unresolved, the Monitor will request that the site Staff enter the deviations in the CCR 
Protocol Deviation Tracking System (PDTS) for deviation reporting to the Sponsor and as 
applicable per institutional and IRB guidance. 
. 
10 STATISTICAL CONSIDERATIONS 
10.1 STATISTICAL HYPOTHESIS 
Primary Objectives: 
• Arm 1 (Sequential Dose Escalation):  
 To evaluate the safety and tolerability of single agent SX-682. 
 To determine the MTD of SX-682 followed by M7824 and CV301 in participants 
with advanced or metastatic solid tumors. If the MTD is not reached the study 
will be focused to describe the safety and tolerability of SX-682 followed by 
M7824 and CV301. 
• Arm 2 (Combination Dose Escalation):  
 To determine the RP2D of SX-682 with M7824 and CV301 in participants with 
advanced or metastatic solid tumors. If the MTD is not reached the study will be 
focused to describe the safety and tolerability of the drug combination. 
• Arm 3 (Expansion): 
 To evaluate preliminary efficacy based on Objective Response Rate (ORR), in 
each disease cohort separately. 
Secondary Objectives: 

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• Arms 1 and 2 (Dose Escalations):  
 To characterize the PK/PD profile of SX-682 as a single agent and in 
combination. 
• All Arms:  
 To evaluate preliminary efficacy: Disease control rate (DCR) and Progression-
free survival (PFS) using RECIST1.1 
10.2 SAMPLE SIZE DETERMINATION 
The trial will begin with two phase I evaluations (Cohort 1, Arms 1 and 2; Dose Escalation) as 
follows: initially participants will be enrolled in Arm 1 involving monotherapy with SX-682 
followed by M7824 + CV301. This will initially include up to 3 dose levels, with 3 participants 
per dose level if no DLTs are experienced. However, if in any of the dose levels, a DLT is 
identified in the 3 participants, 3 more participants will be enrolled in that dose level, with 
subsequent escalation only if there are <=1 DLTs in 6 participants. Thus, up to 18 participants 
may be enrolled in these first 3 dose levels. If there is one or more DLTs identified in in the first 
3 dose levels, escalation will continue to DL4 and 5 using the above 3+3 design. If there are no 
DLTs in the first 3 dose levels, then participants will be enrolled to Arm 2. As a result, 
depending on toxicities identified, between 9 and 30 participants may be treated within this 
sequential dose escalation arm.  
In Arm 2, a combination arm with SX-682 followed by the triplet combination (SX-682, M7824, 
CV301), up to 5 dose levels may be explored. Using a standard 3+3 design, up to 5x6=30 
participants may be included in this arm. Thus, up to 30+30=60 total participants may be treated 
in the phase I portion (Cohort 1, Arms 1 and 2) of the trial. 
The phase II evaluation (Arm 3) will take place separately in two cohorts: 
TNBC: 
Based on prior studies [70-72], the clinical response rate for similar participants with advanced 
disease receiving a single agent checkpoint inhibitor is expected to be 8-10%. Thus, an observed 
response rate of approximately 15% or higher would be desirable. 
In Arm 3, Cohort 2 (TNBC), the trial will be conducted using a Simon minimax two-stage phase 
II trial design [99] to rule out an unacceptably low response rate (CR+PR) of 5% (p0=0.05) in 
favor of an improved response rate of 20% (p1=0.20). With alfa=0.10 (probability of accepting a 
poor treatment=0.10) and beta = 0.20 (probability of rejecting a good treatment=0.20), the first 
stage will enroll 12 evaluable participants, and if 0 of the 12 has a response, then no further 
participants will be accrued in that cohort. If 1 or more of the first 12 participants has a response, 
then accrual would continue until a total of 21 evaluable participants have been treated in that 
cohort. As it may take up to several months to determine if a participant has experienced a 
response, a temporary pause in the accrual may be necessary to ensure that enrollment to the 
second stage is warranted. If there are 1-2 participants with a response out of 21 participants in 
this cohort, this would be an uninterestingly low response rate. If there were 3 or more of 21 
(14.3%) who experienced a response, this would be sufficiently interesting to warrant further 
study in later trials. Under the null hypothesis (5% response rate), the probability of early 
termination is 54.0%. 
HPV negative HNSCC: 

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Based on prior studies [82, 87, 88], the clinical response rate for similar participants with this 
disease is expected to be 13-18%. Thus, an observed response rate of greater than 25% would be 
desirable. 
In Arm 3, Cohort 3 (HPV negative HNSCC), the trial will be conducted using a Simon minimax 
two-stage phase II trial design[99] to rule out an unacceptably low response rate (CR+PR) of 
15% (p0=0.15) in favor of an improved response rate of 40% (p1=0.40). With 
alfa=0.10(probability of accepting a poor treatment=0.10) and beta = 0.20 (probability of 
rejecting a good treatment=0.20), the first stage will enroll 9 evaluable participants, and if 0 to 1 
of the 9 have a response, then no further participants will be accrued in that cohort. If 2 or more 
of the first 9 participants have a response, then accrual would continue until a total of 16 
evaluable participants have been treated in that cohort. As it may take up to several months to 
determine if a participant has experienced a response, a temporary pause in the accrual may be 
necessary to ensure that enrollment to the second stage is warranted. If there are 2-4 participants 
with a response out of 16 participants in this cohort, this would be an uninterestingly low 
response rate. If there were 5 or more of 16 (31.3%) who experienced a response, this would be 
sufficiently interesting to warrant further study in later trials. Under the null hypothesis (15% 
response rate), the probability of early termination is 60.0%. 
It is expected that up to 1.5 years may be required to enroll up to 60 participants in Arms 1 and 2. 
It is then expected that 2-3 years may be required to complete accrual to Arm 3. Thus, accrual is 
expected to be completed in 4-5 years. The total number of evaluable participants is no more 
than 60+21+16=97. To allow for a small number of inevaluable participants, the accrual ceiling 
for treated participants in the dose escalation and expansion cohorts combined will be set at 105 
participants 
10.3 POPULATIONS FOR ANALYSES 
Intention to treat: any subjects who enroll onto the trial and provide consent and who receive at 
least 1 dose of SX-682, will be included in safety analyses in Arms 1 and 2.  
In Arm 3, any participants who receive at least one cycle (defined as 28 days) of SX-682, 
M7824, and CV301 will be included in safety evaluations as well as efficacy evaluations for the 
appropriate cohort. 
10.3.1 Evaluable for toxicity  
All participants will be evaluable for toxicity from the time of their first treatment with SX-682. 
Participant will be eligible for the DLT evaluation if at least ≥85 percent of SX-682 scheduled 
doses were taken and 100% of scheduled doses of M7824 or CV301 were administered within 
the DLT period. 
10.3.2 Evaluable for objective response  
Only those participants who have measurable disease present at baseline, have received at least 
one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for 
response. These participants will have their response classified according to the definitions in 
section 6.3). (Note: Participants who receive at least treatment cycle and exhibit objective 
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10.3.3 Evaluable Non-Target Disease Response 
Participants who have lesions present at baseline that are evaluable but do not meet the 
definitions of measurable disease, have received at least one cycle of therapy, and have had their 
disease re-evaluated will be considered evaluable for non-target disease. The response 
assessment is based on the presence, absence, or unequivocal progression of the lesions.  
10.4 STATISTICAL ANALYSES 
10.4.1 General Approach 
Following a determination of safety, tolerability, and the MTD in Arms 1 and 2, the fraction of 
participants who experience a response in each disease-specific cohort of Arm 3 will be reported 
along with confidence intervals. 
10.4.2 Analysis of the Primary Endpoints 
The toxicity grades per participant will be tabulated and reported by dose level during dose 
escalation (Arms 1 and 2). This will also include separate evaluations for the initial monotherapy 
evaluations preceding the evaluation of the combination at each dose level.  
In Arm 3, the fraction of participants who experience a response in each disease-specific cohort 
will be reported along with 95% two-sided confidence intervals. 
10.4.3 Analysis of the Secondary Endpoint(s) 
10.4.4 PK evaluations will be performed on participants in both dose escalation Arms (both for 
single agent SX-682 and the combination of agents); results will be reported using 
standard descriptive statistics. In Arm 3, separately by cohort, the disease control rate 
(DCR; CR+PR+SD) will be reported as the fraction of participants who experience this 
outcome, along with a 95% two-sided confidence interval for each fraction. Progression 
free survival (PFS) will be calculated using the Kaplan-Meier method, including 
progressions or death without progression as events. Participants who come off study for 
reasons other than progression and choose not to participate in optional imaging will be 
censored in data analysis at the time when they become unfollowable for PFS.  
 
10.4.5 Safety Analyses 
The fraction of participants who experience a toxicity, by grade and type of toxicity, will be 
tabulated per dose level (both single agent and combination of agents) during the Arms 1 and 2 
portion of the trial. Participants who take one dose or more of SX-682 will be evaluable for 
safety.  
10.4.6 Baseline Descriptive Statistics 
Baseline demographic characteristics will be reported. 
10.4.7 Planned Interim Analyses 
As indicated in the two-stage designs, the number of responses after 9 or 12 evaluable 
participants have been treated in the appropriate cohort will be noted and will be used to 
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10.4.8 Sub-Group Analyses 
In Arm 3, analyses will be performed separately by histology. 
10.4.9 Tabulation of individual Participant Data 
None 
10.4.10 
Exploratory Analyses 
All Arms: 
 To evaluate response via iRECIST 
 To evaluate the effect on immune cell subsets and soluble factors in peripheral blood. 
 To evaluate the effect on serum cytokine levels (IL-8, IL-6 and others) in peripheral 
blood. 
 To evaluate the effect on T cell clonality in peripheral blood and tumor samples. 
 To evaluate the effect on antigen-specific T cells responses to CEA, MUC1 and the 
cascade antigen brachyury in peripheral blood. 
 To evaluate the effect on antigen-specific T cell responses to CEA, MUC1 and the 
cascade antigen brachyury in the tumor biopsies.  
 To evaluate the presence of lymphocytic infiltrates and other tumor markers as well as to 
evaluate RNA in situ hybridization for IL-8, TGF-β and other soluble factors in tumor 
biopsies. 
 To evaluate M7824 PK profile in this drug combination  
 To evaluate ADA in this drug combination 
 To evaluate long term (2 years after completion of treatment) clinical outcomes 
 To evaluate CTCs  
In Arms 1 and 2 (Dose-Escalations), the following are the parameters will be evaluated, 
separately per dose level: 
 To evaluate ORR per RECISTv1.1 
In Arm 3 (Expansions) the following are the parameters will be evaluated, separately per cohort. 
  To evaluate changes in circulating free DNA.  
Any exploratory evaluations which generate quantitative measures will be done using descriptive 
statistics including confidence intervals when appropriate. Any statistical tests performed for 
evaluation of exploratory objectives will be done without formal adjustment for multiple 
comparisons, but in the context of the number of tests performed. 
11 COLLABORATIVE AGREEMENTS  
11.1  COOPERATIVE RESEARCH AND DEVELOPMENT AGREEMENT (CRADA) 
A CRADA (03153) is in place with Syntrix for the supply of SX-682. 
A CRADA (02666) is in place with EMD Serono for the supply of M7824. 

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A CRADA (02561) is in place with Bavarian Nordic for the supply of CV301. 
12 HUMAN SUBJECTS PROTECTIONS  
12.1 RATIONALE FOR SUBJECT SELECTION 
No individual who meets the criteria for eligibility will be excluded from participation based on 
their race, ethnicity, gender, or socioeconomic status. Particular attention will be made to acquire 
a broad and diversified population. 
12.2 PARTICIPATION OF CHILDREN 
Children (younger than 18 years) will not be included in this protocol due to the limited data on 
study drugs in children and the different biology of childhood malignancy. 
12.3 PARTICIPATION OF SUBJECTS UNABLE TO GIVE CONSENT 
Adults unable to give consent are excluded from enrolling in the protocol. However, re-consent 
may be necessary and there is a possibility, though unlikely, that subjects could become 
decisionally impaired. For this reason and because there is a prospect of direct benefit from 
research participation (Section 12.4.2), all subjects will be offered the opportunity to fill in their 
wishes for research and care, and assign a substitute decision maker on the “NIH Advance 
Directive for Health Care and Medical Research Participation” form so that another person can 
make decisions about their medical care in the event that they become incapacitated or 
cognitively impaired during the course of the study. Note: The PI or AI will contact the NIH 
Ability to Consent Assessment Team (ACAT) for evaluation to assess ongoing capacity of the 
subjects and to identify an LAR as needed.  . 
Please see section 12.5.1 for consent procedure.   
 
12.4 RISK/BENEFIT ASSESSMENT FOR ALL PARTICIPANTS  
12.4.1 Known Potential Risks  
12.4.1.1 Study Drug Risks 
Risks include the possible occurrence of any of a range of side effects which are listed in the 
Consent Document or sections 1.2.2.2, 1.2.3.1, 1.2.4.1 of this protocol document. Frequent 
monitoring for adverse effects will help to minimize the risks associated with administration of 
the study agents. 
12.4.1.2 Risk of Biopsy 
All care will be taken to minimize risks that may be incurred by tumor sampling. However, there 
are procedure-related risks (such as bleeding, infection and visceral injury) that will be explained 
fully during informed consent. 
12.4.1.3 Risks of local anesthesia and/or light sedation. 
Biopsies will be done under local anesthesia and/or light sedation. Potential side effects 
of sedation include headache, nausea and drowsiness. These side effects usually go away 
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12.4.1.4 Risks of contrast dye used in CT scans  
There is a chance of developing an allergic reaction from the contrast material, which may cause 
symptoms ranging from mild itching or a rash to severe difficulty breathing, shock or rarely, 
death.  The contrast material may also cause kidney problems. 
For IV contrast: Potential side effects include discomfort when the contrast material is injected, 
feeling warm, flushed, a metallic taste, or rarely vomiting or nausea.  
For oral contrast:  Potential side effects include vomiting, nausea, cramping, bloating, 
constipation or diarrhea after drinking the contrast. 
 
12.4.1.5 Risks of exposure to Ionizing Radiation  
This research study involves up to nine (9) CT scans (C/A/P) and up to three (3) CT guided 
biopsies (optional) collected for research purposes only. Subjects undergoing these scans and  
optional biopsies collection will be exposed up to 12.3 rem.  
The CT scans that participant will get in this study will expose them to the roughly the same 
amount of radiation as 41 years of background radiation. The risk of getting cancer from the 
radiation exposure in this study is 1.2 out of 100 (1.2 %) and of getting a fatal cancer is 0.6 out of 
100 (0.6 %)  
 
12.4.1.6 Risks of MRI 
People are at risk for injury from the MRI magnet if they have some kinds of metal in their body.  
It may be unsafe to have an MRI scan for participants with pacemakers or other implanted 
electrical devices, brain stimulators, some types of dental implants, aneurysm clips (metal clips 
on the wall of a large artery), metal prostheses (including metal pins and rods, heart valves, and 
cochlear implants), permanent eyeliner, tattoos, an implanted delivery pump, or shrapnel 
fragments. Welders and metal workers may have small metal fragments in the eye.  
People with fear of confined spaces may become anxious during an MRI. Those with back 
problems may have back pain or discomfort from lying in the scanner.  The noise from the 
scanner is loud enough to damage hearing, especially in people who already have hearing loss.  
There are no known long-term risks of MRI scans. 
 
12.4.1.7 Risks of Gadolinium 
The risks of an IV catheter include bleeding, infection, or inflammation of the skin and vein with 
pain and swelling.   
Mild symptoms from gadolinium infusion occur in fewer than 1% of those who receive it and 
usually go away quickly.  Mild symptoms may include coldness in the arm during the injection, a 
metallic taste, headache, and nausea.  In an extremely small number, fewer than one in 300,000 
people, more severe symptoms have been reported including shortness of breath, wheezing, 
hives, and lowering of blood pressure.  
People with kidney disease are at risk for a serious reaction to gadolinium contrast called 
“nephrogenic systemic fibrosis (NSF)”.  This condition always involves the skin and can also 
involve the muscles, joints and internal organs.  NSF has resulted in a very small number of 
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Most of the gadolinium contrast leaves the body in the urine.  However, the FDA has issued a 
safety alert that indicates small amounts of gadolinium may remain in the body for months to 
years.  The long-term effects of the retained gadolinium are not known.  Some types of 
gadolinium contrast drugs are less likely to remain in the body than others. The gadolinium 
contrast drugs that are less likely to remain in the body will be used on this study. 
 
12.4.1.8 Research Blood Collection Risks 
Risks of blood draws include pain and bruising in the area where the needle is placed, 
lightheadedness, and rarely, fainting and infection. When large amounts of blood are collected, 
low red blood cell count (anemia) can develop.  
12.4.1.9 Risk of Rapid Progression 
Three large studies of bintrafusp alfa were recently stopped when the drug 
manufacturer reviewed data that suggested that the studies would not be likely to prove the study 
treatment better than standard treatments. This data also suggested that there may be a portion of 
patients that have either no benefit from bintrafusp alfa, or that bintrafusp alfa will make the 
tumor grow faster. This has been described with other immunotherapy approaches also with 
studies suggesting this happens in about 15% of cases. 
 
12.4.1.10 
Other Risks 
Risks include the possible occurrence of any of a range of side effects which are listed in the 
Consent Document or this protocol document. Frequent monitoring for adverse effects will help 
to minimize the risks associated with administration of the study agents. 
12.4.2 Known Potential Benefits 
The study drugs may help to control the disease. The results may help the investigators learn 
more about the disease and develop new treatments for participants with this disease. 
12.4.3 Assessment of Potential Risks and Benefits 
Solid tumors treatment needs improved therapy options. Current studies suggest that study 
therapy may have tremendous anti-tumor efficacy.  
A number of clinically appropriate strategies to minimize risks to participants have been built 
into the protocol through the means of inclusion/exclusion criteria, monitoring strategies, and 
management guidelines. Overall, the potential benefit of the study therapy in subjects with solid 
tumors outweigh the risks associated with this drug. 
The potential benefit to a participant that participates in this study is better control of their tumor 
growth and disease recurrence which may or may not have a favorable impact on symptoms 
and/or survival. 
Potential adverse reactions attributable to the administration of the study drug utilized in this trial 
are discussed in Sections 1.2.2.2, 1.2.3.1, 1.2.4.1. All care will be taken to minimize side effects, 
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12.5 CONSENT PROCESS AND DOCUMENTATION 
The informed consent document will be provided as a physical or electronic document to the 
participant or consent designee(s) for review prior to consenting.  A designated study 
investigator will carefully explain the procedures and tests involved in this study, and the 
associated risks, discomforts and benefits. In order to minimize potential coercion, as much time 
as is needed to review the document will be given, including an opportunity to discuss it with 
friends, family members and/or other advisors, and to ask questions of any designated study 
investigator. A signed informed consent document will be obtained prior to entry onto the study. 
The initial consent process as well as re-consent, when required, may take place in person or 
remotely (e.g., via telephone or other NIH approved remote platforms used in compliance with 
policy including HRPP policy 303) per discretion of the designated study investigator and with 
the agreement of the participant/consent designee(s).  Whether in person or remote, the privacy 
of the subject will be maintained. Consenting investigators (and participant/consent designee, 
when in person) will be located in a private area (e.g., clinic consult room). When consent is 
conducted remotely, the participant/consent designee will be informed of the private nature of 
the discussion and will be encouraged to relocate to a more private setting if needed. 
 
Consent will be documented with required signatures on the physical document (which includes 
the printout of an electronic document sent to participant) or as described below, with a manual 
(non-electronic) signature on the electronic document. When required, witness signature will be 
obtained similarly as described for the investigator and participant.  
 
Manual (non-electronic) signature on electronic document: 
When a manual signature on an electronic document is used for the documentation of consent 
at the NIH Clinical Center, this study will use the following to obtain the required signatures: 
• 
Adobe platform (which is not 21 CFR Part 11 compliant); or,   
• 
iMedConsent platform (which is 21 CFR Part 11 compliant) 
During the consent process, participants and investigators will view individual copies of the 
approved consent document on screens at their respective locations (if remote consent); the 
same screen may be used when in the same location but is not required.   
Both the investigator and the participant will sign the document using a finger, stylus or 
mouse.  
Note: Refer to the CCR SOP PM-2, Obtaining and Documenting the Informed Consent 
Process for additional information (e.g., verification of participant identity when obtaining 
consent 
remotely) 
found 
 
at:   
https://ccrod.cancer.gov/confluence/pages/viewpage.action?pageId=73203825. 
 
12.5.1 Consent Process for Adults Who Lack Capacity to Consent to Research Participation 
For participants addressed in section 12.3, an LAR will be identified consistent with Policy 403 
and informed consent obtained from the LAR, as described in Section 12.5 
 

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13 REGULATORY AND OPERATIONAL CONSIDERATIONS 
13.1 STUDY DISCONTINUATION AND CLOSURE 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to study participants, 
investigators, and regulatory authorities. If the study is prematurely terminated or suspended, the 
Principal Investigator (PI) will promptly inform study participants and the Institutional Review 
Board (IRB) and will provide the reason(s) for the termination or suspension. Study participants 
will be contacted, as applicable, and be informed of changes to study visit schedule. 
 Circumstances that may warrant termination or suspension include, but are not limited to: 
• Determination of unexpected, significant, or unacceptable risk to participants 
• Demonstration of efficacy that would warrant stopping  
• Insufficient compliance to protocol requirements 
• Data that are not sufficiently complete and/or evaluable 
• Determination that the primary endpoint has been met 
• Determination of futility 
Study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the sponsor, IRB and Food and Drug Administration (FDA). 
13.2 QUALITY ASSURANCE AND QUALITY CONTROL 
Clinical site will perform internal quality management of study conduct, data and biological 
specimen collection, documentation and completion. An individualized quality management plan 
will be developed to describe a site’s quality management. 
Quality control (QC) procedures will be implemented beginning with the data entry system and 
data QC checks that will be run on the database will be generated. Any missing data or data 
anomalies will be communicated to the site(s) for clarification/resolution. 
Following written Standard Operating Procedures (SOPs), the monitors will verify that the 
clinical trial is conducted and data are generated and biological specimens are collected, 
documented (recorded), and reported in compliance with the protocol, International Conference 
on Harmonisation Good Clinical Practice (ICH GCP), and applicable regulatory requirements 
(e.g., Good Laboratory Practices (GLP), Good Manufacturing Practices (GMP)).  
The investigational site will provide direct access to all trial related sites, source data/documents, 
and reports for the purpose of monitoring and auditing by the sponsor, and inspection by local 
and regulatory authorities. 
13.3 CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical. Therefore, any actual conflict of interest of persons who have 
a role in the design, conduct, analysis, publication, or any aspect of this trial will be disclosed 
and managed. Furthermore, persons who have a perceived conflict of interest will be required to 
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conduct of this trial. The study leadership in conjunction with the NCI has established policies 
and procedures for all study group members to disclose all conflicts of interest and will establish 
a mechanism for the management of all reported dualities of interest. 
13.4 CONFIDENTIALITY AND PRIVACY 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, 
their staff, and the sponsor(s). This confidentiality is extended to cover testing of biological 
samples and genetic tests in addition to the clinical information relating to participants. 
Therefore, the study protocol, documentation, data, and all other information generated will be 
held in strict confidence. No information concerning the study or the data will be released to any 
unauthorized third party without prior written approval of the sponsor.  
All research activities will be conducted in as private a setting as possible. 
The study monitor, other authorized representatives of the sponsor, representatives of the 
Institutional Review Board (IRB), and/or regulatory agencies may inspect all documents and 
records required to be maintained by the investigator, including but not limited to, medical 
records (office, clinic, or hospital) and pharmacy records for the participants in this study. The 
clinical study site will permit access to such records. 
The study participant’s contact information will be securely stored at each clinical site for 
internal use during the study. At the end of the study, all records will continue to be kept in a 
secure location for as long a period as dictated by the reviewing IRB, Institutional policies, or 
sponsor requirements. 
Study participant research data, which is for purposes of statistical analysis and scientific 
reporting, will be stored at NCI CCR. This will not include the participant’s contact or 
identifying information. Rather, individual participants and their research data will be identified 
by a unique study identification number. The study data entry and study management systems 
used by clinical sites and by NCI CCR research staff will be secured and password protected. At 
the end of the study, all study databases will be archived at the NIH. 
To further protect the privacy of study participants, a Certificate of Confidentiality has been 
issued by the National Institutes of Health (NIH).  This certificate protects identifiable research 
information from forced disclosure. It allows the investigator and others who have access to 
research records to refuse to disclose identifying information on research participation in any 
civil, criminal, administrative, legislative, or other proceeding, whether at the federal, state, or 
local level. By protecting researchers and institutions from being compelled to disclose 
information that would identify research participants, Certificates of Confidentiality help achieve 
the research objectives and promote participation in studies by helping assure confidentiality and 
privacy to participants. 
14 PHARMACEUTICAL INFORMATION 
14.1 SX-682 (IND#21166) 
14.1.1 Acquisition and Accountability 
Investigational SX-682 is manufactured and supplied for the trial by Syntrix. Drug will be 
delivered directly to the NIH Pharmacy. Individual bottles with tablets will be prepared for each 
study participant according to assigned dose by NIH Pharmacy personnel. Participants will pick 

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up bottles at NIH Pharmacy and will return bottles and not-used tablets after completion of every 
cycle together with Medication Diary to Study Coordinator. After review of leftover tablets and 
Medication Diary, unused tablets will be returned to pharmacy and disposed by pharmacy 
personnel 
14.1.2 Formulation, Appearance, Packaging, and Labeling 
SX-682 is dispensed as either 25 mg or 100 mg tablets for oral administration.  
SX-682 exhibits 99.4% protein binding.  
The anticipated half-life of the drug varies by dose administered with a 25mg flat dose resulting 
in a half-life of 2.6 hours and a 200 mg flat dose resulting in a half-life is 14 hours.  
14.1.3 Product Storage and Stability 
Store SX-682 between 15 to 30°C. On the basis of available stability data for the API and a drug 
product demonstration batch, SX-682 is projected stable for at least 2 years when stored as 
above. 
14.1.4 Preparation 
SX-682 is dispensed as 25 mg or 100 mg tablets for oral administration. If necessary, the 100 mg 
tablets can be cut in half using a pill splitter; the tablets are pre-scored for this purpose. The 
tablets should not be crushed, chewed, or dissolved before being swallowed.  
14.1.5 Administration 
Please see Section 3.3.2  
14.2 M7824 (IND#21166) 
14.2.1 Acquisition and Accountability 
M7824 is manufactured and supplied for the trial by EMD Serono Research and Development 
Institute. Drug will be delivered directly to the NIH Pharmacy. Individual IV bags will be 
prepared for each study participant according to assigned dose by NIH Pharmacy personnel. IV 
bags will be delivered from NIH Pharmacy to participant unit where drug will be infused to the 
participant. 
14.2.2 Formulation, Appearance, Packaging, and Labeling 
M7824 is provided as a sterile liquid formulation and packaged at a 10 mg/mL concentration in 
USP/ Ph Eur type I 50R vials that are filled with drug product solution to allow an extractable 
volume of 60 mL (600 mg/60 mL). The vials are closed with rubber stoppers in serum format 
complying with USP and Ph Eur with an aluminum crimp seal closure. Each single-use vial 
contains 600mg of M7824, formulated as 10mg/mL of active, 6% (w/v) Trehalose, 40 mM NaCl, 
5 mM Methionine, 0.05% (w/v) Tween 20, 10 mM LHistidine at pH 5.5.  
The liquid formulation is diluted directly with 0.9% sodium chloride solution for injection. The 
estimated volumes of delivery are anticipated to be no more than 250mL. The verified 
concentration range in the infusion solution is 0.16 mg/mL to 9.6 mg/mL.  
14.2.3 Product Storage and Stability 
M7824 drug product must be stored at 2°C to 8°C until use. The storage condition is based on 
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(23°C to 27°C) or higher temperatures for extended periods of time might be subject to 
degradation. 
The chemical and physical in-use stability for the infusion solution of M7824 in 0.9% saline 
solution has been demonstrated for a total of 72 hours at room temperature. However, from a 
microbiological point of view, the diluted solution should be used immediately and is not 
intended to be stored unless dilution has taken place in controlled and validated aseptic 
conditions. If not used immediately, in-use storage times and conditions prior to administration 
are the responsibility of the user. Do not freeze or shake the diluted solution. 
No other drugs should be added to the infusion containers containing M7824. 
14.2.4 Preparation 
Preparation is described in pharmacy manual. 
14.2.5 Administration 
Please see Section 3.3.4 
14.3 CV301 (IND#21166) 
14.3.1 Acquisition and Accountability 
Investigational CV301 vaccines (MVA-BN-CV301 and FPV-CV301) will be supplied by the 
manufacturer, Bavarian Nordic. Drug will be delivered directly to the NIH Pharmacy. Individual 
syringes with the drugs will be prepared for each study participant by NIH Pharmacy personnel. 
Syringes will be delivered from NIH Pharmacy to participant unit where drug will be injected to 
the participant. 
14.3.2 Formulation, Appearance, Packaging, and Labeling 
The manufacturing department of Bavarian Nordic will supply MVA-BN-CV301 and FPV-CV301, 
with each vaccine provided in 2 mL type I borosilicate glass vials closed with sterile bromobutyl 
rubber stoppers, crimped with aluminum caps and covered with polypropylene closures.  
14.3.3 Product Storage and Stability 
Supplies of both the MVA-BN-CV301 and the FPV-CV301 vaccines will be shipped 
temperature controlled and monitored to the clinical trial site. Once at the site, the package 
should be handed over to personnel in charge of vaccine preparation (e.g., the pharmacist or 
representative). Site personnel are responsible for proper storage of vaccine upon receipt.  
Both the MVA-BN-CV301 and the FPV-CV301 vaccines must be shipped to site and stored at a 
minimum temperature of -4°F +/- 9°F (-20°C +/- 5°C) or -80ºC ± 10ºC, avoiding direct light. A 
vial must not be re-frozen once it has been thawed. A provisional shelf life of 2 years at -80°C ± 
10°C has been given. Expiry date may be extended due to real time stability data. Storage at -
20°C ± 5°C is limited to 12 months after moving from -80°C ± 10°C to -20°C ± 5°C. 
14.3.4 Preparation 
MVA-BN-CV301 and FPV-CV301 encode the human MUC-1 and the human CEA gene in 
combination with human TRICOM. No marker gene is present in both recombinant viruses.  

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MVA-BN-CV301 is a liquid-frozen, highly attenuated, live recombinant virus based on the viral 
vector MVA-BN. It is administered as s.c. injection. Packaging and vials will be labeled 
according to the respective product specifications.  
One MVA-BN-CV301 vaccine vial has a nominal titer of 4 x 108 infectious units (Inf.U) in 0.5 
mL of the drug product. 
FPV-CV301 is a liquid-frozen, highly attenuated, live recombinant virus. It is administered as 
s.c. injection. The packages and vials will be labeled according to the respective product 
specifications.  
One FPV-CV301 vaccine vial has a nominal virus titer of 1 x 109 Inf.U in 0.5 mL of the drug 
product. 
14.3.5 Administration 
Please see Section 3.3.3. 

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15 REFERENCES  
1. 
Palena, C., D.H. Hamilton, and R.I. Fernando, Influence of IL-8 on the epithelial-
mesenchymal transition and the tumor microenvironment. Future Oncol, 2012. 8(6): p. 
713-22. 
2. 
David, J.M., et al., The IL-8/IL-8R Axis: A Double Agent in Tumor Immune Resistance. 
Vaccines (Basel), 2016. 4(3). 
3. 
Xie, K., Interleukin-8 and human cancer biology. Cytokine Growth Factor Rev, 2001. 
12(4): p. 375-91. 
4. 
Fernando, R.I., et al., IL-8 signaling plays a critical role in the epithelial-mesenchymal 
transition of human carcinoma cells. Cancer Res, 2011. 71(15): p. 5296-306. 
5. 
Fernando, R.I., et al., IL-8 signaling is involved in resistance of lung carcinoma cells to 
erlotinib. Oncotarget, 2016. 7(27): p. 42031-42044. 
6. 
Dominguez, C., et al., Neutralization of IL-8 decreases tumor PMN-MDSCs and reduces 
mesenchymalization of claudin-low triple-negative breast cancer. JCI Insight, 2017. 
2(21). 
7. 
Ginestier, C., et al., CXCR1 blockade selectively targets human breast cancer stem cells 
in vitro and in xenografts. J Clin Invest, 2010. 120(2): p. 485-97. 
8. 
Posner, M.R., et al., Survival and human papillomavirus in oropharynx cancer in TAX 
324: a subset analysis from an international phase III trial. Ann Oncol, 2011. 22(5): p. 
1071-7. 
9. 
Ang, K.K., et al., Human papillomavirus and survival of patients with oropharyngeal 
cancer. N Engl J Med, 2010. 363(1): p. 24-35. 
10. 
Bilusic, M., et al., Phase I trial of HuMax-IL8 (BMS-986253), an anti-IL-8 monoclonal 
antibody, in patients with metastatic or unresectable solid tumors. J Immunother Cancer, 
2019. 7(1): p. 240. 
11. 
Kirsten, A.M., et al., The safety and tolerability of oral AZD5069, a selective CXCR2 
antagonist, in patients with moderate-to-severe COPD. Pulm Pharmacol Ther, 2015. 31: 
p. 36-41. 
12. 
O'Byrne, P.M., et al., Efficacy and safety of a CXCR2 antagonist, AZD5069, in patients 
with uncontrolled persistent asthma: a randomised, double-blind, placebo-controlled 
trial. Lancet Respir Med, 2016. 4(10): p. 797-806. 
13. 
Jurcevic, S., et al., The effect of a selective CXCR2 antagonist (AZD5069) on human 
blood neutrophil count and innate immune functions. Br J Clin Pharmacol, 2015. 80(6): 
p. 1324-36. 
14. 
Miller, B.E., et al., The pharmacokinetics and pharmacodynamics of danirixin 
(GSK1325756)--a selective CXCR2 antagonist --in healthy adult subjects. BMC 
Pharmacol Toxicol, 2015. 16: p. 18. 

Abbreviated Title: STAT Trial 
Version Date: 08/17/2022 
 
118 
15. 
Madan, A., et al., Efficacy and Safety of Danirixin (GSK1325756) Co-administered With 
Standard-of-Care Antiviral (Oseltamivir): A Phase 2b, Global, Randomized Study of 
Adults Hospitalized With Influenza. Open Forum Infect Dis, 2019. 6(4): p. ofz163. 
16. 
Roberts, G., et al., Randomized, Double-Blind, Placebo-Controlled Study of the Safety, 
Tolerability, and Clinical Effect of Danirixin in Adults With Acute, Uncomplicated 
Influenza. Open Forum Infect Dis, 2019. 6(4): p. ofz072. 
17. 
Schott, A.F., et al., Phase Ib Pilot Study to Evaluate Reparixin in Combination with 
Weekly Paclitaxel in Patients with HER-2-Negative Metastatic Breast Cancer. Clin 
Cancer Res, 2017. 23(18): p. 5358-5365. 
18. 
Goldstein, L., et al. A randomized, placebo-controlled phase 2 study paclitaxel in 
combination with reparixin compared to paclitaxel alone as front-line therapy for 
metastatic Triple-Negative Breast Cancer (fRida). in San Antonio Breast Cancer 
Symposium. 2019. San Antonio, Tx. 
19. 
Blobe, G.C., W.P. Schiemann, and H.F. Lodish, Role of transforming growth factor beta 
in human disease. N Engl J Med, 2000. 342(18): p. 1350-8. 
20. 
Dumont, N. and C.L. Arteaga, Transforming growth factor-beta and breast cancer: 
Tumor promoting effects of transforming growth factor-beta. Breast Cancer Res, 2000. 
2(2): p. 125-32. 
21. 
Formenti, S.C., et al., Focal Irradiation and Systemic TGFbeta Blockade in Metastatic 
Breast Cancer. Clin Cancer Res, 2018. 24(11): p. 2493-2504. 
22. 
Ivanovic, V., et al., Elevated plasma levels of TGF-beta 1 in patients with invasive 
prostate cancer. Nat Med, 1995. 1(4): p. 282-4. 
23. 
Shen, M., et al., FASN-TGF-beta1-PD-L1 axis contributes to the development of 
resistance to NK cell cytotoxicity of cisplatin-resistant lung cancer cells. Biochim 
Biophys Acta Mol Cell Biol Lipids, 2018. 1863(3): p. 313-322. 
24. 
Tsushima, H., et al., High levels of transforming growth factor beta 1 in patients with 
colorectal cancer: association with disease progression. Gastroenterology, 1996. 110(2): 
p. 375-82. 
25. 
Terabe, M., et al., Blockade of only TGF-beta 1 and 2 is sufficient to enhance the efficacy 
of vaccine and PD-1 checkpoint blockade immunotherapy. Oncoimmunology, 2017. 6(5): 
p. e1308616. 
26. 
Vanpouille-Box, C. and S.C. Formenti, Dual Transforming Growth Factor-beta and 
Programmed Death-1 Blockade: A Strategy for Immune-Excluded Tumors? Trends 
Immunol, 2018. 39(6): p. 435-437. 
27. 
Grenga, I., et al., Anti-PD-L1/TGFbetaR2 (M7824) fusion protein induces immunogenic 
modulation of human urothelial carcinoma cell lines, rendering them more susceptible to 
immune-mediated recognition and lysis. Urol Oncol, 2018. 36(3): p. 93 e1-93 e11. 
28. 
Jochems, C., et al., Analyses of functions of an anti-PD-L1/TGFbetaR2 bispecific fusion 
protein (M7824). Oncotarget, 2017. 8(43): p. 75217-75231. 

Abbreviated Title: STAT Trial 
Version Date: 08/17/2022 
 
119 
29. 
Knudson, K.M., et al., M7824, a novel bifunctional anti-PD-L1/TGFbeta Trap fusion 
protein, promotes anti-tumor efficacy as monotherapy and in combination with vaccine. 
Oncoimmunology, 2018. 7(5): p. e1426519. 
30. 
Lan, Y., et al., Enhanced preclinical antitumor activity of M7824, a bifunctional fusion 
protein simultaneously targeting PD-L1 and TGF-beta. Sci Transl Med, 2018. 10(424). 
31. 
Ravi, R., et al., Bifunctional immune checkpoint-targeted antibody-ligand traps that 
simultaneously disable TGFbeta enhance the efficacy of cancer immunotherapy. Nat 
Commun, 2018. 9(1): p. 741. 
32. 
David, J.M., et al., A novel bifunctional anti-PD-L1/TGF-beta Trap fusion protein 
(M7824) efficiently reverts mesenchymalization of human lung cancer cells. 
Oncoimmunology, 2017. 6(10): p. e1349589. 
33. 
Strauss, J., et al., Phase 1 trial of M7824 (MSB0011359C), a bifunctional fusion protein 
targeting PD-L1 and TGF-beta, in advanced solid tumors. Clin Cancer Res, 2018. 
34. 
Goudie, D.R., et al., Multiple self-healing squamous epithelioma is caused by a disease-
specific spectrum of mutations in TGFBR1. Nat Genet, 2011. 43(4): p. 365-9. 
35. 
Morris, J.C., et al., Phase I study of GC1008 (fresolimumab): a human anti-transforming 
growth factor-beta (TGFβ) monoclonal antibody in patients with advanced malignant 
melanoma or renal cell carcinoma. PLoS One, 2014. 9(3): p. e90353. 
36. 
Ardiani, A., et al., Vaccine-mediated immunotherapy directed against a transcription 
factor driving the metastatic process. Cancer Res, 2014. 74(7): p. 1945-57. 
37. 
Kwilas, A.R., et al., A poxviral-based cancer vaccine the transcription factor twist 
inhibits primary tumor growth and metastases in a model of metastatic breast cancer and 
improves survival in a spontaneous prostate cancer model. Oncotarget, 2015. 6(29): p. 
28194-210. 
38. 
Malamas, A.S., et al., Combination therapy with an OX40L fusion protein and a vaccine 
targeting the transcription factor twist inhibits metastasis in a murine model of breast 
cancer. Oncotarget, 2017. 8(53): p. 90825-90841. 
39. 
Rajabi, H. and D. Kufe, MUC1-C oncoprotein integrates a program of EMT, epigenetic 
reprogramming and immune evasion in human carcinomas. Biochim Biophys Acta, 
2017. 1868(1): p. 117-122. 
40. 
Kharbanda, A., et al., MUC1-C confers EMT and KRAS independence in mutant KRAS 
lung cancer cells. Oncotarget, 2014. 5(19): p. 8893-905. 
41. 
Bouillez, A., et al., MUC1-C promotes the suppressive immune microenvironment in non-
small cell lung cancer. OncoImmunology, 2017. 6(9): p. e1338998. 
42. 
Zeng, Y., et al., MUC1 predicts colorectal cancer metastasis: a systematic review and 
meta-analysis of case controlled studies. PLoS One, 2015. 10(9): p. e0138049. 
43. 
Kharbanda, A., et al., Oncogenic MUC1-C promotes tamoxifen resistance in human 
breast cancer. Mol Cancer Res, 2013. 11(7): p. 714-23. 

Abbreviated Title: STAT Trial 
Version Date: 08/17/2022 
 
120 
44. 
Huang, X., et al., MUC1 overexpression predicts worse survival in patients with non-
small cell lung cancer: evidence from an updated meta-analysis. Oncotarget, 2017. 8(52): 
p. 90315-90326. 
45. 
Khodarev, N.N., et al., MUC1-induced transcriptional programs associated with 
tumorigenesis predict outcome in breast and lung cancer. Cancer Res, 2009. 69(7): p. 
2833-7. 
46. 
Raina, D., et al., Dependence on the MUC1-C oncoprotein in non-small cell lung cancer 
cells. Mol Cancer Ther, 2011. 10(5): p. 806-16. 
47. 
Maeda, T., et al., MUC1-C induces PD-L1 and immune evasion in triple-negative breast 
cancer. Cancer Res, 2018. 78(1): p. 205-215. 
48. 
Tsang, K.Y., et al., Analyses of recombinant vaccinia and fowlpox vaccine vectors 
expressing transgenes for two human tumor antigens and three human costimulatory 
molecules. Clin Cancer Res, 2005. 11(4): p. 1597-607. 
49. 
Kaufman, H.L., et al., Poxvirus-based vaccine therapy for patients with advanced 
pancreatic cancer. J Transl Med, 2007. 5: p. 60. 
50. 
Heery, C.R., et al., Docetaxel alone or in combination with a therapeutic cancer vaccine 
(PANVAC) in patients with metastatic breast cancer: a randomized clinical trial. JAMA 
Oncol, 2015. 1(8): p. 1087-95. 
51. 
Mohebtash, M., et al., A pilot study of MUC-1/CEA/TRICOM poxviral-based vaccine in 
patients with metastatic breast and ovarian cancer. Clin Cancer Res, 2011. 17(22): p. 
7164-73. 
52. 
Morse, M.A., et al., A randomized phase II study of immunization with dendritic cells 
modified with poxvectors encoding CEA and MUC1 compared with the same poxvectors 
plus GM-CSF for resected metastatic colorectal cancer. Ann Surg, 2013. 258(6): p. 879-
86. 
53. 
Gulley, J.L., et al., Pilot study of vaccination with recombinant CEA-MUC-1-TRICOM 
poxviral-based vaccines in patients with metastatic carcinoma. Clin Cancer Res, 2008. 
14(10): p. 3060-9. 
54. 
Gatti-Mays, M. Durable Complete Response with PANVAC and Trastuzumab in 
Metastatic Triple Positive Breast Cancer. in Society for Immunotherapy of Cancer. 2017. 
National Harbor, MD. 
55. 
Greenberg, R.N., et al., Safety, immunogenicity, and surrogate markers of clinical 
efficacy for modified vaccinia Ankara as a smallpox vaccine in HIV-infected subjects. J 
Infect Dis, 2013. 207(5): p. 749-58. 
56. 
Overton, E.T., et al., Safety and immunogenicity of modified vaccinia Ankara-Bavarian 
Nordic smallpox vaccine in vaccinia-naive and experienced human immunodeficiency 
virus-infected individuals: an open-label, controlled clinical phase II trial. Open Forum 
Infect Dis, 2015. 2(2): p. ofv040. 
57. 
von Sonnenburg, F., et al., Safety and immunogenicity of modified vaccinia Ankara as a 
smallpox vaccine in people with atopic dermatitis. Vaccine, 2014. 32(43): p. 5696-702. 

Abbreviated Title: STAT Trial 
Version Date: 08/17/2022 
 
121 
58. 
Tsang, K.Y., et al., Generation of human cytotoxic T cells specific for human 
carcinoembryonic antigen epitopes from patients immunized with recombinant vaccinia-
CEA vaccine. J Natl Cancer Inst, 1995. 87(13): p. 982-90. 
59. 
Tsang, K.Y., et al., A human cytotoxic T-lymphocyte epitope and its agonist epitope from 
the nonvariable number of tandem repeat sequence of MUC-1. Clin Cancer Res, 2004. 
10(6): p. 2139-49. 
60. 
Jochems, C., et al., Identification and characterization of agonist epitopes of the MUC1-
C oncoprotein. Cancer Immunol Immunother, 2014. 63(2): p. 161-74. 
61. 
Gatti-Mays, M.E., et al., A Phase 1 Dose Escalation Trial of BN-CV301, a Recombinant 
Poxviral Vaccine Targeting MUC1 and CEA with Costimulatory Molecules. Clin Cancer 
Res, 2019. May 20. pii: clincanres.0183.2019. doi: 10.1158/1078-0432.CCR-19-0183. 
[Epub ahead of print]. 
62. 
Horn, L.A., et al., Simultaneous inhibition of CXCR1/2, TGF-β, and PD-L1 remodels the 
tumor and its microenvironment to drive antitumor immunity. J Immunother Cancer, 
2020. 8(1). 
63. 
Gatti-Mays, M., et al., A Phase I Trial Using A Multi-Targeted Recombinant Ad5 
(CEA/MUC/Brachyury)-based Immunotherapy Vaccine Regimen in Patients with 
Advanced Cancer. 2019, The Oncologist. 
64. 
Brenton, J.D., et al., Molecular classification and molecular forecasting of breast cancer: 
Ready for clinical application? Journal of Clinical Oncology, 2005. 23(29): p. 7350-
7360. 
65. 
Bauer, K.R., et al., Descriptive analysis of estrogen receptor (ER)negative, progesterone 
receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-
negative phenotype - A population-based study from the California Cancer Registry. 
Cancer, 2007. 109(9): p. 1721-1728. 
66. 
Tutt, A., et al., The TNT trial: A randomized phase III trial of carboplatin (C) compared 
with docetaxel (D) for patients with metastatic or recurrent locally advanced triple 
negative or BRCA1/2 breast cancer (CRUK/07/012). Cancer Research, 2015. 75(9): p. 2. 
67. 
Iwamoto, T., et al., Estrogen receptor (ER) mRNA and ER-related gene expression in 
breast cancers that are 1% to 10% ER-positive by immunohistochemistry. J Clin Oncol, 
2012. 30(7): p. 729-34. 
68. 
Landmann, A., et al., Low Estrogen Receptor (ER)-Positive Breast Cancer and 
Neoadjuvant Systemic Chemotherapy: Is Response Similar to Typical ER-Positive or ER-
Negative Disease? Am J Clin Pathol, 2018. 150(1): p. 34-42. 
69. 
Allred, D.C., et al., NCCN Task Force Report: Estrogen Receptor and Progesterone 
Receptor Testing in Breast Cancer by Immunohistochemistry. J Natl Compr Canc Netw, 
2009. 7 Suppl 6: p. S1-S21; quiz S22-3. 
70. 
Dirix, L.Y., et al., Avelumab, an anti-PD-L1 antibody, in patients with locally advanced 
or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study. Breast Cancer Res 
Treat, 2017. 

Abbreviated Title: STAT Trial 
Version Date: 08/17/2022 
 
122 
71. 
Nanda, R., et al., Pembrolizumab in Patients With Advanced Triple-Negative Breast 
Cancer: Phase Ib KEYNOTE-012 Study. J Clin Oncol, 2016. 34(21): p. 2460-7. 
72. 
Rugo, H.S., et al., Safety and Antitumor Activity of Pembrolizumab in Patients with 
Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative 
Advanced Breast Cancer. Clin Cancer Res, 2018. 24(12): p. 2804-2811. 
73. 
Fakhry, C., et al., Improved survival of patients with human papillomavirus-positive head 
and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst, 
2008. 100(4): p. 261-9. 
74. 
Zhang, L., et al., Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in 
recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-
label, phase 3 trial. Lancet, 2016. 388(10054): p. 1883-1892. 
75. 
Vermorken, J.B., et al., Platinum-based chemotherapy plus cetuximab in head and neck 
cancer. N Engl J Med, 2008. 359(11): p. 1116-27. 
76. 
Clavel, M., et al., Randomized comparison of cisplatin, methotrexate, bleomycin and 
vincristine (CABO) versus cisplatin and 5-fluorouracil (CF) versus cisplatin (C) in 
recurrent or metastatic squamous cell carcinoma of the head and neck. A phase III study 
of the EORTC Head and Neck Cancer Cooperative Group. Ann Oncol, 1994. 5(6): p. 
521-6. 
77. 
Baselga, J., et al., Phase II multicenter study of the antiepidermal growth factor receptor 
monoclonal antibody cetuximab in combination with platinum-based chemotherapy in 
patients with platinum-refractory metastatic and/or recurrent squamous cell carcinoma 
of the head and neck. J Clin Oncol, 2005. 23(24): p. 5568-77. 
78. 
Herbst, R.S., et al., Phase II multicenter study of the epidermal growth factor receptor 
antibody cetuximab and cisplatin for recurrent and refractory squamous cell carcinoma 
of the head and neck. J Clin Oncol, 2005. 23(24): p. 5578-87. 
79. 
Leon, X., et al., A retrospective analysis of the outcome of patients with recurrent and/or 
metastatic squamous cell carcinoma of the head and neck refractory to a platinum-based 
chemotherapy. Clin Oncol (R Coll Radiol), 2005. 17(6): p. 418-24. 
80. 
Machiels, J.P., et al., Afatinib versus methotrexate as second-line treatment in patients 
with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing 
on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised 
phase 3 trial. Lancet Oncol, 2015. 16(5): p. 583-94. 
81. 
Saloura, V., et al., An open-label single-arm, phase II trial of zalutumumab, a human 
monoclonal anti-EGFR antibody, in patients with platinum-refractory squamous cell 
carcinoma of the head and neck. Cancer Chemother Pharmacol, 2014. 73(6): p. 1227-39. 
82. 
Ferris, R.L., et al., Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and 
Neck. N Engl J Med, 2016. 375(19): p. 1856-1867. 
83. 
El-Naggar, A.K. and W.H. Westra, p16 expression as a surrogate marker for HPV-
related oropharyngeal carcinoma: a guide for interpretative relevance and consistency. 
Head Neck, 2012. 34(4): p. 459-61. 

Abbreviated Title: STAT Trial 
Version Date: 08/17/2022 
 
123 
84. 
Marur, S., et al., HPV-associated head and neck cancer: a virus-related cancer epidemic. 
Lancet Oncol, 2010. 11(8): p. 781-9. 
85. 
Lydiatt, W.M., et al., Head and Neck cancers-major changes in the American Joint 
Committee on cancer eighth edition cancer staging manual. CA Cancer J Clin, 2017. 
67(2): p. 122-137. 
86. 
Chaturvedi, A.K., et al., Human papillomavirus and rising oropharyngeal cancer 
incidence in the United States. J Clin Oncol, 2011. 29(32): p. 4294-301. 
87. 
Seiwert, T.Y., et al., Safety and clinical activity of pembrolizumab for treatment of 
recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): 
an open-label, multicentre, phase 1b trial. Lancet Oncol, 2016. 17(7): p. 956-965. 
88. 
Bauml, J., et al., Pembrolizumab for Platinum- and Cetuximab-Refractory Head and 
Neck Cancer: Results From a Single-Arm, Phase II Study. J Clin Oncol, 2017. 35(14): p. 
1542-1549. 
89. 
Wolff, A.C., et al., Recommendations for human epidermal growth factor receptor 2 
testing in breast cancer: American Society of Clinical Oncology/College of American 
Pathologists clinical practice guideline update. Arch Pathol Lab Med, 2014. 138(2): p. 
241-56. 
90. 
Fakhry, C., C. Lacchetti, and B. Perez-Ordonez, Human Papillomavirus Testing in Head 
and Neck Carcinomas: ASCO Clinical Practice Guideline Endorsement Summary of the 
CAP Guideline. J Oncol Pract, 2018. 14(10): p. 613-617. 
91. 
Michot, J.M., et al., Immune-related adverse events with immune checkpoint blockade: a 
comprehensive review. Eur J Cancer, 2016. 54: p. 139-148. 
92. 
Strauss, J., et al., Bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and 
PD-L1, in patients with human papillomavirus-associated malignancies. J Immunother 
Cancer, 2020. 8(2). 
93. 
Eisenhauer, E.A., et al., New response evaluation criteria in solid tumours: revised 
RECIST guideline (version 1.1). Eur J Cancer, 2009. 45(2): p. 228-47. 
94. 
Scher, H.I., et al., Design and end points of clinical trials for patients with progressive 
prostate cancer and castrate levels of testosterone: recommendations of the Prostate 
Cancer Clinical Trials Working Group. J Clin Oncol, 2008. 26(7): p. 1148-59. 
95. 
Rustin, G.J., et al., Re: New guidelines to evaluate the response to treatment in solid 
tumors (ovarian cancer). J Natl Cancer Inst, 2004. 96(6): p. 487-8. 
96. 
Bubley, G.J., et al., Eligibility and response guidelines for phase II clinical trials in 
androgen-independent prostate cancer: recommendations from the Prostate-Specific 
Antigen Working Group. J Clin Oncol, 1999. 17(11): p. 3461-7. 
97. 
Vergote, I., et al., Re: new guidelines to evaluate the response to treatment in solid 
tumors [ovarian cancer]. Gynecologic Cancer Intergroup. J Natl Cancer Inst, 2000. 
92(18): p. 1534-5. 
98. 
Seymour, L., et al., iRECIST: guidelines for response criteria for use in trials testing 
immunotherapeutics. Lancet Oncol, 2017. 18(3): p. e143-e152. 

Abbreviated Title: STAT Trial 
Version Date: 08/17/2022 
 
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99. 
Simon, R., Controlled Clinical Trials. 1989. p. 1-10. 
16 APPENDICES 
16.1 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. 
 

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16.2 APPENDIX B: DRUGS KNOWN TO SIGNIFICANTLY PROLONG THE QTC* 
Generic Name* 
 
 
 
Brand Name* 
Aclarubicin 
 
 
 
 
Aclacin and others 
Amiodarone  
 
 
 
Cordarone and others 
Anagrelide 
 
 
 
 
Agrylin and others 
Arsenic trioxide 
 
 
 
Trisenox 
Astemizole 
 
 
 
 
Hismanal 
Azithromycin  
 
 
 
Zithromax and others 
Bepridil 
 
 
 
 
Vascor 
Chloroquine  
 
 
 
Aralen 
Chlorpromazine 
 
 
 
Thorazine and others 
Cilostazol 
 
 
 
 
Pletal 
Ciprofloxacin  
 
 
 
Cipro and others 
Cisapride 
 
 
 
 
Propulsid 
Citalopram 
 
 
 
 
Celexa and others 
Clarithromycin 
 
 
 
Biaxin and others 
Cocaine 
 
 
 
 
Cocaine 
Disopyramide  
 
 
 
Norpace 
Dofetilide 
 
 
 
 
Tikosyn 
Domperidone  
 
 
 
Motilium and others 
Donepezil 
 
 
 
 
Aricept 
Dronedarone  
 
 
 
Multaq 
Droperidol 
 
 
 
 
Inapsine and others 
Erythromycin  
 
 
 
E.E.S. and others  
Escitalopram  
 
 
 
Cipralex and others 
Flecainide 
 
 
 
 
Tambocor and others 
Fluconazole 
 
 
 
 
Diflucan and others 
Gatifloxacin  
 
 
 
Tequin 
Grepafloxacin  
 
 
 
Raxar 
Halofantrine  
 
 
 
Halfan 
Generic Name* 
 
 
 
Brand Name* 
Haloperidol 
 
 
 
 
Haldol (US & UK) and others 
Ibogaine 
 
 
 
 
None 
Ibutilide 
 
 
 
 
Corvert 
Levofloxacin  
 
 
 
Levaquin and others 
Levomepromazine (methotrimeprazine) 
Nosinan and others 
Levomethadyl acetate  
 
 
Orlaam 
Levosulpiride  
 
 
 
Lesuride and others 
Mesoridazine  
 
 
 
Serentil 
Methadone 
 
 
 
 
Dolophine and others 
Moxifloxacin  
 
 
 
Avelox and others 
Ondansetron  
 
 
 
Zofran and others 
Oxaliplatin 
 
 
 
 
Eloxatin 
Papaverine HCl (Intracoronary) 
 
None 
Pentamidine (systemic) 
 
 
Pentam 
  

Abbreviated Title: STAT Trial 
Version Date: 08/17/2022 
 
126 
Pimozide 
 
 
 
 
Orap 
Probucol 
 
 
 
 
Lorelco 
Procainamide  
 
 
 
Pronestyl and others 
Propofol 
 
 
 
 
Diprivan and others 
Quinidine 
 
 
 
 
Quinaglute and others 
Roxithromycin 
 
 
 
Rulide and others 
Sevoflurane 
 
 
 
 
Ultane and others 
Sotalol  
 
 
 
 
Betapace and others 
Sparfloxacin  
 
 
 
Zagam 
Sulpiride 
 
 
 
 
Dogmatil and others 
Sultopride 
 
 
 
 
Barnetil and others 
Terfenadine 
 
 
 
 
Seldane 
Terlipressin 
 
 
 
 
Teripress and others 
Terodiline 
 
 
 
 
Micturin and others  
Thioridazine  
 
 
 
Mellaril and others 
Vandetanib 
  
 
 
 
Caprelsa 
* CredibleMeds.org 

Abbreviated Title: STAT Trial 
Version Date: 08/17/2022 
 
127 
 
16.3 APPENDIX C PARTICIPANT’S MEDICATION DIARY ________________________ 
16.3.1 Lead In 
Participant’s ID _________________________ Treatment LEAD IN:_____________________ 
Participant SX-682 Dose:__________________ Treatment Dates:______________________  
INSTRUCTIONS TO THE PARTICIPANT: 
1. Complete this form for two-week period on the trial.  
2. You will take SX-682 twice a day for every day of two-week period. This drug should be 
taken in a fasting state, meaning no food 2 hours prior to taking the drug and no food 1 
hour after taking the drug.  
3. Record the date, the number of tablets that you took, and when you took them. 
4. If you have any comments or notice any side effects, please record them in the 
comment’s column. 
5. Please bring this form and your bottles (even it is empty) when you come for your clinic 
visit. 
Day 
Date 
Oral SX-682 (every 12 hours) 
Comments 
(Side effects, reason for missing  
dose, etc) 
Morning Dose 
Evening Dose 
Time 
# Tablets Time 
# Tablets  
-14L  
 
 
 
 
 
-13L  
 
 
 
 
 
-12L  
 
 
 
 
 
-11L  
 
 
 
 
 
-10L  
 
 
 
 
 
-9L 
 
 
 
 
 
 
-8L 
 
 
 
 
 
 
-7L 
 
 
 
 
 
 
-6L 
 
 
 
 
 
 
-5L 
 
 
 
 
 
 
-4L 
 
 
 
 
 
 
-3L 
 
 
 
 
 
 
-2L 
 
 
 
 
 
 
-1L 
 
 
 
 
 
 
Participant’s signature:  ___________________________________________________ 

Abbreviated Title: STAT Trial 
Version Date: 08/17/2022 
 
128 
 
16.3.2 Cycles 
Participant’s ID _________________________ Treatment Cycle:_____________________ 
Participant SX-682 Dose:__________________ Treatment Dates:______________________  
INSTRUCTIONS TO THE PARTICIPANT: 
1. Complete one form for each cycle on the trial.  
2. You will take SX-682 twice a day for every day of the cycle. This drug should be taken 
in a fasting state, meaning no food 2 hours prior to taking the drug and no food 1 hour 
after taking the drug.  
3. Record the date, the number of tablets that you took, and when you took them. 
4. If you have any comments or notice any side effects, please record them in the 
comment’s column. 
5. Please bring this form and your bottles (even it is empty) when you come for your clinic 
visit. 
Day 
Date 
Oral SX-682 (every 12 hours) 
Comments 
(Side effects, reason for missing  
dose, etc) 
Morning Dose 
Evening Dose 
Time 
# Tablets 
Time 
# Tablets 
 
1 
 
 
 
 
 
 
2 
 
 
 
 
 
 
3 
 
 
 
 
 
 
4 
 
 
 
 
 
 
5 
 
 
 
 
 
 
6 
 
 
 
 
 
 
7 
 
 
 
 
 
 
8 
 
 
 
 
 
 
9 
 
 
 
 
 
 
10 
 
 
 
 
 
 
11 
 
 
 
 
 
 
12 
 
 
 
 
 
 
13 
 
 
 
 
 
 
14 
 
 
 
 
 
 
15 
 
 
 
 
 
 
16 
 
 
 
 
 
 
17 
 
 
 
 
 
 
18 
 
 
 
 
 
 
19 
 
 
 
 
 
 
20 
 
 
 
 
 
 
21 
 
 
 
 
 
 
22 
 
 
 
 
 
 
23 
 
 
 
 
 
 
24 
 
 
 
 
 
 

Abbreviated Title: STAT Trial 
Version Date: 08/17/2022 
 
129 
Day 
Date 
Oral SX-682 (every 12 hours) 
Comments 
(Side effects, reason for missing  
dose, etc) 
Morning Dose 
Evening Dose 
Time 
# Tablets 
Time 
# Tablets 
 
25 
 
 
 
 
 
 
26 
 
 
 
 
 
 
27 
 
 
 
 
 
 
28 
 
 
 
 
 
 
Participant’s signature: ___________________________________________________