A PHASE 1 STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF ESCALATING DOSES AND TREATMENT INTENSIFICATION OF A VACCINE-BASED IMMUNOTHERAPY REGIMEN-2 (VBIR-2) (PF-06936308) FOR ADVANCED NON-SMALL CELL LUNG CANCER AND METASTATIC TRIPLE-NEGATIVE BREAST CANCER
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer, Triple-negative Breast Cancer
Sponsor: Pfizer

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A PHASE 1 STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS, AND 
PHARMACODYNAMICS OF ESCALATING DOSES AND TREATMENT 
INTENSIFICATION OF A VACCINE-BASED IMMUNOTHERAPY REGIMEN-2 
(VBIR-2) (PF-06936308) FOR ADVANCED NON-SMALL CELL LUNG CANCER 
AND METASTATIC TRIPLE-NEGATIVE BREAST CANCER 
Investigational Product Number:
PF-06936308
Investigational Product Name:
Not Applicable (N/A)
United States (US) Investigational New 
Drug (IND) Number:
European Clinical Trials Database 
(EudraCT) Number:
N/A
Protocol Number:
C3621001
Phase:
1
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) or 
use it for unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified.
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Document History
Document
Version Date
Summary of Changes and Rationale
Amendment 2 
22 Dec 2020
Overarching rationale for the C3621001 
Protocol Amendment 2: Part 1 has been 
completed.  Part 2 – Dose Expansion will 
evaluate the safety and preliminary anti-
tumor activity of VBIR-2 at RP2D in 
participants with NSCLC.  The entire 
protocol has been updated accordingly.
Rationale: Based on the following strategic 
reasons, the Sponsor has decided to focus 
on NSCLC and remove TNBC as a study 
population in Dose Expansion:
a. NSCLC is known to be immuno-
responsive (“Hot” tumor) and may 
remain so in the relapsed setting;
b. More efficient use of resources in a 
population of significantly larger 
prevalence, hence greater unmet 
medical need.
PF-06801591 was changed to sasanlimab 
throughout the document. 
Rationale: Sasanlimab non-proprietary 
name was assigned to PF-06801591.   
Section SOA: Schedule of assessments for 
the treatment period, maintenance period 
and PK in Part 2 were added.  
Rationale: Part 2 (Dose Expansion) was 
added to the study. 

Section SOA: PBMC collection during 
the maintenance period was updated.
Rationale: PBMC collection was updated 
to align with other blood collections.
Section 1.2: Background, Section 1.3 
VBIR2, Section 1.6 Dose Rationale, and 
Section 1.6: Clinical overview were 
updated. 

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Rationale: New information has become 
available. 
• Section 2. Part 1 Objectives and Endpoints 
were updated.  Part 2 Objectives and 
Endpoints were added. 
Rationale: Part 2 (Dose Expansion) of the 
study differ from Part 1. 
• Section 4.1.2 New section: Part 2 
Inclusion Criteria were added.  
Rationale: Population in Part 2 is 
different from Part 1
• Section 4.2.2 New section: Part 2 
Exclusion Criteria were added.  
Rationale: Population in Part 2 is 
different from Part 1
•
Section 5.4.5 Dose reductions was 
updated to include guidance for Part 2.
Rationale: Information from Part 1 was 
use to include guidance for dose 
reductions in Part 2.
 
 
• Section 9.3 Sample size determination; 
Part 2 sample size added.
Rationale: The Part 2 sample size was 
determined non-quantitatively, based on 
typical sample sizes needed for accurate 
statistical prediction of Early Signals of 
Efficacy in the Expansion Cohort.  
• Section 9.4 Efficacy analysis: Clinical 
Benefit Rate (CBR) endpoint added
Rationale: CBR is used in trials using 
immunotherapy.
•
Appendix 4 irRECIST was removed.
Rationale: irRECIST criteria will no 
longer be used.
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
Appendix 7: New section: Alternative 
Measures During Public Emergencies
Rationale: Instructions to address 
COVID-19 related study issues. 
Amendment 1
7 May 2020
Section 1.5 Clinical Overview added.
Rationale: New clinical information from 
the April 2020 PF-06936308 IB (VBIR-2: 
Adenovirus, plasmid DNA and anti-
CTLA4 tremelimumab).
Section 1.6.4.1 Updated PF-06801591 
(anti-PD1) clinical information.
Rationale: New clinical information from 
the October 2019 PF-06801591 (anti-
PD1) IB.
Section 1.6.4.2 Updated VBIR PrCa 
PF-06753512 IB (VBIR PrCa: 
Adenovirus, plasmid DNA and anti-
CTLA4 tremelimumab) and B7791001 
clinical information, including risk of 
myocarditis. 
Rationale: New clinical information from 
the January 2020 VBIR PF-06753512 IB 
(VBIR PrCa: Adenovirus, plasmid DNA 
and anti-CTLA4 tremelimumab) and 
safety reports has been incorporated.
Cardiac troponin I testing was added at 
screening and during treatment (SOA and 
Section 7.1.9).
Rationale: Cardiac monitoring to mitigate 
the potential risk of myocarditis. 
Section 4.2 Exclusion Criteria 1 (brain 
metastases) and 8 (HIV+ participants) 
were updated.
Rationale: Incorporating language from 
the 17Sep2018 and 13May2019 Protocol 
Administrative Change Letters. 
Section 4.2 Exclusion criterion for 
COVID-19/SARS-CoV2 infection added. 

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Rationale: Guidance regarding 
COVID-19/SARS-CoV2 infection was 
required.  
Section 5.4.3 Added recommendations for 
dose interruptions/delays due to 
Non-related Adverse Events.
Rationale: Dose interruptions due to 
reasons other than treatment-related 
toxicity include guidance for 
COVID-19/SARS-CoV2 infection.
Section 5.4.3.3 Dose Modifications: 
Added treatment discontinuation for 
myocarditis of any grade and Grade ≥3 
colitis or diarrhea.
Rationale: Based on emerging safety 
information, additional discontinuation 
criteria for potential new adverse events.
Original protocol
16-March-2018
Not applicable (N/A)
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and IRBs/ ECs.

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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................12
LIST OF FIGURES .................................................................................................................13
APPENDICES .........................................................................................................................13
SCHEDULE OF ACTIVITIES................................................................................................14
1. INTRODUCTION ...............................................................................................................39
1.1. Mechanism of Action/Indication.............................................................................39
1.2. Background and Rationale ......................................................................................39
1.2.1. Non-Small Cell Lung Cancer Treatment Overview ...................................40
1.3. VBIR-2....................................................................................................................43
1.3.1. Rationale for the Components of VBIR-2..................................................43
1.3.2. Selection of Vaccine Antigens (MUC1, MSLN, TERT)............................44
1.4. Nonclinical Safety...................................................................................................47
1.4.1. Nonclinical Toxicity Study for VBIR-2 .....................................................47
1.5. Clinical Overview ...................................................................................................49
1.6. Dose Rationale ........................................................................................................49
1.6.1. Clinical AdC68 (PF-06871923) Dosing.....................................................49
1.6.2. Clinical pDNA (PF-0681925) Dosing........................................................50
1.6.3. Clinical Tremelimumab (PF-06753388) Dosing........................................50
1.6.4. Clinical Sasanlimab Dosing........................................................................51
1.6.4.1. Sasanlimab Clinical Experience B8011001 
(NCT02573259) ................................................................................51
1.6.4.2. Sasanlimab Clinical Experience in B7791001 
(NCT#02616185) ..............................................................................52
1.6.5. Combination of CTLA-4 and PD-1 Monoclonal Antibodies: Safety 
Findings............................................................................................................53
1.6.6. Clinical Dosing VBIR-2 .............................................................................54
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................56
2.1. Part 1: Dose Escalation Objectives and Endpoints .................................................56
2.2. Part 2: Dose Expansion Objectives and Endpoints .................................................57
3. STUDY DESIGN.................................................................................................................58
3.1. Study Overview.......................................................................................................58

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3.1.1. Criteria for Dose Escalation........................................................................59
3.1.2. Dose Expansion (Part 2).............................................................................60
3.2. DLT Definition........................................................................................................62
3.3. MTD Definition.......................................................................................................63
3.4. Toxicities Observed in the Expansion Phase ..........................................................63
3.5. Recommended Part 2 Expansion Dose Definition..................................................63
4. PARTICIPANT ELIGIBILITY CRITERIA........................................................................63
4.1. Inclusion Criteria.....................................................................................................64
4.1.1. Part 1 Inclusion Criteria..............................................................................64
4.1.2. Part 2 Inclusion Criteria..............................................................................65
4.2. Part 1 Exclusion Criteria .........................................................................................67
4.2.1. Part 1 Exclusion Criteria.............................................................................67
4.2.2. Part 2 Exclusion Criteria.............................................................................71
4.3. Lifestyle Requirements (Part 1 and Part 2) .............................................................74
4.4. Sponsor’s Qualified Medical Personnel..................................................................75
5. STUDY TREATMENTS.....................................................................................................75
5.1. Allocation to Treatment ..........................................................................................76
5.2. Participant Compliance ...........................................................................................76
5.3. Investigational Product Supplies.............................................................................77
5.3.1. Dosage Form(s) and Packaging..................................................................77
5.3.2. Preparation and Dispensing........................................................................78
5.4. Administration.........................................................................................................78
5.4.1. Recommended Dose Modifications............................................................79
5.4.2. Dosing Interruptions/Delays due to Treatment Related Toxicity...............80
5.4.3. If these conditions are met within 2 weeks of treatment interruption 
or cycle delay, investigational product(s) may be resumed.  Refer to 
section Dosing Interruptions/Delays due to Non-Related Events....................80
5.4.4. Dosing Interruptions/Delays due to Non-Related Events...........................81
5.4.5. Dose Reductions .........................................................................................81
5.4.5.1. AdC68 Dose Reductions ...........................................................82
5.4.5.2. Tremelimumab Dose Reductions..............................................82
5.4.5.3. Sasanlimab Dose Reductions ....................................................83

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5.5. Investigational Product Storage ..............................................................................85
5.6. Investigational Product Accountability...................................................................86
5.6.1. Destruction of Investigational Product Supplies ........................................86
5.7. Concomitant Treatment(s).......................................................................................87
5.7.1. Prohibited Concomitant Vaccines ..............................................................87
5.7.2. Other Anti-tumor/Anti-Cancer or Experimental Drugs..............................87
5.7.3. Supportive Care ..........................................................................................87
5.7.4. Hematopoietic Growth Factors...................................................................87
5.7.5. Anti-Diarrheal, Anti-Emetic Therapy.........................................................88
5.7.6. Anti-Inflammatory Therapy........................................................................88
5.7.7. Corticosteroids............................................................................................88
5.7.8. Surgery........................................................................................................88
6. STUDY PROCEDURES .....................................................................................................88
6.1. Screening.................................................................................................................88
6.2. Study Period ............................................................................................................88
6.3. End of Treatment.....................................................................................................88
6.4. Follow-up ................................................................................................................89
6.5. Survival Follow-up..................................................................................................89
6.6. Participant Withdrawal............................................................................................89
7. ASSESSMENTS..................................................................................................................91
7.1. Safety Assessment...................................................................................................91
7.1.1. Pregnancy Testing ......................................................................................91
7.1.2. Adverse Events...........................................................................................92
7.1.3. Laboratory Safety Assessment ...................................................................92
7.1.4. Vital Signs and Physical Examination........................................................93
7.1.5. (12-Lead) Electrocardiogram......................................................................94
7.1.6. Monitoring for Potential Immune Mediated Endocrinopathies..................95
7.1.7. Acetylcholine Receptor Testing .................................................................95
7.1.8. Cardiac Safety Monitoring .........................................................................95
7.2. Pharmacokinetics Assessments...............................................................................96
7.2.1. Serum for Assessment of Tremelimumab Pharmacokinetics.....................96

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7.2.2. Serum for Assessment of Sasanlimab Pharmacokinetics...........................97
7.4. Tumor Response Assessments ..............................................................................100
7.5. Tremelimumab and Sasanlimab Immunogenicity Assessments ...........................101
7.7. Other Assessments ................................................................................................103
7.7.1. Tumor and Medical History......................................................................103
8. ADVERSE EVENT REPORTING....................................................................................103
8.1. Requirements.........................................................................................................103
8.1.1. Additional Details On Recording Adverse Events on the CRF................105
8.1.2. Eliciting Adverse Event Information........................................................105
8.1.3. Withdrawal From the Study Due to Adverse Events (see also the 
Participant Withdrawal Section)....................................................................105
8.1.4. Time Period for Collecting AE/SAE Information....................................105
8.1.4.1. Reporting SAEs to Pfizer Safety.............................................105
8.1.4.2. Recording Non-serious AEs and SAEs on the CRF ...............106
8.1.5. Causality Assessment ...............................................................................106
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities ................106
8.2. Definitions.............................................................................................................107
8.2.1. Adverse Events.........................................................................................107
8.2.2. Abnormal Test Findings ...........................................................................108
8.2.3. Serious Adverse Events ............................................................................108
8.2.4. Hospitalization..........................................................................................109
8.3. Severity Assessment..............................................................................................111
8.4. Special Situations ..................................................................................................111
8.4.1. Potential Cases of Drug-Induced Liver Injury..........................................111
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8.4.2. Exposure to the Investigational Product During Pregnancy or 
Breastfeeding, and Occupational Exposure...................................................113
8.4.2.1. Exposure During Pregnancy (EDP) ........................................113
8.4.2.2. Exposure During Breastfeeding ..............................................114
8.4.2.3. Occupational Exposure ...........................................................114
8.4.3. Medication Errors .....................................................................................115
8.4.3.1. Medication Errors....................................................................115
8.5. Medical Device Complaint Reporting Requirements ...........................................115
9. DATA ANALYSIS/STATISTICAL METHODS.............................................................116
9.1. Analysis Sets .........................................................................................................116
9.2. Statistical Methods and Properties ........................................................................117
9.2.1. Statistical Methods for Dose Escalation/De-Escalation ...........................117
9.2.2. Statistical Method for Estimating the MTD .............................................118
9.3. Sample Size Determination...................................................................................118
9.4. Efficacy Analysis ..................................................................................................119
9.5. Safety Analysis......................................................................................................120
9.5.1. Analysis of Primary Endpoint ..................................................................120
9.5.2. Analysis of Secondary Endpoints.............................................................120
9.5.3. ECG ..........................................................................................................120
9.6. Analysis of Pharmacokinetics 
........................................121
9.6.1. Analysis of Pharmacokinetics...................................................................121
9.6.1.1. Tremelimumab Pharmacokinetic Analysis .............................121
9.6.1.2. Sasanlimab Pharmacokinetic Analysis....................................122
9.6.3. Analysis of Immunogenicity Data............................................................122
9.6.4. Population Pharmacokinetic Analysis or 
Pharmacokinetic
 (PK/
Modeling ..............................123
9.7. Data Monitoring Committee .................................................................................123
10. QUALITY CONTROL AND QUALITY ASSURANCE...............................................123
11. DATA HANDLING AND RECORD KEEPING ...........................................................123
11.1. Case Report Forms/Electronic Data Record .......................................................123
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11.2. Record Retention.................................................................................................124
12. ETHICS............................................................................................................................125
12.1. Institutional Review Board/Ethics Committee....................................................125
12.2. Ethical Conduct of the Study ..............................................................................125
12.3. Participant Information and Consent...................................................................125
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP .........................................................................................................................126
13. DEFINITION OF END OF TRIAL.................................................................................127
13.1. End of Trial in All Participating Countries .........................................................127
13.2. End of trial is Defined as Last Subject Last Visit (LSLV)..................................127
14. SPONSOR DISCONTINUATION CRITERIA ..............................................................127
15. PUBLICATION OF STUDY RESULTS........................................................................127
15.1. Communication of Results by Pfizer ..................................................................127
15.2. Publications by Investigators ..............................................................................128
16. REFERENCES ................................................................................................................130

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LIST OF TABLES
Table 1.
PD-1 and PD-L1 expression in breast cancers, according to the 
molecular subtype79 ..................................................................................42
Table 2.
Expansion Phase Components, Dosage, Dosage Form, Route of 
Administration, and Dosing Regimen of the Vaccine-Based 
Immunotherapy Regimen for NSCLC (See Section 5 for detailed 
Study Treatment instructions.)..................................................................55
Table 3.
Decision Rules..........................................................................................59
Table 4.
AdC68 Available Dose Levels (Part 1) ....................................................82
Table 5.
AdC68 Available Dose Levels (Part 2) ....................................................82
Table 6.
Dose Modifications for AdC68 Related Toxicity.....................................82
Table 7.
Tremelimumab Available Dose Levels (Part 1) .......................................83
Table 8.
Tremelimumab Available Dose Levels (Part 2) .......................................83
Table 9.
Dose Modifications for Tremelimumab Related Toxicity When 
Given in Combination with AdC68 and pDNA .......................................83
Table 10.
Sasanlimab Available Dose Levels (Part 1) .............................................84
Table 11.
Sasanlimab Available Dose Levels (Part 2) .............................................84
Table 12.
Dose Modifications for Sasanlimab and/or Tremelimumab  Related 
Toxicity.....................................................................................................85
Table 13.
Safety Laboratory Tests............................................................................92
Table 14.
Requirements for Recording Safety Events on the Case Report 
Form (CRF) and Reporting Safety Events on the Clinical Trial 
Serious Adverse Events Form ................................................................104
Table 15.
Clinical Description of Severity .............................................................111
Table 16.
Medication Errors Reporting on the Clinical Trial Serious Adverse 
Event Form .............................................................................................115
Table 17.
Objective Response Status at each Evaluation.......................................154
Table 18.
Objective Response Status at each Evaluation for Participants  with 
Non-Target Disease Only .......................................................................154

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LIST OF FIGURES
Figure 1.
Study Design.............................................................................................61
Figure 2.
Cardiac Safety Monitoring Algorithm......................................................96
APPENDICES
Appendix 1. Abbreviations....................................................................................................142
Appendix 2. ECOG Performance Status................................................................................149
Appendix 3. RECIST (Response Evaluation Criteria In Solid Tumors) version 
1.1 Guidelines.........................................................................................150
Appendix 4. National Cancer Institute (NCI) Common Terminology Criteria for 
Adverse Events (CTCAE) ......................................................................155
Appendix 5. Management of Immune-related Adverse Events (irAEs)................................156
Appendix 6. Recommended Management Algorithm for Myasthenia Gravis ......................162
Appendix 7. Alternative Measures During Public Emergencies ...........................................163

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SCHEDULE OF ACTIVITIES
The schedule of activities table provides an overview of the protocol visits and procedures.  Refer to the ASSESSMENTS section of 
the protocol for detailed information on each assessment required for compliance with the protocol.
The investigator may schedule visits (unplanned visits) in addition to those listed in the schedule of activities table in order to conduct 
evaluations or assessments required to protect the well-being of the participant.
SCHEDULE OF ACTIVITIES FOR DOSE ESCALATION (PART 1) 
Protocol Activity
Screen
1
(£28 
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2
End of 
Treatment
33
Follow- Up
(Months after EOT visit)
Survival
Follow-up35
Study Day
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
43
Day 
57
Day 
71
Day 
85
Day 
113
Month 134 Month 2
Month 4
Month 6
Post 6-Month 
Follow-up
Cycle Day
Day 
1
Da
y 
29
Day 
57
Da
y 
85
Day 
99
28 to 35 
days
Every 3 Months
Visit Window 
(Days)*
±1
±2
±2
±2
±4
±2
±4
±2
±2
±2
±2
±2
±4
±4
±4
±4
±10
Informed consent2
X
Tumor history3
X
 
 
 
 
 
Medical history7
X
Complete physical 
examination8
X
X
Abbreviated 
physical 
examination8
X
X
X
X
X
X
X
X
X
X
X
X
X
Assessment of skin 
thickness at 
administration sites9
X
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Protocol Activity
Screen
1
(£28 
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2
End of 
Treatment
33
Follow- Up
(Months after EOT visit)
Survival
Follow-up35
Study Day
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
43
Day 
57
Day 
71
Day 
85
Day 
113
Month 134 Month 2
Month 4
Month 6
Post 6-Month 
Follow-up
Cycle Day
Day 
1
Da
y 
29
Day 
57
Da
y 
85
Day 
99
28 to 35 
days
Every 3 Months
Visit Window 
(Days)*
±1
±2
±2
±2
±4
±2
±4
±2
±2
±2
±2
±2
±4
±4
±4
±4
±10
Height
X
Weight
X
X
X
X
Vital signs10
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Performance status11
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory
Unique Screening 
Labs12
X
Hematology13
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Chemistry14
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Coagulation15
X
X
X
X
X
X
X
Cardiac Troponin-I 
(cTnI)16
X
X
X
X
X
Urinalysis17
X
X
X
X
X
X
X
X
X
X
X
Pregnancy Test or 
FSH Level 
(Serum)18
X
X
X
X
X
X
X
X
X
X
X
Contraception 
Check19
X
X
X
X
X
X
X
X
X
X
X
X
X
X
(12 lead) ECG20
X
X
X
X
X
X
X
Registration 
Registration21
X
Study Treatment
Adenovirus 
(AdC68) 
administration22
Refer to Part 1 Schedule of Study Treatment, Pharmacokinetics and Immunogenicity Assessments
Plasmid DNA 
(pDNA)
administration22

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Protocol Activity
Screen
1
(£28 
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2
End of 
Treatment
33
Follow- Up
(Months after EOT visit)
Survival
Follow-up35
Study Day
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
43
Day 
57
Day 
71
Day 
85
Day 
113
Month 134 Month 2
Month 4
Month 6
Post 6-Month 
Follow-up
Cycle Day
Day 
1
Da
y 
29
Day 
57
Da
y 
85
Day 
99
28 to 35 
days
Every 3 Months
Visit Window 
(Days)*
±1
±2
±2
±2
±4
±2
±4
±2
±2
±2
±2
±2
±4
±4
±4
±4
±10
Tremelimumab 
administration –For 
cohorts assigned to 
receive 
tremelimumab22
Sasanlimab 
administration –For 
cohorts assigned to 
receive sasanlimab22
Tumor Assessment
CT scan, MRI scan 
or bone scan23
X
Performed every 8 weeks up to Week 3223
Other samplings
 
AChR antibody25
X
 
 
 
ER, PR, HER2 
Status30
X
Pharmacokinetics 
and Tremelimumab 
ADA
Refer to Part 1 Schedule of Study Treatment, Pharmacokinetics and Immunogenicity Assessments
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Protocol Activity
Screen
1
(£28 
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2
End of 
Treatment
33
Follow- Up
(Months after EOT visit)
Survival
Follow-up35
Study Day
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
43
Day 
57
Day 
71
Day 
85
Day 
113
Month 134 Month 2
Month 4
Month 6
Post 6-Month 
Follow-up
Cycle Day
Day 
1
Da
y 
29
Day 
57
Da
y 
85
Day 
99
28 to 35 
days
Every 3 Months
Visit Window 
(Days)*
±1
±2
±2
±2
±4
±2
±4
±2
±2
±2
±2
±2
±4
±4
±4
±4
±10
Pharmacokinetics 
and 
SasanlimabADA
Other clinical 
assessments
Serious and 
non-serious adverse 
event monitoring31
X
Concomitant 
medications and 
non-drug supportive 
interventions32
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Survival 
Follow-up35
X
* Visit windows during the treatment period are to be calculated based on the previous dosing visit.
Abbreviations: Ĭ = ongoing; AChR = acetylcholine receptor; ADA = anti-drug antibodies; AdC68= Adenovirus; AE = adverse events; CRP= C-Reactive Protein; 
CT = computed tomography; 
; ECG = electrocardiogram; EOT = End of Treatment; ER = estrogen receptors; HER2 = human epidermal growth 
factor receptor 2; hsCRP=high sensitivity C-reactive protein; MRI = magnetic resonance imaging; MSLN = mesothelin; MUGA = multigated acquisition scan; PBMC = peripheral 
blood mononuclear cell; pDNA=plasmid deoxyribonucleic acid; PR = progesterone receptors; (X)=Optional 
1.
Screening: To be obtained within 28 days prior to study entry. 
2.
Informed Consent: Must be obtained prior to undergoing any study specific procedures.  May be collected more than 28 days prior to study entry.  As part of the consenting 
process, participants will be informed of the potential occurrence of immune related adverse events and will be provided with a Patient Information Card.
3.
Tumor History: Will be collected within 28 days prior to study entry.  Includes details of primary diagnosis and treatment history. 
 
 
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Page 18
Protocol Activity
Screen
1
(£28 
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2
End of 
Treatment
33
Follow- Up
(Months after EOT visit)
Survival
Follow-up35
Study Day
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
43
Day 
57
Day 
71
Day 
85
Day 
113
Month 134 Month 2
Month 4
Month 6
Post 6-Month 
Follow-up
Cycle Day
Day 
1
Da
y 
29
Day 
57
Da
y 
85
Day 
99
28 to 35 
days
Every 3 Months
Visit Window 
(Days)*
±1
±2
±2
±2
±4
±2
±4
±2
±2
±2
±2
±2
±4
±4
±4
±4
±10
7.
Medical History: Includes history of disease process other than NSCLC and TNBC (active or resolved), smoking history, and significant concurrent illness.  Includes prior 
treatments and any current medical treatment for any condition.
8.
Complete and abbreviated physical examinations: A neurologic examination must be conducted at Screening to look for potential signs of underlying autoimmune 
disorders.  In addition, all abbreviated physical examinations conducted during Cycle 1 must include a neurologic examination.
9.
Assessment of the Skin and Subcutaneous Tissue Thickness: Assessment of the skin and subcutaneous tissue thickness at the eligible administration sites will be 
performed at screening as described in the TDS-IM Instructions for Use.  The assessment procedure does not need to be repeated during the course of the study unless the 
participant experiences a greater than 10% change in body mass relative to screening.
10. Vital signs: Includes temperature, pulse, and blood pressure (BP) to be recorded in the seated position after approximately 5 minutes of rest.  Vitals signs, including 
temperature, pulse, and BP to be recorded 1-hour post-study drug administration during each cycle on days 1, 29, 57, and 85.
11. Performance status: Use Eastern Cooperative Oncology Group (ECOG) – see Appendix 2.
12. Unique Screening Labs: Active and clinically significant bacterial, fungal, or viral infection, including hepatitis B surface antigen, hepatitis B core antibody, hepatitis C 
antibody, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness is exclusionary per Exclusion Criteria #8.  In 
equivocal cases, subjects may be eligible if they have a negative viral load. Samples will be analyzed locally.
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Page 19
Protocol Activity
Screen
1
(£28 
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2
End of 
Treatment
33
Follow- Up
(Months after EOT visit)
Survival
Follow-up35
Study Day
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
43
Day 
57
Day 
71
Day 
85
Day 
113
Month 134 Month 2
Month 4
Month 6
Post 6-Month 
Follow-up
Cycle Day
Day 
1
Da
y 
29
Day 
57
Da
y 
85
Day 
99
28 to 35 
days
Every 3 Months
Visit Window 
(Days)*
±1
±2
±2
±2
±4
±2
±4
±2
±2
±2
±2
±2
±4
±4
±4
±4
±10
13. Hematology: Complete blood count (CBC) to include hemoglobin, platelets, WBC, Absolute neutrophils, absolute lymphocytes, absolute monocytes,absolute eosinophils, 
and absolute basophils.  If baseline assessment was performed within 72 hours of Cycle 1 Day 1, repeat is not required.  Samples will be analyzed locally. 
14. Blood Chemistry: Should include sodium, potassium, total chloride, bicarbonate or carbon dioxide, BUN (or urea), uric acid, creatinine, glucose (non-fasted), total calcium, 
magnesium, phosphorous and phosphate, albumin, total protein, aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), alkaline phosphatase, total 
bilirubin, amylase, lipase, lactate dehydrogenase (LDH), and TSH + reflex free T4 and free T3.  If baseline assessment was performed within 72 hours of Cycle 1 Day 1, 
repeat is not required.  Samples will be analyzed locally. 
15. Coagulation: Should include Prothrombin Time (PT) or International Normalized Ratio (INR) and Partial Thromboplastin Time (PTT).  Samples will be analyzed locally.  
16. Cardiac Troponin: For participants undergoing screening, circulating levels of cardiac Troponin-I (cTnI) must be measured and found to be within the normal reference 
range within 28 days before study entry, preferably using the central laboratory kits provided.  See Section 7.1.8 for full details.
17. Urinalysis: Dipstick is acceptable.  Microscopic analyses if dipstick abnormal.  Samples will be analyzed locally.
18. Pregnancy Test or FSH Level (Serum): For female participants of childbearing potential, a serum or urine pregnancy test, with sensitivity of at least 25 mIU/mL and assayed 
in a certified laboratory, will be performed on 2 occasions prior to starting study therapy, once at the start of screening and once at the baseline visit immediately before 
investigational product administration.  Pregnancy tests will also be routinely repeated at Day 1 of every treatment cycle during the active treatment period, at the End of 
Treatment visit, at the 28-day Follow-Up Visit, and additionally whenever one menstrual cycle is missed or when potential pregnancy is otherwise suspected.  Additional 
pregnancy tests may also be undertaken if requested by institutional review board/ethics committee (IRB/ECs) or if required by local regulations.  Participants with confrmed 
positive pregnanct test(s) should not be dosed.  For female participants who achieved postmenopausal status and have not experienced their menses for at least 12 consecutive 
months, a serum FSH test must be conducted at screening only to confirm a FSH level within the laboratory’s reference ranges.
19. Contraception Check: The contraception check is to confirm that contraception, if assigned, is used consistently and correctly.  Male participants who are able to father 
children and female participants who are of childbearing potential will need to affirm that they meet the criteria for correct use of 2 of the selected methods of contraception.  
The investigator or his or her designee will discuss with the participant the need to use 2 highly effective contraception methods consistently and correctly and document such 
conversation in the participant’s chart.  In addition, the investigator or his or her designee will instruct the participant to call immediately if one or both selected contraception 
methods are discontinued, or if pregnancy is known or suspected in the participant or the participant’s partner.
20. 12 leads ECGs: A single ECG will be performed at Screening.  At all other time points, three consecutive 12-lead ECGs will be performed approximately 2 minutes apart to 
determine mean QTcF interval.  If the mean QTcF is prolonged (>500 msec), the ECGs should be re-evaluated by a qualified person at the institution for confirmation.  
Following the end of Cycle 2, triplicate ECGs will be performed at Month 12 Day 1, Month 18 Day 1, and may be performed as clinically indicated. 
21. Registration: Participant number and dose level allocation operated by Pfizer Inc.
22. Investigational Product Administration: Treatment to be administered after all other assessments required on that day have been performed.

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Page 20
Protocol Activity
Screen
1
(£28 
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2
End of 
Treatment
33
Follow- Up
(Months after EOT visit)
Survival
Follow-up35
Study Day
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
43
Day 
57
Day 
71
Day 
85
Day 
113
Month 134 Month 2
Month 4
Month 6
Post 6-Month 
Follow-up
Cycle Day
Day 
1
Da
y 
29
Day 
57
Da
y 
85
Day 
99
28 to 35 
days
Every 3 Months
Visit Window 
(Days)*
±1
±2
±2
±2
±4
±2
±4
±2
±2
±2
±2
±2
±4
±4
±4
±4
±10
23. Tumor Assessments: Tumor assessments will include all known or suspected disease sites.  Screening images may be obtained within 5 weeks of registration.  Imaging 
obtained as part of standard of care but within 28 days (-7 days) of registration may be used for screening assessment.  Imaging may include chest, abdomen and pelvis CT or 
MRI scans, and bone scans.  Bone scans will be performed at baseline if disease is suspected and on study as appropriate to follow disease.  Baseline central nervous system 
(CNS) imaging MRI or CT Brain to be conducted only if clinically indicated based on the investigator’s judgement.  CT or MRI scans, as well as bone scans, when indicated, 
are to be done every 8 weeks (±5 days) with the first one to occur 8 weeks after C1D1 Repeat imaging will be completed every 8 weeks up to and including Week 32 or until 
disease progression that requires new treatment modality, permanent discontinuation, or death.  Disease progression will be confirmed with two consecutive timepoints at 
least 4-8 weeks apart in the absence of rapid clinical deterioration.  Tumor assessment should be repeated at the End of Treatment visit if more than 6 weeks have passed since 
the last evaluation. 
25. Acetylcholine receptor (AChR) antibody: Sample to be sent to the central laboratory for analysis.  
 
  The evaluation for AChR antibodies is included to exclude participants who test positive at screening as agreed upon with the 
United States Food and Drug Administration (US FDA) and to confirm requirement for evaluation if myasthenia gravis is suspected.99
 
 
 
 
  
 
30. ER, PR and HER2 Status: Inclusion Criteria 1 (Section 4.1) defines TNBC as HER2 negative by IHC, FISH or CISH, and ō10% ER/PR stain positive.  Results required 
during Screening, prior to participant randomization.
31. Serious and Non-serious Adverse Event Monitoring: Adverse events should be documented and recorded at each visit using the National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI CTC AE) version 5.0.  Participants must be followed for AEs for 6 months after the last study treatment administration or until 
all drug related toxicities have resolved, whichever is later; or earlier than 6 months should the participant commence another anticancer therapy in the meantime.  The time 
period for actively eliciting and collecting AEs and SAEs (“active collection period”) for each participant begins from the time the participant provides informed consent
through and including 6 months after the last study treatment administration or until all drug related toxicities have resolved, whichever is later.  If the participant begins a 
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Page 21
Protocol Activity
Screen
1
(£28 
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2
End of 
Treatment
33
Follow- Up
(Months after EOT visit)
Survival
Follow-up35
Study Day
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
43
Day 
57
Day 
71
Day 
85
Day 
113
Month 134 Month 2
Month 4
Month 6
Post 6-Month 
Follow-up
Cycle Day
Day 
1
Da
y 
29
Day 
57
Da
y 
85
Day 
99
28 to 35 
days
Every 3 Months
Visit Window 
(Days)*
±1
±2
±2
±2
±4
±2
±4
±2
±2
±2
±2
±2
±4
±4
±4
±4
±10
new anticancer therapy, the period for recording non-serious AEs on the CRF ends at the time the new treatment is started.  However, any SAEs occurring during the active 
collection period must still be reported to Pfizer Safety and recorded on the CRF, irrespective of any intervening treatment.
32. Concomitant Treatments: All concomitant medications and non-drug supportive interventions should be recorded in the CRF.
33. End of Treatment Visit: The End of treatment visit will be completed at the time point when a decision is made to discontinue study treatment.  This can occur during 
Cycles 1 or 2 or during the Maintenance Treatment Phase of the study.  Obtain these assessments if not completed in the past two weeks (past 6 weeks for tumor 
assessments).
34. Follow-up: At least 28 days, and no more than 35 days after discontinuation of study treatment, participants will return to complete the required assessments.  Participants 
will then return at Month 2, Month 4 and Month 6 to complete the required assessments.
35. Survival: After treatment discontinuation, participant survival status will be collected every 3 months until death, participant refusal, or lost to follow-up (telephone contact 
acceptable).

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SCHEDULE OF ACTIVITIES FOR MAINTENANCE TREATMENT PERIOD FOR DOSE ESCALATION (PART 1)
Protocol Activity
Maintenance Treatment Period*
Study Month**
Month 9
Month 
10
Month 
11
Month 
12
Month 
13
Month 
14
Month 
15
Month 
16
Month 
17
Month 
18 
Month 
19
Month 
20
Month 
21
Month 22 
and 
every 
month 
thereafte
r
Visit Window (Days)
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
Abbreviated physical 
examination1
X
X
X
X
X
X
X1
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X1
Vital signs2
X
X
X
X
X
X
X
X
X
X
X
X
X
X1
Performance status3
X
X
X
X
X
X
X
X
X
X
X
X
X
X1
Laboratory
Hematology4
X
X
X
X
X
X
X1
Blood Chemistry5
X
X
X
X
X
X
X1
Coagulation6
X
X
X
X11
Cardiac Troponin-I (cTnI)7
X
X
Urinalysis8
X
X
X
X11
Pregnancy Test or FSH Level 
(Serum)9
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Contraception Check10
X
X
X
X
X
X
X
X
X
X
X
X
X
X
(12 lead) ECG12
X
X
X*
Study Treatment
pDNA Administration13
X
X
X
X
X
X
X1
Tremelimumab administration 
for cohorts assigned to receive 
tremelimumab13
X
X
X
X
X
X
X1
Sasanlimab administration for 
cohorts assigned to receive 
sasanlimab13
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Tumor Assessment
CT scan, MRI scan or bone 
scan14
X14
Other Samplings
PK and Tremelimumab ADA
X
X
X
X11
PK and Sasanlimab ADA
X
X
X
X11
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Page 23
Protocol Activity
Maintenance Treatment Period*
Study Month**
Month 9
Month 
10
Month 
11
Month 
12
Month 
13
Month 
14
Month 
15
Month 
16
Month 
17
Month 
18 
Month 
19
Month 
20
Month 
21
Month 22 
and 
every 
month 
thereafte
r
Visit Window (Days)
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
Other clinical assessments
Serious and non-serious adverse 
event monitoring18
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medications and 
non-drug supportive 
interventions19
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Abbreviations: Ĭ = ongoing; ADA = anti-drug antibodies; AdC68= Adenovirus; AE = adverse events; CT = computed tomography; ECG = electrocardiogram; EOT = End of 
Treatment; MRI = magnetic resonance imaging; PBMC = peripheral blood mononuclear cell; pDNA= plasmid deoxyribonucleic acid; SC = Subcutaneous(ly)
* When a decision is made to discontinue study treatment during the Maintenance Treatment Period, the End of Treatment visit assessments should be performed.  The 
participant will then enter the Post Treatment Period of the study.
** Study visit is based on completion of two cycles in the treatment period.  Visit window for the first maintenance treatment visit is to be calculated based on the Cycle 2 Day 85 
dosing date.  The first dose in the maintenance period should occur 28 days after the C2D85 dosing date.  A month is defined as 28 days.
1.
To be assessed every 2 months.
2.
Vital signs: Includes temperature, pulse, and blood pressure (BP) to be recorded in the seated position after approximately 5 minutes of rest.  Vitals signs, including 
temperature, pulse and BP to be recorded 1-hour post-study drug administration during each cycle on days 1, 29, 57, and 85.
3.
Performance status: Use Eastern Cooperative Oncology Group (ECOG) – see Appendix 2.
4.
Hematology: Complete blood count (CBC) to include hemoglobin, platelets, WBC, absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, 
and absolute basophils.  Samples will be analyzed locally.
5.
Blood Chemistry: Should include sodium, potassium, total chloride, bicarbonate or carbon dioxide, BUN (or urea), uric acid, creatinine, glucose, total calcium, magnesium, 
phosphorous and phosphate, albumin, total protein, aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), alkaline phosphatase, total bilirubin, 
amylase, lipase, lactate dehydrogenase (LDH) and TSH + reflex free T4 and free T3.  Samples will be analyzed locally.
6.
Coagulation: Should include Prothrombin Time (PT) or International Normalized Ratio (INR) and Partial Thromboplastin Time (PTT).  Samples will be analyzed locally.
7.
Cardiac Troponin: For participants undergoing screening, circulating levels of cardiac Troponin-I (cTnI) must be measured and found to be within the normal reference 
range within 28 days before study entry, preferably using the central laboratory kits provided.  See Section 7.1.8 for full details. 
8.
Urinalysis: Dipstick is acceptable.  Microscopic analyses if dipstick abnormal.  Samples will be analyzed locally.
9.
Pregnancy Test or FSH Level (Serum): For female participants of childbearing potential, a serum or urine pregnancy test, with sensitivity of at least 25 mIU/mL and assayed 
in a certified laboratory, will be performed on 2 occasions prior to starting study therapy, once at the start of screening and once at the baseline visit immediately before 
investigational product administration.  Pregnancy tests will also be routinely repeated at Day 1 of every treatment cycle during the active treatment period, at the End of 
Treatment visit, at the 28-day Follow-Up Visit, and additionally whenever one menstrual cycle is missed or when potential pregnancy is otherwise suspected.  Additional 
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Protocol Activity
Maintenance Treatment Period*
Study Month**
Month 9
Month 
10
Month 
11
Month 
12
Month 
13
Month 
14
Month 
15
Month 
16
Month 
17
Month 
18 
Month 
19
Month 
20
Month 
21
Month 22 
and 
every 
month 
thereafte
r
Visit Window (Days)
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
pregnancy tests may also be undertaken if requested by institutional review board/ethics committee (IRB/ECs) or if required by local regulations.  Participants with confrmed 
positive pregnanct test(s) should not be dosed.  For female participants who achieved postmenopausal status and have not experienced their menses for at least 12 consecutive 
months, a serum FSH test must be conducted at screening only to confirm a FSH level within the laboratory’s reference ranges.
10. Contraception Check: Male participants who are able to father children and female participants who are of childbearing potential will need to affirm that they meet the 
criteria for correct use of 2 of the selected methods of contraception.  The investigator or his or her designee will discuss with the participant the need to use 2 highly effective 
contraception methods consistently and correctly and document such conversation in the participant’s chart.  In addition, the investigator or his or her designee will instruct 
the participant to call immediately if one or both selected contraception methods are discontinued, or if pregnancy is known or suspected in the participant or the participant’s 
partner.
11. To be assessed every 4 months.
12. Triplicate 12 leads ECGs: At each time point, three consecutive 12 lead ECGs will be performed approximately 2 minutes apart to determine mean QTcF interval.  If the 
mean QTcF is prolonged (>500 msec), the ECGs should be reevaluated by a qualified person at the institution for confirmation.  Additional triplicate ECGs will be performed 
at Month 12 Day 1, Month 18 Day 1, or may be performed as clinically indicated. 
13. Investigational Product Administration: Treatment to be administered after all other assessments required on that day have been performed, including pregnancy test. All 
participants will continue to receive the components to which they were assigned to receive during the treatment period. – note either the tremelimumab or the sasanlimab
may be dose reduced or permanently discontinued after discussion with the Sponsor for participants assigned to receive these components.
14. Tumor Assessments: Tumor assessments will include all known or suspected disease sites.  Imaging may include chest, abdomen and pelvis CT or MRI scans, and bone 
scans.  CT or MRI scans, as well as bone scans, when indicated, are to be done every 12 weeks (±5 days) or when if clinically indicated until disease progression that requires 
new treatment modality, permanent discontinuation, or death.  Disease progression will be confirmed with two consecutive timepoints at least 4-8 weeks apart in the absence 
of rapid clinical deterioration.  
 
  
 
18. Serious and Non-serious Adverse Event Monitoring: Adverse events should be documented and recorded at each visit using the National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI CTC AE) version 5.0.  Participants must be followed for AEs for 6 months after the last study treatment administration or until 
all drug related toxicities have resolved, whichever is later; or earlier than 6 months should the participant commence another anticancer therapy in the meantime.  The time 
period for actively eliciting and collecting AEs and SAEs (“active collection period”) for each participant begins from the time the participant provides informed consent 
through and including 6 months after the last study treatment administration or until all drug related toxicities have resolved, whichever is later.  If the participant begins a 
new anticancer therapy, the period for recording non-serious AEs on the CRF ends at the time the new treatment is started.  However, any SAEs occurring during the active 
collection period must still be reported to Pfizer Safety and recorded on the CRF, irrespective of any intervening treatment.
19. Concomitant Treatments: All concomitant medications and non-drug supportive interventions should be recorded in the CRF.
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Page 25
Schedule of Study Treatment, Pharmacokinetics, Tremelimumab and Sasanlimab Immunogenicity Assessments (Part 1) 
Protocol Activity Screen
(£28 
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2 
End of 
Treatment
Follow- Up
(Months after EOT visit)
Study Day
Day
1
Day
3 -6
Day
8
Day 15Day 22Day 29Day 43Day 57Day 71Day 85 Day 
113
M1
M2
M4
M6
Cycle Day
Day 
1
Day 
29
Day 
57
Day 
85
Day 
99
28-35 
days
Visit Window 
(hours)
±24 hr ±48 hr ±48 hr
Visit Window 
(days)
±2
±4
±2
±4
±2
±2
±2
±2
±2
±4
±4
±4
±4
Study Treatment
AdC681 – all 
participants
X
X
pDNA2 – all 
participants
X
X
X
X
X
X
Tremelimumab3 –
for cohorts 
assigned to 
receive 
tremelimumab
X
X
X
X
X
X
X
X
Sasanlimab 4 – for 
cohorts assigned 
to receive 
sasanlimab
X
X
X
X
X
X
X
X
Pharmacokinetic
s 
Immunogenicity
PK for 
tremelimumab5
X
X6
X6
X6
X6
X
X
X
X
X
X
X
X
X
ADA for 
tremelimumab5
X
X
X
X
X
X
X
X
PK for 
sasanlimab6
X
X8
X8
X8
X8
X
X
X
X
X
X
X
X
X
ADA 
forsasanlimab7
X
X
X
X
X
X
X
X

PF-06936308
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PFIZER CONFIDENTIAL
Page 26
Protocol Activity Screen
(£28 
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2 
End of 
Treatment
Follow- Up
(Months after EOT visit)
Study Day
Day
1
Day
3 -6
Day
8
Day 15Day 22Day 29Day 43Day 57Day 71Day 85 Day 
113
M1
M2
M4
M6
Cycle Day
Day 
1
Day 
29
Day 
57
Day 
85
Day 
99
28-35 
days
Visit Window 
(hours)
±24 hr ±48 hr ±48 hr
Visit Window 
(days)
±2
±4
±2
±4
±2
±2
±2
±2
±2
±4
±4
±4
±4
Study Treatment
Abbreviations: ADA = Anti-drug antibody; Adenovirus (AdC68); EOT = End of Treatment; pDNA = Plasmid deoxyribonucleic acid, PK = Pharmacokinetics 
1.
Adenovirus (AdC68) will be administered intramuscularly on Cycle 1 Day 1 and Cycle 2 Day 1.  Tremelimumab and sasanlimab will be administered after the adenovirus for 
participants assigned to receive these components. 
2.
Plasmid DNA (pDNA) vaccinations will be administered intramuscularly using an electroporation device on Day 29, Day 57 and Day 85 of each cycle.  Tremelimumab and 
sasanlimab will be administered after the pDNA for participants assigned to receive these components.  All pDNA vaccinations should be administered prior to administering 
the tremelimumab and sasanlimab.
3.
Tremelimumab will be administered subcutaneously in close proximity to the vaccine injected muscle and vaccine draining lymph nodes on Day 1, Day 29, Day 57 and 
Day 85 of each cycle.  Tremelimumab will be administered after the adenovirus or pDNA and, for participants assigned to receive sasanlimab, before the sasanlimab.  Both 
tremelimumab injections should be administered prior to administering the sasanlimab.
4.
Sasanlimab will be administered subcutaneously in close proximity to the vaccine injected muscle and vaccine draining lymph nodes on Day 1, Day 29, Day 57 and Day 85 
of each cycle.  Sasanlimab will be administered after the adenovirus or pDNA and after the tremelimumab.
5.
Blood samples for determination of tremelimumab drug concentrations and for detection of ADA/NAb against tremelimumab will be collected as outlined in the schedule of 
activities.  Samples to be collected on dosing days are to be obtained within 6 hours prior to tremelimumab dosing. 
6.
For participants assigned to Cohorts 3A, 6A, and 7A only.
7.
Blood samples for determination of sasanlimab drug concentrations and for detection of ADA/NAb against sasanlimab will be collected as outlined in the schedule of 
activities.  Samples to be collected on dosing days are to be obtained within 6 hours prior to sasanlimab dosing.
8.
For participants assigned to Cohorts 4A and 5A only. 

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SCHEDULE OF ACTIVITIES FOR DOSE EXPANSION (PART 2) 
Protocol Activity
Screen
1
(≤28 
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2
End of 
Treatment
32
Follow- Up
(Months after EOT visit)
Survival
Follow-up34
Study Day
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
43
Day 
57
Day 
71
Day 
85
Day 
113
Month 133 Month 2
Month 4
Month 6
Post 6-Month 
Follow-up
Cycle Day
Day 
1
Day 
29
Day 
57
Day 
85
Day 
99
28 to 35 
days
Every 3 Months
Visit Window 
(Days)*
±1
±2
±2
±2
±4
±2
±4
±2
±2
±2
±2
±2
±4
±4
±4
±4
±10
Informed consent2
X
Tumor history3
X
 
 
Medical history7
X
Complete physical 
examination8
X
X
Abbreviated 
physical 
examination8
X
X
X
X
X
X
X
X
X
X
X
X
X
Assessment of skin 
thickness at 
administration sites9
X
Height
X
Weight
X
X
X
X
Vital signs10
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Performance status11
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory
Unique Screening 
Labs12
X
Hematology13
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Chemistry14
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Coagulation15
X
X
X
X
X
X
X
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Page 28
Protocol Activity
Screen
1
(≤28 
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2
End of 
Treatment
32
Follow- Up
(Months after EOT visit)
Survival
Follow-up34
Study Day
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
43
Day 
57
Day 
71
Day 
85
Day 
113
Month 133 Month 2
Month 4
Month 6
Post 6-Month 
Follow-up
Cycle Day
Day 
1
Day 
29
Day 
57
Day 
85
Day 
99
28 to 35 
days
Every 3 Months
Visit Window 
(Days)*
±1
±2
±2
±2
±4
±2
±4
±2
±2
±2
±2
±2
±4
±4
±4
±4
±10
Cardiac Troponin-I 
(cTnI)16
X
X
X
X
X
Urinalysis17
X
X
X
X
X
X
X
X
X
X
X
Pregnancy Test or 
FSH Level 
(Serum)18
X
X
X
X
X
X
X
X
X
X
X
Contraception 
Check19
X
X
X
X
X
X
X
X
X
X
X
X
X
X
(12 lead) ECG20
X
X
X
X
X
X
X
Registration 
Registration21
X
Study Treatment
Adenovirus 
(AdC68) 
administration22
Refer to Part 2 Schedule of Study Treatment, Pharmacokinetics and Immunogenicity Assessments
Plasmid DNA 
(pDNA) 
administration22
Tremelimumab 
administration22
Sasanlimab 
administration22
Tumor Assessment
CT scan, MRI scan 
or bone scan23
X
Performed every 8 weeks up to Week 3223
(X)
Other samplings
 
AChR antibody25
X
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Page 29
Protocol Activity
Screen
1
(≤28 
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2
End of 
Treatment
32
Follow- Up
(Months after EOT visit)
Survival
Follow-up34
Study Day
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
43
Day 
57
Day 
71
Day 
85
Day 
113
Month 133 Month 2
Month 4
Month 6
Post 6-Month 
Follow-up
Cycle Day
Day 
1
Day 
29
Day 
57
Day 
85
Day 
99
28 to 35 
days
Every 3 Months
Visit Window 
(Days)*
±1
±2
±2
±2
±4
±2
±4
±2
±2
±2
±2
±2
±4
±4
±4
±4
±10
 
 
 
Pharmacokinetics 
and Tremelimumab 
ADA
Refer to Part 2 Schedule of Study Treatment, Pharmacokinetics and Immunogenicity Assessments 
Pharmacokinetics 
and Sasanlimab 
ADA
Other clinical 
assessments
Serious and 
non-serious adverse 
event monitoring30
X
Concomitant 
medications and 
non-drug supportive 
interventions31
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Survival 
Follow-up34
X
* Visit windows during the treatment period are to be calculated based on the previous dosing visit.
Abbreviations: Ĭ = ongoing; AChR = acetylcholine receptor; ADA = anti-drug antibodies; AdC68= Adenovirus; AE = adverse events; CRP= C-Reactive Protein; 
CT = computed tomography; 
ECG = electrocardiogram; EOT = End of Treatment; ER = estrogen receptors; HER2 = human epidermal growth 
factor receptor 2; hsCRP=high sensitivity C-reactive protein; MRI = magnetic resonance imaging; MSLN = mesothelin; MUGA = multigated acquisition scan; PBMC = peripheral 
blood mononuclear cell; pDNA=plasmid deoxyribonucleic acid; PR = progesterone receptors; (X)=Optional 
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Page 30
Protocol Activity
Screen
1
(≤28 
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2
End of 
Treatment
32
Follow- Up
(Months after EOT visit)
Survival
Follow-up34
Study Day
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
43
Day 
57
Day 
71
Day 
85
Day 
113
Month 133 Month 2
Month 4
Month 6
Post 6-Month 
Follow-up
Cycle Day
Day 
1
Day 
29
Day 
57
Day 
85
Day 
99
28 to 35 
days
Every 3 Months
Visit Window 
(Days)*
±1
±2
±2
±2
±4
±2
±4
±2
±2
±2
±2
±2
±4
±4
±4
±4
±10
1.
Screening: To be obtained within 28 days prior to study entry. 
2.
Informed Consent: Must be obtained prior to undergoing any study specific procedures.  May be collected more than 28 days prior to study entry.  As part of the consenting 
process, participants will be informed of the potential occurrence of immune related adverse events and will be provided with a Patient Information Card.
3.
Tumor History: Will be collected within 28 days prior to study entry.  Includes details of primary diagnosis and treatment history. 
 
 
 
 
 
7.
Medical History: Includes history of disease process other than NSCLC (active or resolved), smoking history, and significant concurrent illness.  Includes prior treatments 
and any current medical treatment for any condition.
8.
Complete and abbreviated physical examinations: A neurologic examination must be conducted at Screening to look for potential signs of underlying autoimmune 
disorders.  In addition, all abbreviated physical examinations conducted during Cycle 1 must include a neurologic examination.
9.
Assessment of the Skin and Subcutaneous Tissue Thickness: Assessment of the skin and subcutaneous tissue thickness at the eligible administration sites will be 
performed at screening as described in the TDS-IM Instructions for Use.  The assessment procedure does not need to be repeated during the course of the study unless the 
participant experiences a greater than 10% change in body mass relative to screening.
10. Vital signs: Includes temperature, pulse, and blood pressure (BP) to be recorded in the seated position after approximately 5 minutes of rest.  Vitals signs, including 
temperature, pulse, and BP to be recorded 1-hour post-study drug administration during each cycle on Days 1, 29, 57, and 85.
C
C
I

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Page 31
Protocol Activity
Screen
1
(28 
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2
End of 
Treatment
32
Follow- Up
(Months after EOT visit)
Survival
Follow-up34
Study Day
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
43
Day 
57
Day 
71
Day 
85
Day 
113
Month 133 Month 2
Month 4
Month 6
Post 6-Month 
Follow-up
Cycle Day
Day 
1
Day 
29
Day 
57
Day 
85
Day 
99
28 to 35 
days
Every 3 Months
Visit Window 
(Days)*
1
±2
±2
±2
±4
±2
±4
±2
±2
±2
±2
±2
±4
±4
±4
±4
±10
11. Performance status: Use Eastern Cooperative Oncology Group (ECOG) – see Appendix 2.
12. Unique Screening Labs: Active and clinically significant bacterial, fungal, or viral infection, including hepatitis B surface antigen, hepatitis B core antibody, hepatitis C 
antibody, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness is exclusionary per Exclusion Criteria #9.  In 
equivocal cases, subjects may be eligible if they have a negative viral load. Samples will be analyzed locally.
13. Hematology: Complete blood count (CBC) to include hemoglobin, platelets, WBC, Absolute neutrophils, absolute lymphocytes, absolute monocytes,absolute eosinophils, 
and absolute basophils.  If baseline assessment was performed within 72 hours of Cycle 1 Day 1, repeat is not required.  Samples will be analyzed locally. 
14. Blood Chemistry: Should include sodium, potassium, total chloride, bicarbonate or carbon dioxide, BUN (or urea), uric acid, creatinine, glucose (non-fasted), total calcium, 
magnesium, phosphorous and phosphate, albumin, total protein, aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), alkaline phosphatase, total 
bilirubin, amylase, lipase, lactate dehydrogenase (LDH), and TSH + reflex free T4 and free T3.  If baseline assessment was performed within 72 hours of Cycle 1 Day 1, 
repeat is not required.  Samples will be analyzed locally. 
15. Coagulation: Should include Prothrombin Time (PT) or International Normalized Ratio (INR) and Partial Thromboplastin Time (PTT).  Samples will be analyzed locally.  
16. Cardiac Troponin: For participants undergoing screening, circulating levels of cardiac Troponin-I (cTnI) must be measured and found to be within the normal reference 
range within 28 days before study entry, preferably using the central laboratory kits provided.  See Section 7.1.8 for full details.
17. Urinalysis: Dipstick is acceptable.  Microscopic analyses if dipstick abnormal.  Samples will be analyzed locally.
18. Pregnancy Test or FSH Level (Serum): For female participants of childbearing potential, a serum or urine pregnancy test, with sensitivity of at least 25 mIU/mL and assayed 
in a certified laboratory, will be performed on 2 occasions prior to starting study therapy, once at the start of screening and once at the baseline visit immediately before 
investigational product administration.  Pregnancy tests will also be routinely repeated at Day 1 of every treatment cycle during the active treatment period, at the End of 
Treatment visit, at the 28-day Follow-Up Visit, and additionally whenever one menstrual cycle is missed or when potential pregnancy is otherwise suspected.  Additional 
pregnancy tests may also be undertaken if requested by institutional review board/ethics committee (IRB/ECs) or if required by local regulations.  Participants with confirmed 
positive pregnancytest(s) should not be dosed.  For female participants who achieved postmenopausal status and have not experienced their menses for at least 12 consecutive 
months, a serum FSH test must be conducted at screening only to confirm a FSH level within the laboratory’s reference ranges.
19. Contraception Check: The contraception check is to confirm that contraception, if assigned, is used consistently and correctly. Male participants who are able to father 
children and female participants who are of childbearing potential will need to affirm that they meet the criteria for correct use of 2 of the selected methods of contraception.  
The investigator or his or her designee will discuss with the participant the need to use 2 highly effective contraception methods consistently and correctly and document such 
conversation in the participant’s chart.  In addition, the investigator or his or her designee will instruct the participant to call immediately if one or both selected contraception 
methods are discontinued, or if pregnancy is known or suspected in the participant or the participant’s partner.
20. 12 leads ECGs: A single ECG will be performed at Screening.  At all other time points, 3 consecutive 12-lead ECGs will be performed approximately 2 minutes apart to 
determine mean QTcF interval.  If the mean QTcF is prolonged (>500 msec), the ECGs should be re-evaluated by a qualified person at the institution for confirmation.  

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Page 32
Protocol Activity
Screen
1
(≤28 
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2
End of 
Treatment
32
Follow- Up
(Months after EOT visit)
Survival
Follow-up34
Study Day
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
43
Day 
57
Day 
71
Day 
85
Day 
113
Month 133 Month 2
Month 4
Month 6
Post 6-Month 
Follow-up
Cycle Day
Day 
1
Day 
29
Day 
57
Day 
85
Day 
99
28 to 35 
days
Every 3 Months
Visit Window 
(Days)*
±1
±2
±2
±2
±4
±2
±4
±2
±2
±2
±2
±2
±4
±4
±4
±4
±10
21. Registration: Participant number and dose level allocation operated by Pfizer Inc.
22. Investigational Product Administration: Treatment to be administered after all other assessments required on that day have been performed.
23. Tumor Assessments: Tumor assessments will include all known or suspected disease sites.  Screening images may be obtained within 5 weeks of registration.  Imaging 
obtained as part of standard of care but within 28 days (-7 days) of registration may be used for screening assessment.  Imaging may include chest, abdomen and pelvis CT or 
MRI scans, and bone scans.  Bone scans will be performed at baseline if disease is suspected and on study as appropriate to follow disease.  Baseline central nervous system 
(CNS) imaging MRI or CT Brain to be conducted only if clinically indicated based on the investigator’s judgement.  CT or MRI scans, as well as bone scans, when indicated, 
are to be done every 8 weeks (±5 days) with the first one to occur 8 weeks after C1D1 Repeat imaging will be completed every 8 weeks up to and including Month 8 (Week 
32) or until disease progression that requires new treatment modality, permanent discontinuation, or death.  Disease progression will be confirmed with 2 consecutive 
timepoints at least 4-8 weeks apart in the absence of rapid clinical deterioration.  Tumor assessment should be repeated at the End of Treatment visit if more than 6 weeks 
have passed since the last evaluation. 
25. Acetylcholine receptor (AChR) antibody: Sample to be sent to the central laboratory for analysis.  
 
The evaluation for AChR antibodies is included to exclude participants who test positive at screening as agreed upon with the 
United States Food and Drug Administration (US FDA) and to confirm requirement for evaluation if myasthenia gravis is suspected.99
 
 
 
 
  
 
30. Serious and Non-serious Adverse Event Monitoring: Adverse events should be documented and recorded at each visit using the National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI CTC AE) version 5.0.  Participants must be followed for AEs for 6 months after the last study treatment administration or until 
all drug related toxicities have resolved, whichever is later; or earlier than 6 months should the participant commence another anticancer therapy in the meantime.  The time 
period for actively eliciting and collecting AEs and SAEs (“active collection period”) for each participant begins from the time the participant provides informed consent 
through and including 6 months after the last study treatment administration or until all drug related toxicities have resolved, whichever is later.  If the participant begins a 
CCI
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Page 33
Protocol Activity
Screen
1
(≤28 
days)
Treatment Period
Post Treatment
Cycle 1
Cycle 2
End of 
Treatment
32
Follow- Up
(Months after EOT visit)
Survival
Follow-up34
Study Day
Day 
1
Day 
8
Day 
15
Day 
22
Day 
29
Day 
43
Day 
57
Day 
71
Day 
85
Day 
113
Month 133 Month 2
Month 4
Month 6
Post 6-Month 
Follow-up
Cycle Day
Day 
1
Day 
29
Day 
57
Day 
85
Day 
99
28 to 35 
days
Every 3 Months
Visit Window 
(Days)*
±1
±2
±2
±2
±4
±2
±4
±2
±2
±2
±2
±2
±4
±4
±4
±4
±10
new anticancer therapy, the period for recording non-serious AEs on the CRF ends at the time the new treatment is started.  However, any SAEs occurring during the active 
collection period must still be reported to Pfizer Safety and recorded on the CRF, irrespective of any intervening treatment.
31. Concomitant Treatments: All concomitant medications and non-drug supportive interventions should be recorded in the CRF.
32. End of Treatment Visit: The End of treatment visit will be completed at the time point when a decision is made to discontinue study treatment.  This can occur during 
Cycles 1 or 2 or during the Maintenance Treatment Phase of the study.  Obtain these assessments if not completed in the past 2 weeks (past 6 weeks for tumor assessments).
33. Follow up: At least 28 days, and no more than 35 days after discontinuation of study treatment, participants will return to complete the required assessments.  Participants 
will then return at Month 2, Month 4 and Month 6 to complete the required assessments.
34. Survival: After treatment discontinuation, participant survival status will be collected every 3 months until death, participant refusal, or lost to follow-up (telephone contact 
acceptable).
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Page 34
SCHEDULE OF ACTIVITIES FOR MAINTENANCE TREATMENT PERIOD FOR DOSE EXPANSION (PART 2)
Protocol Activity
Maintenance Treatment Period*
Study Month**
Month 9 Month 
10
Month 
11
Month 
12
Month 
13
Month 
14
Month 
15
Month 
16
Month 
17
Month 
18 
Month 
19
Month 
20
Month 
21
Month 22 and 
every month 
thereafter
Visit Window (Days)
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
Abbreviated physical 
examination1
X
X
X
X
X
X
X1
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X1
Vital signs2
X
X
X
X
X
X
X
X
X
X
X
X
X
X1
Performance status3
X
X
X
X
X
X
X
X
X
X
X
X
X
X1
Laboratory
Hematology4
X
X
X
X
X
X
X1
Blood Chemistry5
X
X
X
X
X
X
X1
Coagulation6
X
X
X
X11
Cardiac Troponin-I (cTnI)7
X
X
Urinalysis8
X
X
X
X11
Pregnancy Test or FSH Level 
(Serum)9
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Contraception Check10
X
X
X
X
X
X
X
X
X
X
X
X
X
X
(12 lead) ECG12
X
X
X*
Study Treatment
pDNA Administration13
X
X
X
X
X
X
X1
Tremelimumab 
administration13
X
X
X
X
X
X
X1
Sasanlimab administration13
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Tumor Assessment
CT scan, MRI scan or bone 
scan14
X14
Other Samplings
PK and Tremelimumab ADA
Refer to Part 2 Schedule of Study Treatment, Pharmacokinetics and Immunogenicity Assessments 
PK and Sasanlimab ADA
Other clinical assessments
Serious and non-serious 
adverse event monitoring18
X
X
X
X
X
X
X
X
X
X
X
X
X
X
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Page 35
Protocol Activity
Maintenance Treatment Period*
Study Month**
Month 9 Month 
10
Month 
11
Month 
12
Month 
13
Month 
14
Month 
15
Month 
16
Month 
17
Month 
18 
Month 
19
Month 
20
Month 
21
Month 22 and 
every month 
thereafter
Visit Window (Days)
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
Concomitant medications and 
non-drug supportive 
interventions19
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Abbreviations: →= ongoing; ADA = anti-drug antibodies; AdC68= Adenovirus; AE = adverse events; CT = computed tomography; ECG = electrocardiogram; EOT = End of 
Treatment; MRI = magnetic resonance imaging; PBMC = peripheral blood mononuclear cell; pDNA= plasmid deoxyribonucleic acid; SC = Subcutaneous(ly)
* When a decision is made to discontinue study treatment during the Maintenance Treatment Period, the End of Treatment visit assessments should be performed.  The 
participant will then enter the Post Treatment Period of the study.
** Study visit is based on completion of 2 cycles in the treatment period.  Visit window for the first maintenance treatment visit is to be calculated based on the Cycle 2 Day 85 
dosing date.  The first dose in the maintenance period should occur 28 days after the C2D85 dosing date.  A month is defined as 28 days.
1.
Abbreviated Physical Examination: To be assessed every 2 months.
2.
Vital signs: Includes temperature, pulse, and blood pressure (BP) to be recorded in the seated position after approximately 5 minutes of rest.  On days of study drug 
administration, vitals signs, including temperature, pulse and BP are to be recorded 1-hour post-study drug administration.
3.
Performance status: Use Eastern Cooperative Oncology Group (ECOG) – see Appendix 2.
4.
Hematology: Complete blood count (CBC) to include hemoglobin, platelets, WBC, absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, 
and absolute basophils.  Samples will be analyzed locally.
5.
Blood Chemistry: Should include sodium, potassium, total chloride, bicarbonate or carbon dioxide, BUN (or urea), uric acid, creatinine, glucose ( non-fasted), total calcium, 
magnesium, phosphorous and phosphate, albumin, total protein, aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), alkaline phosphatase, total 
bilirubin, amylase, lipase, lactate dehydrogenase (LDH) and TSH + reflex free T4 and free T3.  Samples will be analyzed locally.
6.
Coagulation: Should include Prothrombin Time (PT) or International Normalized Ratio (INR) and Partial Thromboplastin Time (PTT).  Samples will be analyzed locally.
7.
Cardiac Troponin: For participants undergoing screening, circulating levels of cardiac Troponin-I (cTnI) must be measured and found to be within the normal reference 
range within 10 days of Month 9 and Month 12.  See Section 7.1.8 for full details.  
8.
Urinalysis: Dipstick is acceptable.  Microscopic analyses if dipstick abnormal.  Samples will be analyzed locally.
9.
Pregnancy Test or FSH Level (Serum): For female participants of childbearing potential, a serum or urine pregnancy test, with sensitivity of at least 25 mIU/mL and assayed 
in a certified laboratory, will be performed on 2 occasions prior to starting study therapy, once at the start of screening and once at the baseline visit immediately before 
investigational product administration.  Pregnancy tests will also be repeated monthly during the Maintenance Treatment Period.  Additional pregnancy tests may also be 
undertaken if requested by institutional review board/ethics committee (IRB/ECs) or if required by local regulations.  Participants with confirmed positive pregnancy test(s) 
should not be dosed.  For female participants who achieved postmenopausal status and have not experienced their menses for at least 12 consecutive months, a serum FSH 
test must be conducted at screening only to confirm a FSH level within the laboratory’s reference ranges.
10. Contraception Check: Male participants who are able to father children and female participants who are of childbearing potential will need to affirm that they meet the 
criteria for correct use of 2 of the selected methods of contraception.  The investigator or his or her designee will discuss with the participant the need to use 2 highly effective 
contraception methods consistently and correctly and document such conversation in the participant’s chart.  In addition, the investigator or his or her designee will instruct 

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Protocol Activity
Maintenance Treatment Period*
Study Month**
Month 9 Month 
10
Month 
11
Month 
12
Month 
13
Month 
14
Month 
15
Month 
16
Month 
17
Month 
18 
Month 
19
Month 
20
Month 
21
Month 22 and 
every month 
thereafter
Visit Window (Days)
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
±7
the participant to call immediately if one or both selected contraception methods are discontinued, or if pregnancy is known or suspected in the participant or the participant’s 
partner.
11. To be assessed every 4 months.
12. Triplicate 12 leads ECGs: At each time point, three consecutive 12 lead ECGs will be performed approximately 2 minutes apart to determine mean QTcF interval.  If the 
mean QTcF is prolonged (>500 msec), the ECGs should be reevaluated by a qualified person at the institution for confirmation.  Additional triplicate ECGs will be performed 
at Month 12 Day 1, Month 18 Day 1, or may be performed as clinically indicated. 
13. Investigational Product Administration: Treatment to be administered after all other assessments required on that day have been performed, including pregnancy test. All 
participants will continue to receive the components to which they were assigned to receive during the treatment period. – note either the tremelimumab or the sasanlimab  
may be dose reduced or permanently discontinued after discussion with the Sponsor for participants assigned to receive these components.
14. Tumor Assessments: Tumor assessments will include all known or suspected disease sites.  Imaging may include chest, abdomen and pelvis CT or MRI scans, and bone 
scans.  CT or MRI scans, as well as bone scans, when indicated, are to be done every 12 weeks (±5 days) or when if clinically indicated until disease progression that requires 
new treatment modality, permanent discontinuation, or death.  Disease progression will be confirmed with 2 consecutive timepoints at least 4-8 weeks apart in the absence of 
rapid clinical deterioration.  
 
  
 
18. Serious and Non-serious Adverse Event Monitoring: Adverse events should be documented and recorded at each visit using the National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI CTC AE) version 5.0.  Participants must be followed for AEs for 6 months after the last study treatment administration or until 
all drug related toxicities have resolved, whichever is later; or earlier than 6 months should the participant commence another anticancer therapy in the meantime.  The time 
period for actively eliciting and collecting AEs and SAEs (“active collection period”) for each participant begins from the time the participant provides informed consent 
through and including 6 months after the last study treatment administration or until all drug related toxicities have resolved, whichever is later.  If the participant begins a 
new anticancer therapy, the period for recording non-serious AEs on the CRF ends at the time the new treatment is started.  However, any SAEs occurring during the active 
collection period must still be reported to Pfizer Safety and recorded on the CRF, irrespective of any intervening treatment.
19. Concomitant Treatments: All concomitant medications and non-drug supportive interventions should be recorded in the CRF.
CCI

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Schedule of Study Treatment, Pharmacokinetics, Tremelimumab and Sasanlimab Immunogenicity Assessments (Part 2)
Protocol Activity
Screen
(28 
days)
Treatment Period
Maintenance 
End of Treatment
Post Treatment
Cycle 1
Cycle 2 
Every 4 months 
starting at Month 10
End of Treatment
Follow- Up
(Months after EOT visit)
Study Day
Day
1
Day 
29
Day 
57
Day 
85
Day 
113
M1
M2
M4
M6
Cycle Day
Day 1
Day 
29
Day 
57
Day 
85
28-35 
days
Visit Window 
(days)
2
2
2
2
2
2
2
4
4
4
Study Treatment
AdC681
X
X
pDNA2
X
X
X
X
X
X
X2
Tremelimumab3
X
X
X
X
X
X
X
X
X3
Sasanlimab4
X
X
X
X
X
X
X
X
X4
Pharmacokinetics 
Immunogenicity
PK for 
tremelimumab5
X
X
X
X
X
X
X
X
X
X
X
ADA/NAb for 
tremelimumab5
X
X
X
X
X
X
X
X
X
PK for 
Sasanlimab6
X
X
X
X
X
X
X
X
X
X
X
ADA/NAb for 
Sasanlimab6
X
X
X
X
X
X
X
X
X
Abbreviations: ADA = Anti-drug antibody; Adenovirus (AdC68); EOT = End of Treatment; pDNA = Plasmid deoxyribonucleic acid, PK = Pharmacokinetics 
1.
Adenovirus (AdC68) will be administered intramuscularly on Cycle 1 Day 1 and Cycle 2 Day 1.  Tremelimumab and sasanlimab will be administered after the adenovirus 
for participants assigned to receive these components. 
2.
Plasmid DNA (pDNA) vaccinations will be administered intramuscularly using an electroporation device on Day 29, Day 57 and Day 85 of each cycle.  During the 
Maintenance period, pDNA vaccinations will be administered every 2 months.  All pDNA vaccinations should be administered prior to administering the tremelimumab and 
sasanlimab.
3.
Tremelimumab will be administered subcutaneously in close proximity to the vaccine injected muscle and vaccine draining lymph nodes on Day 1, Day 29, Day 57 and 
Day 85 of each cycle.  During the Maintenance period, tremelimumab will be administered every 2 months.  Tremelimumab (both injections) will be administered after the 
adenovirus or pDNA and before the sasanlimab.  

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Protocol Activity
Screen
(28 
days)
Treatment Period
Maintenance 
End of Treatment
Post Treatment
Cycle 1
Cycle 2 
Every 4 months 
starting at Month 10
End of Treatment
Follow- Up
(Months after EOT visit)
Study Day
Day
1
Day 
29
Day 
57
Day 
85
Day 
113
M1
M2
M4
M6
Cycle Day
Day 1
Day 
29
Day 
57
Day 
85
28-35 
days
Visit Window 
(days)
2
2
2
2
2
2
2
4
4
4
Study Treatment
4.
Sasanlimab will be administered subcutaneously in close proximity to the vaccine injected muscle and vaccine draining lymph nodes on Day 1, Day 29, Day 57 and Day 85 
of each cycle.  During the Maintenance period, sasanlimab will be administered each month.  Sasanlimab will be administered after the adenovirus or pDNA and after the 
tremelimumab.
5.
Blood samples for determination of tremelimumab drug concentrations and for detection of ADA/NAb against tremelimumab will be collected as outlined in the schedule of 
activities.  Samples to be collected on dosing days are to be obtained within 6 hours prior to tremelimumab dosing. 
6.
Blood samples for determination of sasanlimab drug concentrations and for detection of ADA/NAb against sasanlimab  will be collected as outlined in the schedule of 
activities.  Samples to be collected on dosing days are to be obtained within 6 hours prior to sasanlimab dosing.

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1. INTRODUCTION
1.1. Mechanism of Action/Indication
PF-06936308 is a vaccine-based immunotherapy regimen-2 (VBIR-2) that is currently being 
investigated in participants with advanced non-small cell lung cancer (NSCLC) and 
metastatic triple-negative breast cancer (mTNBC).
1.2. Background and Rationale
Lung cancer is the second most common cancer in both men and women, it accounts for 
approximately 160,000 deaths each year in the United States (US).  About 80-85% of lung 
cancers are histologically classified as Non-Small Cell Lung Cancer (NSCLC), which 
includes 2 major sub-types: 1) Non-squamous carcinoma (including adenocarcinoma, 
large-cell carcinoma (rare), and other cell types), and 2) Squamous cell (epidermoid) 
carcinoma. 1  The 5-year survival rate of metastatic NSCLC is 4%.16  
Triple-negative breast cancer accounts for 15% to 20% of breast cancers and is histologically 
defined by a lack of estrogen receptor (ER) and progesterone receptor (PR) expression as 
well as absence of human epidermal growth factor 2 (HER2) overexpression and/or 
amplification.4,6  Following neoadjuvant and/or adjuvant chemotherapy,7,8,9,10 patients with 
TNBC have a higher incidence of early visceral recurrence, with a subsequent median 
survival of approximately 1 year.2,3,11
Given these extraordinarily low survival rates, there is a need for new therapies with 
acceptable side-effect profiles to provide long-term disease control in these patient 
populations.
Recent advances in understanding methods to increase immune surveillance and to reduce 
native immune tolerance have yielded encouraging therapeutic advances in a variety of tumor 
types, including NSCLC.12,13,14,15  Unfortunately, these current approaches generally 
encompass the use of single-agent immunotherapy, in which only a sub-group of patients 
respond, or show a long-term survival benefit.  
In contrast, PF-06936308 is a multi-agent, combination approach to the immune treatment of 
NSCLC.  The multi-agent regimen consists of a series of priming and booster vaccinations 
containing three antigens, along with 2 immune checkpoint inhibitors, delivered in support of 
the vaccinations.  It is hoped that this multi-agent approach will more thoroughly induce, 
expand, and maintain the pool of T-cells providing the anti-tumor responses at the sites of 
metastatic NSCLC.  As NSCLC is known to express the tumor antigens encoded and 
expressed by the vaccine, (see below), and as NSCLC is associated with a so-called 
“inflamed” tumor microenvironment (indicating a an intrinsic level of anti-tumor T-cell 
infiltration), it is hope this regimen will induce clinically significant responses in participants 
with metastatic NSCLC that will reduce tumor burden, delay disease progression, and 
ultimately lead to prolonged overall survival.

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VBIR-2 Regimen
The VBIR-2 (PF-06936308) regimen consists of 4 components: 
(1) PF-06871923 (AdC68), a replication incompetent chimpanzee adenovirus, 
delivered as a priming vaccination intramuscularly.  AdC68 contains the 3 selected non-small 
cell lung cancer-associated antigens mucin 1 (MUC1), mesothelin (MSLN) and telomerase 
reverse transcriptase (TERT); 
(2) PF-06871925, a plasmid DNA (pDNA) construct that encodes the same 3 tumor 
antigens as in the AdC68 viral vector.  The pDNA is also delivered intramuscularly, and is 
used as a boost vaccination at pre-specified intervals after the viral vector is delivered;
(3) PF-06753388 (tremelimumab), an anti-cytotoxic T lymphocyte-associated 
antigen-4 (CTLA-4) monoclonal antibody given subcutaneously (SC) in conjunction with 
each vaccination.
(4) PF-06801591 (sasanlimab), an anti-programmed death-1 (PD-1) monoclonal 
antibody also given SC in conjunction with each vaccination.
1.2.1. Non-Small Cell Lung Cancer Treatment Overview 
Limitations of Treating Activating Genetic Mutations
Numerous genetic changes have been associated with lung cancer that may serve as 
activators of the malignant process.  Epidermal growth factor receptor (EGFR) is expressed 
or overexpressed in the majority of NSCLC tumors.17,18,19  Agents targeting EGFR include 
tyrosine kinase inhibitors (TKIs), such as gefitinib,17 erlotinib,18 and afatinib.19  In metastatic 
NSCLC harboring activating EGFR mutations, these treatments may result in some patients 
obtaining response rates exceeding 60%, accompanied by median Overall Survival exceeding 
2 years.  Unfortunately, most patients progress in about 9 months, which in 50% of cases is 
due to a secondary, T790M mutation in exon 20.  In addition to EGFR mutations, 
abnormalities in the anaplastic lymphoma kinase (ALK) gene have been identified in a subset 
of NSCLC patients.  These gene rearrangements, which appear mutually exclusive with both 
EGFR and KRAS (Proto-Oncogene) gene mutations, render cancers highly responsive to 
ALK inhibitors including crizotinib20 and ceritinib.21  
For the majority of patients diagnosed with advanced-stage NSCLC without targetable driver 
gene mutations, platinum-based doublet chemotherapy (ChTx) has been the standard of care 
(SOC) for over 30 years.  With the exception of bevacizumab,22,23 and despite extensive 
study of multiple targeted and cytotoxic agents, addition of a third agent to platinum-doublet 
chemotherapy has not been shown to improve progression-free survival (PFS) or overall 
survival (OS) over platinum-doublet chemotherapy.24  Targeting driver mutations responsible 
for tumor progression (EGFR receptor and the echinoderm microtubule-associated 
protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) EML4-ALK receptor) is 
modestly effective; however resistance to these therapies inevitably ensues.25,26,27  

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Advantages of Immunotherapy Regimens with Checkpoint Inhibitors
Checkpoint inhibitors, tumor vaccines, and cellular therapies induce formation of specific 
tumor-directed cytotoxic T cells capable of destroying cancer cells.    This process may 
involve T-cell memory and longer-term, ongoing anti-tumor effects, which may possibly 
provide longer overall survival benefits compared to current therapies, as described below.
Checkpoint inhibitors, including anti-PD-1 and anti-CTLA-4, have recently been tested for 
efficacy in NSCLC, and shown success in the immunotherapy-naïve setting.28,29,30  Initial use 
of the checkpoint inhibitors ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) for the 
treatment of NSCLC demonstrated encouraging clinical results, especially in patients with 
program death-ligand 1 (PD-L1) expression in >50% of their tumor cells.35  In first-line 
NSCLC, patients with PD-L1+ >50% were treated with nivolumab 3 mg/kg every 2 weeks 
(Q2W) plus ipilimumab 1 mg/kg every 12 weeks (Q12W), or every 6 weeks (Q6W).  The 
ORR was 47% for the ipi/nivo combination versus 23% for nivolumab alone.  Median 
duration of response was not reached with median follow-up times of 12.8 months.37   
Participants had a tolerable safety profile, although Grade 3 or Grade 4 treatment-related 
adverse events (TRAEs) were observed in 37% of patients, including increased lipase, 
pneumonitis, adrenal insufficiency and colitis.  
More recently, in 2018, new standards of care have emerged in treatment-naïve, NSCLC 
without sensitizing EGFR or ALK mutations, using regimens consisting of PD-axis inhibitors 
combined with a variety of chemotherapy or other novel agents.  In KEYNOTE 189, 
pemetrexed and platinum-based chemotherapy, along with pembrolizumab, was administered 
in a Phase 3 trial, and compared to patients receiving the same regimen without 
pembrolizumab.147  Those patients receiving pembrolizumab in addition to the pemetrexed 
and platinum-based chemotherapy achieved a superior 12-month OS of 69.2 % versus 
49.4%, HR = 0.49 and a mPFS of 8.8 months versus 4.9 months.  Both groups had the same 
safety profile of 65 – 67 % Grade 3 AEs.  Similarly, in IMpower150, patients with non-
squamous, treatment-naïve NSCLC without EGFR or ALK driver mutations were treated 
with bevacizumab plus carboplatin plus paclitaxel (BCP), or atezolizumab plus BCP (ABCP) 
every 3 weeks for 4 or 6 cycles, followed by maintenance therapy with atezolizumab, 
bevacizumab, or both.  Patients treated with ABCP achieved an improved mPFS (8.3 versus 
6.8 months, HR = 0.62) and mOS (19.2 versus 14.7 months, HR = 0.78).148
Triple-Negative Breast Cancer 
Triple-negative breast cancer accounts for 15% to 20% of breast cancers and is histologically 
defined by a lack of estrogen receptor and progesterone receptor expression and the absence 
of HER2 overexpression and/or amplification.4,6  Triple-negative breast cancer is a 
heterogeneous disease, not only on the molecular level, but also on the pathologic and 
clinical levels.  The majority of patients with TNBC respond with high sensitivity to 
chemotherapies including anthracyclines and taxanes in the neoadjuvant or adjuvant settings.  
Responses to chemotherapy occur, but are often short lived and are frequently accompanied 
by considerable toxicity.39,40,41,42,43  After neoadjuvant and/or adjuvant chemotherapy, 
patients with TNBC have a higher incidence of early visceral recurrence,7,8,9,10 with a 

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subsequent median survival of approximately 1 year.11  The lack of ER, PR and HER2 
expression precludes the use of targeted therapies, and the only approved systemic treatment 
option is chemotherapy.  Various chemotherapy regimens (single agent taxane, capecitabine 
or combinations paclitaxel + gemcitabine, platinum + gemcitabine) are used in first-line 
therapy for mTNBC; they are associated with an ORR of 25-35%, a modest PFS (median 
PFS of less than 6 months) and a median OS of less than 12 months.46  Given the suboptimal 
outcomes with chemotherapy, new therapies for mTNBC are urgently needed. 
Classification of Immunoresponsiveness of Tumors
Tumors can be broadly categorized as inflamed or noninflamed.47,48,49
Representative images of tumor CD8 Immunohistochemistry (IHC) shows three patterns 
T cells.  Tumors with preexisting immunity are represented by an abundance of tumor 
infiltrating lymphocytes (TILs), dense functional CD8+ T-cell infiltration reflected by 
interferon gamma (IFNɤ) signaling, expression of checkpoint markers including PD-L1, and 
high mutational burden.  These characteristics reflect highly inflamed tumors.  The collective 
clinical evidence to date suggests that checkpoint inhibitors largely act by reinvigorating 
preexisting antitumor T-cell responses and are most effective in inflamed tumors.50,68,69,70  In 
a study investigating the relationship between TILs at diagnosis and clinical outcome after
anthracycline-based chemotherapy, the results reported significant prognostic association for 
TNBC but not for luminal breast cancers.  Patients with TNBC with at least 50% TILs 
(10.5% of patients) had a 5-year disease-free survival of 89% compared with 62% in luminal 
breast cancers (p = 0.018, hazard ratio 0.29, 95% confidence interval 0.11–0.81).71
PD-1/PD-L1 expression has been studied by various methods in different cancer subtypes.72  
PD-1 and PD-L1 expression in various breast cancer subtypes are summarized in Table 1
below.  Triple-negative breast cancer is frequently (70%–100%) infiltrated with PD-1+ TILs.  
Recent clinical trials have demonstrated that blocking of the PD-1/PD-L1 pathway induces 
an objective and durable remission in patients with advanced solid tumors.12,15,73,74,75  The 
efficacy of these agents has been primarily linked to the expression of PD-L1 in the tumor 
cells and PD-1 on activated T lymphocytes.76,77,78,79
Table 1.
PD-1 and PD-L1 expression in breast cancers, according to the molecular 
subtype79

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Immune checkpoint inhibitors in breast cancer: Cytotoxic T-lymphocyte-associated protein 
4 is an inhibitory receptor found on CD8+ and CD4+ T cells, and is constitutively expressed 
on regulatory T cells (Treg cells).80  CTLA-4 functions to attenuate co-stimulatory signaling 
by competing with the stimulatory receptor CD28 expressed by T cells for the ligands 
CD80 and CD86 presented by antigen-presenting cells.81  The United States (US) Food and 
Drug Administration (FDA) approved the use of combination of nivolumab and ipilimumab 
in treatment for patients with unresectable or metastatic melanoma without a proto-oncogene 
protein B-raf (BRAF) mutation.  Very promising Phase I and II trials have been reported on 
increased activity of the combined blockade of CTLA4 and PD-1, nivolumab and 
ipilimumab,82 durvalumab and tremelimumab83 and pembrolizumab and ipilimumab84 in 
NSCLC, with an ORR up to 40% across all the studies.85  Hence combination therapy with 
anti-CTLA-4 and anti-PD-1 therapy may also have application in TNBC patients.  Several 
lines of evidence indicate that a greater number of TILs in the tumor stroma is associated 
with a higher probability of cure in patients with early stage TNBC.86
In KEYNOTE-012,44 a multicenter, nonrandomized Phase 1b trial, the safety and antitumor 
activity of PD-1 inhibitor pembrolizumab was assessed in patients with heavily pretreated, 
advanced TNBC.  In this trial of 111 TNBC patients whose tumor samples were screened for 
PD-L1 expression, 58.6% had PD-L1-positive tumors and 32 women were enrolled; 
single-agent pembrolizumab was given intravenously at 10 mg/kg every 2 weeks to patients 
with advanced PD-L1–positive tumors.  Common toxicities were mild (eg, arthralgia, 
fatigue, myalgia, and nausea).  Among the 27 patients who were evaluable for antitumor 
activity, the overall response rate was 18.5%.44
Part 1 (dose escalation) included participants with advanced NSCLC and mTNBC for whom 
no standard therapy is available.  TNBC will not be included in Part 2 (dose expansion).
1.3. VBIR-2 
1.3.1. Rationale for the Components of VBIR-2
General Background of T-Cell Activity in Cancer Therapy
High titers of tumor antigen-specific T cells can be induced by a variety of methods 
including checkpoint inhibition, genetic modification (chimeric antigen receptor T cells), and 
ex-vivo stimulation or incubation with antigen and anti-gen presenting cells51.  Each of these 
methods has demonstrated the ability to reduce tumor burden in a variety of cancers.  In 
addition to these approaches, a cancer vaccine will also induce large numbers of polyclonal, 
tumor antigen-associated T cells.  It has been shown that using a viral vector carrying tumor-
associated antigens, increases in circulating, vaccine-induced T-cells increase after each 
vaccination, but require multiple boost vaccinations with additional tumor-specific antigens 
before high T-cell titers can be reached.  
Vaccine-induced T cells are expected to be of lower avidity of normal tissues, due to thymic 
deletion of high-avidity T cells that are specific for self-antigens.  The slower induction of 
T cells by vaccines, along with thymic deletion of high avidity T cells, might explain the 
good safety profile observed to date in patients treated with cancer vaccines. 

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Hypothesis of Increased Anti-tumor Activity with VBIR-2
To date, anti-tumor activity with current clinical trial vaccines have been encouraging but not 
yet significantly superior to other clinical immunotherapy trials.  We expect VBIR-2 to 
overcome previous vaccine shortcomings (poor target choice, ineffective vaccine technology, 
immunosuppressive tumor microenvironment) based on the following design improvements: 
(a) Instead of selecting single antigens and in most cases single epitopes as tumor 
associated antigens (TAAs), VBIR-2 applied a stringent selection and validation process of 
indication-specific tumor associated antigens (TAAs) (Section 1.3.2).  To avert tumor escape 
and target a broader major histocompatibility complex (MHC) restriction-independent patient 
population, VBIR-2 encodes three TAA proteins instead of only single-antigen protein or 
peptides; 
(b) To maximize the TAA-specific immunogenicity, a potent heterologous AdC68 
prime/pDNA boost vaccination regimen combined with concomitant tremelimumab 
administration was selected to boost an enhanced induction and expansion of TAA-specific 
T cells; 
(c) To maintain the functionality of TAA-specific T cells in an immunosuppressive 
tumor microenvironment, sasanlimab injections are given with every vaccine administration.  
The combination of all four components (vaccine prime, pDNA boost, anti-CTLA-4 
tremelimumab, anti-PD-1 sasanlimab) may allow for the induction and maintenance of high 
titers of durable and functional TAA-specific immune responses.
1.3.2. Selection of Vaccine Antigens (MUC1, MSLN, TERT)
A multi-antigen, multi-indication VBIR-2 offers the potential benefit of mitigating the risk of 
immune escape by the tumor while increasing the likelihood of activating tumor-specific 
immune responses in a broad patient population.  The 3 TAAs (MUC1, MSLN, and 
TERT) were selected based on the following 2 criteria: 1) Over expression in NSCLC and 
TNBC tumors in comparison to surrounding healthy tissues (Pfizer Internal Report 
VR-VTR-10375: Evaluation of MUC1, MSLN and TERT Antigen Expression in Human 
Tumor Tissues via Immunohistochemical Analysis), and 2) Evidence that cellular and/or 
humoral immune responses to the selected antigens correlate with clinical activity with 
acceptable safety profile in the clinic.37,88,89
Evidence for selecting the 3 antigens, based on the above criteria, is a follows.  Human tumor 
tissues from different stages of NSCLC (n=100) and TNBC (n=32) and five additional solid 
tumors spanning different stages including some metastatic tissues were evaluated by IHC.  
According to the H-score classification using an antigen-specific semi-quantitative IHC 
assay, positive anti-MUC1 and anti-TERT staining was detected in the majority of NSCLC 
and TNBC cancer tissues evaluated (94% and 100% of TNBC and 79% and 91% of NSCLC, 
respectively).  Additionally anti-MSLN-staining was detected in 56% of TNBC and 30% of 
NSCLC tumor tissues analyzed.  Consistent with literature, the results confirmed good 
coverage of the different stages of TNBC and NSCLC by the three antigens.90  Consequently, 

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MUC1, MSLN, and TERT were selected as vaccine antigens of VBIR-2.  High level 
expression of these antigens were also found in ovarian and pancreatic cancers suggesting 
these cancer types as additional promising target indications. 
Antigen Descriptions
MUC1 (mucin 1, cell surface associated): MUC1 is a heavily glycosylated transmembrane 
protein generally expressed on the epithelial surface of a variety of organs, where it serves a 
protective function against toxin or pathogen infiltration into internal tissues.  MUC1 has 
been used as a safe vaccine target antigen, and clinical trial results have shown direct 
correlation between MUC1-specific immunogenicity and clinical activity.93
In a Phase 2b part of a randomized, double-blind, placebo-controlled, Phase 2b/3 trial, n = 
222 previously untreated patients were enrolled with stage IV NSCLC without a known 
activating EGFR mutation and with MUC1 expression in at least 50% of tumor cells.  
Patients were randomized 1:1 to TG4010 vaccine, which delivers full-length human MUC1 
and human IL-2 by a recombinant vaccinia virus (n = 111) or placebo (n= 111) from the 
beginning of chemotherapy every week for 6 weeks and then every 3 weeks up to 
progression or discontinuation due to toxicity.  The median overall survival (mOS) for 
non-squamous (non-sq) NSCLC was 14.6 months in the vaccine + chemotherapy arm versus 
10.8 months in the placebo + chemotherapy arm.  No Grade 3 or 4 or serious adverse events 
were deemed to be related to TG4010 only. 
TERT (telomerase reverse transcriptase): Human TERT is the catalytic subunit of the 
telomerase enzyme which functions to increase the number of telomere DNA repeats 
protecting chromosome ends, extending the replicative capacity of the DNA.  In healthy 
tissues, TERT activity is minimal, ensuring that cells are able to replicate only for a fixed 
number of times.  A few human cell types with increased replication requirements, such as 
stem cells or germline cells, or activated lymphocytes, show increased TERT expression.95,96  
TERT overexpression is extremely prevalent in almost all cancer types.  
In general terms, elevated TERT levels are present in over 85% of tumors where increased 
cellular life span has been observed.97  In a clinical trial with canine B cell lymphosarcoma 
animals, animals that received ChTx plus the canine TERT vaccine demonstrated induction 
of TERT-specific cellular responses and almost tripled the mOS compared to the ChTx-only 
control arm.89 Moreover, in a phase I/II trial with 22 previously treated stage III-IV NSCLC 
patients, patients showing an increased immune response to the Vx-001 TERT-specific 
vaccine showed a significantly increased mTTP and mOS.98 The correlation of anti-TERT 
immune responses and increased survival, manageable safety profile as well as the 
expression of TERT on almost all cancers, make TERT an attractive cancer vaccine target.
More specifically related to NSCLC, TERT is overexpressed in more than 85% of NSCLC 
and is associated with poor prognosis.98  In a recent Phase I/II trial with 22 previously treated 
stage III-IV NSCLC patients, subjects showing an immune response to the Vx-001 
TERT-specific vaccine showed an increased median time to progression (mTTP) and median 
overall survival (mOS) relative to those with no evidence of T cell response.37 TERT572 
specific T-cell responders had a mTTP of 4.2 months (immune responders, n=16) versus 

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2.1 months (non-responders, n=5); p=0.046 and a mOS of 30 months (immune responders, 
n = 16) versus 4.1 months (non-immune responders, n=5); p=0.012.37  The subcutaneously 
administered TERT572 peptide vaccine + Montanide was well tolerated with the main 
toxicity being local skin reactions seen in n=8 (36.4%)of subjects. 
MSLN (mesothelin): Human MSLN is a glycophosphatidylinositol (GPI)-anchored 
glycoprotein present on the surface of cells lining the pleura, peritoneum and pericardium, 
and is involved in cellular recognition and/or adhesion145. The MSLN gene encodes a 
71-kilodalton (kDa) precursor protein that is processed to a 40-kDa Mesothelin 
membrane-bound protein and a 31-kDa secreted megakaryocyte potentiating factor (MPF) 
protein.90  MSLN is overexpressed in several human tumors including NSCLC (reference 
IHC Pfizer internal study report VR-VTR-10375),  mesothelioma, ovarian, pancreatic 
adenocarcinoma, and triple-negative breast cancer.90  In two phase II trials with pancreatic 
cancer patients, the cancer vaccine (GVAX) pancreatic vaccine induced MSLN-specific 
cellular responses; the increased response magnitude/or correlated with increased 
disease-free survival and/or overall survival, making it an attractive cancer vaccine 
candidate.88,89 In terms of the amount of MSLN within NSCLC, human tumor tissues from 
different stages of NSCLC have been evaluated by IHC.90  According to the H-score
classification using an antigen-specific semi-quantitative IHC assay, anti-MSLN-staining 
was detected in 30% of NSCLC tumors. From the standpoint of clinical utility, a live-
attenuated Listeria monocytogene (LM) engineered to express MSLN (CRS-207) was used in 
a Phase 1 trial, to vaccinate 17 treatment refractory patients (3 with NSCLC) in a dose 
escalation of up to 4 intravenous doses at 21 day intervals.  CRS-207 was well tolerated with 
37% of the patient population surviving for >15 months including 2/3 with NSCLC.146  
MSLN specific immune responses recorded and SD reported in 1 NSCLC patient. 
Summary of Components of VBIR-2
VBIR-2 (PF-06936308) for advanced NSCLC and mTNBC consists of the following 
components:
1. A priming immunization administered IM with a replication-deficient adenovirus 
vector derived from chimpanzee that expresses three tumor-associated antigens –
MUC1, MSLN, and TERT (AdC68, PF-06871923);
2. Boost vaccinations with plasmid deoxyribonucleic acid (PF-06871925, pDNA), 
encoding the same three antigens administered IM with an electroporation device 
[intramuscular TriGrid Delivery System Version 2.0 (TDS-IM) V 2.0];
3. An anti-CTLA4 monoclonal antibody tremelimumab (PF-06753388) given SC in 
conjunction with each vaccination; and 
4. An anti-PD-1 monoclonal antibody sasanlimab (PF-06801591) also given SC in 
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
Part 1 of C3621001 evaluated the safety and tolerability of the vaccine 
components (AdC68 and pDNA) alone and in combination with increasing doses 
of tremelimumab and sasanlimab. 

Part 2 (Expansion) of the study will utilize the following doses: AdC68 6 ×1011
VP, 5 mg of pDNA, 80 mg of tremelimumab and 300 mg of sasanlimab. 
Tremelimumab will be given locally by SC injection with the priming and boost 
vaccinations.  This monoclonal antibody has been shown to increase responder frequency 
and enhance the breadth and magnitude of the T-cell response to the selected cancer vaccine 
antigens.
Sasanlimab, is a humanized, hinge region-stabilized IgG4 monoclonal antibody (mAb) 
specific for human PD-1 that can selectively and reversibly bind to human PD-1, 
thereby blocking the interaction between PD-1 and PD-L1/programmed death-ligand 2 
(PD-L2).  It will be injected subcutaneously at an anatomic location close to the injection 
sites of the vaccine vector and tremelimumab.  The objective of using sasanlimab is to help 
maintain the activity of VBIR-induced T cells during the activation, expansion, and the intra-
turmoral effector phase of antigen-specific T cell responses.
1.4. Nonclinical Safety
1.4.1. Nonclinical Toxicity Study for VBIR-2
The local and systemic toxicity of AdC68/pDNA+tremelimumab was assessed with and 
without sasanlimab in sexually mature cynomolgus monkeys.  AdC68 (6 x 1011 viral particles 
(VP)/animal) plus tremelimumab (150 mg/animal) with and without sasanlimab (20 mg/kg) 
were administered on Day 1 (prime), followed by 2 boost doses of pDNA (5 mg/animal) plus 
tremelimumab (150 mg/animal) with and without sasanlimab (20 mg/kg) administered 28 
and 56 days later.  The number of doses is supported by data indicating that the TAA-specific 
CD8 and CD4 IFNT-cell titers reached a plateau following one AdC68 priming dose and 
two pDNA boosts.  Necropsy was conducted 8 and 29 days following the last boost dose 
administered.  The toxicokinetics of sasanlimab and tremelimumab and the immunogenicity 
of sasanlimab, tremelimumab, TERT, MUC1, and MSLN were evaluated.
The systemic exposure of tremelimumab was higher (~2.6x) in females compared to males, 
at the fixed dose of 150 mg.  The male body weights were ~2.3x those of females (6.9 to 
8.8 kg for males and 3.0 to 3.9 kg for females).  Therefore, the observed difference in 
exposure between males and females was attributed to differences in body weight.  The 
systemic exposure of sasanlimab (dose adjusted for body weight; 20 mg/kg) was similar in 
male and female animals. For tremelimumab, exposure was similar in cynomolgus monkeys 
administered AdC68/pDNA+tremelimumab alone or with sasanlimab.  In general, exposures 
for both tremelimumab and sasanlimab were lower on Days 29 and 57 compared with Day 1, 
due to anti-drug antibodies (ADA).  The incidence of ADA (on Day 57) to tremelimumab
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when co-administered with sasanlimab.  The incidence of ADA to sasanlimab when 
co-administered with tremelimumab was 100%. 
Administration of AdC68/pDNA+tremelimumab alone or with sasanlimab was not 
associated with any effects on clinical signs, body weights or body weight changes, food 
consumption, ophthalmology, electrocardiology, body temperature, urinalysis, gross 
pathology, or organ weights.  Injection site reactions were observed on Days 29 and 57 in 
cynomolgus monkeys administered AdC68/pDNA+tremelimumab alone or with sasanlimab.  
Following the first dose (Days 3-8) and at the end of the dosing phase, administration of 
AdC68/pDNA+tremelimumab alone or with sasanlimab was associated with transient, 
nonadverse changes in clinical pathology parameters including increased lymphocytes, 
monocytes, basophils, large unstained cells, fibrinogen, globulins, and C-reactive protein 
compared to control values that were interpreted to be in response to immune stimulation 
following vaccine administration.  
Administration of AdC68/pDNA+tremelimumab alone or with sasanlimab to cynomolgus 
monkeys was not associated with any macroscopic observations or organ weight changes at 
the end of the dosing or recovery phases of the study (Days 65 and 86, respectively).  
Microscopically, AdC68/pDNA+tremelimumab- and/or AdC68/pDNA+tremelimumab+
sasanlimab-related increases in mononuclear cell infiltrates in the pituitary gland, pancreas, 
heart, urinary bladder, sciatic nerve, and injection sites were observed.  This finding was 
adverse in the pituitary gland of one female treated with AdC68/pDNA+tremelimumab +
sasanlimab at the end of the dosing phase due to increased severity and the widespread 
infiltrative nature of the mononuclear cells; however, no mononuclear cell infiltrates were 
present in any monkeys treated with AdC68/pDNA+tremelimumab + sasanlimab at the end 
of the recovery phase (Day 86).  Minimal treatment-related nonadverse pituitary gland 
infiltrates were present in AdC68/pDNA+tremelimumab-treated males at both the end of 
dosing and end of recovery phase.  The female animal noted previously with mononuclear 
cell infiltrates in the pituitary gland also had nonadverse scattered multifocal perivascular 
infiltrates of lymphocytes and plasma cells in the pancreas.  This female also had the highest 
exposure to tremelimumab on Days 29 and 57 of the ten animals in the dose group (eg, Area 
Under the Curve (AUC)= 74,400 µg·h/mL for this female on Day 57, compared with a mean 
AUC of 20,700 µg·h/mL for the remaining 4 animals in the group), and did not have 
detectable ADA to tremelimumab at the completion of the dosing period.  Exposure to 
tremelimumab and other anti-CTLA4 or anti-PD-1 inhibitors has been previously associated 
with pituitary mononuclear cell infiltrates in monkeys and hypophysitis in humans.52,53  In 
the heart and urinary bladder, treatment-related mononuclear cell infiltrates were interpreted 
to reflect an exacerbation of background findings and were fully recovered by the end of the 
recovery phase on Day 86.  The chronic active inflammation observed at the injection sites 
was reversible and a typical finding related to IM and SC injections.54,55,56,57,58,59,60,61  
Infiltrates in and around the sciatic nerve were minimal and were fully reversed in 
AdC68/pDNA+tremelimumab -treated monkeys and partially reversed in monkeys treated 
with AdC68/pDNA+tremelimumab + sasanlimab.

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A robust increase in IFN-γ cellular responses to each of the vaccine antigens (MSLN, MUC1 
and TERT) and a robust serum immunoglobulin G (IgG) antibody response to both MUC1 
and MSLN were seen in all animals in both the AdC68/pDNA+tremelimumab alone or with 
sasanlimab dose groups post-vaccination.
In summary, administration of a repeat dose (once per 28 days) of 
AdC68/pDNA+tremelimumab alone or with sasanlimab in sexually mature cynomolgus 
monkeys was generally well tolerated.
1.5. Clinical Overview
Part 1 will enroll up to 40 participants at escalating doses of the VBIR-2 regimen.
The clinical experience with PF-06936308 support the safety and design of Protocol 
C3621001 and the continuation of the clinical development of PF-06936308 in participants 
with NSCLC.
1.6. Dose Rationale
Below are listed the rationales for the doses of the various components:
1.6.1. Clinical AdC68 (PF-06871923) Dosing
Anticipated efficacy and safety were considered when selecting the AdC68 dose range for 
clinical testing.  The dose ranges of 1 x 109 to 5 x 1011 VP of a modified adenovirus antigen 
delivery system have shown a tolerable safety profile in participants with colorectal cancer as 
well as dose-dependent immune responses to a self-antigen.62  Previously, high doses of 
different adenovirus vectors were evaluated preclinically.  The absence of germ line
transmission was demonstrated in mice and baboons.63,64  In a separate study in nonhuman 
primates (NHPs), a dose of 5 x 1012 VP/kg was found to be well tolerated.65  Importantly, 
repeated administration did not appear to alter the toxicity/tolerability profile.66  It is also 
important to note that these animals were dosed IV per kg body weight, making the total dose 
substantially higher than the highest dose planned in this study (6 x 1011 VP IM total dose).  
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Furthermore, since the administration in this study is IM, the systemic safety profile is 
anticipated to be more favorable.63  Higher doses of adenovirus, up to 2 x 1011 VP/kg (total 
dose in excess of 1 x 1013 VP), when administered directly into the hepatic artery are 
tolerated in participants with partial ornithine transcarbamylase deficiency.67
In the VBIR-2 nonclinical toxicity study (AdC68, pDNA, tremelimumab and sasanlimab ) in 
monkeys, the safety and VBIR-2 antigen-specific T-cell responses were evaluated following 
administration of AdC68 at 6 x 1011 VP using the same dosing frequency as planned for the 
VBIR-2 Phase 1 study.  As described in Section 1.4, findings were limited to the injection 
sites and the draining lymph nodes, as well as mononuclear cell infiltrates in a number of 
tissues, consistent with those observed with other anti-CTLA4 or anti-PD-1 inhibitors.  
Administration of AdC68 at 6 x 1011 VP with tremelimumab and sasanlimab led to 
substantial and sustained increases in MUC1-, MSLN-, and TERT-specific IFN-T-cell 
responses, which were further boosted by the pDNA with tremelimumab and sasanlimab  
treatment.  Thus, the AdC68 dose at 6 x 1011 VP was generally safe and efficacious in 
inducing immune responses in monkeys.
Based on the above pre-clinical safety and VBIR-2 antigen-specific immune response data in 
NHPs, and the clinical safety data from the ongoing Prostate Cancer VBIR study (PrCa 
VBIR)99 (also using 6 x 1011 VP administered IM), a dose of 2 x 1011 VP administered IM 
has been selected as the starting dose for AdC68 in Part 1 of the study.  The highest dose of 
AdC68 planned to be elevated in this study is 6 x 1011 VP.
1.6.2. Clinical pDNA (PF-0681925) Dosing
Efficacy and safety were factors considered to select the pDNA dose for clinical testing.  
DNA doses of 0.2 to 8 mg have been reportedly delivered in clinical trials by other sponsors 
using the Ichor Intramuscular TriGrid Delivery System (TDS-IM) electroporation device.  In 
NHPs, the data collected to date demonstrated that electroporation of a DNA dose of 5 mg 
can effectively and reproducibly boost AdC68 vector primed IFN-CD8 T-cell responses to 
a self-antigen in the presence of tremelimumab.  A pDNA dose of 10 mg was well tolerated 
but no significant benefit on the magnitude or responder frequency of the IFN-CD8 T-cell 
response was observed (the results are from PrCaVBIR NHP studies; VR-VTR-10228; The 
Impact of pDNA Dose on Vaccine-Specific Immune Responses at Boost Vaccinations). 
Thus, a dose of 5 mg is selected for the pDNA for clinical testing.
1.6.3. Clinical Tremelimumab (PF-06753388) Dosing
More than 1000 participants with cancer have been treated with tremelimumab as 
single-agent or in combination with another anti-cancer treatment.  Clinical safety data for 
tremelimumab, at intravenous (IV) doses ranging from 0.01 to 15 mg/kg, indicate an 
acceptable safety profile in participants with cancer.  The established maximum tolerated 
dose (MTD) for single-agent therapy is 15 mg/kg IV every 12 weeks, a dose level that has 
been extensively studied in a Phase 3 trial in participants with melanoma.101  Diarrhea, 
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with tremelimumab.  Another important event observed related to tremelimumab was 
hypopituitarism.
Monthly dosing, as planned for this study, was tested in the clinic in participants with 
melanoma, where administration of up to 10 mg/kg IV monthly,102 was tolerated with no 
dose-limiting toxicity observed.  The most frequent treatment-related AEs being diarrhea, 
rash, and pruritus.  Frequency of Grade 3/4 AEs was 27% in the participants dosed with 
10 mg/kg tremelimumab alone, compared to 16.3 % in participants treated with nivolumab 
alone, and 27.3 % of participants treated with ipilimumab alone.  Treatment-related adverse 
events leading to therapy discontinuation occurred in 36.4, 7.7, and 14.8 % of participants, 
respectively (most commonly diarrhea, fatigue, and pruritus).
1.6.4. Clinical Sasanlimab Dosing 
Binding of the programmed cell death protein-1 ligands, PD-L1 and PD-L2, to the 
programmed cell death protein-1 (PD-1) receptor found on T cells inhibits T-cell 
proliferation, cytokine production, and its cytotoxic functions.  Upregulation of PD-1 ligands 
occurs in certain tumor types, and signaling through this pathway can contribute to the 
inhibition of active T-cell immune surveillance of tumors.103  In syngeneic mouse tumor 
models, blocking PD-1 activity resulted in decreased tumor growth.  Approval of 
nivolumab/Opdivo(a fully human immunoglobulin G4 [IgG4] anti-PD-1 antibody [Ab]), 
pembrolizumab/Keytruda(a humanized IgG4 anti-PD-1 Ab), Atezolizumab/Tecentriq(a 
humanized IgG1 anti-PD-L1 Ab), durvalumab/Imfizi® (a humanize IgG1 anti-PD-1 
antibody), and avelumab/Bavencio(a fully human IgG1 anti-PD-L1 Ab) for the treatment 
of multiple tumor indications provide compelling evidence that blockage of the 
PD-1 pathway is a validated immunotherapeutic approach (Opdivo® United States Package 
Insert (USPI), 2020; Tecentriq® USPI, 2019; Keytruda® USPI, 2020; ImfinziTM USPI, 2020; 
Bavencio® USPI, 2019).104,105,106,107,108
1.6.4.1. Sasanlimab Clinical Experience B8011001 (NCT02573259)
B8011001 is an ongoing Phase 1, open-label, multi-center, multiple-dose, dose escalation 
and expansion, safety, PK, and PD study of sasanlimab.  The primary purpose of this study is 
to evaluate safety and early signs of efficacy.  This clinical study was divided into a dose 
escalation (Part A) phase and a dose expansion (Part B) phase.  One hundred forty-six 
participants have been dosed on the study.  No dose limiting toxicity was observed and there 
was no maximum tolerated dose identified.
Part A Dose Escalation evaluated 4 pre-specified IV dose levels (0.5, 1, 3, and 10 mg/kg 
administered every 3 weeks [Q3W]), and 1 subcutaneous (SC) dose level (300 mg 
administered every 4 weeks [Q4W]) in adult participants with locally advanced or metastatic 
melanoma, squamous cell cancer of head and neck, ovarian cancer, sarcoma, small cell lung 
cancer, adenocarcinoma of salivary gland, endometrial adenocarcinoma, malignant peritoneal 
neoplasm, esophageal adenocarcinoma or renal cell carcinoma.  Participants had progressive 
disease on ≥1 prior line of therapy for locally advanced or metastatic disease or refused 
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had adequate renal, bone marrow, liver, and cardiac function, with Eastern Cooperative 
Oncology Group (ECOG) performance status 0 or 1.  Forty participants were enrolled into 
Part A with 25 participants total enrolled into the IV dose cohorts and 15 participants 
enrolled into the SC dose cohort.  
Part B Dose Expansion evaluated the 300 mg SC dose in a population of 106 participants.  
This included 68 participants with locally advanced or metastatic non-small cell lung cancer 
(NSCLC) and 38 participants with locally advanced or metastatic urothelial carcinoma who 
were anti-PD-1 or anti-PD-L1 treatment-naïve and who had progressive disease on or were 
intolerant to systemic therapy or for whom standard of care systemic therapy was refused or 
unavailable.  Participants with NSCLC could have received up to 1 line of prior systemic 
therapy for locally advanced or metastatic disease and if they had known epidermal growth 
factor receptor (EGFR) activating mutation or an anaplastic lymphoma kinase (ALK) 
rearrangement were required to have, in addition, at least 1 targeted therapy for their disease.  
Participants with UC could have received up to 2 lines of prior systemic therapies for locally 
advanced or metastatic disease.  The selected participants had adequate renal, bone marrow, 
liver, and cardiac function, with ECOG performance status 0 or 1.  All participants received 
300 mg of sasanlimab SC every 4 weeks. 
1.6.4.2. Sasanlimab Clinical Experience in B7791001 (NCT#02616185)
B7791001 is a study of a similar vaccine-based immunotherapy regimen in prostate cancer 
using prostate directed antigens (VBIR PrCA).  
 
 
 
 
 
 
 
 
 
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1.6.5. Combination of CTLA-4 and PD-1 Monoclonal Antibodies: Safety Findings
Available data suggest that, in both metastatic NSCLC, small-cell lung cancer (SCLC) and 
melanoma, combined PD-1 and CTLA-4 blockade produce a higher tumor response rate and 
longer disease control than PD-1 or CTLA-4 blockade alone.  Unfortunately, these improved 
results are associated with an increased rate of toxicity.
In the pretreated NSCLC population, pembrolizumab given iv at 2 or 10 mg/kg every 
3 weeks combined with ipilimumab iv either at 1 or 3 mg/kg every 3 weeks for four doses 
was associated with 49% serious treatment-related adverse event rate, compared to 10% with 
pembrolizumab monotherapy.  The most frequent serious adverse events were diarrhea in 
6% and pneumonitis in 8% of participants.  The recommended dosage for future trials was 
pembrolizumab 2 mg/kg plus ipilimumab 1 mg/kg both given every 3 weeks 
intravenously.116
Similarly a combination of nivolumab (anti-PD-1) plus ipilimumab has been tested.35  
Serious treatment-related adverse events were observed in 48% of participants; grade 3–4 
adverse events were seen in 55% of participants (most commonly diarrhea, fatigue, and 
pruritus) compared to 16.3% in participants treated with nivolumab alone, and 27.3 % of 
participants treated with ipilimumab alone.  Combined therapy resulted in 35% of 
participants discontinuing treatment as compared to 7.7% and 14.8% of participants treated 
with nivolumab and ipilimumab, respectively. 
In a Phase 1b study of durvalumab (anti-PD-1) and tremelimumab, there was an increased 
rate of serious adverse events of 42%, compared to 8% with durvalumab monotherapy. 
Durvalumab 20 mg/kg given iv every 4 weeks plus tremelimumab 3 mg/kg iv was more 
toxic, with an increased rate of diarrhea and colitis, without improved efficacy relative to 
tremelimumab 1 mg/kg. In participants with tremelimumab 1 mg/kg, most adverse events 
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were manageable and did not require treatment discontinuation. Overall, treatment-related 
adverse events and grade 3 or 4 adverse events were more frequent with the regimen of
durvalumab 10 mg/kg every 2 weeks plus tremelimumab 1 mg/kg, compared to the regimen
with durvalumab 20 mg/kg every 4 weeks plus tremelimumab at 1 mg/kg. Given the above, 
durvalumab 20 mg/kg every 4 weeks plus tremelimumab 1 mg/kg regimen has been selected 
for assessment in phase 3 studies.117,118
In a study of nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung 
cancer (CheckMate 032),119 two (2) schedules of administration were compared: nivolumab 
1 mg/kg plus ipilimumab 3 mg/kg versus nivolumab 3 mg/kg plus ipilimumab 1 mg/kg.  The 
percentage of grade 3 / 4 toxicities was 30% with 3mg/kg ipilimumab and 19% with 1 mg/kg 
ipilimumab.
Considering the data reported in the literature about the combination anti-PD-1 (or PD-L1) 
and anti CTLA-4 inhibitors, the dose and frequency of anti CTLA4 appears to be the major 
determinant of toxicity, compared to dose levels of PD-1 or PD-L1. 
1.6.6. Clinical Dosing VBIR-2
The proposed VBIR-2 (PF-06936308) clinical dosage, dosage form, route of administration, 
and dosing regimen are outlined in Table 2.  There are 2 treatment phases in VBIR-2:
(a) Active Treatment Phase:
Each VBIR-2 cycle will be initiated with an intramuscular AdC68 priming vaccination 
accompanied by subcutaneous administrations of tremelimumab and sasanlimab.  Three 
monthly intramuscular pDNA boost vaccinations by electroporation, along with concomitant 
administrations of tremelimumab and sasanlimab subcutaneously will follow the AdC68
vaccination.  The single AdC68 priming vaccination followed by 3pDNA boost vaccinations 
(each given monthly) concludes 1 treatment cycle of 4 months duration. The second 
treatment cycle will be initiated with another priming of intramuscular AdC68 vaccination, 
with later boost vaccinations of pDNA, along with a subcutaneous administration of
tremelimumab and sasanlimab, as noted for Cycle 1.  The second treatment cycle will follow 
the same injection schedule as outlined for the first cycle. The activities during the Active 
Treatment Phase are outlined in the Schedule of Activities for Active Treatment.
(b) Maintenance Treatment Phase: 
Following the second treatment cycle the participants enter a “Maintenance Phase”, 
consisting of monthly doses of sasanlimab with pDNA and tremelimumab, given at every-
other-month intervals. A description of this Maintenance Phase is outlined in the Schedule of 
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Table 2.
Expansion Phase Components, Dosage, Dosage Form, Route of 
Administration, and Dosing Regimen of the Vaccine-Based 
Immunotherapy Regimen for NSCLC (See Section 5 for detailed Study 
Treatment instructions.)
Component
Dosage 
Form
Dose
Route of 
Administration
Dosing Regimen
AdC68
Liquid
6e11 VP 
Bilateral IM 
injection
Priming dose (administered on Cycle 
1 Day 1)
pDNA*
Liquid
5 mg
Bilateral IM 
injection with 
electroporation
Every 4 weeks after AdC68 dose for a 
total of 3 doses
Tremelimumab*
Liquid
80 mg
Bilateral SC 
injection
Every 4 weeks for a total of 4 doses 
per cycle given on the day of AdC68 
or pDNA administration
Sasanlimab**
Liquid
300 mg
Bilateral SC 
injection
Every 4 weeks for a total of 4 doses 
given on the day of AdC68 or pDNA 
administration
Abbreviations: AdC68 = Adenovirus C68; IM = Intramuscular; SC = Subcutaneous.
*Maintenance Treatment Schedule for pDNA and tremelimumab after Month 8 will be administered every other 
month starting with Month 10.
**Maintenance Treatment Schedule for sasanlimab starting at Month 9 will continue to be administered monthly.
Treatment will be continued until disease progression, unacceptable toxicity, death, or participant’s or investigator’s 
decision.
(1) Single Reference Safety Document for VBIR-2
Additional information for VBIR-2 may be found in the single reference safety document 
(SRSD), which for this study is the PF-06936308 Investigator Brochure for: AdC68 
(PF-06871923), plasmid DNA (PF-06871925), sasanlimab (PF-06801591) and 
tremelimumab (PF-06753388).
(2) Single Reference Safety Document for Intramuscular TriGrid Electroporation 
Delivery System
The SRSD for the Ichor Intramuscular TriGrid Delivery System electroporation device is the 
TrigridDelivery System Version 2.0 Investigator Brochure. 
Additional reference information can be found in the individual tremelimumab IB and the 
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2. STUDY OBJECTIVES AND ENDPOINTS
2.1. Part 1: Dose Escalation Objectives and Endpoints
Primary Objective(s): Part 1
Primary Endpoint(s): Part 1
•
To assess safety and tolerability of
increasing dose levels of VBIR-2.
•
To characterize the dose limiting toxicities 
(DLTs) and overall safety profile of 
escalated doses of VBIR-2.
•
To assess safety and tolerability at 
increasing dose levels of VBIR-2 
components in successive cohorts of 
participants s in order to estimate the 
Maximum Tolerated Dose (MTD) and 
select the Recommended Phase 2 Dose 
(RP2D)/schedule.
•
Incidence and grade of treatment-emergent 
adverse events including DLTs (following 
the 28-day DLT observation period). 
•
Adverse Events as characterized by type, 
frequency, severity, timing, seriousness, and 
relationship to study therapy.
•
Laboratory abnormalities as characterized 
by type, frequency, severity, and timing.
Secondary Objective(s): 
Secondary Endpoint(s): 
•
To evaluate the PK of tremelimumab and 
of sasanlimab after SC administration.
•
To evaluate the anti-drug antibody (ADA) 
response of tremelimumab and sasanlimab 
after SC administration with the other 
components.
•
Tremelimumab and sasanlimab single-dose 
PK parameters, including the maximum 
concentration (Cmax), time to maximum 
concentration (Tmax), and if data permit, area 
under the concentration-time curve (AUC) 
from time zero extrapolated to infinity 
(AUC0-∞); and trough concentrations after 
multiple dosing (Ctrough).
•
Incidence and titers of ADA and 
neutralizing antibodies against 
tremelimumab and against sasanlimab.
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•
To document any preliminary evidence of 
anti-tumor activity.
•
Objective tumor response, as assessed using 
the Response Evaluation Criteria in Solid 
Tumor (RECIST) version 1.1 by calculating 
the Objective Response Rate (ORR) and 
Progression-Free Survival (PFS).
2.2. Part 2: Dose Expansion Objectives and Endpoints
Primary Objective(s): Part 2
Primary Endpoint(s): Part 2
•
To document preliminary evidence of 
anti-tumor activity using the Clinical 
Benefit rate (CBR) in participants with 
NSCLC.
•
To assess safety and tolerability of 
VBIR-2 in participants with NSCLC.
•
CBR (proportion of participants who 
achieve Complete Response, Partial 
Response  or Stable Disease for > 6 months)
using the Response Evaluation Criteria in 
Solid Tumor (RECIST) version 1.1 
(Appendix 3).
•
Adverse Events as characterized by type, 
frequency, severity, timing, seriousness, and 
relationship to study therapy.
•
Laboratory abnormalities as characterized 
by type, frequency, severity, and timing.
Secondary Objective(s): 
Secondary Endpoint(s): 
•
To document preliminary evidence of 
anti-tumor activity in participants with 
NSCLC.
•
To evaluate the PK of tremelimumab and 
of sasanlimab after SC administration.
•
To evaluate the anti-drug antibody (ADA) 
response of tremelimumab and sasanlimab 
after SC administration with the other 
components.
•
Objective Response Rate (ORR), Duration 
of Response (DOR) and Progression-Free 
Survival (PFS) using RECIST version 1.1 
(Appendix 3).
•
Overall survival (OS).
•
Tremelimumab and sasanlimab trough 
concentrations after multiple dosing (Ctrough) 
at various time points.
•
Incidence and titers of ADA and 
neutralizing antibodies against 
tremelimumab and against sasanlimab.
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3. STUDY DESIGN
3.1. Study Overview
This is a Phase 1, open label, multi-center, multiple dose, safety, PK, PD and 
immunogenicity study evaluating the components of VBIR-2 (PF-06936308), now solely in 
participants with advanced or metastatic NSCLC or TNBC.  
The study is divided into two parts, Dose Escalation (Part 1) in participants with NSCLC and 
TNBC without acceptable alternative treatment options, followed by Dose Expansion (Part 2) 
in participants with NSCLC who have progressed on or after treatment with platinum-based 
chemotherapy and treatment with ≤1 immune checkpoint inhibitor, given concurrently or 
sequentially with chemotherapy.    
Dose Escalation (Part 1)
The Dose Escalation (Part 1) completed its determination of MTD after 6 cohorts. It enrolled  
36 participants in Part 1.  It included participants for whom no standard therapy was available
for advanced or metastatic NSCLC or TNBC, without restrictions as to the prior number of 
lines of immunotherapy or chemotherapy.  
Six dose escalation cohorts were investigated:
•
AdC68 2 x 10
11 VP +5 mg pDNA. 
•
AdC68 6 x 1011 VP +5 mg pDNA:
•
If needed – dose reduction of the AdC68 dose to 2 x 1011 VP is allowed.
•
AdC68 6 x 10
11 VP +5 mg pDNA +40 mg tremelimumab.*
•
AdC68 6 x 1011 VP +5 mg pDNA +40 mg tremelimumab +130 mg sasanlimab*:
•
AdC68 6 x 1011 VP +5 mg pDNA +40 mg tremelimumab +300 mg sasanlimab;
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•
AdC68 6 x 10
11 VP +5 mg pDNA +80 mg tremelimumab +300 mg sasanlimab.*
* If needed – dose reduction of the tremelimumab or sasanlimab dose is allowed.
3.1.1. Criteria for Dose Escalation
The principles of modified toxicity probability interval (mTPI) design,140 will be utilized for 
the dose escalation portion of the study. 
An mTPI design, targeting a DLT rate of 27.5% and an acceptable DLT equivalence interval 
(22.5% to 32.5%), will be utilized in the dose escalation phase.
The dose levels to be evaluated are given in Figure 1.  If a high DLT rate is observed at the 
starting dose, the study may explore a lower dose or may be stopped.
Each cohort would enroll 2 to 4 DLT evaluable participants and at least 6 and up 
to 12 participants would be enrolled at a dose level that is predicted to be the MTD as per the 
mTPI method.  Dose cohorts with an acceptable safety profile may be expanded up to N=12 
to further assess safety,
 pharmacokinetics, 
.  
Decisions to enroll additional participants at dose levels already cleared for safety will be 
based on clinical judgment.
The mTPI method relies upon a statistical probability algorithm, calculated using all 
participants treated in the current dose level to determine one of the following dose-finding 
decisions: the subsequent dose should be escalated, maintained at the current dose, or 
de-escalated in the next cohort of 2 to 4 participants, or the trial should be terminated.  It is 
currently envisaged that AdC68 6 x 10
11 VP +5 mg pDNA +150 mg tremelimumab +300 mg 
ANTI-PD-1 (PF-06801591) will potentially be the highest dose level. 
Table 3.
Decision Rules
Number of participants treated at current dose
#DLTs
1
2
3
4
5
6
7
8
9
10
11
12
0
E
E
E
E
E
E
E
E
E
E
E
E
1
D
S
S
S
E
E
E
E
E
E
E
E
2
U
D
S
S
S
S
S
S
S
E
E
3
U
U
D
D
S
S
S
S
S
S
4
U
U
U
U
D
S
S
S
S
5
U
U
U
U
U
D
S
S
6
U
U
U
U
U
U
U
•
Columns indicate number of participants in the cohort and rows indicate number of participants with DLTs
•
E= Escalate to the next higher dose; S: Stay at the same dose; D: De-escalate to the previous lower dose; U: De-escalate to the 
previous lower dose and the current dose will never be used again in the trial 
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If a participant discontinues close to Day 28 for reasons other than toxicity and due to an 
evident non drug-related event, the participant may be deemed evaluable for safety if safety 
assessments have been unremarkable and the investigator and sponsor’s medical monitor 
both agree that the participant is evaluable for DLT safety observation.
The dose escalation Part 1 of the study will stop if any of the following criteria is met:
The maximum sample size has been achieved (approximately 36 participants in total as per 
the current dosing schedule); 
6 to 12 participants have been enrolled at a dose level that is predicted to be the MTD 
according to Table 3;
All dose levels explored appear to be overly toxic, and the MTD cannot be determined;
All candidate dose levels have been tested and deemed safe.
As an example, if the total number of participants (cumulative in the study) treated at the 
current dose is 4, the following dosing rules are applied:
0-1 DLT -> escalate;
1 DLT -> remain at the same dose;
2 DLTs -> De-escalate to the previous or intermediate lower dose;
3-4 DLTs -> De-escalate and consider current dose as intolerable.
Activation of each cohort will occur no sooner than 28 days after the first 2-4 participants 
receive the first AdC68 vaccination, but may occur later if the sponsor and investigators 
determine additional safety data is needed.  The Pfizer clinical team and investigators will 
review all available safety data from the previous and current cohorts prior to making a 
decision to dose escalate.  If no safety issues that would prohibit dose escalating are 
observed, the next cohort of participants would be open for accrual. 
If dose escalation continues up to a predefined Maximum Feasible Dose (MFD), the 
escalation is halted without a maximum tolerated dose (MTD) estimate.  In those 
circumstances, the MFD may be the recommended Phase 2 dose (RP2D).
3.1.2. Dose Expansion (Part 2)
The Expansion Phase will enroll participants in 1 cohort of participants with metastatic or 
locally-advanced NSCLC who have previously received treatment with a platinum-based 
chemotherapy regimen and not more than one treatment with an immune checkpoint inhibitor 
regimen either concurrently or sequentially with the chemotherapy.

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Participants will participate in the active treatment period of the study for approximately 
9 months.  This includes a 28 day screening period followed by 2 cycles of vaccine 
treatment, totaling 8 months in duration. After completion of the active treatment phase 
(vaccine prime, pDNA boosts, checkpoint inhibitor support), participants will then enter the 
maintenance phase of the study (pDNA boosts only with checkpoint inhibitor support).
Treatment will continue until: disease progression, unacceptable toxicity, death or 
participant’s or investigator’s decision occurs. Since the treatment effect of cancer 
immunotherapy can often be delayed, participants will be encouraged to continue on study 
treatment for at least 24 weeks before an investigator considers removing the participant due 
to disease progression, as long as (a) Participant and investigator agree; (b) Participant
continues to meet all other study protocol eligibility criteria; (c) Toxicity remains acceptable; 
and (d) No deterioration of participant performance status.  Disease progression will be 
confirmed with 2 consecutive timepoints at least 4-8 weeks apart in the absence of rapid 
clinical deterioration.
Participants who demonstrate clinical benefit with manageable toxicity and who are willing 
to continue receiving study treatment will be given the opportunity to continue treatment 
upon agreement between the investigator and sponsor.  When the participant discontinues 
treatment, they will then enter a 6 month post-dose follow-up period to assess safety 
 
  The end of the study is the last participant last visit.
The overall design is presented in Figure 1 below:
Figure 1.
Study Design
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3.2. DLT Definition
Severity of adverse events (AEs) will be graded according to Common Terminology Criteria 
for Adverse Events (CTCAE) version 5.0.  For the purpose of dose escalation, any of the 
following AEs occurring in the first 28 days following the first AdC68 vaccination that are 
considered possibly related to study treatment and are not considered related to 
disease/progression will be classified as DLTs:
Hematologic:

Grade ≥3 neutropenia lasting >7 days.

Febrile neutropenia (febrile neutropenia is defined as an absolute neutrophil count 
<1.0 × 109/L with a single temperature of >38.3C, or 101F, or a sustained
temperature of 38C, or 100.4F, for more than one hour).

Grade 3 neutropenic infection.

Grade 3 thrombocytopenia with ≥ Grade 2 clinically significant bleeding (for 
bleeding events with no grading available, clinically significant bleeding is defined as 
requiring hospitalization or urgent medical intervention).

Grade 3 anemia lasting more than 7 days.

Grade 3 lymphopenia lasting more than 14 days.
Nonhematologic:

Grade ≥3 AEs that are considered non-hematologic, non-hepatic major organ toxicity 
(excluding alopecia of any grade; Grade 3 nausea/vomiting or diarrhea <72 hours with 
adequate antiemetic and other supportive care; ≥ Grade 3 electrolyte abnormality that 
lasts <24 to 72 hours, is not clinically complicated, and resolves spontaneously or 
responds to conventional medical interventions).

Grade 3 flu-like symptoms lasting greater than 3 days with adequate treatment.

Fever of >40.0°C, or 104.0°F, lasting for more than 3 days with adequate treatment.

Concurrent aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 
>3x upper limit of normal (ULN) and total bilirubin >2x ULN (potential Hy’s law 
case).

Nonhematologic laboratory abnormalities: Grade ≥3 laboratory abnormalities either 
associated with symptoms or associated with worsening of an existing condition or 
that suggests a new disease process or that requires additional active management 
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assessments, further diagnostic investigation or specific treatment).In addition, 
clinically important or persistent toxicities that are not included in the above criteria 
may be considered a DLT following review by Pfizer and the investigators.  All DLTs 
need to represent a clinically significant shift from baseline.
The following AEs will not be adjudicated as DLTs:

Isolated Grade 3 laboratory abnormalities that are not associated with clinical 
sequelae and are corrected with supplementation/appropriate management within 
72 hours of onset.
3.3. MTD Definition
The MTD is defined as the highest dose with true toxicity probabilities in the equivalence 
interval (EI) where the EI is defined as (22.5%, 32.5%).
Even though the mTPI model may select an MTD with an incidence of DLTs that is higher 
than 32.5% since mTPI decision rules are based on unit probability mass (UPM) and not on 
point estimates of the DLT rate (see Section 9.2.1), doses with an incidence of DLT >32.5% 
(eg, 3 out of 9) cannot be declared as the MTD.  In practice, model recommendations may be 
overridden by clinical judgment, and MTD with an incidence of DLTs that is higher than 
32.5% will not be considered acceptable to be selected as MTD. 
3.4. Toxicities Observed in the Expansion Phase
Adverse events that meet the same grading criteria as the DLT criteria listed above will be 
discussed promptly by Pfizer and Investigators during the next available Safety meeting.  At
the meeting, the details of the toxicity will be presented, and actions to be taken (if any) will 
be discussed, which may involve individual participants, or the Expansion Cohort as a whole.
3.5. Recommended Part 2 Expansion Dose Definition
The RP2D is the dose chosen for further investigation based on Phase 1 study results.  If the 
MTD proves to be clinically feasible for long-term administration in a reasonable number of 
participants, then this dose usually becomes the RP2D.  Further experience with the MTD 
may result in a RP2D dose lower than the MTD.
The Expansion Dose recommended for Part 2 is: AdC68 6 ×1011 VP, 5 mg of pDNA, 80 mg 
of tremelimumab and 300 mg of sasanlimab.  
4. PARTICIPANT ELIGIBILITY CRITERIA
This study can fulfill its objectives only if appropriate participants are enrolled.  The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate.  All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
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4.1. Inclusion Criteria
Participant eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before participants are included in the study.
Participants, for each assigned part, must meet all of the following inclusion criteria to be 
eligible for enrollment in the study:
4.1.1. Part 1 Inclusion Criteria
1. Histological or cytological diagnosis of advanced NSCLC or metastatic TNBC 
(defined as HER2 negative by IHC, fluorescence in situ hybridization (FISH) or
chromogenic in situ hybridization (CISH) and ≤10% ER/PR stain positive by IHC) 
with progressive disease that is resistant to standard therapy or for which no standard 
therapy is available or is refused by the participant. 
2. A mandatory archived formalinfixed paraffin embedded (FFPE) tumor tissue block 
(preferred) must be provided.  If an FFPE tumor tissue block cannot be provided, sites 
should contact sponsor for approval to submit slides.  For Part 1, if an archived FFPE 
tissue is not available, a de novo (ie, fresh) tumor sample can substitute and should be 
obtained in accordance with local institutional practice for tumor biopsies. 
3. Females and/or male participants age 18 years. 
4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
5. Measurable disease as per RECIST v. 1.1. 
6. Adequate Bone Marrow Function, including:
a.
Absolute Neutrophil Count (ANC) 1,500/mm3 or 1.5 x 109/L;
b. Platelets 100,000/mm3 or 100 x 109/L;
c.
Hemoglobin 9 g/dL. 
7. Adequate Renal Function, including:
a.
Estimated creatinine clearance 60 mL/min as calculated using the method 
standard for the institution.  In unequivocal cases, a 24 hour urine can be collected 
and used to estimate the creatinine clearance more accurately. 
8. Adequate Liver Function, including:
a.
Total serum bilirubin 1.5 x ULN unless the participant has documented Gilbert 
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b. Aspartate and Alanine aminotransferase (AST and ALT) 2.5 x ULN; 
5.0 x ULN if there is liver involvement by the tumor; 
c.
Alkaline phosphatase 2.5 x ULN (5 x ULN in case of bone metastasis). 
9. Resolved acute effects of any prior therapy to baseline severity or National Cancer 
Institute (NCI) CTCAE V5.0 Grade 1 except for adverse events (AEs) not 
constituting a safety risk by investigator judgment.
10. Serum or urine pregnancy test (for females of childbearing potential) negative at 
screening.
11. Female participants of nonchildbearing potential must meet at least 1 of the following 
criteria:

Achieved postmenopausal status, defined as follows: cessation of regular menses 
for at least 12 consecutive months with no alternative pathological or 
physiological cause; status may be confirmed with a serum follicle-stimulating 
hormone (FSH) level confirming the postmenopausal state;

Have undergone a documented hysterectomy and/or bilateral oophorectomy; 

Have medically confirmed ovarian failure. 
All other female participants (including female participants with tubal ligations) 
are considered to be of childbearing potential. 
12. Evidence of a personally signed and dated informed consent document indicating that 
the participant [or a legally acceptable representative/parent(s)/legal guardian] has 
been informed of all pertinent aspects of the study].
13. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and 
other procedures. 
4.1.2. Part 2 Inclusion Criteria
1. Histological or cytological diagnosis of locally advanced or metastatic NSCLC 
(squamous or non-squamous histology) meeting the following criteria:
a.
Receipt of at least 1, but not more than 2, prior treatment regimens in the 
advanced disease setting.  In addition to participants with established metastatic or 
recurrent disease, the advanced disease setting also includes participants with 
platinum-based adjuvant, neoadjuvant, or definitive chemoradiation therapy given 
for locally advanced disease followed by recurrent or metastatic disease within 6 
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b. Prior treatment must have included an anti-PD-1/PD-L1 and a platinum-based 
chemotherapy, which may have been given in combination, or sequentially;
c.
Prior treatment must have included an appropriate TKI if activating mutations are 
present, eg, EGFR/ALK/ROS1/BRAF/RET/TRK;
d. Most recent treatment must have included anti-PD-1/PD-L1 for at least 4 months, 
without radiographic disease progression, followed by confirmed radiographic 
disease progression on or within 12 weeks of the last dose;
e.
No more than 1 prior anti-PD-1/PD-L1 treatment regimen may have been given;
f.
Prior anti-PD-1/PD-L1 may not have been discontinued permanently for toxicity.
g. No prior treatment may have been given with any immunologic therapy other than 
anti PD-1 or PD-L1.
2. A mandatory archived formalinfixed paraffin embedded (FFPE) tumor tissue block 
(preferred) must be provided.  If an FFPE tumor tissue block cannot be provided, sites 
should contact sponsor for approval to submit slides.  If an archived FFPE tissue is not 
available, a de novo (ie, fresh) tumor sample can substitute and should be obtained in 
accordance with local institutional practice for tumor biopsies. 
3. Females and/or male participants age 18 years. 
4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
5. Measurable disease as per RECIST v. 1.1. 
6. Adequate Bone Marrow Function, including:
a.
Absolute Neutrophil Count (ANC) 1,500/mm3 or 1.5 x 109/L;
b. Platelets 100,000/mm3 or 100 x 109/L;
c.
Hemoglobin 9 g/dL. 
7. Adequate Renal Function, including:
a.
Estimated creatinine clearance 60 mL/min as calculated using the method 
standard for the institution.  In unequivocal cases, a 24 hour urine can be collected 
and used to estimate the creatinine clearance more accurately. 
8. Adequate Liver Function, including:
a.
Total serum bilirubin 1.5 x ULN unless the participant has documented Gilbert 
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b. Aspartate and Alanine aminotransferase (AST and ALT) 2.5 x ULN; 
5.0 x ULN if there is liver involvement by the tumor; 
c.
Alkaline phosphatase 2.5 x ULN (5 x ULN in case of bone metastasis).
9. Resolved acute effects of any prior therapy to baseline severity or National Cancer 
Institute (NCI) CTCAE V5.0 Grade 1 except for adverse events (AEs) not 
constituting a safety risk by investigator judgment. Participants with hypothyroidism 
or hypopituitarism resulting from immunotherapy who are stable on chronic hormone 
replacement therapy are eligibile, as are participants with adrenal insufficiency 
receiving doses <15mg/day or prednisone. 
10. Serum or urine pregnancy test (for females of childbearing potential) negative at 
screening.
11. Female participants of nonchildbearing potential must meet at least 1 of the following 
criteria:

Achieved postmenopausal status, defined as follows: cessation of regular menses 
for at least 12 consecutive months with no alternative pathological or 
physiological cause; status may be confirmed with a serum follicle-stimulating 
hormone (FSH) level confirming the postmenopausal state;

Have undergone a documented hysterectomy and/or bilateral oophorectomy; 

Have medically confirmed ovarian failure. 
All other female participants (including female participants with tubal ligations) 
are considered to be of childbearing potential. 
12. Evidence of a personally signed and dated informed consent document indicating that 
the participant or a legally acceptable representative has been informed of all pertinent 
aspects of the study].
13. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and 
other procedures. 
4.2. Part 1 Exclusion Criteria
Participants, for each assigned part, with any of the following characteristics/conditions will 
not be included in the study:
4.2.1. Part 1 Exclusion Criteria
1. Participants with known symptomatic brain metastases, with the following two 
exceptions:

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a.
Participants with previously diagnosed brain metastases are eligible if they have 
completed their treatment and have recovered from the acute effects of radiation 
therapy or surgery prior to study entry, have discontinued corticosteroid treatment 
for these metastases for at least 4 weeks and are neurologically stable for 
3 months (confirmed by MRI)
b. Participants with newly diagnosed brain metastases identified by a screening brain 
MRI who are clinically asymptomatic are eligible if the Investigator deems their 
clinical status acceptable for participation in the trial and all other inclusion and 
exclusion criteria are satisfied, including being neurologically stable for 3 months 
since the screening brain MRI.  A baseline MRI at screening is to be conducted 
only if clinically indicated based on the treating Investigator’s judgement
2. History of prior malignancy other than the disease under study within the past 3 years 
excluding successfully resected treated basal cell carcinoma or squamous cell 
carcinoma of the skin or adequately treated carcinoma in situ.
3. Participants with intolerance to or who have had (Grade 3) allergic or anaphylactic 
reaction to antibodies or infused therapeutic proteins.
4. Major surgery within 4 weeks prior to study entry.
5. Radiation therapy within 4 weeks prior to study entry. 
6. Systemic anticancer therapy within 4 weeks prior to study entry.
7. Participant has AE(s) due to cancer therapeutics administered >4 weeks earlier, which 
have not recovered to CTCAE Grade 1 (except alopecia, and except for AEs not 
constituting a safety risk by investigator judgment).
8. Active and clinically significant bacterial, fungal, or viral infection, including hepatitis 
B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus 
(HIV) or acquired immunodeficiency syndrome (AIDS)related illness. 
HIV seropositive participants, who are healthy and low-risk for AIDS-related 
outcomes,143 may qualify for inclusion in the study after discussion with the Sponsor. 
The following criteria for immune status and HIV ongoing therapy must be met for a 
HIV seropositive participant to be eligible for the study: 
a.
Immune status criteria: 

CD4+ T-cell counts ≥350 cells/μL at the study start;

No history of AIDS-defining opportunistic infections; 

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
Only remote AIDS-defining opportunistic infections in the past and none 
in one year prior to study start.
b. Ongoing HIV therapy criteria: 

Must be receiving recommended concurrent ART treatment according to 
NIH guidelines;144

Began ART treatment >4 weeks prior to study start (to ensure ART is 
tolerated and toxicities are not confused with study drug toxicities);

HIV viral load <400 copies/mL for >4 weeks prior to study start (to ensure 
ART is tolerated and HIV controlled). 
Anti-retroviral medications should be listed as concomitant medication.
Equivocal cases of viral hepatitis may be eligible if they have a negative viral load.  
9. Receipt of an immunosuppressive dose of corticosteroids (ie, 10 mg prednisone daily 
or equivalent)  or other immunosuppressive medication (eg, methotrexate, rapamycin) 
within 2 weeks of registration.  Note: Participants with adrenal insufficiency may take 
5 mg of prednisone or equivalent daily.  Topical applications, inhaled sprays, eye 
drops or local injections of corticosteroids are allowed.  Low dose corticosteroids for a 
short duration [5 mg once daily (QD) prednisone for 2 weeks] as symptomatic 
treatment and upon with discussion with the sponsor is allowed.
10. History of or active autoimmune disorders (including but not limited to: myasthenia 
gravis, thyroiditis, pneumonitis, rheumatoid arthritis, multiple sclerosis, systemic lupus 
erythematosus, scleroderma) and other conditions that disorganize or alter the immune 
system.  Active inflammatory gastrointestinal disease, Crohn’s disease, ulcerative 
colitis, and primary sclerosing cholangitis are excluded, however, gastroesophageal 
reflux disease under treatment with protonpump inhibitors is allowed (assuming no 
drug interaction potential).
11. Acetylcholine receptor binding antibody ≥0.5 nmol/L. 
12. Abnormal neurologic examination at screening indicating possible underlying 
autoimmune disorder(s).
13. Any of the following in the previous 12 months or currently: myocardial infarction, 
severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic 
congestive heart failure, cerebrovascular accident, transient ischemic attack or 
symptomatic pulmonary embolism, as well as ongoing cardiac dysrhythmias of NCI 
CTCAE Grade 2, atrial fibrillation or any grade, or QTc interval >470 msec at 
screening. 

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14. Individuals in whom a skin-fold measurement of the cutaneous and subcutaneous 
tissue for two or more eligible injection sites exceeds 50 millimeters (mm).
15. Bleeding diathesis or condition associated with prolonged bleeding time that would 
contraindicate IM injection.
16. Current use of any implanted electronic stimulation device, such as cardiac demand 
pacemakers, automatic implantable cardiac defibrillator, nerve stimulators, or deep 
brain stimulators.
17. Presence of any surgical or traumatic metal implants at the site of administration 
(medial deltoid muscles or overlying skin or vastus lateralis muscle).
18. Hypertension that cannot be controlled by medications (>150/100 mmHg despite 
optimal medical therapy).
19. Participation in other studies involving investigational drug(s) within 4 weeks prior to 
study entry. 
20. Known or suspected hypersensitivity to any of the VBIR-2 components. 
21. Other acute or chronic medical or psychiatric condition, including recent (within the 
past year) or active suicidal ideation or behavior or laboratory abnormality that may 
increase the risk associated with study participation or investigational product 
administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator, would make the participant inappropriate for entry into 
this study.
22. COVID-19/SARS-CoV2: SARS-CoV2 testing is not mandated for entry into this 
protocol.  However, testing should follow local clinical practice standards and 
requirements.  A positive result on an approved test, even if the participant is 
asymptomatic, excludes a participant from this trial.
23. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or 
participants who are Pfizer employees, including their family members, directly 
involved in the conduct of the study.
24. Fertile male participants and female participants of childbearing potential who are 
unwilling or unable to use 2 highly effective methods of contraception as outlined in 
this protocol for the duration of the study and for at least 5 months after the last dose 
of investigational product [per Section 4.3 below].

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4.2.2. Part 2 Exclusion Criteria
Participants with any of the following characteristics/conditions will not be included in the 
study:
1. Participants with known symptomatic brain metastases, with the following 2
exceptions:
a.
Previously Diagnosed Brain Metastases: Participants with previously diagnosed 
brain metastases are eligible if (a) they have completed their treatment and have 
recovered from the acute effects of radiation therapy or surgery prior to study 
entry, (b) have discontinued corticosteroid treatment for these metastases for at 
least 4 weeks and are neurologically stable for 3 months (confirmed by MRI).
b. Screening-Detected Brain Metastases: Participants with newly diagnosed brain 
metastases identified by a screening brain MRI who are clinically asymptomatic 
are eligible if (a) the Investigator deems their clinical status acceptable for 
participation in the trial and (b) all other inclusion and exclusion criteria are 
satisfied, including being neurologically stable for 3 months since the screening 
brain MRI.  A baseline MRI at screening is to be conducted only if clinically 
indicated, based on the treating Investigator’s judgement.
2. History of prior malignancy other than the disease under study within the past 3 years 
excluding successfully resected treated basal cell carcinoma or squamous cell 
carcinoma of the skin or adequately treated carcinoma in situ.
3. Participants with high-volume or visceral spread of disease, or those who are 
symptomatic from their disease, such that they are at risk for life threatening 
complications in the short term. Examples include participants with uncontrolled 
pleural, pericardial, or peritoneal effusions; pulmonary lymphangitis; and over 50% 
liver involvement.  Note: Participants with indwelling catheter(s) for drainage, or 
requirement for intermittent drainage no more frequently than monthly, will be 
considered eligible.
4. Participants with intolerance to or who have had (Grade 3) allergic or anaphylactic 
reaction to antibodies or infused therapeutic proteins.
5. Major surgery within 4 weeks prior to first dose.
6. External beam radiation therapy to large areas of the thorax or other sites within 4 
weeks prior to first dose; focal, palliative radiation within 2 weeks of first dose.
7. Systemic anticancer therapy within 2 weeks prior to first dose.
8. Participant has AE(s) due to cancer therapeutics administered >4 weeks earlier, which 
have not recovered to CTCAE Grade 1 (except alopecia, and except for AEs not 
constituting a safety risk by investigator judgment).

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9. Active and clinically significant bacterial, fungal, or viral infection, including hepatitis 
B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus 
(HIV) or acquired immunodeficiency syndrome (AIDS) related illness. 
HIV seropositive participants, who are healthy and low-risk for AIDS-related 
outcomes,143 may qualify for inclusion in the study after discussion with the Sponsor. 
The following criteria for immune status and HIV ongoing therapy must be met for a 
HIV seropositive participant to be eligible for the study: 
a.
Immune status criteria: 

CD4+ T-cell counts ≥350 cells/μL at the study start;

No history of AIDS-defining opportunistic infections; 

Only remote AIDS-defining opportunistic infections in the past and none 
in 1 year prior to study start.
b. Ongoing HIV therapy criteria: 

Must be receiving recommended concurrent ART treatment according to 
NIH guidelines;144

Began ART treatment >4 weeks prior to study start (to ensure ART is 
tolerated and toxicities are not confused with study drug toxicities);

HIV viral load <400 copies/mL for >4 weeks prior to study start (to ensure 
ART is tolerated and HIV controlled). 
Anti-retroviral medications should be listed as concomitant medication.
Equivocal cases of viral hepatitis may be eligible if they have a negative viral load.  
10. Receipt of an immunosuppressive dose of corticosteroids (ie, 10 mg prednisone daily 
or equivalent)  or other immunosuppressive medication (eg, methotrexate, rapamycin) 
within 2 weeks of registration.  Note: Participants with adrenal insufficiency may take 
5 mg of prednisone or equivalent daily.  Topical applications, inhaled sprays, eye 
drops or local injections of corticosteroids are allowed.  Low dose corticosteroids for a 
short duration [5 mg once daily (QD) prednisone for 2 weeks] as symptomatic 
treatment and upon with discussion with the sponsor is allowed.
11. History of or active autoimmune disorders (including but not limited to: myasthenia 
gravis, thyroiditis, pneumonitis, rheumatoid arthritis, multiple sclerosis, systemic lupus 
erythematosus, scleroderma) and other conditions that alter the immune system.  
Active inflammatory gastrointestinal disease, Crohn’s disease, ulcerative colitis, and 

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primary sclerosing cholangitis are excluded; however, non-immune mediated 
gastroesophageal reflux disease (esophagitis/gastritis) under treatment with proton 
pump inhibitors is allowed (assuming no drug interaction potential).
12. Acetylcholine receptor binding antibody ≥0.5 nmol/L.
13. Abnormal neurologic examination at screening indicating possible underlying 
autoimmune disorder(s).
14. Any of the following in the previous 12 months or currently: myocardial infarction, 
severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic 
congestive heart failure, cerebrovascular accident, transient ischemic attack or 
symptomatic pulmonary embolism, as well as ongoing cardiac dysrhythmias of NCI 
CTCAE Grade 2, atrial fibrillation of any grade, or QTc interval >470 msec at 
screening.
15. Cardiac Troponin-I (cTnI) must be measured and found to be within the normal 
reference range before the administration of the first dose.  Abnormal circulating 
levels of cTnI are exclusionary.
16. Individuals in whom a skin-fold measurement of the cutaneous and subcutaneous 
tissue for 2 or more eligible injection sites exceeds 50 millimeters (mm).
17. Bleeding diathesis or condition associated with prolonged bleeding time that would 
contraindicate IM injection.
18. Current use of any implanted electronic stimulation device, such as cardiac demand 
pacemakers, automatic implantable cardiac defibrillator, nerve stimulators, or deep 
brain stimulators.
19. Presence of any surgical or traumatic metal implants at the site of administration 
(medial deltoid muscles or overlying skin or vastus lateralis muscle).
20. Hypertension that cannot be controlled by medications (>150/100 mmHg despite 
optimal medical therapy).
25. Severely symptomatic Chronic Obstructive Pulmonary Disease (eg, requiring 
ambulatory oxygen).
21. Participation in other studies involving investigational drug(s) within 4 weeks prior to 
study entry. 
22. Known or suspected hypersensitivity to any of the VBIR-2 components. 
23. Other acute or chronic medical or psychiatric condition, including recent (within the 
past year) or active suicidal ideation or behavior or laboratory abnormality that may 
increase the risk associated with study participation or investigational product 
administration or may interfere with the interpretation of study results and, in the 

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judgment of the investigator, would make the participant inappropriate for entry into 
this study.
24. COVID-19/SARS-CoV2: SARS-CoV2 testing is not mandated for entry into this 
protocol.  However, testing should follow local clinical practice standards and 
requirements.  A positive result on an approved test, even if the participant is 
asymptomatic, excludes a participant from this trial.
25. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or 
participants who are Pfizer employees, including their family members, directly 
involved in the conduct of the study.
26. Fertile male participants and female participants of childbearing potential who are 
unwilling or unable to use 2 highly effective methods of contraception as outlined in 
this protocol for the duration of the study and for at least 5 months after the last dose 
of investigational product [per Section 4.3 below].
4.3. Lifestyle Requirements (Part 1 and Part 2) 
The investigator or his or her designee, in consultation with the participant, will confirm that 
the participant has selected an appropriate method of contraception for the individual 
participant [and his or her partner(s)] from the permitted list of contraception methods (see 
list below) and will confirm that the participant has been instructed in its consistent and 
correct use.  At time points indicated in the Schedule of Activities, the investigator or 
designee will inform the participant of the need to use 2 highly effective methods of 
contraception consistently and correctly and document the conversation, and the participant’s 
affirmation, in the participant’s chart.  In addition, the investigator or designee will instruct 
the participant to call immediately if 1 or both of the selected contraception methods is 
discontinued or if pregnancy is known or suspected in the participant or partner. 
In addition, the investigator or designee will instruct the participant to call immediately if the 
selected contraception method is discontinued or if pregnancy is known or suspected in the 
participant or partner. 
Highly effective methods of contraception are those that, alone or in combination, result in a 
failure rate of less than 1% per year when used consistently and correctly (ie, perfect use) and 
include:
1. Correctly placed copper-containing intrauterine device (IUD).
2. Male condom or female condom used WITH a spermicide (ie, foam, gel, film, cream, 
or suppository).  For countries where spermicide is not available or condom plus 
spermicide is not accepted as highly effective contraception, this option is not 
appropriate.
3. Male sterilization with absence of sperm in the postvasectomy ejaculate. 

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4. Bilateral tubal ligation/ bilateral salpingectomy or bilateral tubal occlusive procedure 
(provided that occlusion has been confirmed in accordance with the device’s label).
a.
All sexually active male participants must agree to prevent potential transfer to 
and exposure of partner(s) to drug through ejaculate by using a condom 
consistently and correctly, beginning with the first dose of investigational product 
and continuing for; at least 5 months after the last dose of [investigational product 
OR comedication].
4.4. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor’s appropriately qualified medical personnel for the 
study is documented in the study contact list located in the supporting Study Manual and in 
the team SharePoint Site.
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with an Emergency Contact Card (ECC).  
The ECC contains, at a minimum, (a) Protocol and investigational product identifiers; (b) 
Participant study numbers; (c) At least 2 emergency phone numbers, active 24 hours/day, 7 
days/week, all holidays and weekends, providing a method to contact both the Principal 
Investigator and the Research Site; and (d) a Pfizer Call Center number. 
The ECC is to be used only by outside medical personnel, not involved in the research study, 
primarily as a means of contacting the Principal Investigator or Research Site related to the 
care of a study participant.  The Pfizer Call Center information is to be used only in the event 
that, after calling the phone numbers of both the Principal Investigator and Research Site 
Staff, neither could not be reached in case of an Emergency.  
The ECC should be used only in the event that the established communication pathways 
between the Principal Investigator, the Research site, and the Study Team are not available.  
Importantly, the ECC is intended to augment, and not to replace, the established 
communication pathways between the Principal Investigator, the Research site, and the Study 
Team for advice on medical issues arising during the study. The ECC is not intended for use 
by the participant directly; if a participant calls the Pfizer Call Center directly, the participant 
will be directed back to the Principal Investigator or Research site.
5. STUDY TREATMENTS
For the purposes of this study, and per International Conference on Harmonisation (ICH) 
guidelines, investigational product is defined as a pharmaceutical form of an active 
ingredient or placebo being tested or used as a reference/comparator in a clinical trial, 
including a product with a marketing authorization when used or assembled (formulated or 
packaged) in a way different from the approved form, or when used for an unapproved 
indication, or when used to gain further information about an approved use (ICH E6 1.33).

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For this study, the investigational product VBIR-2 (PF-06936308) consists of:
Reagent
PF #
AdC68, an adenovirus prime vaccination
PF-06871923
pDNA, aPlasmid DNA boost vaccination
PF-06871925
Tremelimumab, an CTLA4 monoclonal antibody
PF-06753388
Sasanlimab, an anti-PD-1 monoclonal antibody
PF-06801591
5.1. Allocation to Treatment
Eligible participants will be enrolled to receive components of VBIR-2 in an open-labeled, 
unblinded manner.  In Part 1, participants will be successively assigned to the next available 
treatment slot at a dose level decided on after the previous cohort’s safety evaluation and 
ongoing observations of earlier enrolled participants. 
Dose level allocation will be performed by the sponsor after participants have given their 
written informed consent and have completed the necessary baseline assessments. The site 
staff will email a completed Registration Form to the designated sponsor study team member.  
The sponsor will assign a participant identification number documenting participant 
enrollment. 
No participant shall receive investigational product until the investigator or designee has 
received the following information in writing from the sponsor:

Confirmation of the participant’s enrollment;

Specification of the dose level for that participant;

Permission to proceed with dosing the participant. 
The sponsor or designee will notify the other sites of the inclusion of a new participant, and 
will inform study sites about the next possible enrollment date.
5.2. Participant Compliance
All doses of adenovirus, pDNA, tremelimumab and sasanlimab will be administered by the 
appropriately designated study staff at the investigational site.  The site will complete the 
required dosage Preparation Record located in the Investigational Product manual.  The use 
of the Preparation Record is preferred but it does not preclude the use of an existing 
appropriate clinical site documentation system.  The existing clinical site’s documentation 
system should capture all pertinent/required information on the preparation and 
administration of the dose.  This may be used in place of the Preparation Record after 
approval from the Pfizer monitor. 
Participants who fail to comply with the study requirements may be withdrawn from the 
study. 

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5.3. Investigational Product Supplies 
All components of VBIR-2 will be supplied by Pfizer.  VBIR-2 consists of the following 
components: Adenovirus (AdC68), plasmid DNA (pDNA), tremelimumab and sasanlimab.  
Sites will be provided with the following supplies:

PF-06871923 AdC68 Solution for Injection 3 x 1011 VP/mL;

PF-06871925 pDNA Solution for Injection 2.5 mg/mL;

PF-06753388 Tremelimumab Solution for Injection 100 mg/mL;

TDS-IM V 2.0 electroporation device and associated supplies (eg, cartridges) for 
pDNA administration;

PF-06801591 Sasanlimab Solution for Injection 50 mg/mL.
Study centers will receive a supply of clinical trial materials upon site activation with 
instructions on how to confirm drug receipt.  Resupplies will be made during the course of 
the study based on need.  Study centers will supply commonly available sterile syringes and 
needs for IM and SC administration.  The details on drug supply will be provided in the 
Investigational Product Manual (IP Manual).  The study monitor should be contacted for any 
issues related to drug supplies.
5.3.1. Dosage Form(s) and Packaging
PF-06871923 AdC68 Solution for Injection is presented as a sterile solution for 
intramuscular administration.  Each vial contains AdC68 at 3 x 1011 VP/mL in an aqueous 
buffered solution.  Each vial is filled with an adequate volume to eject a minimum 1.0 mL 
from a syringe with an IM needle attached.  The vial is sealed with a stopper and an overseal 
and labeled according to local regulatory requirements.  Two vials will be dispensed per 
participant, regardless of dose, to facilitate bilateral injection.
PF-06871925 pDNA Solution for Injection, 2.5 mg/mL, is presented as a sterile solution for 
intramuscular administration.  Each glass prefilled syringe (PFS) contains pDNA at 
2.5 mg/mL in aqueous buffered solution.  The PFS is filled with an adequate volume to eject 
1.0 mL when administered using the TDS-IM V 2.0 electroporation device.  The PFS is 
sealed with a plunger stopper and a tip cap and labeled according to local regulatory 
requirements.  Two (2) prefilled syringes will be dispensed per participant.
Each TDS-IM V 2.0 6mm Application cartridge, for unique use, for intramuscular 
administration of the pDNA solution will be supplied in a sterile tray (one cartridge/tray) 
labeled according to local regulatory requirements.
PF-06753388 Tremelimumab Solution for Injection is presented as a sterile solution.  Each 
vial contains tremelimumab at 100 mg/mL in aqueous buffered solution.  The vial is filled 
with an adequate volume to eject a minimum 0.75 mL from a syringe with a SC needle 

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attached.  The vial is sealed with a stopper and an overseal and labeled according to local 
regulatory requirements.  Two vials will be dispensed per participant, regardless of dose, to 
facilitate bilateral injection.
PF-06801591 Sasanlimab Solution for Injection 50 mg/mL is presented as a sterile solution.  
Each vial contains 100 mg of sasanlimab in 2 mL of aqueous buffered solution, and contains 
a sufficient amount to ensure an extractable volume of 2 mL.  Each vial is sealed with a 
stopper and an overseal, and labeled according to local regulatory requirements.
5.3.2. Preparation and Dispensing
AdC68, tremelimumab and sasanlimab are provided as single use vials; pDNA is provided as 
a single use prefilled syringe.  They will be packaged and dispensed in cartons with tamper 
evident seals.  The cartons should not be opened until the drug is to be administered.  For the 
adenovirus, pDNA, tremelimumab and sasanlimab, see the Investigational Product (IP) 
manual and the TDS-IM V 2.0 Instructions for Use for instructions on how to prepare the 
investigational products for administration.
The TDS-IM v2.0 6mm Application cartridges for the administration of the plasmid are 
provided for single use, and will be packaged and dispensed in cartons with tamper evident 
seals.  The cartons should not be opened until the time of administration.
Investigational product should be prepared and dispensed by an appropriately qualified and 
experienced member of the study staff (eg, physician, nurse, physician’s assistant, nurse 
practitioner, pharmacy assistant/technician, or pharmacist) as allowed by local, state, and 
institutional guidance. 
Only qualified personnel who are familiar with procedures that minimize undue exposure to 
themselves and to the environment should undertake the preparation, handling, and safe 
disposal of biologic agents. 
5.4. Administration
All AdC68 intramuscular injections are given bilaterally.  AdC68 will be administered on 
Day 1 of Cycles 1 and 2.  Please refer to the IP manual for full instructions on the dosage and 
administration.
Plasmid DNA intramuscular injections are given bilaterally.  pDNA will be administered 
beginning on Day 29 of Cycles 1 and 2 and will then be given at 4 week intervals.  After 
Cycle 2, pDNA will continue to be administered every 2 months in the Maintenance 
Treatment Period.  Please refer to the IP manual for full instructions on the dosage and 
administration of the pDNA and to the TDS-IM V 2.0 Instructions for Use document for the 
set up and use of the electroporation device.  The TDS-IM device should be operated by 
clinical personnel that have completed the necessary training on device operation.

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All IM injections (AdC68 and pDNA) will be given bilaterally in the deltoid muscles or in 
the vastus lateralis muscles of the quadriceps.  Preference should be given to the vastus
lateralis muscles when possible.
Tremelimumab will be administered bilaterally subcutaneously at 4 week intervals during 
Cycles 1 and 2 on the same day as the AdC68 or pDNA dosing as described in the 
SCHEDULE OF ACTIVITIES.  After Cycle 2, tremelimumab will continue to be 
administered every 2 months in the Maintenance Treatment Period.  Both AdC68 and pDNA 
injections should be given prior to tremelimumab administration.  Please refer to the IP 
manual for full instructions on the dosage and administration of tremelimumab.  
Tremelimumab is to be administered in close proximity to the vaccination site.  If the 
vaccination is administered in the vastus lateralis, the tremelimumab is to be administered SC 
in either the lower quadrants of the abdomen or the quadriceps.  If the vaccination is 
administered in the deltoid, the tremelimumab is to be administered SC bilaterally in the 
outer triceps.
Sasanlimab will be administered bilaterally subcutaneously at 4 week intervals on the same 
day as the AdC68 or pDNA and tremelimumab during Cycles 1 and 2 as described in the 
SCHEDULE OF ACTIVITIES.  The AdC68 or pDNA as well as the tremelimumab doses 
should be given prior to sasanlimab administration.  During the Maintenance Treatment 
Period, participants will continue to be dosed with sasanlimab at monthly intervals until 
confirmed disease progression per RECIST.  Please refer to the IP manual for full 
instructions on the dosage and administration of sasanlimab.  Sasanlimab is to be 
administered in close proximity to the vaccination site.  If the vaccination is administered in 
the vastus lateralis, the sasanlimab is to be administered SC bilaterally in the lower quadrants 
of the abdomen.  If the vaccination is administered in the deltoid, the sasanlimab is to be 
administered SC bilaterally in the outer triceps.
5.4.1. Recommended Dose Modifications
Every effort should be made to administer investigational product on the planned dose and 
schedule.
In the event of significant toxicity, dosing may be delayed and/or reduced as described 
below.  In the event of multiple toxicities, dose modification should be based on the worst 
toxicity observed.  Participants are to be instructed to notify investigators at the first 
occurrence of any adverse symptom.
Dose modifications may occur in one of three ways:

Within a cycle: dosing interruption until adequate recovery and dose reduction, if 
required, during a given treatment cycle; 

Between cycles: next cycle administration may be delayed due to persisting toxicity 
when a new cycle is due to start;

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
In the next cycle: dose reduction may be required in a subsequent cycle based on 
toxicity experienced in the previous cycle. 
5.4.2. Dosing Interruptions/Delays due to Treatment Related Toxicity
Participants experiencing Grade 3 or 4 potentially treatment related toxicity or intolerable 
Grade 2 toxicity despite supportive care should have their treatment with all of the 
components interrupted/delayed.  Appropriate follow-up assessments should be done until 
adequate recovery occurs as assessed by the investigator.
Re-treatment following treatment interruption for treatment related toxicity or at the start of 
any new cycle may not occur until all of the following parameters have been met:

ANC 1,000/mm3. 

Platelets count 50,000/mm3. 

Non-hematologic toxicities have returned to baseline or Grade 1 severity (or, at the 
investigator discretion, Grade 2 if not considered a safety risk for the participant).
If a treatment delay results from worsening of hematologic or biochemical parameters, the 
frequency of relevant blood tests should be increased as clinically indicated.
5.4.3. If these conditions are met within 2 weeks of treatment interruption or cycle 
delay, investigational product(s) may be resumed.  Refer to section Dosing 
Interruptions/Delays due to Non-Related Events
If participants require treatment interruption for reasons other than treatment-related  toxicity 
(eg, surgery) lasting >4weeks, treatment resumption should be decided in consultation with 
the Sponsor.  
In the event of active SARS-CoV2 infection confirmed (positive by regulatory authority-
approved test) or presumed (test pending/clinical suspicion), the following criteria apply:

For symptomatic participants with active SARS-CoV2 infection, investigational 
treatment should be delayed for at least 14 days from start of symptoms.

This delay is intended to allow resolution of symptoms of SARS-CoV2 infection.

Prior to restarting treatment, the participants should be afebrile for 72 hours and 
SARS-CoV2-related symptoms should have recovered to ≤Grade 1 for a minimum of 
72 hours.

Discuss with the Sponsor prior to restarting treatment.

Consider potential drug-drug interactions (as described per study protocol) for any 
concomitant medication administered for treatment of SARS-CoV2 infection.

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Dose Reductions for adverse events requiring dose reduction at the time of treatment 
resumption. 
If these conditions are not met, treatment resumption must be delayed up to a maximum of 
2 weeks.  If these parameters have not been met after 2 weeks of dosing interruption or 
2 weeks of new cycle delay, permanent discontinuation of treatment should be considered.  
Treatment resumption for participants recovering from treatment-related toxicity after 
>2 weeks of treatment interruption or cycle delay may be considered only if the participant is 
deemed to be deriving obvious clinical benefit per the investigator’s best medical judgment 
and needs to be agreed between the investigator and the sponsor.
5.4.4. Dosing Interruptions/Delays due to Non-Related Events 
If participants require treatment interruption for reasons other than treatment-related toxicity 
(eg, surgery) lasting >4weeks, treatment resumption should be decided in consultation with 
the Sponsor.  
In the event of active SARS-CoV2 infection confirmed (positive by regulatory 
authority-approved test) or presumed (test pending/clinical suspicion), the following criteria 
apply:

For symptomatic participants  with active SARS-CoV2 infection, investigational 
treatment should be delayed for at least 14 days from start of symptoms.

This delay is intended to allow resolution of symptoms of SARS-CoV2 infection.

Prior to restarting treatment, the participants should be afebrile for 72 hours and 
SARS-CoV2-related symptoms should have recovered to ≤Grade 1 for a minimum of 
72 hours.

Discuss with the Sponsor prior to restarting treatment.

Consider potential drug-drug interactions (as described per study protocol) for any 
concomitant medication administered for treatment of SARS-CoV2 infection.
5.4.5. Dose Reductions
Following dose interruption or cycle delay due to toxicity, the investigational product(s) may 
need to be reduced when treatment is resumed.
No specific dose adjustments are recommended for Grade 1/2 treatment-related toxicity, 
unless otherwise specified.  However, investigators should always manage their participants 
according to their medical judgment based on the particular clinical circumstances.

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5.4.5.1. AdC68 Dose Reductions
Changes in the dose levels for AdC68 will be discussed with the sponsor.  Dose reduction of 
adenovirus by 1 dose level may be allowed in Part 1 depending on the type and severity of 
toxicity encountered.  No dose level reduction is allowed in Part 2.  All dose 
modifications/adjustments must be clearly documented in the participant’s source notes and 
CRF.
Once a dose has been reduced for a given participant, all subsequent cycles should be 
administered at that dose level for that participant, unless further dose reduction is required.  
Dose re-escalation for adenovirus is not allowed.
Table 4.
AdC68 Available Dose Levels (Part 1)
Dose Level
AdC68*
+1
6 x 1011 VP
Starting
2 x 1011 VP
Table 5.
AdC68 Available Dose Levels (Part 2)
Dose Level
AdC68*
Starting 
6 x 1011 VP
-1
2 x 1011 VP
Table 6.
Dose Modifications for AdC68 Related Toxicity
Toxicity
Grade ½
Grade 3
Grade 4
Non-hematologic 
(other than irAE 
management 
described in 
Appendix 5)
Continue at the same 
dose level.
Withhold dose until toxicity is 
Grade 1, or has returned to 
baseline, then resume treatment at 
the same dose level or reduce the 
dose by 1 level at the discretion of 
the investigator*.
Discontinue treatment.
Hematologic
Continue at the same 
dose level.
Withhold dose until toxicity is 
Grade 2, or has returned to 
baseline, then resume treatment at 
the same dose level.
Discontinue treatment.
* Nausea, vomiting, or diarrhea must persist at Grade 3 despite maximal medical therapy to require dose 
modification.
5.4.5.2. Tremelimumab Dose Reductions
Changes in the dose levels for tremelimumab will be discussed with the sponsor.  A dose 
reduction of tremelimumab by 1 dose level (from 80 mg to 40 mg) may be allowed 
depending on the type and severity of toxicity encountered.  In addition, an intermediate dose 
may be considered.  Participants requiring a dose level lower than 40 mg will be discontinued 
from treatment and enter into the follow-up phase unless otherwise agreed between the 
investigator and sponsor.  Algorithms for the management of suspected pulmonary, 

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gastrointestinal (GI), liver, endocrine, skin, neurological and renal toxicities have been 
developed (See Appendix 5).  All dose modifications/adjustments must be clearly 
documented in the participant’s source notes and case report form (CRF).
Once a dose has been reduced for a given participant, all subsequent cycles should be 
administered at that dose level, unless further dose reduction is required.  Dose re-escalation 
for tremelimumab is not allowed.
Table 7.
Tremelimumab Available Dose Levels (Part 1)
Dose Level
Tremelimumab
Starting 
40 mg
+1
80 mg
Table 8.
Tremelimumab Available Dose Levels (Part 2)
Dose Level
Tremelimumab
Starting 
80 mg
-1
40 mg
Table 9.
Dose Modifications for Tremelimumab Related Toxicity When Given in 
Combination with AdC68 and pDNA
Toxicity
Grade ½
Grade 3
Grade 4
Non-hematologic
Continue at the same 
dose level.
Withhold dose until toxicity is 
Grade 1, or has returned to 
baseline, then resume treatment at 
the same dose level or reduce the 
dose by 1 level at the discretion of 
the investigator.*
Discontinue treatment.
Hematologic
Continue at the same 
dose level.
Withhold dose until toxicity is 
Grade 2, or has returned to 
baseline, then resume treatment at 
the same dose level.
Discontinue treatment.
* Nausea, vomiting, or diarrhea must persist at Grade 3 despite maximal medical therapy to require dose 
modification.
5.4.5.3. Sasanlimab Dose Reductions
Events including, but not limited to, pneumonitis, colitis, creatinine and liver function test 
(LFT) elevation should be monitored carefully with this class of agents.  Dose reductions 
may be required for sasanlimab, tremelimumab or potentially both compounds depending on 
the event and the severity of the toxicity.  Dose reductions of sasanlimab from 300 mg to 130 
mg may be allowed.  In addition an intermediate dose may be considered.  All dose 
modifications/adjustments must be clearly documented in the participant’s source notes and 
CRF.

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Table 10.
Sasanlimab Available Dose Levels (Part 1)
Dose Level
Sasanlimab
Starting
130 mg
+1
    300 mg
Table 11.
Sasanlimab Available Dose Levels (Part 2)
Dose Level
Sasanlimab
Starting
300 mg
-1
130 mg
Algorithms for the management of suspected pulmonary, GI, liver, endocrine, skin, 
neurological and renal toxicities have been developed (See Appendix 5).
Participants requiring >4 weeks of dose interruption should be considered for discontinuation 
of treatment with sasanlimab.  Participants may be allowed to resume dosing with the 
AdC68, pDNA and tremelimumab without sasanlimab  for one dose with plans to resume 
sasanlimab at the next dosing time point if agreed upon by the investigator and sponsor.   
Participants who discontinue sasanlimab due to toxicity will be allowed to remain in the 
study and continue treatment with the other components.
The following serves as demonstrating general rules.  Action may differ in specific cases 
based on evaluation by the investigator and the sponsor.

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Table 12.
Dose Modifications for Sasanlimab and/or Tremelimumab  Related 
Toxicity
Toxicity
Grade 1
Grade 2
Grade 3
Grade 4
Non-hematologic
Continue at the 
same dose level.
For pneumonitis, 
endocrinopathy, colitis, 
creatinine, AST, ALT, 
or total bilirubin 
elevations, withhold 
dose until toxicity is 
Grade ≤1, or has 
returned to baseline, 
then resume at the 
same dose level or 
reduce by 1 level 
(considering each 
compound separately) 
at the discretion of the 
investigator.
For all other events, 
continue at the same 
dose level.
For pneumonitis, colitis, 
endocrinopathy, 
creatinine, AST, ALT or 
total bilirubin elevations, 
or pruritus discontinue 
treatment.** 
For all other events 
withhold dose until 
toxicity is Grade 1, or
has returned to baseline, 
then resume treatment at 
the same dose level or 
reduce the dose by 
1 level (considering each 
compound separately) at 
the discretion of the 
investigator.*  
Treatment may resume 
with VBIR-2 with an 
interruption of 
sasanlimab for one dose 
at the discretion of the 
investigator. 
Discontinue 
treatment.**
Hematologic
Continue at the 
same dose level.
Continue at the same 
dose level.
Withhold dose until 
toxicity is Grade 2, or 
has returned to baseline, 
then resume treatment at 
the same dose level.
Discontinue 
treatment.**
* Nausea, vomiting, or diarrhea must persist at Grade 3 despite maximal medical therapy to require dose 
modification.
** For Grade ≥3 colitis or pneumonitis, discontinue treatment permanently.  For any grade of myocarditis 
discontinue treatment permanently.  For all other conditions participants may be allowed to remain in the 
study to receive the VBIR-2 2 after the toxicity is Grade ≤1 or returned to baseline, and only if agreed 
upon by the Investigator and Sponsor.
5.5. Investigational Product Storage 
The investigator, or an approved representative, eg, pharmacist will ensure that all 
investigational products are stored in a secured area with controlled access under required 
storage conditions and in accordance with applicable regulatory requirements.
Investigational products should be stored in their original containers and in accordance with 
the labels. 
Upon receipt at the site, all drug product should be immediately transferred, in its original 
container, to the appropriate monitored storage area.  Current storage conditions for 

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AdC68 vials are frozen (-20C5C).  The current storage conditions for the pDNA, 
tremelimumab and sasanlimab are refrigerated (2-8C). 
Any storage conditions stated in the SRSD will be superseded by the storage conditions 
stated on the product label.  Please see the Instructions for Use for details on storage of the 
TDS-IM device.
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated, and/or room-temperature products).  This should 
be captured from the time of investigational product receipt throughout the study.  Even for 
continuous monitoring systems, a log or site procedure that ensures active evaluation for 
excursions should be available.  The intent is to ensure that the minimum and maximum 
temperature is checked each business day to confirm that no excursion occurred since the last
evaluation and to provide the site with the capability to store or view the minimum/maximum 
temperature for all nonworking days upon return to normal operations.  The operation of the 
temperature monitoring device and storage unit (for example, refrigerator), as applicable, 
should be regularly inspected to ensure they are maintained in working order. 
Any excursions from the product label storage conditions should be reported to Pfizer upon 
discovery.  The site should actively pursue options for returning the product to the storage 
conditions described in the labeling, as soon as possible.  Deviations from the storage 
requirements, including any actions taken, must be documented and reported to Pfizer. 
Once an excursion is identified, the investigational product must be quarantined and not used 
until Pfizer provides permission to use the investigational product.  It will not be considered a 
protocol deviation if Pfizer approves the use of the investigational product after the 
temperature excursion.  Use of the investigational product prior to Pfizer approval will be 
considered a protocol deviation.  Specific details regarding information the site should report 
for each excursion will be provided to the site.
5.6. Investigational Product Accountability 
The investigator site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the investigational product supplies.  All investigational products will be 
accounted for using a drug accountability form/record. 
5.6.1. Destruction of Investigational Product Supplies 
The sponsor or designee will provide guidance on the destruction of unused investigational 
product (eg, at the site).  If destruction is authorized to take place at the investigator site, the 
investigator must ensure that the materials are destroyed in compliance with applicable 
environmental regulations, institutional policy, and any special instructions provided by 
Pfizer, and all destruction must be adequately documented.

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5.7. Concomitant Treatment(s)
Concomitant treatment considered necessary for the participant’s well-being may be given at 
discretion of the treating physician.
All concomitant treatments, blood products, as well as nondrug interventions received by 
participants from screening until the end of study visit will be recorded on the CRF.
5.7.1. Prohibited Concomitant Vaccines
No vaccines (licensed or investigational) other than study vaccine, influenza, COVID-19 and 
pneumococcal vaccines should be given during the study within 30 days prior to or after 
dosing.  Other vaccines may be administered only if medically necessary (eg, tetanus post 
exposure prophylaxis). 
For participants who receive tremelimumab, live attenuated vaccines should not be 
administered within 30 days prior to or after dosing with tremelimumab.  The administration 
of inactivated vaccines are allowed.
5.7.2. Other Anti-tumor/Anti-Cancer or Experimental Drugs
No additional anti-tumor treatment will be permitted while participants are receiving study 
treatment.  Additionally, the concurrent use of select vitamins or herbal supplements is not 
permitted
5.7.3. Supportive Care 
Palliative and supportive care for disease related symptoms may be administered at the 
investigator’s discretion and according to any available American Society of Clinical 
Oncology (ASCO) guidelines. 
Participants currently being treated with denosumab or bisphosphonates (eg, zoledronate) for 
bone disease may continue treatment while participating in this study.  However, initiation of 
treatment with these types of compounds should be avoided while participating in the study.
Palliative radiotherapy on study is permitted for the treatment of painful bony lesions 
providing the lesions were known at the time of study entry and the investigator clearly 
indicates that the need for palliative radiotherapy is not indicative of disease progression.
Participants currently being treated with a gonadotropin-releasing hormone agonist (GnRH 
agonist) may continue treatment while on clinical study C3621001 as long as the GnRH 
agonist treatment has been well tolerated for at least 3 months prior to study entry.
5.7.4. Hematopoietic Growth Factors
Primary prophylactic use of granulocyte-colony stimulating factors is not permitted during 
Cycle 1, but they may be used to treat treatment emergent neutropenia as indicated by the 
current American Society of Clinical Oncology guidelines.2  

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Erythropoietin may be used at the investigator’s discretion for the supportive treatment of 
anemia. 
5.7.5. Anti-Diarrheal, Anti-Emetic Therapy
Primary prophylaxis of diarrhea, nausea and vomiting is not permitted prior to the first dose 
of AdC68, tremelimumab and/or sasanlimab.  Primary prophylaxis on subsequent dosing 
days is at the investigator’s discretion.  The choice of the prophylactic drug is up to the 
investigator with sponsor approval and assuming the drug is not prohibited as specified in 
Section 5.7, as well as the duration of treatment assuming there is no known or expected 
drug-drug interaction.  If so, then it must be approved by the sponsor.
5.7.6. Anti-Inflammatory Therapy
Anti-inflammatory or narcotic analgesic may be offered as needed assuming there is no 
known or expected drug-drug interaction and assuming the drug is not included in the 
Concomitant Treatment(s) Section 5.7. 
5.7.7. Corticosteroids 
Chronic, systemic corticosteroid use for palliative or supportive purpose is not permitted.  
The short term use of corticosteroids (eg, 5 mg q.d. of prednisone for 2 weeks) as 
symptomatic treatment on an individual basis and upon discussion with the sponsor is 
allowed.  Acute emergency administration, topical applications, inhaled sprays, eye drops, or 
local injections of corticosteroids are allowed. 
5.7.8. Surgery 
Caution is advised on theoretical grounds for any surgical procedures during the study.  The 
appropriate interval of time between surgery and administration of VBIR-2 required to 
minimize the risk of impaired wound healing and bleeding has not been determined.  
Stopping all components of VBIR-2 is recommended at least 7 days prior to surgery.  
Postoperatively, the decision to reinitiate treatment should be based on a clinical assessment 
of satisfactory wound healing and recovery from surgery.
6. STUDY PROCEDURES 
6.1. Screening
For screening procedures see the Schedule of Activities and ASSESSMENTS sections.
6.2. Study Period
For the treatment period procedures, see the Schedule of Activities and ASSESSMENTS
sections.
6.3. End of Treatment
The End of treatment visit will be completed at the time point when a decision is made to 
discontinue study treatment.  This can occur during Cycles 1 or 2 or during the Maintenance 

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Treatment Phase of the study.  Obtain the specified EOT assessments (see Schedule of 
Activities) if not completed in the past two weeks (past 6 weeks for tumor assessments).
6.4. Follow-up 
For follow-up procedures see the Schedule of Activities and ASSESSMENTS sections.
6.5. Survival Follow-up
After treatment discontinuation, participant survival status will be collected every 3 months 
until death, participant refusal, or lost to follow-up (telephone contact acceptable).
6.6. Participant Withdrawal 
Withdrawal of consent:
Participants who request to discontinue receipt of study treatment will remain in the study 
and must continue to be followed for protocol specified follow-up procedures.  The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with them or persons previously authorized by the participant to provide this information.  
Participants should notify the investigator in writing of the decision to withdraw consent 
from future follow-up, whenever possible.  The withdrawal of consent should be explained in 
detail in the medical records by the Investigator, as to whether the withdrawal is only from 
further receipt of investigational product, or also from study procedures and/or posttreatment 
study follow-up; this information should be entered on the appropriate CRF page.  In the 
event that survival status (whether the participant is alive or dead) is being measured, and if 
publicly available information is part of the origin of this data, it is important that collecting 
this information should be carried out only as appropriately directed in accordance with local 
law.
Lost to follow-up:
All reasonable efforts must be made to locate participants to determine and report their 
ongoing status.  This includes follow-up with persons authorized by the participant as noted 
above.  “Lost to Follow-up” is defined by the inability to reach the participant after a 
minimum of 2 documented phone calls, faxes, or e-mails as well as lack of response by the 
participant to 1 letter sent by registered mail.  All attempts should be documented in the 
participant’s medical records.  If it is determined that the participant has died, the site will 
use locally-permissible methods to obtain the cause and the date of death.  If the 
investigator’s use of a third-party representative to assist in the follow-up portion of the study 
has been included in the participant’s informed consent, then the Investigator may use a 
sponsor-retained third-party representative to assist site staff with obtaining the participant’s 
contact information or other public survival status data necessary to complete the follow-up 
portion of the study.  The site staff and representative will consult publicly available sources, 
such as public health registries and databases, in order to obtain updated contact information.  
If, after all attempts, the participant remains lost to follow-up, then the last-known-alive date 

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as determined by the Investigator should be reported and documented in the participant’s 
medical records.
Participants may withdraw from treatment at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety (see also the 
Withdrawal From the Study Due to Adverse Events (see also the Participant Withdrawal
Section) or behavioral reasons, or the inability of the participant to comply with the 
protocol-required schedule of study visits or procedures at a given investigator site. 
Reasons for withdrawal of study treatment may include:

Objective disease progression; 

Global deterioration of health status requiring discontinuation;

Unacceptable toxicity;

Pregnancy;

Significant protocol violation;

Lost to follow-up;

Participant refused further treatment;

Study terminated by sponsor;

Death.
Reasons for withdrawal from study follow-up may include:

Completed study follow-up;

Study terminated by sponsor;

Lost to follow-up;

Refused further follow-up;

Death.
If a participant does not return for a scheduled visit, every effort should be made to contact 
the participant.  All attempts to contact the participant and information received during 
contact attempts should be documented in the participant’s medical record. Regardless of the 
circumstance, every effort should be made to document participant outcome, if possible.  The 
Investigator should inquire about the reason for withdrawal, request that the participant 

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return for a final visit, if applicable, and follow-up with the participant regarding any 
unresolved AEs.
If the participant refuses further visits, the participant should continue to be followed for 
survival (if survival is a secondary endpoint) unless the participant withdraws consent for 
disclosure of future information or for further contact.  In this case, no further study-specific 
evaluations should be performed and no additional data should be collected.  The Sponsor 
may retain and continue to use any data collected before such withdrawal of consent.
7. ASSESSMENTS
Every effort should be made to ensure that the protocol-required tests and procedures are 
completed as described.  However, it is anticipated that occasionally there may be 
circumstances outside of the control of the investigator that may make it unfeasible to 
perform the test.  In these cases the investigator must take all steps necessary to ensure the 
safety and well-being of the participant.  When a protocol-required test cannot be performed, 
the investigator will document the reason for this and any corrective and preventive actions 
that he or she has taken to ensure that normal processes are adhered to as soon as possible.  
The study team will be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, shipment 
instructions and contact information will be provided to the investigator site prior to initiation 
of the study.
7.1. Safety Assessment
Safety assessments will include collection of AEs, serious adverse events (SAEs), vital signs 
and physical examination, electrocardiogram (ECG [12-lead]), laboratory assessments, 
including pregnancy tests and verification of concomitant treatments.
7.1.1. Pregnancy Testing 
All pregnancy tests used in this study, either urine or serum, must have a sensitivity of at 
least 25 mIU/mL and must be performed by a certified laboratory.  For female participants of 
childbearing potential, 2 negative pregnancy tests are required before receiving study 
treatment(s) (1 negative pregnancy test at screening and 1 at the baseline visit immediately 
before study treatment administration).  Following a negative pregnancy test result at 
screening, appropriate contraception must be commenced and the second negative pregnancy 
test result will then be required at the baseline visit and within 5 days after the first day of the 
menstrual period (counting the first day of the menstrual period as Day 1) before the 
participant may receive the study treatment.  In the absence of regular menstrual bleeding, 
the study candidate should have used 2 forms of contraception for at least 1 month before the 
second pregnancy test.  Pregnancy tests will also be routinely repeated at (pre-dose) every 
cycle (Days 1, 29, 57, and 85) during the active treatment period, at the end of study 
treatment, at the 28-day Follow-Up visit to confirm that the participant has not become 
pregnant during the study.  Pregnancy tests will also be done whenever 1 menstrual cycle is 
missed or when potential pregnancy is otherwise suspected, and may be repeated if requested 

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by institutional review boards (IRBs)/ethics committees (ECs) or if required by local 
regulations.  In the case of a positive confirmed pregnancy, the participant will be withdrawn 
from administration of investigational product, but may remain in the study.
For female participants who achieved postmenopausal status and have not experienced their 
menses since at least 12 consecutive month, a serum FSH test must be conducted at screening 
only, in order to confirm a FSH level within the laboratory’s reference ranges for post 
menopause.
7.1.2. Adverse Events
Assessment of adverse events will include the type, incidence, severity (graded by the NCI 
CTCAE version 5.0) timing, seriousness, and relatedness.
7.1.3. Laboratory Safety Assessment
Hematology and blood chemistry will be drawn at the time points described in the Schedule 
of Activities and analyzed at local laboratories.
Table 13.
Safety Laboratory Tests
Hematology
Chemistry
Coagulation
Urinalysis
Pregnancy 
Test
Hemoglobin
ALT
PT or INR
Urine dipstick for 
urine protein: If 
positive collect 24-hr 
and microscopic 
(Reflex Testing)
For female 
participants of 
childbearing 
potential, serum 
or urine (see 
Section 7.1.1)
Platelets
AST
PTT
WBC
Alk Phos
Absolute Neutrophils
Sodium
Absolute Lymphocytes
Potassium
Absolute Monocytes
Magnesium
Urine dipstick for 
urine blood: If 
positive collect a 
microscopic (Reflex 
Testing)
Absolute Eosinophils
Total Chloride
Absolute Basophils
Total calcium
Total bilirubin1
BUN or Urea
Creatinine
Viral Tests2 (at Screening)
Uric Acid
Hepatitis B surface antigen2
Glucose (nonfasted)
Hepatitis B core antibody2
Albumin
Hepatitis C antibody2
Phosphorous or 
Phosphate
Human immunodefiency virus (HIV)2
Lactate 
dehydrogenase
Lipase
Amylase
Bicarbonate or 
carbon dioxide
Total protein
TSH + reflex free T4 
and free T3

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Table 13.
Safety Laboratory Tests
Hematology
Chemistry
Coagulation
Urinalysis
Pregnancy 
Test
1.
For potential Hy’s Law cases, in addition to repeating AST and ALT, laboratory tests should include 
albumin, creatine kinase, total bilirubin, direct and indirect bilirubin, gamma-glutamyl transferase, 
prothrombin time (PT)/INR, alkaline phosphatase, total bile acids and acetaminophen drug and/or 
protein adduct levels. 
2.
Hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, and human 
immunodeficiency virus (HIV).  Samples will be analyzed locally.
7.1.4. Vital Signs and Physical Examination
Participants will have a physical examination to include weight, vital signs, assessment of 
ECOG performance status and height; height will be measured at screening only.
A complete physical examination (PE) will be performed at Screening and at the End of 
Treatment visit for each participant and will include an assessment of all body systems.  A 
neurologic examination must be conducted at Screening to look for potential signs of 
underlying autoimmune disorders.  Findings of all physical examinations should be recorded 
in the source documents, and any change from baseline considered by the investigator to be 
clinically significant should be recorded as an adverse event in the CRF.
Abbreviated PEs should be performed as appropriate per the Schedule of Activities (SOA), 
and on an as needed basis for assessment of adverse events.  Abbreviated exams should be 
targeted to specific symptoms or complaints and be consistent with local standard of care.  
However, a neurologic examination must be performed during each exam conducted during 
Cycle 1.
Weight and body surface area (BSA) do not need to be performed at each visit; however 
participants should be monitored throughout the study for significant weight change. 
Vital signs should include measurements of blood pressure, pulse, and temperature (oral, 
temporal, tympanic or axillary).  On dosing days, vital signs should be measured prior to 
administration of any of the study treatments.  Sitting blood pressure (BP) and pulse after 
approximately 5 minutes rest should be measured with the participant’s arm supported at the 
level of the heart and recorded to the nearest mmHg.  The same arm shouldbe used 
throughout the trial.  A properly-sized and calibrated blood pressure cuff should be used to 
measure blood pressure.  The use of automated devices for measuring BP is acceptable.  
Vitals signs, including temperature, pulse, and BP to be recorded 1-hour post-study drug 
administration during each Cycle on Days 1, 29, 57, and 85.
Assessment of the skin and subcutaneous tissue thickness at the eligible administration sites 
will be performed at screening as described in the TDS-IM V 2.0 Instructions for Use.  The 
assessment procedure does not need to be repeated during the course of the study unless the 
participant experiences a greater than 10% change in body mass relative to screening.

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7.1.5. (12-Lead) Electrocardiogram
Electrocardiogram machines to be utilized in this study will be supplied by a third party 
vendor. 
At screening, a single 12-lead ECG tracing (with a 10-second rhythm strip) will be obtained.  
For Cycle 1 Day 1 and all subsequent specified time points (see Schedule of Activities), 
triplicate 12-lead ECG tracings (with a 10-second rhythm strip) will be obtained.
Generally, baseline and all corresponding time point ECGs should not be collected within 
3 hours after food or beverage consumption and should be performed after the participant has 
rested quietly for at least 10 minutes in a supine position.  All 12 lead ECGs should be 
confirmed by a qualified person at the institution and will be reviewed by a central 
laboratory. 
At each time point, (see the Schedule of Activities), three consecutive ECGs will be 
performed at approximately 2 minutes apart to determine the mean QTcF interval.  If the 
mean QTcF is prolonged (value of >500 msec), the ECGs should be re-evaluated by a 
qualified person at the institution for confirmation.  If manual reading verifies a QTcF of 
>500 msec, immediate correction for reversible causes (including electrolyte abnormalities, 
hypoxia and concomitant medications for drugs with the potential to prolong the QTcF 
interval) should be performed.  In addition, repeat ECGs should be immediately performed 
hourly for at least 3 hours until the QTcF interval falls below 500 msec.  If QTcF interval 
reverts to less than 500 msec, and in the judgment of the investigator(s) and sponsor it is 
determined to be due to cause(s) other than investigational product, treatment may be 
continued with regular ECG monitoring.  If in that timeframe the QTcF intervals rise above 
500 msec the investigational product will be held until the QTcF interval decreases to 
500 msec.  Participants will then re-start the investigational product at the next lowest dose
level.  If the QTcF interval has still not decreased to 500 msec after 2-weeks, or if at any time 
a participant has a QTcF interval >515 msec or becomes symptomatic, the participant will be 
removed from the study.  Additional triplicate ECGs may be performed as clinically 
indicated. 
Prior to concluding that an episode of prolongation of the QTcF interval is due to 
investigational product, thorough consideration should be given to potential precipitating 
factors (eg, change in participant clinical condition, effect of concurrent medication, 
electrolyte disturbance) and possible evaluation by specialist.
If the participant experiences a cardiac or neurologic AE (specifically syncope, dizziness, 
seizures, or stroke), an ECG (triplicate) should be obtained at the time of the event. 
Prior to concluding that an episode of prolongation of the QTcF interval is due to 
investigational product, thorough consideration should be given to potential precipitating 
factors (eg, change in participant clinical condition, effect of concurrent medication, 
electrolyte disturbance) and possible evaluation by specialist.

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When matched with PK sampling, the ECG must be carried out before each PK sample 
drawing such that the PK sample is collected at the nominal time (ie, the timing of the PK 
collections over rides the timing of the ECG collections). 
7.1.6. Monitoring for Potential Immune Mediated Endocrinopathies
Participants will be monitored for clinical signs and symptoms of hypophysitis, adrenal 
insufficiency (including Addisonian crisis), and hyper- or hypothyroidism.  Laboratory 
evaluation will be performed as clinically indicated based on symptoms.  For example, the 
development of symptoms of adrenal insufficiency, such as unexplained nausea, vomiting 
and hypotension, would trigger prompt evaluation (Cosyntropin Stimulation Testing) and 
treatment (systemic glucocorticoids).  Symptoms suggestive of an inflammatory pituitary 
process with mass effect, such as diplopia, visual field abnormalities and severe headache, 
call for urgent pituitary imaging and evaluation for hypopituitarism, with specific attention to 
the pituitary-adrenal axis.  Symptoms of disordered thyroid metabolism, such as changes in 
bowel frequency, fatigue, unexplained weight loss or gain should prompt evaluation of 
thyroid function tests, with a focus on free thyroid hormone levels (T3 and T4) given the 
possibility that thyroid stimulating hormone levels may be unreliable due to 
immune-mediated pituitary dysfunction.
7.1.7. Acetylcholine Receptor Testing
A blood sample will be collected at screening for central evaluation of acetylcholine receptor
(AChR) antibodies. 
 
 
reatment decisions will be made based on the clinical diagnosis.  The evaluation 
for AChR antibodies is included to exclude participants who test positive at screening as 
agreed upon with the US FDA and to confirm requirement for evaluation if myasthenia 
gravis is suspected.99
7.1.8. Cardiac Safety Monitoring
The algorithm for cardiac Safety Monitoring is shown in Figure 2 below. 
For participants undergoing screening, circulating levels of cardiac Troponin-I (cTnI) must 
be measured and found to be within the normal reference range within 28 days before study 
entry, preferably using the central laboratory kits provided.  Dosing should not proceed until 
results within the normal reference range have been received by the Investigator.  For any 
results above of the normal reference range (even if borderline), the participant should be 
referred to a cardiologist by the Investigator for complete cardiac workup and repeat cardiac 
troponin.  The participant can only enter the study after cardiac evaluation, troponin findings 
within the normal reference range, cardiac clearance, and the Sponsor’s approval. 
For participants ongoing in the study, circulating levels of cardiac Troponin-I (cTnI) must be 
measured within 10 days of dosing on the days shown in the SOA (ie, C1D29, C1D57, 
C1D85, C2D29, month 9 and month 12) and found to within the normal reference range.  No 
dosing of participants can occur unless the cTnI is within the normal reference range.  For 
any results above the normal reference range (even if borderline) the participant must be 
referred by the Investigator to a cardiologist for complete work-up and repeat cTnI.  Dosing 
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can only occur after cardiac evaluation, cTnI findings within the normal reference range, 
cardiac clearance, and the Sponsor’s approval. 
While central laboratory testing for cTnI is preferred, it requires a minimum of 3 days to 
return results.  Therefore, local laboratory testing of cTnI may be used, but only if the timing 
of measuring cTnI by the central laboratory test (minimum 3 day turnaround time) puts an 
undue burden or risk on the participant.  The use of cardiac troponin-T is strongly 
discouraged, but could be used in place of cTnI if the central laboratory test puts an undue 
burden or risk on the participant.
Figure 2.
Cardiac Safety Monitoring Algorithm
7.2. Pharmacokinetics Assessments
7.2.1. Serum for Assessment of Tremelimumab Pharmacokinetics
Blood samples (approximately 3 mL whole blood) to provide a minimum of 1 mL of serum 
for measurement of serum tremelimumab concentrations will be collected from participants 
receiving tremelimumab.  The samples will be collected into appropriately labeled tubes at 
time points outlined in the Schedule of Activities.  The PK sampling schedule may be 
modified based on emerging PK data, but the total number of PK samples will remain the 
same. 
In addition to samples collected at the scheduled times, an additional blood sample for 
determination of serum tremelimumab concentration should be collected from participants 
experiencing unexpected and/or serious AEs and the date and time of blood sample 
collection and of last dosing prior to PK collection documented on the CRF.

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Where noted in the Schedule of Activities, blood samples for tremelimumab concentrations 
will be collected at approximately the same time as other assessments such as PD samples 
and ECGs (first ECG then PK collection), wherever possible. 
All efforts will be made to obtain the PK samples at the scheduled nominal time relative to 
dosing.  However, samples obtained within the protocol specified time window will be 
considered compliant with the protocol, and the exact time of the sample collection will 
always be noted on the CRF.  If a scheduled blood sample collection cannot be completed for 
any reason, the missed sample time may be re-scheduled with agreement of the clinical 
investigator, participant, and sponsor.
PK samples will be assayed for tremelimumab using a validated analytical method at a 
central laboratory in compliance with Pfizer standard operating procedures (SOPs). 
The PK samples must be processed and shipped as indicated in the instructions provided to 
the investigator site to maintain sample integrity. Any deviations from the PK sample 
handling procedure (eg, sample collection and processing steps, interim storage or shipping 
conditions), including any actions taken, must be documented and reported to the 
sponsor. On a case-by-case basis, the sponsor may make a determination as to whether 
sample integrity has been compromised.  Any deviation from the specified sample handling 
procedure resulting in compromised sample integrity will be considered a protocol deviation.
As part of understanding the PK of the investigational product, samples may be used for 
evaluation of the bioanalytical method, 
  
These data will not be included in the Clinical Study Report (CSR).
7.2.2. Serum for Assessment of Sasanlimab Pharmacokinetics
Blood samples (approximately 5 mL whole blood) to provide a minimum of 2 mL of serum 
for measurement of serum sasanlimab concentrations will be collected from participants 
receiving sasanlimab.  The samples will be collected into appropriately labeled tubes at time 
points outlined in the Schedule of Activities.  The PK sampling schedule may be modified 
based on emerging PK data, but the total number of PK samples will remain the same. 
In addition to samples collected at the scheduled times, an additional blood sample for 
determination of serum sasanlimab concentration should be collected from participants 
experiencing unexpected and/or serious AEs and the date and time of blood sample 
collection and of last dosing prior to PK collection documented on the CRF.
Where noted in the Schedule of Activities, blood samples for sasanlimab concentrations will 
be collected at approximately the same time as other assessments such as 
 
ECGs (first ECG then PK collection), wherever possible. 
All efforts will be made to obtain the PK samples at the scheduled nominal time relative to 
dosing.  However, samples obtained within the protocol specified time window will be 
considered compliant with the protocol, and the exact time of the sample collection will 
always be noted on the CRF.  If a scheduled blood sample collection cannot be completed for 
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any reason, the missed sample time may be re-scheduled with agreement of the clinical 
investigator, participant, and sponsor.
PK samples will be assayed for sasanlimab using a validated analytical method in 
compliance with Pfizer standard operating procedures (SOPs). 
The PK samples must be processed and shipped as indicated in the instructions provided to 
the investigator site to maintain sample integrity. Any deviations from the PK sample 
handling procedure (eg, sample collection and processing steps, interim storage or shipping 
conditions), including any actions taken, must be documented and reported to the 
sponsor. On a case-by-case basis, the sponsor may make a determination as to whether 
sample integrity has been compromised.  Any deviation from the specified sample handling 
procedure resulting in compromised sample integrity will be considered a protocol deviation.
As part of understanding the PK of the investigational product, samples may be used for 
evaluation of the bioanalytical method, 
  
These data will not be included in the Clinical Study Report (CSR).
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7.4. Tumor Response Assessments
Tumor assessments will include all known or suspected sites of disease.  Screening images 
may be obtained within 5 weeks of registration.  Imaging obtained as part of standard of care 
that are performed within 28 days (-7 days) of registration may be used for screening 
assessment.  Imaging will include (a) CT scan (computerized tomography) of the chest, 
abdomen and pelvis, or magnetic resonance imaging (MRI) of these same areas, and (b) bone 
scan, for participants with known or suspected bone metastases.  Baseline brain imaging (CT 
or MRI) is not required, except in the case of symptomatic participants to rule out brain 
metastases (see Section 4).
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The same imaging technique (CT scan or MRI) used to characterize lesions identified at 
baseline should be employed when performing on-study tumor assessments.  As the intention 
of administration of VBIR-2 is to activate an anti-tumor immune response in the vaccine 
draining lymph nodes, the inguinal (limb) and axillary (arm) lymph nodes should not be used 
as target lesions, since injections of antigens may be given in the upper arm or thigh. It is 
possible that lymph nodes draining the upper arm or thigh may become enlarged following 
administration of the VBIR-2, and may not accurately reflect the status of underlying disease.
Anti-tumor activity will be assessed through radiological tumor assessments conducted at 
baseline; during treatment as specified in the SOA; whenever disease progression is 
suspected (eg, symptomatic deterioration); and at the time of withdrawal from treatment (if 
not done in the previous 6 weeks).
Assessment of response will be made using RECIST version 1.1 (Appendix 3). 
All participants’ files and radiologic images must be available for source verification and for 
potential peer review.  In addition, historical images (collected up to one year prior to study 
entry) may be requested for potential peer review.
7.5. Tremelimumab and Sasanlimab Immunogenicity Assessments
In participants receiving tremelimumab, blood samples (approximately 5 mL, to provide at 
least 2 mL of serum) will be collected to detect anti-drug antibodies (ADA) and neutralizing 
antibody (NAb) against tremelimumab (~1 mL each of ADA and NAb).  Similarly, in 
participants receiving sasanlimab, blood samples (approximately 5 mL, to provide at least 2 
mL of serum) will be collected to detect ADA and NAb against sasanlimab (~1 mL each of 
ADA and NAb).  The sampling schedule is specified in the SOA.
Samples will be analyzed using a validated analytical method in compliance with Pfizer 
SOPs.  The ADA sample analysis will follow a tiered approach of screening, confirmation, 
and titer determination.  Only those samples tested positive for ADA will be further tested for 
NAb. 
The immunogenicity samples must be processed and shipped as indicated in the instructions 
provided to the investigator site to maintain sample integrity. Any deviations from the 
immunogenicity sample handling procedure (eg, sample collection and processing steps, 
interim storage or shipping conditions), including any actions taken, must be documented and 
reported to the sponsor.  On a case-by-case basis, the Sponsor may make a determination as 
to whether sample integrity has been compromised.  Any deviation from the specified sample 
handling procedure resulting in compromised sample integrity will be considered a protocol 
deviation.
As part of understanding the immunogenicity of the investigational product, samples may be 
used for evaluation of the bioanalytical method. 
 
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7.7. Other Assessments
7.7.1. Tumor and Medical History
History of the participant’s disease under study including details of the primary diagnosis and 
treatment history will be collected within 28 before the start of treatment.  In addition, a 
history of disease process other than the cancer under study (active or resolved) and 
concurrent illnesses will be collected.  This will also include prior treatments and any current 
medical treatments for any condition.
8. ADVERSE EVENT REPORTING
8.1. Requirements
The Table 14 below summarizes the requirements for recording safety events on the CRF and 
for reporting safety events on the Clinical Trial (CT) Serious Adverse Event (SAE) Report 
Form to Pfizer Safety.  These requirements are delineated for 3 types of events: (1) SAEs; 
(2) non-serious adverse events (AEs); and (3) exposure to the investigational product under 
study during pregnancy or breastfeeding, and occupational exposure. 
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Table 14.
Requirements for Recording Safety Events on the Case Report Form 
(CRF) and Reporting Safety Events on the Clinical Trial Serious Adverse 
Events Form
Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 
24 Hours of Awareness
SAE
All
All
Non-serious AE
All
None
Exposure to the investigational 
product under study during 
pregnancy or breastfeeding, and 
occupational exposure
All (regardless of whether 
associated with an AE), 
except occupational 
exposure
Exposure during pregnancy, exposure 
via breastfeeding, occupational 
exposure (regardless of whether 
associated with an AE)
All observed or volunteered events regardless of treatment group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
paragraphs.
Events listed in the table above that require reporting to Pfizer Safety on the CT SAE Report 
Form within 24 hours of awareness of the event by the investigator are to be reported 
regardless of whether the event is determined by the investigator to be related to an 
investigational product under study.  In particular, if the SAE is fatal or life-threatening, 
notification to Pfizer Safety must be made immediately, irrespective of the extent of available 
event information.  This time frame also applies to additional new (follow-up) information on 
previously forwarded reports.  In the rare situation that the investigator does not become 
immediately aware of the occurrence of an event, the investigator must report the event 
within 24 hours after learning of it and document the time of his/her first awareness of the 
event.
For each event, the investigator must pursue and obtain adequate information both to 
determine the outcome and to assess whether it meets the criteria for classification as an SAE 
(see the Serious Adverse Events section below).  In addition, the investigator may be 
requested by Pfizer Safety to obtain specific follow-up information in an expedited fashion.  
This information is more detailed than that recorded on the CRF.  In general, this will include 
a description of the event in sufficient detail to allow for a complete medical assessment of 
the case and independent determination of possible causality.  Any information relevant to 
the event, such as concomitant medications and illnesses, must be provided.  In the case of a 
participant death, a summary of available autopsy findings must be submitted as soon as 
possible to Pfizer Safety.  Any pertinent additional information must be reported on the CT 
SAE Report Form; additional source documents (eg, medical records, CRF, laboratory data) 
are to be sent to Pfizer Safety ONLY upon request.

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As part of ongoing safety reviews conducted by the sponsor, any non-serious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE.  To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study.
8.1.1. Additional Details On Recording Adverse Events on the CRF
All events detailed in the table above will be recorded on the AE page(s) of the CRF.  It 
should be noted that the CT SAE Report Form for reporting of SAE information is not the 
same as the AE page of the CRF.  When the same data are collected, the forms must be 
completed in a consistent manner.  AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE Report 
Form for reporting of SAE information.
8.1.2. Eliciting Adverse Event Information
The investigator is to record on the CRF all directly observed AEs and all AEs spontaneously 
reported by the study participant or legally acceptable representative.  In addition, each study 
participant/legally acceptable representative will be questioned about the occurrence of AEs 
in a non-leading manner.
8.1.3. Withdrawal From the Study Due to Adverse Events (see also the Participant 
Withdrawal Section)
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted below, and recorded on the CRF. 
When a participant withdraws from the study because of an SAE, the SAE must be recorded 
on the CRF and reported, as appropriate, on the CT SAE Report Form, in accordance with 
the Requirements section above.
8.1.4. Time Period for Collecting AE/SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving investigational product), through and including 
a minimum of 6 months; except as indicated below after the last administration of the 
investigational product.

For participants who are screen failures, the active collection period ends when screen 
failure status is determined.
8.1.4.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period are reported to Pfizer 
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SAEs occurring in a participant after the active collection period has ended are reported to 
Pfizer Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety.
Follow up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
If a participant begins a new anticancer therapy, SAEs occurring during the above-indicated 
active collection period must still be reported to Pfizer Safety irrespective of any intervening 
treatment.
8.1.4.2. Recording Non-serious AEs and SAEs on the CRF
During the active collection period, both non-serious AEs and SAEs are recorded on the 
CRF.
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.
If a participant begins a new anticancer therapy, the recording period for non-serious AEs 
ends at the time the new treatment is started; however, SAEs must continue to be recorded on 
the CRF during the above-indicated active collection period.
8.1.5. Causality Assessment
The investigator’s assessment of causality must be provided for all AEs (serious and 
non-serious); the investigator must record the causal relationship on the CRF, and report such 
an assessment in accordance with the SAE reporting requirements, if applicable.  An 
investigator’s causality assessment is the determination of whether there exists a reasonable 
possibility that the investigational product caused or contributed to an AE; generally the facts 
(evidence) or arguments to suggest a causal relationship should be provided.  If the 
investigator does not know whether or not the investigational product caused the event, then 
the event will be handled as “related to investigational product” for reporting purposes, as 
defined by the sponsor.  If the investigator’s causality assessment is “unknown but not 
related” to investigational product, this should be clearly documented on study records. 
In addition, if the investigator determines that an SAE is associated with study procedures, 
the investigator must record this causal relationship in the source documents and CRF, and 
report such an assessment in the dedicated section of the CT SAE Report Form and in 
accordance with the SAE reporting requirements.
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities
AE reporting, including suspected unexpected serious adverse reactions will be carried out in 
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8.2. Definitions
8.2.1. Adverse Events
An AE is any untoward medical occurrence in a study participant administered a product or 
medical device; the event need not necessarily have a causal relationship with the treatment 
or usage.  Examples of AEs include, but are not limited to: 

Abnormal test findings;

Clinically significant signs and symptoms;

Changes in physical examination findings;

Hypersensitivity;

Drug abuse;

Drug dependency.
Additionally, AEs may include signs and symptoms resulting from:

Drug overdose;

Drug withdrawal;

Drug misuse; 

Drug interactions;

Extravasation;

Exposure during pregnancy (EDP);

Exposure via breastfeeding;

Medication error;

Occupational exposure.
Worsening of signs and symptoms of the malignancy under study should be recorded as AEs 
in the appropriate section of the CRF.  Disease progression assessed by measurement of 
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8.2.2. Abnormal Test Findings
Abnormal objective test findings should be recorded as AEs when any of the following 
conditions are met: 

Test result is associated with accompanying symptoms; and/or

Test result requires additional diagnostic testing or medical/surgical intervention; 
and/or

Test result leads to a change in study dosing (outside of any protocol-specified dose 
adjustments) or discontinuation from the study, significant additional concomitant 
drug treatment, or other therapy; and/or

Test result is considered to be an AE by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE.  Any abnormal test result that is determined to be an error does not require 
recording as an AE.
8.2.3. Serious Adverse Events
A serious adverse event is any untoward medical occurrence at any dose that:

Results in death;

Is life-threatening (immediate risk of death);

Requires inparticipant hospitalization or prolongation of existing hospitalization;

Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions);

Results in congenital anomaly/birth defect.
Or that is considered to be:

An important medical event.
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the participant or may require intervention to prevent one of the other AE outcomes, the 
important medical event should be reported as serious.
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
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Progression of the malignancy under study (including signs and symptoms of progression) 
should not be reported as an SAE unless the outcome is fatal within the active collection 
period.  Hospitalization due to signs and symptoms of disease progression should not be
reported as an SAE.  If the malignancy has a fatal outcome during the study or within the 
active collection period, then the event leading to death must be recorded as an AE on the 
CRF and as an SAE with Common Terminology Criteria for Adverse Events (CTCAE) 
Grade 5 (see the Severity Assessment section).
Medical device complaints may meet the SAE reporting requirement criteria (see the Medical 
Device Complaint Reporting Requirements section).  An incident is any malfunction (ie, the 
failure of a device to meet its performance specifications or to perform as intended; 
performance specifications include all claims made in the labeling for the device) that, 
directly or indirectly, might lead to or might have led to the death of a participant, or user, or 
of other persons, or to a serious deterioration in their state of health. 
A serious injury that can cause a serious deterioration in state of health can include:

A life-threatening illness, even if temporary in nature;

A permanent impairment of a body function or permanent damage to a body 
structure; 

A condition necessitating medical or surgical intervention to prevent the above 
2 bulleted items;
Examples: clinically relevant increase in the duration of a surgical procedure; a 
condition that requires hospitalization or significant prolongation of existing 
hospitalization;

Any indirect harm as a consequence of an incorrect diagnostic or in vitro diagnostic 
device test results when used within the manufacturer’s instructions for use;

Fetal distress, fetal death, or any congenital abnormality or birth defects.
8.2.4. Hospitalization
Hospitalization is defined as any initial admission (even less than 24 hours) in a hospital or 
equivalent healthcare facility, or any prolongation of an existing admission.  Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, or neurological floor to a 
tuberculosis unit).  An emergency room visit does not necessarily constitute a hospitalization; 
however, the event leading to the emergency room visit is assessed for medical importance.
Hospitalization does not include the following:

Rehabilitation facilities;

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
Hospice facilities;

Respite care (eg, caregiver relief);

Skilled nursing facilities;

Nursing homes;

Same-day surgeries (as outpatient/same-day/ambulatory procedures).
Hospitalization or prolongation of hospitalization in the absence of a precipitating clinical 
AE is not in itself an SAE.  Examples include: 

Admission for treatment of a preexisting condition not associated with the 
development of a new AE or with a worsening of the preexisting condition (eg, for 
workup of a persistent pretreatment laboratory abnormality);

Social admission (eg, participant has no place to sleep);

Administrative admission (eg, for yearly physical examination);

Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol);

Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery);

Hospitalization for observation without a medical AE;

Preplanned treatments or surgical procedures.  These should be noted in the baseline 
documentation for the entire protocol and/or for the individual participant;

Admission exclusively for the administration of blood products.
Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not 
be reported as SAEs.  However, the medical condition for which the procedure was 
performed should be reported if it meets the definition of an SAE.  For example, an acute 
appendicitis that begins during the reporting period should be reported if the SAE 
requirements are met, and the resulting appendectomy should be recorded as treatment of the 
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8.3. Severity Assessment
Table 15.
Clinical Description of Severity
GRADE
Clinical Description of Severity
0 
No change from normal or reference range (This grade is not included in the Version 5.0 
CTCAE document but may be used in certain circumstances).
1
MILD adverse event
2
MODERATE adverse event
3
SEVERE adverse event
4
LIFE-THREATENING consequences; urgent intervention indicated
5
DEATH RELATED TO adverse event
Note the distinction between the severity and the seriousness of an AE.  A severe event is not 
necessarily an SAE.  For example, a headache may be severe (interferes significantly with 
the participant’s usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs, listed above.
8.4. Special Situations
8.4.1. Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.”  In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome.  These participants fail to adapt and therefore are 
“susceptible” to progressive and serious liver injury, commonly referred to as drug-induced 
liver injury (DILI).  Participants who experience a transaminase elevation above 3 times the 
upper limit of normal (× ULN) should be monitored more frequently to determine if they are 
an “adaptor” or are “susceptible.”
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (Tbili) elevations (>2 × ULN) by several days 
or weeks.  The increase in Tbili typically occurs while AST/ALT is/are still elevated above 
3 × ULN (ie, AST/ALT and Tbili values will be elevated within the same lab sample).  In 
rare instances, by the time Tbili elevations are detected, AST/ALT values might have 
decreased.  This occurrence is still regarded as a potential DILI.  Therefore, abnormal 
elevations in either AST OR ALT in addition to Tbili that meet the criteria outlined below 
are considered potential DILI (assessed per Hy’s law criteria) cases and should always be 
considered important medical events, even before all other possible causes of liver injury 
have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions.  Participants who present 

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with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and Tbili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a Tbili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available;

For participants with baseline AST OR ALT OR Tbili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).

Preexisting values of Tbili above the normal range: Tbili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).
Rises in AST/ALT and Tbili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor. 
The participant should return to the Investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.  The possibility of hepatic 
neoplasia (primary or secondary) should be considered. In addition to repeating 
measurements of AST and ALT and Tbili, laboratory tests should include albumin, creatine 
kinase (CK), direct and indirect bilirubin, gamma-glutamyl transferase (GGT), prothrombin 
time (PT)/international normalized ratio (INR), total bile acids, alkaline phosphatase and 
acetaminophen drug and/or protein adduct levels.  Consideration should also be given to 
drawing a separate tube of clotted blood and an anticoagulated tube of blood for further 
testing, as needed, for further contemporaneous analyses at the time of the recognized initial 
abnormalities to determine etiology.  A detailed history, including relevant information, such 
as review of ethanol, acetaminophen (either by itself or as a coformulated product in 
prescription or over-the-counter medications), recreational drug, supplement (herbal) use and 
consumption, family history, sexual history, travel history, history of contact with a 
jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and potential 
occupational exposure to chemicals, should be collected.  Further testing for acute hepatitis 
A, B, C, D, and E infection and liver imaging (eg, biliary tract) may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
Tbili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found.  Such potential DILI (Hy’s law) 

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cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.
8.4.2. Exposure to the Investigational Product During Pregnancy or Breastfeeding, and 
Occupational Exposure
Exposure to the investigational product under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.4.2.1. Exposure During Pregnancy (EDP)
For both unapproved/unlicensed products and for marketed products, an EDP occurs if:

A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes or is found to be pregnant after discontinuing and/or 
being exposed to the investigational product;

An example of environmental exposure would be a case involving direct contact 
with a Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant 
and has been exposed to chemotherapeutic products).

A male has been exposed (eg, because of treatment or environmental exposure) to the 
investigational product prior to or around the time of conception and/or is exposed 
during his partner’s pregnancy.
If a participant or participant’s partner becomes or is found to be pregnant during the 
participant’s treatment with the investigational product, the investigator must report this 
information to Pfizer Safety on the CT SAE Report Form and an EDP supplemental form, 
regardless of whether an SAE has occurred.  In addition, the investigator must submit 
information regarding environmental exposure to a Pfizer product in a pregnant woman (eg, a 
participant reports that she is pregnant and has been exposed to a cytotoxic product by
inhalation or spillage) to Pfizer Safety using the EDP supplemental form.  This must be done 
irrespective of whether an AE has occurred and within 24 hours of awareness of the 
exposure.  The information submitted should include the anticipated date of delivery (see 
below for information related to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP supplemental form.  In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth.  In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 

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integrity of the terminated fetus should be assessed by gross visual inspection (unless 
pre-procedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported to Pfizer Safety as SAEs 
follows: 

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the investigational product. 
Additional information regarding the EDP may be requested by the sponsor.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays).  In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner.  The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.4.2.2. Exposure During Breastfeeding
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated SAE, to Pfizer Safety within 24 hours of the investigator’s awareness, using the 
CT SAE Report Form.  An exposure during breastfeeding report is not created when a Pfizer 
drug specifically approved for use in breastfeeding women (eg, vitamins) is administered in 
accord with authorized use.  However, if the infant experiences an SAE associated with such 
a drug’s administration, the SAE is reported together with the exposure during breastfeeding.
8.4.2.3. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE.
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the CT SAE Report Form, regardless of whether there is an associated 
SAE.  Since the information does not pertain to a participant enrolled in the study, the 
information is not recorded on a CRF; however, a copy of the completed CT SAE Report 
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8.4.3. Medication Errors 
Other exposures to the investigational product under study may occur in clinical trial settings, 
such as medication errors. (see Table 16).
Table 16.
Medication Errors Reporting on the Clinical Trial Serious Adverse Event 
Form
Safety Event
Recorded on the CRF
Reported on the CT 
SAE Report Form to 
Pfizer Safety Within 
24 Hours of Awareness
Medication errors 
All (regardless of whether 
associated with an AE)
Only if associated with 
an SAE
8.4.3.1. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong participant, or at the wrong time, or based on the investigational 
product administration, such as inadvertent exposure, or at the wrong dosage strength. 
Medication errors include:

Medication errors involving participant exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the participating participant.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of medication dosing error, the sponsor should be notified within 24 hours.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and non-serious, are recorded on an AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
8.5. Medical Device Complaint Reporting Requirements 
All medical device complaints, regardless of whether the medical device complaint is 
associated with an AE, will be recorded on the applicable pages within the CRF.  This 
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product.  An incident or malfunction is an event that might have led to death or serious 
deterioration in health, or if it occurred again might lead to death or serious deterioration in 
health.
Pfizer is to be notified of all medical device complaints within 24 hours of the investigator’s 
awareness of the event. 
9. DATA ANALYSIS/STATISTICAL METHODS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a statistical analysis plan (SAP), which will be 
maintained by the sponsor.  The SAP may modify what is outlined in the protocol where 
appropriate; however, any major modifications of the primary endpoint definitions or their 
analyses will also be reflected in a protocol amendment.
9.1. Analysis Sets 
For safety evaluation, participants should have received at least one of the regimen 
components.  For efficacy 
 evaluation, participants should have 
received at least one dose of all components administered on Cycle 1 Day 1.  See Section 9.4
for definitions related to efficacy.
Participants who receive the designated investigational product of interest and have at least 
one post-dose drug concentration measurement will be included in the PK data analysis. 
1. Safety analysis set.
The safety analysis set includes all enrolled participants who receive at least one dose
of one of the components of the regimen.
2. Full analysis set.
The full analysis set includes all enrolled participants.
3. Per protocol analysis set.
The per protocol (PP) analysis set includes all enrolled participants who receive at 
least one dose of all regimen components administered on Cycle 1 Day 1 of study 
medication and who do not have major protocol deviations during the 28 days after 
the first vaccination.
4. Modified Intention-to-Treat analysis set.
 modified 
Intention-to-Treat (mITT), which is defined as all enrolled participants who received 
at least one dose of all regimen components administered on Cycle 1 Day 1.  
 
 a participant 
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must have at least 1 valid and determinate assay result related to the proposed 
analysis.  Participants who have no valid and determinate assay result related to any 
proposed analysis will be excluded from the mITT analysis set.
5. PK analysis set.
The PK parameter analysis population is defined as all enrolled participants treated 
who have sufficient information to estimate at least 1 of the PK parameters of interest 
and who have no major protocol deviations influencing the PK assessment.
6. Immunogenicity analysis set.
The immunogenicity analysis set includes all enrolled participants who receive at 
least one dose of the VBIR-2 component that is the subject of the immunogenicity 
assessment (tremelimumab or sasanlimab).
9.2. Statistical Methods and Properties
9.2.1. Statistical Methods for Dose Escalation/De-Escalation
Many alternative designs have been proposed to the standard 3+3 design for Phase 1 dose 
escalation studies that improve its accuracy, efficiency and statistical validity.  This study 
will utilize the mTPI design (Ji et al., 2010).140
The mTPI design (Ji et al., 2010)140 uses a Bayesian statistics framework and a beta/binomial 
hierarchical model to compute the posterior probability of 3 dosing intervals that reflect the 
relative difference between the toxicity rate of each dose level to the target rate (pT = 0.275).  
If the toxicity rate of the currently used dose level is far smaller than pT, the mTPI will 
recommend escalating the dose level; if it is close to target probability (pT), the mTPI will 
recommend continuing at the current dose; if it is far greater than pT, the mTPI will 
recommend de-escalating the dose level.  These rules are conceptually similar to those used 
by the 3+3 design, except the decisions of a mTP design are based on posterior probabilities 
calculated under a coherent probability model. 
Being a model-based design, mTPI automatically and appropriately tailors dose-escalation 
and de-escalation decisions for different studies with different toxicity parameters.  More 
importantly, all the dose-escalation decisions for a given study can be pre-calculated under 
the mTPI design and presented in a two-way table (Table 3).  It is currently envisaged that 
AdC68 6 x 1011 VP + 5 mg pDNA + 150 mg tremelimumab + 300 mg sasanlimab will 
potentially be the highest dose level.
Thus, compared to other advanced model-based designs published in the literature, the mTPI 
design is logistically less complicated and easier to implement. 
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Decision rules are based on calculating posterior probabilities of 3 dosing i intervals 
corresponding to under, proper, and over dosing in terms of toxicity.  Specifically, the 
underdosing interval is defined as (0; pT-e1), the over-dosing interval (pT+e2, 1), and the 
proper-dosing interval (pT- e1, pT+ e2), where e1 and e2 are small fractions.  In this study, e1 
is selected as 0.05 and e2 is selected as 0.05, therefore, the target interval for the DLT rate is 
(0.225, 0.325).  The 27.5% target, the symmetry of the Equivalence Interval, and its upper 
limit were chosen based on safety considerations.  The prior distribution of DLT is set as a 
beta (0.5, 0.5), and the threshold probability for early termination and dose exclusion is set to 
0.95.  Even though the upper limit of the mTPI is higher than 27.5%, doses with an incidence 
of DLT >27.5% (eg, 3 out of 9) cannot be declared as the MTD. 
The 3 dosing intervals are associated with 3 different dose-escalation decisions.  The 
underdosing interval corresponds to a dose-escalation I, overdosing corresponds to a dose 
de-escalation (D/U), and proper dosing corresponds to remaining at the current dose (S). 
9.2.2. Statistical Method for Estimating the MTD
As previously described, the estimated MTD is the highest tested dose level with a DLT rate 
≤32.5% in at least 6 DLT-evaluable participants.  It is assumed that higher doses result in 
higher toxicity rates.  But, due to the relatively low number of participants that may be 
potentially allocated to any dose combination, this assumption may be incorrect, allowing for 
higher dose levels to be tested.
Clinical judgment will be exercised in taking forward doses to the expansion cohort(s), in 
case no clear choice exists between more than 1 competing MTD.  This decision will be 
based upon the combination of data related to safety, anti-tumor activity, and clinical 
judgment of the investigators and the sponsor.
9.3. Sample Size Determination
It is anticipated that each of the cohorts will aim to enroll 2-4 participants, with the exception 
of the cohort with the anticipated MTD dose that will aim to enroll up to 12 participants.  
Due to the dynamic nature of the Bayesian allocation procedure, the sample size of the mTPI 
approach cannot be determined in advance.  It is estimated approximately 36 DLT evaluable 
participants may be enrolled in the dose escalation stage in order to have a reliable and 
accurate estimate of the MTD.  The actual sample size for the dose escalation may be 
smaller, depending on the underlying dose toxicity profile.  
At least 6 and up to 12 participants should be enrolled at a dose level that is predicted to be 
the MTD as per the mTPI method.  Dose cohorts with an acceptable safety profile may be 
expanded up to N=12 to further assess safety,
 pharmacokinetics, 
  Decisions to enroll additional participants at dose levels already cleared 
for safety will be based on clinical judgment of the investigators and the sponsor considering 
all evaluable safety,
 data.
The expansion phase of the study (Part 2) will consist of 1 cohort of participants with 
metastatic or locally-advanced NSCLC. Approximately 30 participants will be enrolled for 
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the dose expansion.  A Bayesian approach will be used to estimate the objective response rate 
(ORR) and clinical benefit rate (CBR) in the study indications. As an example of this 
approach related to ORR, assuming a non informative prior (ie, Jeffrey’s prior), if 14 out of 
30 participants (46.7%) achieve a CR or PR, this would translate into a posterior probability 
(Beta Binomial) of 77% that the true ORR/clinical benefit rate is not inferior to 20%.  (See 
Definitions of ORR and CBR in Section 9.4).
9.4. Efficacy Analysis
In this First-In-Patient study anti-tumor activity is a secondary 
 objective.  The 
main analysis populations will be based on mITT and EP (see Section Analysis Sets).
Disease response will be presented in the form of participant data listings that include, but are 
not limited to starting dose, disease response at each visit, and best overall response.  In 
addition, progression date, death date, date of first response and last disease assessment date, 
and date of last contact will be listed.
Summary of objective response rates (ORR) and clinical benefit rate (CBR) will be provided 
by descriptive statistics. 
Progression -free survival (PFS) is the time from start date to date of first documentation of 
progression, or death due to any cause.  Progression is defined as the appearance of local, 
regional or distant disease of the same type after complete response or progression of 
pre-existing lesions.  It does not include second primary malignancies of unrelated types. 
Overall survival (OS) is the time from start date to date of death due to any cause.
Duration of Response (DOR) is defined as the duration of overall response measured from 
the time measurement criteria are met for complete response (CR) or partial response (PR) 
(whichever is first recorded) until the first date that recurrent or progressive disease is 
objectively documented (taking as reference for progressive disease the smallest 
measurements recorded since the treatment started).
Duration of Stable Disease (DOSD) is defined as stable disease measured from the start of 
the treatment until the criteria for progression are met, taking as reference the smallest 
measurements recorded since the treatment started, including the baseline measurements. 
Clinical Benefit Rate (CBR) is defined as the proportion of participants who achieved anti-
tumor responses of  Complete Response (CR), Partial Response (PR), or Stable Disease for > 
6 months (SD).
The Kaplan--Meier methods will be used to analyze all time to event endpoints.  Details of 
these endpoint analyses methods will be included in the Statistical Analysis Plan.
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9.5. Safety Analysis 
The main analyses of DLTs will be based on the Per Protocol analysis set.  Participants not 
meeting the criteria for inclusion in the Per Protocol Analysis set (ie, not evaluable for 
assessment of DLTs) will be replaced.  Summaries and analyses of other safety parameters 
will include all participants in the Safety Analysis Set (see Section Analysis Sets).
9.5.1. Analysis of Primary Endpoint 
Dose Limiting Toxicity (DLT) is the primary endpoint of Part 1 of the study.  The occurrence 
of DLTs observed in the dosing cohorts will govern the dose escalation as described in 
Section 3.1.  If a participant is withdrawn from study for any reason other than a DLT prior 
to completion of the 28-day safety observation period, a replacement participant will be 
assigned for the same dose as the replaced participant.  The properties of the statistical 
methods for the analyses of DLTs are described in section Statistical Methods and Properties.  
Adverse Events constituting DLTs will be listed per dose level.  Adverse Events (AEs) will 
be graded by the investigator according to the CTCAE version 5.0 and coded using the 
Medical Dictionary for Regulatory Activities (MedDRA).  The focus of AE summaries will 
be on Treatment Emergent-Emergent Adverse Events, those with initial onset or increasing 
in severity after the first dose of study treatment.  The number and percentage of participants 
who experienced any AE, SAE, treatment related AE, and treatment related SAE will be 
summarized according to worst toxicity grades.  The summaries will present AEs both on the 
entire study period by dose and by cycle.
9.5.2. Analysis of Secondary Endpoints 
Laboratory Tests Abnormalities
The number and percentage of participants who experienced laboratory test abnormalities 
will be summarized according to worst toxicity grade observed for each lab assay.  The 
analyses will summarize laboratory tests both on the entire study period and by cycle (Cycle 
1 and Cycles beyond 1).  Shift tables will be provided to examine the distribution of 
laboratory toxicities.
For laboratory tests without CTCAE grade definitions, results will be categorized as normal, 
abnormal or not done.
9.5.3. ECG 
The analysis of ECG results will be based on participants in the safety analysis set with 
baseline and on-treatment ECG data.  Baseline is defined as the pre-dose ECG collected 
before the first dose of any component of the study treatment.
ECG measurements (an average of the triplicate measurements) will be used for the 
statistical analysis and all data presentations.  Any data obtained from ECGs repeated for 
safety reasons after the nominal time-points will not be averaged along with the preceding 
triplicates.  Interval measurements from repeated ECGs will be included in the outlier 
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QT intervals will be corrected for heart rate (QTc) using standard correction factors (ie, 
Frederica’s).  Data will be summarized and listed for QT, HR, PR interval, QRS, and QTcF 
by cohort.  Individual QT intervals will be listed by time and cohort.  Descriptive statistics 
(n, mean, median, standard deviation, minimum, and maximum) will be used to summarize 
the absolute corrected QT interval and changes from baseline in corrected QT after treatment 
by cohort and time point.  For each participant and by treatment, the maximum change from 
baseline will be calculated as well as the maximum post-baseline interval across time-points.  
Categorical analysis will be conducted for the maximum change from baseline in corrected 
QT and the maximum post-baseline QT interval.
Shift tables will be provided for baseline versus worst on treatment corrected QT using 
Maximum CTC AE Grade.  Shift tables will also be provided for ECG abnormality at 
baseline versus on treatment (yes, no, not done: (n, %)).  Participants experiencing 
clinically -relevant morphological ECG changes will be summarized (including frequency 
and percentage).
If applicable, the effect of relevant drug concentrations on corrected QT change from 
baseline will be explored graphically.  Additional concentration -corrected QT analyses may 
be performed.  Data may be pooled with other study results and/or explored further with 
PK/PD models.
9.6. Analysis of Pharmacokinetics 
 
9.6.1. Analysis of Pharmacokinetics 
9.6.1.1. Tremelimumab Pharmacokinetic Analysis
The concentration -time data for tremelimumab will be summarized descriptively (n, mean, 
standard deviation, coefficient of variation (CV), median, minimum, maximum, geometric 
mean and its associated CV) by dose, and nominal time for both Part 1 and Part 2.
For participants assigned to Cohorts 3A and 6A , the concentration -time data of 
tremelimumab after the first dose will be analyzed individually by noncompartmental 
methods to determine PK parameters.  The PK parameters to be estimated will include the 
maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), and 
area under the plasma concentration versus time curve following the first dose from time 0 to 
the last time point prior to the second tremelimumab dose (AUClast) and if data permit or if 
considered appropriate, area under the plasma concentration versus time curve from 
time 0 extrapolated to infinity (AUCinf), terminal elimination half-life- (t1/2), apparent serum 
clearance (CL/F), apparent volume of distribution (Vz/F).  The PK parameters will be 
summarized descriptively (n, mean, standard deviation, coefficient of variation (CV), 
median, minimum, maximum, geometric mean and its associated CV) by dose.
Individual participant and median profiles of the concentration time data, after the first 
tremelimumab dose, will be plotted by dose, using nominal times.  Individual and median 
profiles will be presented on both linear-linear and log-linear scales.
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9.6.1.2. Sasanlimab Pharmacokinetic Analysis
The concentration -time data for sasanlimab will be summarized descriptively (n, mean, 
standard deviation, CV, median, minimum, maximum, geometric mean and its associated 
CV) by dose, and nominal time for both Part 1 and Part 2.
For participants assigned to Cohorts 4A and 5A, the concentration -time data of sasanlimab
after the first dose will be analyzed individually by noncompartmental methods to determine 
PK parameters.  The PK parameters to be estimated will include the following: (a) the 
maximum plasma concentration (Cmax), (b) time to maximum plasma concentration (Tmax), 
and (c) area under the plasma concentration versus time curve following the first dose from 
time 0 to the last time point prior to the second sasanlimab dose (AUClast). If data permit or if 
considered appropriate, other analyses may include: (a) area under the plasma concentration 
versus time curve from time 0 extrapolated to infinity (AUCinf), (b) terminal elimination 
half-life (t1/2), (c) apparent serum clearance (CL/F), and (d) apparent volume of distribution 
(Vz/F).  The PK parameters will be summarized descriptively (n, mean, standard deviation, 
coefficient of variation (CV), median, minimum, maximum, geometric mean and its 
associated CV) by dose).
Individual participant and median profiles of the concentration-time data after the first 
sasanlimab dose will be plotted by dose using nominal times.  Individual and median profiles 
will be presented on both linear-linear and log-linear scales.
9.6.3. Analysis of Immunogenicity Data
The percentage of participants with positive tremelimumab ADA and NAb will be 
summarized by each cohort.  For participants with positive ADA or NAb, the magnitude 
(titer), time of onset, and duration of ADA or NAb response will also be described, if data 
permit.
The percentage of participants with positive sasanlimab ADA and NAb will be summarized 
by cohort.  For participants with positive ADA or NAb, and if data permits, the magnitude 
(titer), time of onset, and duration of ADA or NAb response will be described.
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9.6.4. Population Pharmacokinetic Analysis or Pharmacokinetic/
 
(PK
) Modeling 
PK 
 data from this study may be analyzed using modeling approaches and may also 
be pooled with data from other studies to investigate any association between tremelimumab 
or sasanlimab exposure 
 or significant safety and/or efficacy endpoints.  The 
results of these analyses, if performed, may be reported separately.
9.7. Data Monitoring Committee 
This study will not use a data monitoring committee (DMC).
10. QUALITY CONTROL AND QUALITY ASSURANCE
Pfizer or its agent will conduct periodic monitoring visits during study conduct to ensure that 
the protocol and Good Clinical Practices (GCPs) are being followed.  The monitors may 
review source documents to confirm that the data recorded on CRFs are accurate.  The 
investigator and institution will allow Pfizer monitors/auditors or its agents and appropriate 
regulatory authorities direct access to source documents to perform this verification.  This 
verification may also occur after study completion.
During study conduct and/or after study completion, the investigator site may be subject to 
review by the IRB/EC, and/or to quality assurance audits performed by Pfizer, or companies 
working with or on behalf of Pfizer, and/or to inspection by appropriate regulatory 
authorities.
The investigator(s) will notify Pfizer or its agents immediately of any regulatory inspection 
notification in relation to the study.  Furthermore, the investigator will cooperate with Pfizer 
or its agents to prepare the investigator site for the inspection and will allow Pfizer or its 
agent, whenever feasible, to be present during the inspection.  The investigator site and 
investigator will promptly resolve any discrepancies that are identified between the study 
data and the participant’s medical records.  The investigator will promptly provide copies of 
the inspection findings to Pfizer or its agent.  Before response submission to the regulatory 
authorities, the investigator will provide Pfizer or its agents with an opportunity to review 
and comment on responses to any such findings.
It is important that the investigator(s) and their relevant personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process.
11. DATA HANDLING AND RECORD KEEPING
11.1. Case Report Forms/Electronic Data Record
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study.
A CRF is required and should be completed for each included participant.  The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
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third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer.  The investigator shall ensure that the 
CRFs are securely stored at the study site in [encrypted electronic and/or paper] form and 
will be [password protected or secured in a locked room] to prevent access by unauthorized 
third parties.
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety, and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring, and available when required.  The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs are true.  Any corrections to entries made in the CRFs or source 
documents must be dated, initialed, and explained (if necessary) and should not obscure the 
original entry.
In most cases, the source documents are the hospital or the physician’s chart.  In these cases, 
data collected on the CRFs must match the data in those charts. 
In some cases, the CRF may also serve as the source document.  In these cases, a document 
should be available at the investigator site and at Pfizer that clearly identifies those data that 
will be recorded on the CRF, and for which the CRF will stand as the source document.
11.2. Record Retention
To enable evaluations and/or inspections/audits from regulatory authorities or Pfizer, the 
investigator agrees to keep records, including the identity of all participating participants 
(sufficient information to link records, eg, CRFs and hospital records), all original signed 
informed consent documents, copies of all CRFs, safety reporting forms, source documents, 
and detailed records of treatment disposition, and adequate documentation of relevant 
correspondence (eg, letters, meeting minutes, and telephone call reports).  The records should 
be retained by the investigator according to ICH guidelines, according to local regulations, or 
as specified in the clinical study agreement (CSA), whichever is longer.  The investigator 
must ensure that the records continue to be stored securely for so long as they are retained.
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or to an independent third party arranged by Pfizer. 
Investigator records must be kept for a minimum of 15 years after completion or 
discontinuation of the study or for longer if required by applicable local regulations. 
The investigator must obtain Pfizer’s written permission before disposing of any records, 
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12. ETHICS
12.1. Institutional Review Board/Ethics Committee 
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents, eg, 
recruitment advertisements, if applicable, from the IRB/EC.  All correspondence with the 
IRB/EC should be retained in the investigator file.  Copies of IRB/EC approvals should be 
forwarded to Pfizer.
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the participants.  
In that event, the investigator must notify the IRB/EC and Pfizer in writing immediately after 
the implementation.
12.2. Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, legal and regulatory 
requirements and the general principles set forth in the International Ethical Guidelines for 
Biomedical Research Involving Human Subjects (Council for International Organizations of 
Medical Sciences 2002), ICH Guideline for Good Clinical Practice, and the Declaration of 
Helsinki. 
12.3. Participant Information and Consent
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant personal data.  
Such measures will include omitting participant names or other directly identifiable data in 
any reports, publications, or other disclosures, except where required by applicable law.
The personal data will be stored at the study site in [encrypted electronic and/or paper] form 
and will be [password protected or secured in a locked room] to ensure that only authorized 
study staff have access.  The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster.  In the event of a potential personal data breach, the study site shall be responsible 
for determining whether a personal data breach has in fact occurred and, if so, providing 
breach notifications as required by law.
To protect the rights and freedoms of natural persons with regard to the processing of 
personal data, when study data are compiled for transfer to Pfizer and other authorized 
parties, participant names will be removed and will be replaced by a single, specific, 
numerical code, based on a numbering system defined by Pfizer.  All other identifiable data 
transferred to Pfizer or other authorized parties will be identified by this single, 
subject-specific code. The investigator site will maintain a confidential list of participants 
who participated in the study, linking each participant’s numerical code to his or her actual 
identity.  In case of data transfer, Pfizer will maintain high standards of confidentiality and 
protection of participants’ personal data consistent with the Clinical Study Agreement and 
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The informed consent documents and any participant recruitment materials must be in 
compliance with ICH GCP, local regulatory requirements, and legal requirements, including 
applicable privacy laws.
The informed consent documents used during the informed consent process and any 
participant recruitment materials must be reviewed and approved by Pfizer, approved by the 
IRB/EC before use, and available for inspection.
The investigator must ensure that each study participant or his or her legally acceptable 
representative is fully informed about the nature and objectives of the study, the sharing of 
data relating to the study and possible risks associated with participation, including the risks 
associated with the processing of the participant’s personal data.  The investigator further 
must ensure that each study participant[, or his or her legally acceptable representative, or 
parent(s) or legal guardian if a minor,] is fully informed about his or her right to access and 
correct his or her personal data and to withdraw consent for the processing of his or her 
personal data. 
Whenever consent is obtained from a participant’s legally acceptable representative, the 
participant’s assent (affirmative agreement) must subsequently be obtained when the 
participant has the capacity to provide assent, as determined by the IRB/EC.  If the 
investigator determines that a participant’s decisional capacity is so limited he or she cannot 
reasonably be consulted, then, as permitted by the IRB/EC and consistent with local 
regulatory and legal requirements, the participant’s assent may be waived with source 
documentation of the reason assent was not obtained.  If the study participant does not 
provide his or her own consent, the source documents must record why the participant did 
not provide consent (eg, minor, decisionally impaired adult), how the investigator determined 
that the person signing the consent was the participant’s legally acceptable representative, the 
consent signer’s relationship to the study participant (eg, parent, spouse), and that the 
participant’s assent was obtained or waived.  If assent is obtained verbally, it must be 
documented in the source documents.
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each participant or the participant’s legally acceptable representative before any 
study-specific activity is performed unless a waiver of informed consent has been granted by 
an IRB/EC.  The investigator will retain the original of each participant’s signed consent 
document.
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, Pfizer should be informed immediately. 
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 

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of any serious breaches of this protocol or of ICH GCP that the investigator becomes aware 
of.
13. DEFINITION OF END OF TRIAL
13.1. End of Trial in All Participating Countries 
13.2. End of trial is Defined as Last Subject Last Visit (LSLV).
14. SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/EC, investigational product safety problems, or at the discretion 
of Pfizer.  In addition, Pfizer retains the right to discontinue development of VBIR-2 at any 
time.
If a study is prematurely terminated, Pfizer will promptly notify the investigator.  After 
notification, the investigator must contact all participating participants and the hospital 
pharmacy (if applicable) within an acceptable time period per the institutional policy and 
IRB/EC following receipt of notification.  As directed by Pfizer, all study materials must be 
collected and all CRFs completed to the greatest extent possible.
15. IN THE CASE OF PREMATURE TERMINATION (EG, THE SPONSOR
DISCONTINUES DEVELOPMENT), THE STUDY WILL BE CLOSED NO LATER 
THAN 2 YEARS FROM THE FIRST DOSE OF THE LAST 
SUBJECT.PUBLICATION OF STUDY RESULTS
15.1. Communication of Results by Pfizer
Pfizer fulfills its commitment to publicly disclose clinical trial results through posting of the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and or www.pfizer.com, along with other public registries in 
accordance with applicable local laws and regulations. 
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study, or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in participants) that evaluate the safety and/or efficacy of a 
Pfizer product, regardless of the geographical location in which the study is conducted.  US 
Basic Results are submitted for posting within 1 year of the primary completion date (PCD) 
for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.

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PCD is defined as the date that the final participant was examined or received an intervention 
for the purposes of final collection of data for the primary outcome, whether the clinical 
study concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.
www.pfizer.com
Pfizer posts Public Disclosure Synopses (CSR synopses in which any data that could be used 
to identify individual participants has been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the US Basic Results document is 
posted to www.clinicaltrials.gov.
15.2. Publications by Investigators
Pfizer supports the exercise of academic freedom and has no objection to publication by the 
Principal Investigator (PI) of the results of the study based on information collected or 
generated by the PI, whether or not the results are favorable to the Pfizer product.  However, 
to ensure against inadvertent disclosure of confidential information or unprotected 
inventions, the investigator will provide Pfizer with an opportunity to review any proposed 
publication or other type of disclosure of the results of the study (collectively, “publication”) 
before it is submitted or otherwise disclosed.
The investigator will provide any publication to Pfizer at least 30 days before it is submitted 
for publication or otherwise disclosed.  If any patent action is required to protect intellectual 
property rights, the investigator agrees to delay the disclosure for a period not to exceed an 
additional 60 days.
The investigator will, on request, remove any previously undisclosed confidential 
information before disclosure, except for any study- or Pfizer product-related information 
necessary to the appropriate scientific presentation or understanding of the study results.
If the study is part of a multicenter study, the investigator agrees that the first publication is 
to be a joint publication covering all investigator sites, and that any subsequent publications 
by the PI will reference that primary publication.  However, if a joint manuscript has not 
been submitted for publication within 12 months of completion or termination of the study at 
all participating sites, the investigator is free to publish separately, subject to the other 
requirements of this section.
For all publications relating to the study, the institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II — “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 

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Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors.
Publication of study results is also provided for in the CSA between Pfizer and the 
institution.  In this section entitled Publications by Investigators, the defined terms shall have 
the meanings given to them in the CSA.
If there is any conflict between the CSA and any attachments to it, the terms of the CSA 
control.  If there is any conflict between this protocol and the CSA, this protocol will control 
as to any issue regarding treatment of study participants, and the CSA will control as to all 
other issues.

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113. Abdul-Hassan Tawbi H, Burgess MA, Crowley J, et al. Safety and efficacy of PD-1 
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124. Taube JM, Klein A, Brahmer JR, et al. Association of PD-1, PD-1 ligands, and other 
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138. Kumar R, Collins D, Dolly S, et al. Targeting the PD-1/PD-L1 axis in non-small cell 
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Appendix 1. Abbreviations
The following is a list of abbreviations that may be used in the protocol.  
Abbreviation
Term
Ab
anti-body
ABCP
atezolizumab plus BCP
AChR
acetylcholine receptor
ACRIN
American College of Radiology Imaging Network
ADA
anti-drug antibodies
AdC68
a chimpanzee adenovirus 68
AE
adverse event
AIDS
acquired immunodeficiency syndrome
ALK WT
Anaplastic lymphoma kinase wild-type
ALT
alanine aminotransferase
ANC
absolute neutrophil count
ANOVA
analysis of variance
ART
antiretroviral therapy
ASCO
American Society of Clinical Oncology
AST
aspartate aminotransferase
AUC
area under the curve
AUCinf
area under the curve plasma concentration versus time curve 
from time 0 extrapolated to infinity
AUClast
area under the curve plasma concentration following the first 
dose from time 0 to last time point
BCP
bevacizumab plus carboplatin plus paclitaxel
BCT
blood collection tube
BID
twice daily
BP
blood pressure
BRAF
proto-oncogene protein B-raf
BSA
body surface area
BUN
blood urea nitrogen
C
Cycle
CAR
chimeric antigen receptor
CBR
clinical benefit rate
CL/F
apparent serum clearance
Cmax
maximum plasma concentration
C1D1
cycle 1 day 1
CHF
congestive heart failure
cHL
classical Hodgkin lymphoma
ChTx
chemotherapy treatment
CI
confidence interval
CCI

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Abbreviation
Term
CISH
chromogenic in situ hybridization
CK
creatine kinase
CL
Clearance
CLL
chronic lymphocytic leukemia
CNS
central nervous system
COVID-19
coronavirus disease of 2019
CR
complete response
CRF
case report form
CRM
Continual Reassessment Method
CSA
clinical study agreement
CSF
cerebrospinal fluid
CSR
clinical study report
CT
computed tomography
CT
clinical trial
CTA
clinical trial application
CTCAE
Common Terminology Criteria for Adverse Events
CTLA4
Anti-cytotoxic T Lymphocyte-associated antigen 4
cTnI
cardiac troponin-I
CV
coefficient of variation
DILI
drug-induced liver injury
DLI
donor lymphocyte infusion
DLT
dose-limiting toxicity
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DR
duration of Response
DU
dispensable unit
D/U
dose de-escalation
DOR
duration of response
DOSD
duration of stable disease
EC
ethics committee
ECC
emergency contact card
ECG
Electrocardiogram
ECOG
Eastern Cooperative Oncology Group
E-DMC
external data monitoring committee
EDP
exposure during pregnancy
EDTA
ethylenediaminetetraacetic acid
EFS
event-free survival
Eg
for example
EGFR
epidermal growth factor receptor
EI
equivalence interval
CCI

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Abbreviation
Term
EML4
echinoderm microtubule-associated protein-like 4
EP
evaluable population
ER
estrogen receptor
Etc
‘and other things’ or ‘and so forth’
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration (United States)
FFPE
formalin-fixed paraffin-embedded
FIP
first in patient
FISH
fluorescence in situ hybridization
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GI
gastrointestinal
GnRH
gonadotropin-releasing hormone agonist
GPI 
glycophosphatidylinositol
GVAX
cancer vaccine
GVHD
graft versus host disease
HBV
hepatitis B virus
HCC
hepatocellular carcinoma
HCV
hepatitis C virus
HER2
human epidermal growth factor 2
Hgb
Hemoglobin
HIV
human immunodeficiency virus
HR
heart rate / hazard ratio
IB
investigator’s brochure
ICH
International Conference on Harmonisation
ICOS
inducible T-cell costimulatory
ID
Identification
Ie
that is
IFN
Interferon
Ig
Immunoglobulin
IgG4
immunoglobulin G4
IHC
immunohistochemistry
IM
intramuscular
IP
investigational product
IND
investigational new drug application
INR
international normalized ratio
IP manual
Investigational Product manual
IRB
institutional review board
IRC
internal review committee

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Abbreviation
Term
irCR
immune related – complete response
irPD
immune related – progressive disease
irPR
immune related – partial response
irSD
immune related – stable disease
IRT
interactive response technology
ISR
injection site reaction
IUD
intrauterine device
IV
intravenous
IWR
interactive Web-based response
kDa
kilodalton
KRAS
proto-oncogene
LAG3
lymphocyte activation gene 3
LDH
lactate dehydrogenase
LFT
liver function test
LM
listeria monocytogene
LSLV
last subject last visit
LVEF
left ventricular ejection fraction
mAb
monoclonal antibody
MCC
Merkel cell carcinoma
MD
multiple dose
MedDRA
Medical Dictionary for Regulatory Activities
MFD
maximum feasible dose
MG
myasthenia gravis
MHC
major histocompatibility complex
mITT
modified intend to treat
mNSCLC
metastatic non-small cell lung cancer
mOS
median overall survival
MPF
megakaryocyte potentiating factor
mPFS
median progression-free survival
MRI
magnetic resonance imaging
MSLN
mesothelin
MTD
maximum tolerated dose
mTNBC
metastatic triple negative breast cancer
mTPI
modified toxicity probability interval
mTTP
median time to progression
MUC1
mucin 1, cell surface associated
N/A
not applicable
NAb
neutralizing antibody
NCI 
National Cancer Institute 
CCI

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Abbreviation
Term
NCI CTCAE
National Cancer Institute Common Terminology Criteria for 
Adverse Events
NHPs
nonhuman primates
NK
natural killer
NSCLC
non-small cell lung cancer
OBD
optimal biological dose
OR
Objective Response or Overall Response
ORR
objective response rate
OS
overall survival
PCD
primary completion date
PD
pharmacodynamics
PD
progressive disease
PD-1
programmed death – 1
PD-L1
programmed death – ligand 1
pDNA
Plasmid deoxyribonucleic acid
PET
positron emission tomography
PFS
Progression-Free Survival
PFS
prefilled syringe
PI
principal investigator
PK
Pharmacokinetic
PGx
pharmacogenomics
PP
per protocol
PR
partial response
PR
progesterone receptor
PrCa
prostate cancer
PrCaVBIR
Prostate Cancer Vaccine-based Immunotherapy Regimen
PS
performance status
PSA
Prostate specific antigen
PSCA
Prostate stem cell antigen
PSMA
Prostate specific membrance antigen
pT
Target probability
PT
prothrombin time
PTT
partial thromboplastin time
QD
every day
QT
time between the start of the Q wave and the end of the T 
wave
QTcF
QT interval with Fridericia's correction
QxW
Every x# of Weeks, ie, Q2W, Q4W, Q6W, Q12W)
RCC
renal cell carcinoma
RD
Response/Remission Duration 
RECIST
Response Evaluation Criteria in Solid Tumors
CCI

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Abbreviation
Term
RET
rearranged during transfection
RFS
Relapse-Free Survival
ROS1
ROS proto-oncogene 1, receptor tyrosine kinase
RP2D
recommended Phase 2 dose
RR
response rate
SAE
serious adverse event
SAP
statistical analysis plan
SARS-CoV2
severe acute respiratory syndrome coronavirus 2
SC
Subcutaneous
SCCHN
squamous cell carcinoma of the head and neck
SCLC
small cell lung cancer
SD
single dose / stable disease
SGOT
serum glutamic-oxaloacetic transaminase
SGPT
serum glutamic-pyruvic transaminase
SOA
Schedule of Activities
SOP
standard operating procedure
SRSD
single reference safety document
T1/2
terminal elimination half-life
Tmax
time to maximum plasma concentration
Tbili
total bilirubin
TAAs
tumor associated antigens
TBR
tumor background ratio
TERT
telomerase reverse transcriptase
TILs
tumor infiltrating lymphocytes
TKIs
tyrosine kinase inhibitors
TDS-IM
(Ichor) Intramuscular TriGrid Delivery System 
TNBC
triple negative breast cancer
TRAEs
treatment-related adverse events
TRK
tyrosine receptor kinase
TSH
thyroid stimulating hormone
TTP
time to progression
ULN
upper limit of normal
UPM
unit probability mass
US
United States
USPI
United States Package Insert
UVB
ultraviolet B 
VBIR-2
Vaccine-based immunotherapy regimen - 2
VP
viral particles
Vz/F
volume of distribution
CCI
CCI

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Abbreviation
Term
WBC
white blood cell 
WHO
World Health Organization
WT
wild-type

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Appendix 2. ECOG Performance Status
Grade
ECOG Performance Status
0
Fully active, able to carry on all pre-disease performance without restriction.
1
Restricted in physically strenuous activity but ambulatory and able to carry 
out work of a light or sedentary nature, eg, light house work, office work.
2
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
Capable of only limited self-care, confined to bed or chair more than 50% of 
waking hours.
4
Completely disabled.  Cannot carry on any self-care.  Totally confined to bed 
or chair.
5
Dead.
*As published in Am J Clin Oncol 5:649 655, 1982

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Appendix 3. RECIST (Response Evaluation Criteria In Solid Tumors) version 
1.1 Guidelines
Adapted from E.A. Eisenhauer, et al: New response evaluation criteria in solid tumours: 
Revised RECIST guideline (version 1.1).  European Journal of Cancer 45 (2009) 228–247. 
CATEGORIZING LESIONS AT BASELINE
Measurable Lesions
Lesions that can be accurately measured in at least one dimension.

Lesions with longest diameter twice the slice thickness and at least 10 mm or greater 
when assessed by CT or MRI (slice thickness 5-8 mm).

Lesions with longest diameter at least 20 mm when assessed by Chest X-ray. 

Superficial lesions with longest diameter 10 mm or greater when assessed by caliper. 

Malignant lymph nodes with the short axis 15 mm or greater when assessed by CT.
NOTE: The shortest axis is used as the diameter for malignant lymph nodes, longest 
axis for all other measurable lesions. 
Non-measurable disease 
Non-measurable disease includes lesions too small to be considered measurable (including 
nodes with short axis between 10 and 14.9 mm) and truly non-measurable disease such as
pleural or pericardial effusions, ascites, inflammatory breast disease, leptomeningeal disease, 
lymphangitic involvement of skin or lung, clinical lesions that cannot be accurately measured 
with calipers, abdominal masses identified by physical exam that are not measurable by 
reproducible imaging techniques.

Bone disease: Bone disease is non-measurable with the exception of soft tissue 
components that can be evaluated by CT or MRI and meet the definition of 
measurability at baseline.

Previous local treatment: A previously irradiated lesion (or lesion subjected to other 
local treatment) is non-measurable unless it has progressed since completion of 
treatment.
Normal sites

Cystic lesions: Simple cysts should not be considered as malignant lesions and should 
not be recorded either as target or non-target disease.  Cystic lesions thought to 
represent cystic metastases can be measurable lesions, if they meet the specific 
definition above.  If non-cystic lesions are also present, these are preferred as target 
lesions.

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
Normal nodes: Nodes with short axis <10 mm are considered normal and should not 
be recorded or followed either as measurable or non-measurable disease.
Recording Tumor Assessments 
All sites of disease must be assessed at baseline.  Baseline assessments should be done as 
close as possible prior to study start.  For an adequate baseline assessment, all required scans 
must be done within 28 days prior to treatment and all disease must be documented 
appropriately.  If baseline assessment is inadequate, subsequent statuses generally should be 
indeterminate. 
Target lesions
All measurable lesions up to a maximum of 2 lesions per organ, 5 lesions in total, 
representative of all involved organs, should be identified as target lesions at baseline.  
Target lesions should be selected on the basis of size (longest lesions) and suitability for 
accurate repeated measurements.  Record the longest diameter for each lesion, except in the 
case of pathological lymph nodes for which the short axis should be recorded.  The sum of 
the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target lesions 
at baseline will be the basis for comparison to assessments performed on study. 

If two target lesions coalesce the measurement of the coalesced mass is used.  If a 
large target lesion splits, the sum of the parts is used.

Measurements for target lesions that become small should continue to be recorded.  If 
a target lesion becomes too small to measure, 0 mm should be recorded if the lesion is 
considered to have disappeared; otherwise a default value of 5 mm should be 
recorded.
NOTE: When nodal lesions decrease to <10 mm (normal), the actual measurement 
should still be recorded.
Non-target disease 
All non-measurable disease is non-target.  All measurable lesions not identified as target 
lesions are also included as non-target disease.  Measurements are not required but rather 
assessments will be expressed as ABSENT, INDETERMINATE, PRESENT/NOT 
INCREASED, INCREASED.  Multiple non-target lesions in one organ may be recorded as a 
single item on the case report form (eg, ‘multiple enlarged pelvic lymph nodes’ or ‘multiple 
liver metastases’).

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OBJECTIVE RESPONSE STATUS AT EACH EVALUATION
Disease sites must be assessed using the same technique as baseline, including consistent 
administration of contrast and timing of scanning.  If a change needs to be made the case 
must be discussed with the radiologist to determine if substitution is possible.  If not, 
subsequent objective statuses are indeterminate. 
Target disease

Complete Response (CR): Complete disappearance of all target lesions with the 
exception of nodal disease.  All target nodes must decrease to normal size (short axis 
<10 mm).  All target lesions must be assessed.

Partial Response (PR): Greater than or equal to 30% decrease under baseline of the 
sum of diameters of all target measurable lesions.  The short diameter is used in the 
sum for target nodes, while the longest diameter is used in the sum for all other target 
lesions.  All target lesions must be assessed. 

Stable: Does not qualify for CR, PR or Progression.  All target lesions must be 
assessed.  Stable can follow PR only in the rare case that the sum increases by less 
than 20% from the nadir, but enough that a previously documented 30% decrease no 
longer holds. 

Objective Progression (PD): 20% increase in the sum of diameters of target 
measurable lesions above the smallest sum observed (over baseline if no decrease in 
the sum is observed during therapy), with a minimum absolute increase of 5 mm. 

Indeterminate.  Progression has not been documented, and 

one or more target measurable lesions have not been assessed; 

or assessment methods used were inconsistent with those used at baseline;

or one or more target lesions cannot be measured accurately (eg, poorly visible unless 
due to being too small to measure);

or one or more target lesions were excised or irradiated and have not reappeared or 
increased. 
Non-target disease

CR: Disappearance of all non-target lesions and normalization of tumor marker 
levels.  All lymph nodes must be ‘normal’ in size (<10 mm short axis).

Non-CR/Non-PD: Persistence of any non-target lesions and/or tumor marker level 
above the normal limits. 

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
PD: Unequivocal progression of pre-existing lesions.  Generally the overall tumor 
burden must increase sufficiently to merit discontinuation of therapy.  In the presence 
of stable disease (SD) or PR in target disease, progression due to unequivocal 
increase in non-target disease should be rare. 

Indeterminate: Progression has not been determined and one or more non-target sites 
were not assessed or assessment methods were inconsistent with those used at 
baseline.
New Lesions 
The appearance of any new unequivocal malignant lesion indicates PD.  If a new lesion is 
equivocal, for example due to its small size, continued assessment will clarify the etiology.  
If repeat assessments confirm the lesion, then progression should be recorded on the date of 
the initial assessment.  A lesion identified in an area not previously scanned will be 
considered a new lesion.
Supplemental Investigations

If CR determination depends on a residual lesion that decreased in size but did not 
disappear completely, it is recommended the residual lesion be investigated with 
biopsy or fine needle aspirate.  If no disease is identified, objective status is CR.

If progression determination depends on a lesion with an increase possibly due to 
necrosis, the lesion may be investigated with biopsy or fine needle aspirate to clarify 
status. 
Subjective progression
Participants requiring discontinuation of treatment without objective evidence of disease 
progression should not be reported as PD on tumor assessment CRFs.  This should be 
indicated on the end of treatment CRF as off treatment due to Global Deterioration of Health 
Status.  Every effort should be made to document objective progression even after 
discontinuation of treatment. 

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Table 17.
Objective Response Status at each Evaluation
Target Lesions
Non-target Disease
New Lesions
Objective status
CR
CR
No
CR
CR
Non-CR/Non-PD
No
PR
CR
Indeterminate or Missing
No
PR
PR
Non-CR/Non-PD, 
Indeterminate, or Missing
No
PR
SD
Non-CR/Non-PD, 
Indeterminate, or Missing
No
Stable
Indeterminate or 
Missing
Non-PD
No
Indeterminate
PD
Any
Yes or No
PD
Any
PD
Yes or No
PD
Any
Any
Yes
PD
Table 18.
Objective Response Status at each Evaluation for Participants  with 
Non-Target Disease Only
Non-target Disease
New Lesions
Objective status
CR
No
CR
Non-CR/Non-PD
No
Non-CR/Non-PD
Indeterminate
No
Indeterminate
Unequivocal progression
Yes or No
PD
Any
Yes
PD

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Appendix 4. National Cancer Institute (NCI) Common Terminology Criteria for 
Adverse Events (CTCAE)
The NCI CTCAE (Version 5.0 dated November 27, 2017) has been placed in the Study 
Manual for this protocol.  Alternatively, the NCI CTCAE may be reviewed on-line at the 
following NCI website: 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm

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Appendix 5. Management of Immune-related Adverse Events (irAEs) 
Management of irAEs including Myasthenia Gravis
Gastrointestinal irAEs
Severity of Diarrhea/Colitis (NCI-
CTCAE v5.0)
Initial Management
Follow-up Management
Grade 1
Diarrhea: <4 stools/day over Baseline
Colitis: asymptomatic
-Continue study treatment.
-Symptomatic treatment (eg,
loperamide).
-Close monitoring for worsening 
symptoms.
-Educate patient to report 
worsening immediately.
-If worsens:
Treat as Grade 2, 3 or 4.
Grade 2
Diarrhea: 4 to 6 stools per day over
Baseline; IV fluids indicated <24 hours; 
not interfering with ADL
Colitis: abdominal pain; blood in stool
-Withhold study treatment. 
-Symptomatic treatment.
-If improves to Grade ≤1: Resume 
study treatment.
-If persists >5-7 days or recurs:
Treat as Grade 3 or 4.
Grade 3 to 4
Diarrhea (Grade 3): ≥7 stools per day 
over Baseline; incontinence; IV fluids 
≥24 h; interfering with ADL
Colitis (Grade 3): severe abdominal pain, 
medical intervention indicated, 
peritoneal signs
Grade 4: life-threatening, perforation
-Withhold for Grade 3.
-Permanently discontinue study 
treatment for Grade 4 or 
recurrent Grade 3.
-1.0 to 2.0 mg/kg/day 
prednisone IV or equivalent.
-Add prophylactic antibiotics 
for opportunistic infections.
-Consider lower endoscopy.
-If improves:
-Continue steroids until Grade ≤1, 
then taper over at least 1 month; 
resume study treatment following 
steroids taper (for initial Grade 3).
-If worsens, persists >3 to 5 days, 
or recurs after improvement:
-Add infliximab 5mg/kg (if no 
contraindication).
-Note: infliximab should not be 
used in cases of perforation or 
sepsis.

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Dermatological irAEs
Grade of Rash
(NCI-CTCAE v5.0)
Initial Management
Follow-up Management
Grade 1 to 2
Covering ≤30% body surface area
-Continue study treatment.  
-Symptomatic therapy (for 
example, antihistamines, topical 
steroids).
-If persists >1 to 2 weeks or recurs: 
-Withhold study treatment; 
-Consider skin biopsy.
-Consider 0.5-1.0 mg/kg/day 
prednisone or equivalent.  Once 
improving, taper steroids over at least 
1 month, consider prophylactic 
antibiotics for opportunistic 
infections, and resume study 
treatment following steroids taper.
-If worsens: Treat as Grade 3 to 4.
Grade 3 to 4
Grade 3: Covering >30% body
surface area;
Grade 4: Life
threatening 
consequences
-Withhold study treatment for 
Grade 3.
-Permanently discontinue for 
Grade 4 or recurrent Grade 3.
-Consider skin biopsy.
-Dermatology consult.
-1.0 to 2.0 mg/kg/day prednisone 
or equivalent.
-Add prophylactic antibiotics for 
opportunistic infections.
-If improves to Grade ≤1:
-Taper steroids over at least 1 month; 
resume study treatment following 
steroids taper (for initial Grade 3).

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Pulmonary irAEs
Grade of Pneumonitis 
(NCI-CTCAE v5.0)
Initial Management
Follow-up Management
Grade 1
Radiographic changes only
-Consider withholding study 
treatment.
-Monitor for symptoms every 
2 to 3 days.
-Consider Pulmonary and 
Infectious Disease consults.
-Re-assess at least every 3 weeks. 
-If worsens: Treat as Grade 2 or 
Grade 3 to 4.
Grade 2
Mild to moderate new symptoms
-Withhold study treatment. 
-Pulmonary and Infectious 
Disease consults.
-Monitor symptoms daily; 
consider hospitalization.
-1.0 to 2.0 mg/kg/day 
prednisone or equivalent.
-Add prophylactic antibiotics 
for opportunistic infections.
-Consider bronchoscopy, lung 
biopsy.
-Re-assess every 1 to 3 days If 
improves:
-When symptoms return to Grade 
≤1, taper steroids over at least 1 
month, and then resume study 
treatment following steroids taper.
-If not improving after 2 weeks or 
worsening: Treat as Grade 3 to 4.
Grade 3 to 4
Grade 3: Severe new symptoms; 
New/worsening hypoxia;
Grade 4: Life-threatening
-Permanently discontinue 
study treatment. 
-Hospitalize.
-Pulmonary and Infectious 
Disease consults.
-1.0 to 2.0 mg/kg/day 
prednisone or equivalent.
-Add prophylactic antibiotics 
for opportunistic infections.
-Consider bronchoscopy, lung 
biopsy.
If improves to Grade ≤1:
-Taper steroids over at least 1 
month.
-If not improving after 48 hours or 
worsening: Add additional 
immunosuppression (for example, 
infliximab, cyclophosphamide, IV.
-immunoglobulin, or 
mycophenolate mofetil).

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Hepatic irAEs
Grade of Liver
Test Elevation 
(NCI-CTCAE v5.0)
Initial Management
Follow-up Management
Grade 1
Grade 1 AST or ALT
> ULN to 3.0 x ULN 
and/or Total bilirubin 
> ULN to
1.5 x ULN
-Continue study treatment.
-Continue liver function monitoring.
-If worsens: Treat as Grade 2 or 3 - 4.
Grade 2
AST or ALT >3.0 to ≤5
x ULN and/or total
bilirubin >1.5 to ≤3 x 
ULN
-Withhold study treatment.
-Increase frequency of monitoring to 
every 3 days.
-If returns to Grade ≤1:
-Resume routine monitoring; resume 
study treatment.
-If elevation persists >5 to 7 days or 
worsens: 
-Treat as Grade 3 to 4.
Grade 3 to 4
AST or ALT >5 x ULN 
and/or total bilirubin >3
x ULN
-Permanently discontinue study 
treatment.
-Increase frequency of monitoring to 
every 1 to 2 days.
-1.0 to 2.0 mg/kg/day prednisone or 
equivalent.
-Add prophylactic antibiotics for 
opportunistic infections.
-Consult 
gastroenterologist/hepatologist.
-Consider obtaining MRI/CT scan of 
liver and liver biopsy if clinically 
warranted.
-If returns to Grade ≤1:
-Taper steroids over at least 1 month.
-If does not improve in >3 to 5 days, 
worsens or rebounds:
-Add mycophenolate mofetil 1 gram (g) 
twice daily.
-If no response within an additional 3 to 5 
days, consider other immunosuppressants 
per local guidelines.

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Renal irAEs
Grade of Creatinine
Increased (NCI-CTCAE v5.0)
Initial Management
Follow-up 
Management
Grade 1
Creatinine increased > ULN to 1.5 x
ULN
-Continue study treatment.
-Continue renal function 
monitoring 
-If worsens: Treat as Grade 
2 to 3 or 4.
Grade 2 to 3
Creatinine increased >1.5 and ≤6 x 
ULN
-Withhold study treatment.  
-Increase frequency of monitoring to 
every 3 days.
-1.0 to 2.0 mg/kg/day prednisone or 
equivalent.
-Add prophylactic antibiotics for 
opportunistic infections.
-Consider renal biopsy.
-If returns to Grade ≤1:
-Taper steroids over at least 
1 month, and resume 
study treatment following 
steroids taper.
-If worsens:
-Treat as Grade 4.
Grade 4
Creatinine increased >6 x ULN
-Permanently discontinue study treatment. 
-Monitor creatinine daily.
-1.0 to 2.0 mg/kg/day prednisone or 
equivalent.
-Add prophylactic antibiotics for 
opportunistic infections Consider renal 
biopsy.
-Nephrology consult.
-If returns to Grade ≤1:
Taper steroids over at least 
1 month.

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Cardiac irAEs
Myocarditis
Initial Management
Follow-up Management
New onset of cardiac signs or 
symptoms and / or new laboratory 
cardiac biomarker elevations (eg, 
troponin, CK-MB, BNP) or cardiac 
imaging abnormalities suggestive of 
myocarditis.
-Withhold study treatment.
-Hospitalize.
-In the presence of life threatening cardiac 
decompensation, consider transfer to a 
facility experienced in advanced heart 
failure and arrhythmia management.
-Consult cardiologist to establish etiology 
and rule-out immune-mediated 
myocarditis.
-Guideline based supportive treatment as per 
cardiology consult.*
-Consider myocardial biopsy if 
recommended per cardiology consult.
-If symptoms improve and 
immune-mediated 
etiology is ruled out, re-
start study treatment.
-If symptoms do not 
improve/worsen, viral 
myocarditis is excluded, 
and immune-mediated 
etiology is suspected or 
confirmed following 
cardiology consult, 
manage as immune-
mediated myocarditis.
Immune-mediated myocarditis.
-Permanently discontinue study treatment.
-Guideline based supportive treatment as 
appropriate as per cardiology consult.*
1.0 to 2.0 mg/kg/day prednisone or 
equivalent.
-Add prophylactic antibiotics for 
opportunistic infections.
Once improving, taper 
steroids over at least 1 
month.
If no improvement or 
worsening, consider 
additional 
immunosuppressants (eg, 
azathioprine, cyclosporine 
A).
*Local guidelines, or eg. ESC or AHA guidelines
ESC guidelines website:  https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines AHA guidelines 
website:
http://professional.heart.org/professional/GuidelinesStatements/UCM_316885_Guidelines-Statements.jsp.

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Appendix 6. Recommended Management Algorithm for Myasthenia Gravis
Recommended Management Algorithm for Myasthenia Gravis 

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Appendix 7. Alternative Measures During Public Emergencies
The alternative study measures described in this section are to be followed during public 
emergencies, including the COVID-19 pandemic.  This appendix applies for the duration of 
the COVID-19 pandemic and will become effective for other public emergencies only upon 
written notification from Pfizer. 
Use of these alternative study measures are expected to cease upon the return of business as 
usual circumstances (including the lifting of any quarantines and travel bans/advisories). 
Eligibility
While SARS-CoV2 testing is not mandated for this study, local clinical practice standards for 
testing should be followed.  A participant should be excluded if he/she has a positive test 
result for SARS-CoV2 infection, is known to have asymptomatic infection, or is suspected of 
having SARS-CoV2.  Participants with active infections are excluded from study 
participation as per exclusion criterion #9 (Part 2): Active and clinically significant bacterial, 
fungal or viral infection.  When the infection resolves, the participant may be considered for 
re-screening. 
Alternative Facilities for Safety Assessments
Laboratory Testing
If a study participant is unable to visit the site for protocol-specified safety laboratory 
evaluations, testing may be conducted at a local laboratory if permitted by local 
regulations. The local laboratory may be a standalone institution or within a hospital.  The 
safety laboratory evaluations included in Section 7.1.3 may be performed at a local 
laboratory.
If a local laboratory is used, qualified study site personnel must order, receive, and review 
results prior to dosing.  Site staff must collect the local laboratory reference ranges and 
certifications/accreditations for filing at the site. Laboratory test results are to be provided to 
the site staff as soon as possible.  The local laboratory reports should be filed in the 
participant’s source documents/medical records.  Relevant data from the local laboratory 
report should be recorded on the CRF. 
Study Intervention
If the safety of a trial participant is at risk because they cannot complete required evaluations 
or adhere to critical mitigation steps, then discontinuing that participant from study 
intervention must be considered.

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The following is recommended for the continued administration of the investigational 
products for participants who have active confirmed (positive by regulatory authority-
approved test) or presumed (test pending/clinical suspicion) SARS-CoV2 infection:

For symptomatic participants with active SARS-CoV2 infection, study intervention 
should be delayed for at least 14 days from the start of symptoms.  This delay is 
intended to allow the resolution of symptoms of SARS-CoV2 infection.

Prior to restarting treatment, the participant should be afebrile for 72 hours, and 
SARS-CoV2-related symptoms should have recovered to ≤ Grade 1 for a minimum of 
72 hours.  Notify the study team when treatment is restarted.

Continue to consider potential drug-drug interactions as described in Section 5.7 for 
any concomitant medication administered for treatment of SARS-CoV2 infection.
Adverse Events and Serious Adverse Events
If a participant has COVID-19 during the study, this should be reported as an AE or SAE and 
appropriate medical intervention provided.  Temporary discontinuation of the study 
intervention may be medically appropriate until the participant has recovered from 
COVID-19. 
It is recommended that the investigator discuss temporary or permanent discontinuation of 
study intervention with the study medical monitor.