A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND EXPANSION STUDY EVALUATING THE SAFETY AND PHARMACODYNAMICS OF PF-07263689, EITHER ALONE OR IN COMBINATION WITH AN ANTI-PD-1 ANTIBODY, IN PREVIOUSLY TREATED PARTICIPANTS WITH SELECTED LOCALLY ADVANCED OR METASTATIC SOLID TUMORS
Phase: PHASE1
Conditions: Renal Cell Cancer, Melanoma, Non-Small-Cell Lung Cancer, Hepatocellular Cancer, Bladder Cancer, Sarcoma, Head and Neck Cancer, Colorectal Cancer, Ovarian Cancer, Squamous Cell Carcinoma
Sponsor: Pfizer

PF-07263689 
Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
Page 1 
 
 
 
 
 
 
 
 
 
A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND EXPANSION STUDY 
EVALUATING THE SAFETY AND PHARMACODYNAMICS OF PF-07263689, 
EITHER ALONE OR IN COMBINATION WITH AN ANTI-PD-1 ANTIBODY, IN 
PREVIOUSLY TREATED PARTICIPANTS WITH SELECTED LOCALLY 
ADVANCED OR METASTATIC SOLID TUMORS 
 
 
Study Intervention Number: 
PF-07263689 
Study Intervention Name: 
NA 
CCI 
 
 
EudraCT Number: 
NA 
ClinicalTrials.gov ID: 
NA 
Protocol Number: 
C4651001 
Phase: 
1 
Brief Title: Phase 1 Study of PF-07263689 in Participants with Selected Advanced 
Solid Tumors 
 
 
 
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. 

PF-07263689 
Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
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Document History 
 
Document 
Version Date 
Amendment 1 
20 July 2021 
Original protocol 
03 June 2021 
 
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and IRBs/ ECs and any protocol administrative 
clarification letter. 
 
Amendment 1 (20-July-2021) 
 
Overall Rationale for the Amendment: The primary purpose of this amendment is to 
incorporate feedback received from the FDA. In addition, clarification, administrative and 
typographical modifications were made. 
 
 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1.1. Synopsis; 
Section 3.1. Dose 
Escalation; Section 3.2 
Dose Escalation; Section 
9.3.3.2. Sasanlimab 
Pharmacokinetic Analysis 
Secondary objectives and 
statistical consideration were 
included for Part 1 and Part 2 
sasanlimab’s PK and 
immunogenicity. 
Sasanlimab’s PK and 
immunogenicity were previously 
omitted. 
Section 1.1. Synopsis; 
Section 1.2. Schema; 
Section 2.3. Benefit/Risk 
Assessment; Section 4.1.1. 
Dose Escalation (Part 1) 
Part 1B will include CCI 
Due to potential overlapping 
CCI 
clinical safety 
signals and mitigate overall risk to 
patients. 
Section 1.1. Synopsis 
Section 1.2. Schema, 
Section 2.3. Benefit/Risk 
Assessment; Section 4.1.1. 
Dose Escalation (Part 1) 
In Part 1A monotherapy, 
CCI 
To adequately capture acute and 
subacute adverse events for Part 1A 
monotherapy and mitigate overall 
risk to patients. 
Section 1.1. Synopsis 
Section 1.2. Schema; 
Section 4.1.1. Dose 
Escalation (Part 1); Section 
4.3. Justification of Dose; 
Section 4.3.1. Starting 
In Part 1A, the provisional 
dose for each dose level has 
been revised to half log dose 
increments. CCI 
(which is one log level below 
Given the MOA based on a 
replicative oncolytic virus and gene 
therapy platform, a more 
conservative dosing approach has 
been adapted. 

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Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
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Section # and Name 
Description of Change 
Brief Rationale 
Dose; 4.3.2 Criteria for 
Dose Escalation and 9.3.2 
Primary 
Endpoint(s)/Estimand(s)/ 
Analysis 
the NOAEL) is included, and 
the dose levels above NOAEL 
have been removed in this 
amendment. 
Section 1.3. Schedule of 
Activities; Section 2.3.1. 
Risk Assessment; Section 
8.2.4. Vital Signs; Section 
8.2.6 Echocardiogram or 
MUGA; Section 10.2. 
Appendix 2: Clinical 
Laboratory Assessments; 
Section 10.8.3.4. 
Echocardiogram or MUGA 
The following assessments 
have been added in the SOA 
and throughout the protocol: 
• 
Cardiac Biomarkers (CPK 
and troponin levels) 
• 
Echocardiogram or 
MUGA 
• 
Pulse oximetry 
Safety assessments added as the 
combination of PF-07263689 and 
sasanlimab may potentially lead to 
increased CCI 
. 
Section 1.1. Synopsis; 
Section 5.1. Inclusion 
Criteria; Section 5.2. 
Exclusion Criteria 
The eligibility criteria were 
modified: 
• 
Participants with 
persistent non- 
hematologic toxicities of 
Grade ≥ 3 (NCI-CTCAE 
v5.0), including 
symptoms and objective 
findings from treatment, 
such as chemotherapy, 
kinase inhibitors, 
immunotherapy, 
experimental agents, 
radiation or surgery. 
• 
Creatinine clearance was 
increased to ≥60 mL/min 
except for participants 
with RCC in which the 
CrCl cut-off will be ≥30 
mL/min. 
• 
In Part 1, participants who 
are HIV, HBV or HCV 
positive will be excluded. 
• 
Participants with a history 
of myocarditis or 
congestive heart failure, 
as well as unstable angina, 
serious uncontrolled 
cardiac arrhythmia, or 
myocardial infarction 6 
To further ensure patient safety and 
to reduce any potential CCI 
, 
possible allergic reaction to 
antiviral agents and the safety of 
immunocompromised patients. 

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Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
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Section # and Name 
Description of Change 
Brief Rationale 
months prior to study 
entry. 
• 
Participants with active 
ILD/pneumonitis or a 
history of 
ILD/pneumonitis 
requiring treatment with 
systemic steroids. 
• 
Participants whose 
baseline pulse oximetry is 
less than 92% “on Room 
air”. 
• 
Participants with an LVEF 
<50% by echocardiogram 
or MUGA. 
• 
Participants with known 
allergic history to antiviral 
agents. 
Duplicate inclusion criterion 
regarding participants 
compliance with study 
procedures was removed. 
Section 1.1., Synopsis; 
Section 1.3. Schedule of 
Activities; Section 4.3.4. 
Late Toxicity Definition 
and Management; Section 
7.1 Discontinuation of 
Study Intervention; Section 
8.3.1. Time Period and 
Frequency for Collection 
AE and SAE Information 
All participants will be 
monitored for immune related 
toxicities for at least 90 days. 
Clarified duration of monitoring 
for possible delayed toxicities from 
the combination treatment. 
Section 4.3.3. DLT 
Definition; Section 4.3.3.2. 
Non- Hematologic DLTs; 
The DLT criteria were 
updated to include CRS, 
myocarditis, as well as any 
grade ≥ 3 toxicity of any 
duration affecting vital organs. 
To further mitigate risk to patients. 
Section 10.3.5. Guidance 
for Immune-Related 
Adverse Events 
The immune-related adverse 
events for checkpoint inhibitor 
table was updated. 
This table was previously 
incomplete. 
Section 7.1.3. Cardiac 
Adverse Events 
Added text to indicate that 
participants with Grade ≥ 3 
To reduce the increase risk of 
recurrent/serious cardiac toxicity. 

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Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
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Section # and Name 
Description of Change 
Brief Rationale 
myocarditis will be 
discontinued from the study. 
Section 8.3.8 Adverse 
Events of Special Interest 
CCI 
 
To ensure patients safety and to 
reduce any potential CCI 
 
Section 9.3.2. Primary 
Endpoint(s)/Estimand(s)/ 
Analysis 
The stopping criteria for 
safety were revised to pause 
enrollment if early experience 
uncovers important safety 
problems. 
To mitigate risk to additional 
patients. 

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Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
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TABLE OF CONTENTS 
LIST OF TABLES ................................................................................................................... 14 
1. PROTOCOL SUMMARY ................................................................................................... 15 
1.1. Synopsis ................................................................................................................... 15 
1.2. Schema..................................................................................................................... 26 
1.3. Schedule of Activities .............................................................................................. 27 
2. INTRODUCTION ................................................................................................................ 50 
2.1. Study Rationale ........................................................................................................ 50 
2.2. Background .............................................................................................................. 50 
2.2.1. Oncolytic Viruses ........................................................................................ 50 
2.2.2. PF-07263689 ............................................................................................... 51 
2.2.3. Sasanlimab .................................................................................................. 52 
2.2.3.1. Sasanlimab, an Anti-PD-1 Antibody: Clinical Experience 
in Study B8011001 (NCT02573259) ................................................. 52 
2.2.4. Nonclinical Pharmacology .......................................................................... 52 
2.2.4.1. In vitro and In vivo Pharmacology ............................................ 52 
2.2.5. Nonclinical Pharmacokinetics and Metabolism .......................................... 54 
2.2.6. Nonclinical Safety ....................................................................................... 54 
2.2.7. Clinical Overview ....................................................................................... 54 
2.3. Benefit/Risk Assessment ......................................................................................... 54 
2.3.1. Risk Assessment ......................................................................................... 56 
2.3.2. Benefit Assessment ..................................................................................... 58 
2.3.3. Overall Benefit/Risk Conclusion ................................................................ 58 
3. OBJECTIVES, ENDPOINTS, AND ESTIMANDS ............................................................ 58 
3.1. Dose Escalation (Part 1) .......................................................................................... 58 
3.2. Dose Expansion (Part 2) .......................................................................................... 60 
4. STUDY DESIGN ................................................................................................................. 61 
4.1. Overall Design ......................................................................................................... 61 
4.1.1. Dose Escalation (Part 1) .............................................................................. 62 
4.1.2. Dose Expansion (Part 2) ............................................................................. 63 
4.2. Scientific Rationale for Study Design ..................................................................... 63 
4.2.1. Dose Level Review Committee .................................................................. 63 

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4.2.2. Choice of Contraception/Barrier Requirements .......................................... 64 
4.2.3. Collection of Retained Research Samples ................................................... 64 
4.3. Justification of Dose ................................................................................................ 64 
4.3.1. Starting Dose ............................................................................................... 65 
4.3.2. Criteria for Dose Escalation ........................................................................ 65 
4.3.3. DLT Definition............................................................................................ 66 
4.3.3.1 Hematological DLTs ................................................................... 66 
4.3.3.2. Non-Hematologic DLTs ............................................................ 66 
4.3.3.3. Other DLTs (Part 1B Only) ....................................................... 67 
4.3.4. Late Toxicity Definition and Management ................................................. 68 
4.3.5. MTD Definition .......................................................................................... 68 
4.3.6. Recommended Phase 2 Dose Definition ..................................................... 68 
4.4. End of Study Definition ........................................................................................... 69 
5. STUDY POPULATION ...................................................................................................... 69 
5.1. Inclusion Criteria ..................................................................................................... 69 
5.2. Exclusion Criteria .................................................................................................... 72 
5.3. Lifestyle Considerations .......................................................................................... 77 
5.3.1. Contraception .............................................................................................. 77 
5.3.2. Accidental Exposures and Viral Shedding Considerations ......................... 78 
5.3.2.1. Contacts Exhibiting Symptoms of Viral Infections ................... 79 
5.4. Screen Failures ......................................................................................................... 80 
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY .................................. 80 
6.1. Study Intervention(s) Administered ......................................................................... 80 
6.1.1. Administration ............................................................................................. 81 
6.1.1.1. PF-07263689.............................................................................. 81 
6.1.1.2. Sasanlimab ................................................................................. 82 
6.1.2. Order of Administration (Part 1B and Part 2) ............................................. 82 
6.2. Preparation, Handling, Storage and Accountability ................................................. 82 
6.2.1. Preparation and Dispensing ......................................................................... 83 
6.2.2. Additional Instructions for PF-07263689 ................................................... 84 
6.2.2.1. Special Handling of PF-07263689 ............................................ 84 

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Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
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6.2.2.2. Transport of PF-07263689 .........................................................84 
6.2.2.3. Handling and Thawing ..............................................................84 
6.2.2.4. Cleaning/Disinfection and Disposal ...........................................84 
6.2.2.5. Spills or Environmental Contamination ....................................85 
6.3. Measures to Minimize Bias: Randomization and Blinding .....................................85 
6.3.1. Allocation to Study Intervention .................................................................85 
6.4. Study Intervention Compliance ...............................................................................86 
6.5. Dose Modification ...................................................................................................86 
6.5.1. PF-07263689 ...............................................................................................86 
6.5.2. Sasanlimab ..................................................................................................86 
6.6. Continued Access to Study Intervention After the End of the Study ......................88 
6.7. Treatment of Overdose ............................................................................................88 
6.8. Concomitant Therapy ..............................................................................................89 
6.8.1. Other Prohibited and/or Limited use of Anti-tumor/Anti-Cancer or 
Experimental Drugs, or Procedures .................................................................90 
6.8.2. Agents with Potential Inhibitory Activity Against Vaccinia Viruses .........90 
6.8.3. Supportive Care ...........................................................................................90 
6.8.3.1. Supportive Care for Superficial Skin Lesion(s) ........................90 
6.8.3.2. Supportive Care for Infusion Related Reactions .......................91 
6.8.3.3. Supportive Care for CRS ...........................................................91 
6.8.3.4. Supportive Care for Hypersensitivity Reactions Types 1 
and 3 ...................................................................................................92 
6.8.3.5. Supportive Care for Immune-Related Adverse Events .............92 
6.8.4. Hematopoietic Growth Factors ...................................................................93 
6.8.5. Antidiarrheal, Antiemetic Therapy .............................................................93 
6.8.6. Corticosteroids ............................................................................................93 
6.8.7. Anti-Inflammatory Therapy. .......................................................................94 
6.8.8. Vaccines Administration .............................................................................94 
6.8.9. Surgery ........................................................................................................94 
6.8.10. Radiation Therapy .....................................................................................94 
6.8.11. Rescue Medicine .......................................................................................94 
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 

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Final Protocol, Amendment 1, 20 July 2021 
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DISCONTINUATION/WITHDRAWAL ............................................................................95 
7.1. Discontinuation of Study Intervention .....................................................................95 
7.1.1. Potential Cases of Acute Kidney Injury ......................................................96 
7.1.2. ECG Changes ..............................................................................................96 
7.1.3. Cardiac Adverse Events ..............................................................................97 
7.2. Participant Discontinuation/Withdrawal From the Study .......................................97 
7.2.1. Withdrawal of Consent ...............................................................................97 
7.3. Lost to Follow-Up ...................................................................................................98 
8. STUDY ASSESSMENTS AND PROCEDURES ...............................................................98 
8.1. Efficacy Assessments ..............................................................................................99 
8.1.1. Tumor Response Assessments ....................................................................99 
8.2. Safety Assessments ................................................................................................100 
8.2.1. Participant Demographics and Other Baseline Characteristics .................100 
8.2.2. Physical Examinations ..............................................................................100 
8.2.3. Skin Monitoring ........................................................................................101 
8.2.4. Vital Signs .................................................................................................101 
8.2.5. Electrocardiograms ....................................................................................101 
8.2.6. Echocardiogram or MUGA .......................................................................102 
8.2.7. Clinical Safety Laboratory Assessments ...................................................102 
8.2.8. Pregnancy Testing .....................................................................................103 
8.2.9. Vector Shedding Kinetics and Infectivity Assessments: ..........................103 
8.2.10. Mouth Swab and Urine Specimens .........................................................104 
8.2.11. Photographs of Skin Lesions ..................................................................105 
8.3. Adverse Events, Serious Adverse Events, and Other Safety Reporting ...............105 
8.3.1. Time Period and Frequency for Collecting AE and SAE Information .....105 
8.3.1.1. Reporting SAEs to Pfizer Safety .............................................106 
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF .................106 
8.3.2. Method of Detecting AEs and SAEs .........................................................107 
8.3.3. Follow-Up of AEs and SAEs ....................................................................107 
8.3.4. Regulatory Reporting Requirements for SAEs .........................................107 
8.3.5. Environmental Exposure, Exposure During Pregnancy or 
Breastfeeding, and Occupational Exposure ...................................................108 

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Final Protocol, Amendment 1, 20 July 2021 
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8.3.5.1. Exposure During Pregnancy ....................................................108 
8.3.5.2. Exposure During Breastfeeding ...............................................110 
8.3.5.3. Occupational Exposure ............................................................111 
8.3.6. Cardiovascular and Death Events ..............................................................111 
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs ............................................................................111 
8.3.8. Adverse Events of Special Interest ...........................................................111 
8.3.8.1. Lack of Efficacy ......................................................................111 
8.3.9. Medical Device Deficiencies ....................................................................111 
8.3.10. Medication Errors ....................................................................................112 
8.4. Pharmacokinetics ...................................................................................................113 
8.5. Genetics .................................................................................................................113 
8.5.1. Specified Genetics .....................................................................................113 
8.5.2. Retained Research Samples for Genetics ..................................................113 
8.6. Biomarkers .............................................................................................................114 
8.6.1. Tumor Biopsies .........................................................................................114 
8.6.2. Whole Blood, Plasma, Serum ...................................................................116 
8.6.3. Retained Research Samples for Biomarkers .............................................116 
8.7. Immunogenicity Assessments ...............................................................................116 
8.7.1. PF-07263689 Immunogenicity Assessments ............................................116 
8.7.2. Sasanlimab Immunogenicity Assessments ................................................117 
8.8. Health Economics ..................................................................................................117 
9. STATISTICAL CONSIDERATIONS ...............................................................................117 
9.1. Statistical Hypotheses ............................................................................................117 
9.2. Analysis Sets ..........................................................................................................118 
9.3. Statistical Analyses ................................................................................................118 
9.3.1. General Considerations .............................................................................119 
9.3.2. Primary Endpoint(s)/Estimand(s)/Analysis ...............................................119 
9.3.3. Secondary Endpoint(s)/Estimands Analysis .............................................120 
9.3.3.1. Efficacy Endpoint(s) ................................................................120 
9.3.3.2. Viral Load Kinetics and Vector Shedding Analysis ................121 
9.3.3.3. Analysis of Immunogenicity Data ...........................................121 

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Final Protocol, Amendment 1, 20 July 2021 
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CCI 
9.3.4. Tertiary/Exploratory Endpoints ................................................................122 
9.3.5. Other Safety Analyses ...............................................................................122 
9.3.5.1. Electrocardiogram Analyses ....................................................122 
9.3.5.2. AEs ..........................................................................................124 
9.3.5.3. Laboratory Test Abnormalities ................................................124 
9.4. Interim Analyses ....................................................................................................124 
 
 
 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS.........................................................................................................126 
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ..............126 
10.1.1. Regulatory and Ethical Considerations ...................................................126 
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP .......................................................................126 
10.1.2. Financial Disclosure ................................................................................127 
10.1.3. Informed Consent Process ......................................................................127 
10.1.4. Data Protection ........................................................................................128 
10.1.5. Committees Structure ..............................................................................128 
10.1.5.1. Data Monitoring Committee ..................................................128 
10.1.6. Dissemination of Clinical Study Data .....................................................128 
10.1.7. Data Quality Assurance ...........................................................................130 
10.1.8. Source Documents ..................................................................................131 
10.1.9. Study and Site Start and Closure .............................................................131 
10.1.10. Publication Policy .................................................................................132 
10.1.11. Sponsor’s Qualified Medical Personnel ................................................133 
10.2. Appendix 2: Clinical Laboratory Assessments ....................................................134 
CCI 

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10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting ....................................................................136 
10.3.1. Definition of AE ......................................................................................136 
10.3.2. Definition of an SAE ...............................................................................137 
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During 
the Active Collection Period ..........................................................................139 
10.3.4. Reporting of SAEs ..................................................................................142 
10.3.5. Guidance for Immune-Related Adverse Events .....................................143 
10.4. Appendix 4: Contraceptive and Barrier Guidance ...............................................149 
10.4.1. Male Participant Reproductive Inclusion Criteria ..................................149 
10.4.2. Female Participant Reproductive Inclusion Criteria ...............................149 
10.4.3. Woman of Childbearing and Non-Childbearing Potential ......................150 
10.4.4. Contraception Methods ...........................................................................151 
CCI 
 
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-Up Assessments 
and Study Intervention Rechallenge Guidelines ......................................................154 
10.7. Appendix 7: ECG Findings of Potential Clinical Concern ..................................156 
10.8. Appendix 8: Alternative Measures During Public Emergencies .........................158 
10.8.1. Eligibility ................................................................................................158 
10.8.2. Telehealth Visits ......................................................................................158 
10.8.3. Alternative Facilities for Safety Assessments .........................................159 
10.8.3.1. Laboratory Testing ................................................................159 
10.8.3.2. Imaging ..................................................................................159 
10.8.3.3. Electrocardiograms ................................................................159 
10.8.3.4. Echocardiogram or MUGA ...................................................159 
10.8.4. Study Intervention ...................................................................................159 
10.8.5. Home Health Visits .................................................................................160 
10.8.6. Adverse Events and Serious Adverse Events..........................................160 
10.8.7. Efficacy Assessments ..............................................................................161 
10.8.8. Independent Oversight Committees ........................................................161 
10.9. Appendix 9: Detailed Dose Escalation/De-Escalation Scheme for BLRM 
Design ......................................................................................................................161 
10.9.1. Statistical Model for Monotherapy ..........................................................161 

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10.9.2. Statistical Model for Combination with Sasanlimab .............................. 162 
10.9.3. Sensitivity Analysis ................................................................................. 163 
10.10. Appendix 10: RECIST (Response Evaluation Criteria In Solid Tumors) 
version 1.1 Guidelines.............................................................................................. 165 
10.11. Appendix 11: CRS Mitigation and Management .............................................. 170 
10.12. Appendix 12: ECOG Performance Status ......................................................... 174 
10.13. Appendix 13: Sasanlimab Subcutaneous Injection Site Location Diagram ...... 175 
10.14. Appendix 14: Preliminary Clinical Summary for Study B8011001 Phase 1 
FIH (PF-06801591) .................................................................................................. 177 
10.14.1. Study Design ......................................................................................... 177 
10.14.2. Exposure ............................................................................................... 177 
10.14.3. Summary of Safety ............................................................................... 178 
10.14.3.1. Dose Limiting Toxicities (DLTs) ........................................ 178 
10.14.3.2. Adverse Events .................................................................... 178 
CCI 
 
10.14.4. Summary of Efficacy ............................................................................ 180 
10.14.5. Summary of Clinical Pharmacology ..................................................... 180 
10.14.6. Conclusions ........................................................................................... 180 
10.15. Appendix 15: Abbreviations .............................................................................. 181 
11. REFERENCES ................................................................................................................. 187 

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LIST OF TABLES 
Table 1. 
Schedule of Assessments – Monotherapy (Part 1A) .................................27 
Table 2. 
Schedule of Assessments – Combination Therapy (Part 1B and Part 
2) ...............................................................................................................33 
Table 3. 
Schedule of Activities: EOT, Post-Treatment, and Survival Follow- 
up (Parts 1A, 1B, and 2) ............................................................................42 
Table 4. 
Viral Shedding, ECG, Immunogenicity, and Biomarker Schedule of 
Assessments (Part 1A) ..............................................................................45 
Table 5. 
PK, Viral Shedding, ECG, Immunogenicity, and Biomarker 
Schedule of Assessments: PF-07263689 Combination with 
Sasanlimab (Part 1B and Part 2) ...............................................................47 
Table 6. 
Provisional Dose Levels in Dose Escalation .............................................65 
Table 7. 
Sasanlimab Recommended Treatment Modifications for Drug- 
Related Toxicity (Excluding irAEs) .........................................................87 
CCI 
 
 
Table 9. 
Table 10. 
Table 11. 
Table 12. 
Table 13. 
 
Table 14. 
Table 15. 
Table 16. 
Safety QTcF Assessment ........................................................................ 123 
Laboratory Tests ..................................................................................... 134 
Management of Immune-Related Adverse Events .................................. 143 
Objective Response Status at each Evaluation ........................................ 168 
Objective Response Status at each Evaluation for Patients with 
Non-Target Disease Only ........................................................................ 169 
ASTCT CRS Revised Grading System ................................................... 170 
Definition of High Dose Vasopressor ..................................................... 171 
Part 1 and Part 2 Cohort Enrollment Details ........................................... 178 

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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Brief Title: Phase 1 Study of PF-07263689 in Participants with Selected Advanced Solid 
Tumors 
 
Rationale 
 
PF-07263689 is an oncolytic virus that selectively grows in and kills cancer cells. In addition 
to its direct cytolytic activity, it has the capability to stimulate innate and adaptive immune 
reactions against tumor cells. PF-07263689 is also genetically engineered to express an 
IL-2gv therapeutic payload as a strategy to alter the tumor microenvironment to potentially 
reverse checkpoint refractoriness and induce killing of uninfected bystander tumor cells. It is 
delivered systemically for infection of disseminated disease that can stimulate systemic 
antitumor immune responses in patients with or without prior anti-PDx therapies. 
 
Objectives, Endpoints, and Estimands 
Dose Escalation (Part 1): 
Objectives 
Endpoints 
Estimands 
Primary: 
• 
Part 1A: To assess safety 
and tolerability at 
increasing dose levels of 
PF-07263689 in successive 
cohorts of participants with 
select locally 
advanced/metastatic solid 
tumors, until the MTD is 
estimated or the MFD dose 
is reached. 
• 
First cycle DLTs. 
• 
AEs as characterized by type, 
frequency, severity (as graded by 
NCI CTCAE version 5.0, except 
CRS, which will be graded by 
ASTCT criteria), timing, 
seriousness, and relationship to 
study treatment. 
• The primary estimand for 
incidence of DLTs in Part 1 is 
DLT rate estimated based on 
data from DLT-evaluable 
participants during the DLT 
evaluation period, which is 
the first 28 days after the first 
dose of study intervention. 
The attributes of this 
estimand are provided in 
Section 9. 
• 
Part 1B: To assess safety 
and tolerability 
PF-07263689 in 
combination with 
sasanlimab in successive 
cohorts of participants with 
select locally 
advanced/metastatic solid 
tumors, in order to 
estimate and select the 
combination 
RP2D/schedule. 
• 
Laboratory abnormalities as 
characterized by type, frequency, 
severity (as graded by NCI 
CTCAE version 5.0), and timing. 

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Page 16 
 
 
 
Objectives 
Endpoints 
Estimands 
Secondary: 
• 
To evaluate preliminary 
antitumor activity. 
• 
ORR, as assessed using the 
RECIST version 1.1. 
• 
Time to event endpoints: DOR, 
PFS, TTP by RECIST 1.1. 
• The key secondary estimand 
in Part 1 is to evaluate the 
treatment effect of 
PF-07263689 assessed by 
ORR, based on investigator 
assessment per RECIST 1.1, 
in the response evaluable 
analysis population. The 
attributes of this estimand are 
provided in Section 9. 
• 
To evaluate the viral load 
kinetics following first and 
second dose of 
PF-07263689. 
• 
To collect sasanlimab drug 
concentration data in Part 
1B for evaluation of 
sasanlimab PK. 
• 
Viral load kinetics parameters of 
PF-07263689 in blood, including 
Cmax, Tmax, and AUClast. 
• 
Trough concentrations of 
sasanlimab for selected cycles 
• NA 
• 
To characterize the viral 
shedding of PF-07263689. 
• 
Viral titers CCI 
• NA 
PF-07263689 
dose. 
• 
To evaluate the 
immunogenicity of 
PF-07263689 and 
sasanlimab following 
monotherapy and 
combination 
administration. 
• 
Incidence and titers of ADA 
against PF-07263689 and 
sasanlimab. 
• 
Incidence and titers of anti-IL2 
antibodies. 
• NA 
CCI 
• 
To assess viral replication 
and transgene expression 
of PF-07263689 in both 
tumors and blood of 
participants. 
• 
CCI 
• NA 
• 
To explore the 
pharmacodynamic effect of 
PF-07263689 in both 
tumor and blood of 
participants. 
• CCI 
• NA 
 

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Objectives 
Endpoints 
Estimands 
CCI 
• 
To explore additional 
biomarkers associated with 
clinical response and to 
elucidate the potential 
MOA and mechanism of 
resistance to PF-07263689. 
• 
CCI 
• NA 
 
 
Dose Expansion (Part 2) 
 
Objectives 
Endpoints 
Estimands 
Primary: 
• 
To confirm safety and 
tolerability of PF-07263689 at 
the RP2D in combination 
therapy in participants with 
selected tumor types. 
• 
To evaluate preliminary 
evidence of antitumor activity of 
PF-07263689 in combination 
therapy in participants with 
selected tumor types. 
• 
AEs as characterized by type, 
frequency, severity (as graded 
by NCI CTCAE version 5.0, 
except CRS, which will be 
graded by ASTCT criteria), 
timing, seriousness, and 
relationship to study therapy. 
• 
Laboratory abnormalities as 
characterized by type, 
frequency, severity (as graded 
by NCI CTCAE version 5.0), 
and timing. 
• 
ORR as determined by RECIST 
version 1.1. 
• The primary estimand in 
Part 2 is to evaluate the 
treatment effect of PF- 
07263689 in combination 
with PF-06801591 
assessed by the ORR, 
based on investigator 
assessment per RECIST 
1.1, in the response 
evaluable analysis 
population. The attributes 
of this estimand are 
provided in Section 9. 
Secondary: 
• 
To further evaluate the viral 
load kinetics following 
PF-07263689 administration. 
• 
Viral load kinetics parameters of 
PF-07263689 in blood, 
including Cmax, Tmax, and 
AUClast. 
• NA 
• 
To collect sasanlimab drug 
concentration data in Part 2 for 
evaluation of sasanlimab PK. 
• 
Trough concentrations of 
sasanlimab for selected cycles 

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PFIZER CONFIDENTIAL 
Page 18 
 
 
 
Objectives 
Endpoints 
Estimands 
• 
To characterize the viral 
shedding of PF-07263689. 
• 
Viral titers CCI 
• NA 
PF-07263689 
dose. 
• 
To further evaluate the 
immunogenicity of 
PF-07263689 and sasanlimab. 
• 
Incidence and titers of ADA 
against PF-07263689 and 
sasanlimab. 
• 
Incidence and titers of anti- IL-2 
antibodies. 
• NA 
• 
To evaluate preliminary 
antitumor activity through time 
to event time points. 
• 
DCR, DOR, PFS, and TTP by 
RECIST version 1.1. 
• NA 
• 
To assess overall survival of 
participants treated with 
PF-07263689. 
• 
Overall survival. 
• NA 
CCI 
• 
To assess viral replication and 
transgene expression of 
PF-07263689 in tumors of 
participants. 
• 
To explore the 
pharmacodynamic effect of 
PF-07263689 in both tumor and 
blood. 
• 
To explore additional 
biomarkers associated with 
clinical response and to 
elucidate the potential mode of 
action and mechanism of 
resistance to PF-07263689. 
• 
CCI 
• NA 
 
 
 
 
 
 
 
 

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Page 19 
 
 
CCI 
CCI 
Overall Design 
Brief Summary 
The proposed Phase 1, open-label, multicenter, multiple dose, dose escalation, and dose 
expansion study will evaluate the safety, tolerability, viral load kinetics and shedding, PD, 
and anti-tumor activity of PF-07263689, either alone or in combination with sasanlimab (an 
investigational anti-PD-1 antibody), in participants with locally advanced or metastatic solid 
tumors who have exhausted all standard of care therapies available to them. The study 
consists of 2 parts: Part 1 dose escalation for PF-07263689 monotherapy (Part 1A) and 
combination with sasanlimab (Part 1B) and Part 2 dose expansion for the combination 
therapy. 
 
The study will evaluate weekly IV dosing of PF-07263689 for 4 total doses, either as a 
monotherapy or in combination with sasanlimab administered at 300 mg SC Q4W. In the 
combination therapy arm, administration of sasanlimab will start concurrently with 
PF-07263689 and continue beyond the end of the PF-07263689 treatment course until 
disease progression, intolerable toxicity, withdrawal of consent, or until the study is 
completed. Alternative PF-07263689 regimens may also be evaluated if supported by 
emerging data. 
 
For Part 1A, participants will be assessed for radiological response on Day 43 (±5 days). 
Additional scans may be performed every 6 weeks (±7 days) following Day 43. For Part 1B 
and Part 2, all participants will be assessed for radiographic response every 6 weeks 
(±7 days) for up to 6 months followed by every 12 weeks (±7 days) until starting new 
anticancer therapy or at time of radiographic progression, whichever is earlier. Urine, saliva, 
and infusion site swabs will be collected to assess viral shedding during treatment and up to 
60 days after last dose of PF-07263689 as indicated in the SoA. Any skin lesions that appear 
will be swabbed to assess for virus shedding. Participants will continue to be followed for 
survival and long-term safety until death, withdrawal of consent, or the end of the entire 
study. 
 
Dose Escalation (Part 1) 
 
Participants with any advanced or metastatic solid tumor indications known to have approved 
therapies using immune checkpoint inhibitors or anti-vascular endothelial growth factor 
agents are eligible for Part 1. Participants must have exhausted all standard of care therapy 
for the primary tumor type available to them. Participants with immune checkpoint inhibitor- 
sensitive tumor types (eg, NSCLC, RCC, UC, melanoma) are expected to be treated in a 
post-anti-PD-1/PD-L1 (hereafter referred to as anti-PDx) failure setting in Part 1. Tumor 
types in which anti-PDx antibody therapy is not indicated, such as ovarian and MSS CRC, 
may be treated in any post-standard of care setting. 
 
Participants will be hospitalized 
PF-07263689 for monitoring. In Part 1A, 
the 
in each dose escalation cohort will be staggered by 

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Page 20 
 
 
CCI 
CCI 
 mitigate against unexpected immune-related adverse reactions. In Part 1B 
(PF-07263689 in combination with sasanlimab), the CCI 
 
of participants of potential overlapping adverse 
reactions prior to enrolling the remaining participants in Part 1B. There is no formal 
staggering for subsequent participants in each dose cohort. 
 
Part 1A Monotherapy Dose Escalation: A BLRM along with EWOC will be utilized to guide 
dose escalation and to determine the monotherapy MTD if MFD is not reached. Dose 
escalation from the determined 
. After the last 
participant at the MTD or the MFD has finished all doses of PF-07263689, the monotherapy 
RP2D will be determined based on all available safety, efficacy, and viral load kinetics and 
shedding data. During the dose escalation process, intermediate doses may be tested based on 
BLRM. 
 
Part 1B Combination Dose Escalation: Dose escalation of PF-07263689 in combination with 
sasanlimab will CCI 
PF-07263689, CCI 
MTD of  
, as 
guided by the BLRM and EWOC criteria. If started below the monotherapy MTD, 
PF-07263689 may be escalated to MTD or the MFD in the combination. After completing 
PF-07263689 dosing, participants will remain on sasanlimab 300 mg SC Q4W until disease 
progression, intolerable toxicity, withdrawal of consent, or until the study is completed. The 
combination therapy RP2D will be determined based on all available safety, efficacy, and 
PK/PD data during the combination dose escalation process. 
 
Dose Expansion (Part 2) 
 
Part 2 will further evaluate PF-07263689 in combination with sasanlimab at the preliminary 
combination RP2D from Part 1B. Sasanlimab will be administered at 300 mg SC Q4W in 
tumor-specific arms of post-PDx failure NSCLC (Arm A), post-PDx failure RCC (Arm B), 
post-PDx failure melanoma (Arm C), and PDx-naïve refractory CRC (Arm D), at 
approximately 15 to 20 participants per arm. Initially, 3 tumor-specific arms will commence 
based on preliminary data from Part 1, with the option to subsequently open the fourth arm 
based on emerging data. For the post-PDx indications, Arms A, B, and C may be limited to 
participants with primary or secondary resistance to PDx inhibitors after discussion with 
investigators. 
 
Number of Participants 
Approximately 120 participants are expected to be enrolled in the study overall, including 
approximately 40 DLT evaluable participants for Part 1 and approximately 80 participants 
(15 to 20 per cohort) for Part 2. 

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Protocol C4651001 
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PFIZER CONFIDENTIAL 
Page 21 
 
 
Study Population and Specific Inclusion/Exclusion Criteria 
 
Key inclusion and exclusion criteria are listed below: 
 
Inclusion Criteria 
Participants must meet the following key inclusion criteria to be eligible for enrollment into 
the study: 
 
• Histological or cytological diagnosis of locally advanced/metastatic solid tumor 
indications known to have approved therapies using immune checkpoint 
inhibitors or anti-vascular endothelial growth factor agents. 
 
• Participants should have exhausted all available standard of care therapy or for 
whom no standard therapy is available for their tumor type. Participants who have 
actively declined available standard of care therapies are eligible upon 
documentation of refusal. 
 
• Participants with solid tumors with FDA-approved anti-PDx antibody therapy 
should have received at least 1 prior anti-PDx therapy. 
 
• Participants with prior anti-PDx must have documentation of primary or 
secondary resistance to last prior anti-PDx therapy according to Society for 
Immunotherapy of Cancer Immunotherapy Resistance Taskforce (Kluger et al, 
2020) as follows: 
 
• Primary resistance: drug exposure for at least 6 weeks with best response of 
PD, or SD for < 6 months (including PD at any time after stopping PDx for 
any reason unrelated to toxicity if best response while receiving anti-PDx 
therapy was PD or SD < 6 months). 
 
• Secondary resistance: drug exposure for at least 6 months with best response 
of CR or PR or SD ≥ 6 months. If prior PDx was stopped prior to PD, PD 
must have occurred within 12 weeks after the last dose of PDx. 
 
• Participants entering the study in the expansion cohort have at least 1 measurable 
lesion as defined by RECIST version 1.1 that has not been previously irradiated. 
 
• Dose Escalation (Part 1A and 1B): Participants with any advanced or metastatic 
solid tumor indications known to have approved therapies using immune 
checkpoint inhibitors or anti-vascular endothelial growth factor agents. 

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Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
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• Dose Expansion (Part 2): Participants with the following indications must have 
exhausted all relevant available standard of care or have documented intolerability 
to such therapies. 
 
• NSCLC (≥2L): Participants with NSCLC must have received prior anti-PDx 
therapies. NSCLC participants with driver mutations must have received prior 
available targeted therapy(ies) (eg, participant with BRAF V600E mutation 
must have also received BRAF inhibitor with or without MEK inhibitor) or 
have documented intolerability. 
 
• RCC (≥2L): Participants with RCC must have received prior anti-PDx 
therapies. RCC participants must also have received prior anti-VEGF therapy. 
 
• Melanoma (≥2L): Participants with melanoma must have received prior 
anti-PDx therapy with or without anti-CTLA-4. Melanoma participants with 
driver mutations must have received prior available targeted therapies. 
 
• MSS CRC: Participants with CRC must have received regimen containing 
combinations of pyridimine analog-containing combination chemotherapy 
with anti-VEGF (as appropriate), anti-EGFR (as appropriate if RAS 
wild-type), and/or encorafenib (if BRAF V600E). 
 
• Participants must have recently obtained (≤1 year prior to Day 1) archival FFPE 
tumor tissue sample available. If archival FFPE ≤1 year is not available a fresh 
tumor sample must be collected at screening. If the archival sample is older than 1 
year and a biopsy during screening cannot be performed safely, the investigator 
must contact the sponsor to discuss eligibility prior to enrollment. 
 
• ECOG PS 0-1. 
• Adequate hematologic, renal, and liver functions. 
Exclusion Criteria 
Participants with any of the following characteristics/conditions will be excluded: 
• Participants with any other active malignancy within 3 years prior to planned first 
dose, except for adequately treated basal cell or squamous cell skin cancer, or 
carcinoma in situ of the cervix, Bowen’s disease. Other indolent, secondary 
cancers may be permitted after discussion with sponsor. 

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Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
Page 23 
 
 
• Participants sustaining recent major surgery defined as a complex procedure 
performed under regional or general anesthesia with a recovery period of at least 
4 weeks prior to planned first dose. Exceptions include: 
 
• Minor surgical procedures require at least 1-week period prior to planned first 
dose. 
 
• Participants having an implantable port placed can enter the study 1 week 
after the port is placed, assuming no complications have occurred, and the port 
is functioning normally. 
 
• Known or suspected hypersensitivity to, allergic history of, or prior treatment 
within the past 10 years on any vaccinia oncolytic, pox virus, or antiviral agents. 
 
• Known or suspected hypersensitivity to any anti-PDx antibody if planned to 
receive combination therapy with sasanlimab. 
 
• Participants with a history of myocarditis or congestive heart failure (as defined 
by New York Heart Association (NYHA) Functional Classification III or IV), as 
well as unstable angina, serious uncontrolled cardiac arrhythmia, or myocardial 
infarction 6 months prior to study entry. 
 
• Participants with active ILD/pneumonitis or a history of ILD/pneumonitis 
requiring treatment with systemic steroids. 
 
• Participants with an LVEF <50% by echocardiogram or MUGA. 
• Systemic anticancer therapy and chemotherapy within 4 weeks prior to planned 
first dose (6 weeks for mitomycin C or nitrosoureas). Prior targeted or endocrine 
therapy require an interval of 2 weeks or 5 half-lives (whichever is shorter) prior 
to planned first dose. If the last immediate anticancer treatment contained an 
antibody based agent(s) (approved or investigational), then an interval of 4 weeks 
or 5 half-lives (whichever is shorter) of the agent(s) prior to receiving the study 
intervention treatment is required. With last prior anti-PDx therapy, the washout 
period may be extended based on emerging clinical data. 
 
• Recent transfusion of RBCs or platelets within 4 weeks prior may be 
exclusionary. Discuss with the sponsor if participant had recent transfusion(s). 
 
• Participants requiring chronic systemic immunosuppressants. 
• History of Grade ≥3 immune mediated AE (including AST/ALT elevations that 
were considered drug-related and cytokine release syndrome) that was considered 
related to prior immune modulatory therapy (eg, immune checkpoint inhibitors, 
co-stimulatory agents, etc.) and required immunosuppressive therapy. 

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Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
Page 24 
 
 
• Known symptomatic brain metastases requiring steroids. 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 
(requires MRI confirmation). 
 
• History of or ongoing severe inflammatory skin condition or severe eczema (as 
determined by the investigator) having required medical treatment. 
 
• Any prior or planned organ transplant. 
• Active bleeding disorder, including gastrointestinal bleeding, as evidenced by 
hematemesis, significant hemoptysis or melena in the past 6 months. 
 
• Presence of any open, active wound requiring treatment for proper healing. 
Intervention Groups and Duration 
 
Participants in Part 1A will receive weekly IV dosing of PF-07263689 for 4 weeks. 
Participants will be in the study for approximately 130 days, including the Screening 
(≤28 days), Treatment (43 days), and Follow-up (30, 45, 60 and 90 days) Periods. 
Additionally, survival follow-up will occur by telephone Q12W (±7 days). 
 
Participants in Part 1B and Part 2 will receive weekly IV dosing of PF-07263689 for 4 weeks 
in combination with 300 mg sasanlimab SC Q4W. In general, participants will be in the 
study for approximately 130 days or longer depending if the participants continue to benefit 
from PF-07263689 and sasanlimab. Treatment with study intervention will continue until 
either disease progression, unacceptable toxicity, participant refusal, or whichever is earliest, 
unless the investigator and medical monitor agree to treatment beyond disease progression 
based on individual benefit/risk assessments or agree to discontinue treatment or the study is 
terminated. Additional, survival follow-up will occur by telephone Q12W (±7 days). 
 
No dose delay or dose reductions of PF-07263689 are allowed. Participants may only miss or 
skip one dose of PF-07263689. No dose reductions of sasanlimab are allowed, but doses of 
sasanlimab may be skipped or delayed for a cycle based on persisting toxicity. 
 
The end of the study will be the date of the last visit of the last participant or 2 years after the 
last participant receives their first dose (whichever occurs first). The study may also be 
terminated at any time at the discretion of the sponsor. Any additional treatment beyond 
2 years shall be discussed and approved by the sponsor. 
 
A participant is considered to have completed the study if he/she has completed all phases of 
the study including the EOT visit. 

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PFIZER CONFIDENTIAL 
Page 25 
 
 
, which satisfies the EWOC criterion. 
CCI 
Data Monitoring Committee or Other Independent Oversight Committee: No 
 
This study will not use a DMC. However, a DLRM will convene for dose escalation 
decisions. The actual dose selected at each dose decision may be at or below the statistical 
model’s (ie, BLRM) recommended dose as determined by the members of the DLRM after 
considering all safety information. The review team will be composed of investigator(s), 
Pfizer GCL, Pfizer Study Clinician, and Pfizer Study Manager. Additional members may be 
added as needed (eg, Clinical Pharmacologist Lead, Translational Oncology, Safety Risk 
Lead or designee, and Pfizer Biostatistics representative). A quorum, defined as >50% of the 
participating investigators or their qualified designee (ie, subinvestigator or research nurse or 
study coordinator possessing hard copy documentation [eg, email] of the investigator’s vote 
regarding the dose level review), must be in attendance for the DLRM. Participating 
investigators are defined as those whose sites have been initiated for screening and 
enrollment of patients. The DLRM will be rescheduled if a quorum is not reached. 
 
Statistical Methods 
 
For Part 1, determination of MTD will be performed using the DLT evaluable set, if MTD is 
achieved prior to the maximum feasible dose. 
 
The dose escalation in the Part 1 of the study will be guided by a Bayesian analysis of DLT 
data for PF-07263689 using a 2-parameter BLRM (Part 1A) or for the combination of 
PF-07263689 and sasanlimab using a 5-parameter BLRM (Part 1B). Weakly informative 
prior distributions based on preclinical/expert opinion information will be chosen for the 
logistic parameters in Part 1A; the observed DLT data in Part 1A and DLT data of 
sasanlimab will be used to form prior distribution for the BLRM in Part 1B. Dosing decisions 
are guided by the EWOC principle (Rogatko 2007). 
 
 
 
For Part 2, ORR will be a primary endpoint, along with safety and tolerability assessment. 
ORR evaluation, as well as other secondary efficacy endpoints. 

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Page 26 
 
 
1.2. Schema 
 
 
 
 
• Indications: Any advanced/metastatic solid tumor 
known to have approved therapies using immune 
checkpoint inhibitors or anti-VEGF agents 
• Primary Objective: Safety, MTD (Part 1A)/RP2D (Part 
1B) 
Part 2: Dose Expansion 
 
• Indications: Post-PDx failure NSCLC, post- 
PDx RCC, post-PDx melanoma; PDX-naïve 
MSS CRC tumor-specific arms will open 
based on emerging data 
• Primary Objective: Safety, Efficacy 
Part 1A: 
Monotherapy 
Part 1B: 
Combination 
 
Part 2: Combination Dose 
Expansion 
 
 
Arm A 
 
 
Arm B 
 
 
Arm C 
 
 
Arm D 
 
 
 
 
PF-07263689 regimen: IV once weekly for 4 doses (Q1W x 4) 
PF-07263689 dose range: CCI 
 
Sasanlimab: 300mg SC Q4W; Each SC cycle = 28 days 
Paired biopsies: In Part 1, paired de novo tumor biopsy samples pre-treatment and on-treatment (C1D8 ± 1 day) will be 
required from 5 participants each in Part 1 at or below MTD and Part 1B at or below MTD + sasanlimab. In Part 2, paired de 
novo tumor biopsy samples will be collected from 5-8 participants in each arm unless biopsy samples cannot be obtained safely. 
* The starting dose of PF-07263689 for Part 1B will be at or one dose lower than the MTD from Part 1A. 
Part 1A, dosing of initial participants CCI 
 
against unexpected adverse drug reaction 
as follows: Each dose level: CCI 
 
Part 1B, dosing of the CCI 
 against possible overlapping adverse 
drug reaction as follows prior to enrolling the remaining participants in Part 1B. 
 
Part 2 Dose Expansion: Initially, 3 tumor-specific arms will commence based on preliminary data from Part 1, with the option 
to open the fourth arm based on emerging data. For the post-PDx indications, Arms A, B, and C may be limited to participants 
with primary or secondary resistance after discussion with investigators. 
MTD / RP2D 
n = 6-12 
Paired biopsies 
Dose Level 3 
N = 2-4 
MTD + 
sasanlimab* 
n= 6-12 
Paired biopsies 
Dose Level 2 
N = 2-4 
MTD-1 + 
sasanlimab* 
n = 2-4 
Dose Level 1 
N = 2-4 
Post-PDx failure NSCLC 
(n = 15-20) 
Post-PDx failure RCC (n = 15-20) 
PDx-naïve MSS CRC 
(n = 15-20) 
Post-PDx melanoma (n = 15-20) 

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Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
Page 27 
 
 
 
1.3. Schedule of Activities 
The SoA table provides an overview of the protocol visits and procedures. Refer to the STUDY ASSESSMENTS AND 
PROCEDURES 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 SoA table, to conduct evaluations or 
assessments required to protect the well-being of the participant. 
 
Table 1. 
Schedule of Assessments – Monotherapy (Part 1A) 
 
Visit Identifier 
Abbreviations used in this 
table may be found in 
Appendix 12. 
SCREENIN 
G 
TREATMENT 
NOTES 
Days 
≤28 
1 
2 
3 
4 
8 
9 
10 
15 
22 
29 
43 
• See Table 3 for EOT and 
follow-up visit schedules 
Visit Window 
0 
±4h* 
±4h* 
±4h* 
±1d 
±4h 
* 
±4h 
* 
±1d 
±1d 
±5d 
±5d 
*±4h is relative to the most 
current dosing 
General Assessments 
Informed Consent 
X 
• Informed consent must be 
obtained prior to undergoing any 
study-specific procedures. 
Registration 
X 
• Participant enrollment number 
and dose level allocation 
assigned by Pfizer Inc. 
Demographics and Medical 
History 
X 
• Includes tumor histology and 
other medical history. 
Complete Physical 
Examination 
X 
• Includes height only at 
screening. 
• Includes skin assessment. 
Brief Physical Examination 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
• Daily while hospitalized. 
• Includes skin assessments for 
any lesions. 
Overall Skin Monitoring 
X 
X 
X 
X 
X 
• Participants should be monitored 
not only for infusion site 
reactions but also any skin 

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Page 28 
 
 
 
Table 1. 
Schedule of Assessments – Monotherapy (Part 1A) 
 
Visit Identifier 
Abbreviations used in this 
table may be found in 
Appendix 12. 
SCREENIN 
G 
TREATMENT 
NOTES 
Days 
≤28 
1 
2 
3 
4 
8 
9 
10 
15 
22 
29 
43 
• See Table 3 for EOT and 
follow-up visit schedules 
Visit Window 
0 
±4h* 
±4h* 
±4h* 
±1d 
±4h 
* 
±4h 
* 
±1d 
±1d 
±5d 
±5d 
*±4h is relative to the most 
current dosing 
lesions in whole body following 
PF-07263689 administration. 
• Refer to Section 8.2.3. 
ECOG Performance Status 
X 
X 
X 
X 
X 
X 
Weight 
X 
X 
X 
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
• Measure vitals prior to the 
PF-07263689 treatment. 
• Daily while hospitalized; collect 
temperature (oral preferred), 
pulse rate, BP every 6 hrs (±10 
min) and as needed during 
inpatient monitoring. 
Pulse Oximetry (SpO2) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Triplicate 12-lead ECGs 
X 
Refer to Table 4.Viral Shedding, ECG, Immunogenicity, and Biomarker 
Schedule of Assessments (Part 1A) 
X 
• Perform prior to dosing. 
• Additional triplicate ECGs may 
be performed as clinically 
indicated. 
• See Section 8.2.5. 
Echocardiogram or MUGA 
X 
Assess as baseline. Additional testing as clinically indicated. 
• Echocardiogram or MUGA; 
imaging methods must be 
consistent throughout the study 
for individual participants. 
AE Assessments 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
• Document AEs as described in 
Section 8.3 and Appendix 3. 

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Page 29 
 
 
 
Table 1. 
Schedule of Assessments – Monotherapy (Part 1A) 
 
Visit Identifier 
Abbreviations used in this 
table may be found in 
Appendix 12. 
SCREENIN 
G 
TREATMENT 
NOTES 
Days 
≤28 
1 
2 
3 
4 
8 
9 
10 
15 
22 
29 
43 
• See Table 3 for EOT and 
follow-up visit schedules 
Visit Window 
0 
±4h* 
±4h* 
±4h* 
±1d 
±4h 
* 
±4h 
* 
±1d 
±1d 
±5d 
±5d 
*±4h is relative to the most 
current dosing 
• SAEs identified during LTFU 
will be reported to Pfizer Safety 
only if considered reasonably 
related to study intervention. 
Concomitant Treatment(s) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
• All concomitant treatment and 
Non-Drug Supportive 
Interventions should be recorded 
on the CRF through the 
treatment period. Only 
subsequent anti-cancer therapy 
initiated after end of study 
treatment(s) will be reported at 
the follow-up visits. 
Laboratory Assessments 
Hematology 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood Chemistry 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation 
X 
X 
X 
X 
X 
X 
X 
• PT or INR and PTT/aPTT. 
Endocrinology 
X 
X 
X 
X 
• TSH, ACTH, Free T4. 
Cardiac biomarkers 
X 
X 
X 
X 
X 
X 
X 
• CPK and troponin 
Hepatitis Serology 
X 
• HbsAg, anti-HCV antibody 
• If anti-HCV Ab test is positive, 
perform HCV RNA test. 

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Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
Page 30 
 
 
 
Table 1. 
Schedule of Assessments – Monotherapy (Part 1A) 
 
Visit Identifier 
Abbreviations used in this 
table may be found in 
Appendix 12. 
SCREENIN 
G 
TREATMENT 
NOTES 
Days 
≤28 
1 
2 
3 
4 
8 
9 
10 
15 
22 
29 
43 
• See Table 3 for EOT and 
follow-up visit schedules 
Visit Window 
0 
±4h* 
±4h* 
±4h* 
±1d 
±4h 
* 
±4h 
* 
±1d 
±1d 
±5d 
±5d 
*±4h is relative to the most 
current dosing 
Tumor Markers 
X 
X 
• CA125 for OvCA; CEA for 
CRC; CA 15-3 for BRCA; PSA 
for prostate cancer. 
Pregnancy Testing/ 
Contraception Check 
X 
X 
• See Section 5.3.1 and 
Section 8.2.8. 
Urinalysis 
X 
X 
• No need to repeat on Day 1 if 
baseline assessment performed 
within 7 days of Day 1 
• Dipstick is acceptable at 
minimum at screening and EOT. 
• Samples analyzed locally. 
Viral Shedding Assessments 
Whole Blood Sample for 
Viral Load Kinetics of 
PF-07263689 
Refer to Table 4. Viral Shedding, ECG, Immunogenicity, and Biomarker Schedule of 
Assessments (Part 1A) 
Injection Site Swab for Viral 
Shedding 
Refer to Table 4. Viral Shedding, ECG, Immunogenicity, and Biomarker Schedule of 
Assessments (Part 1A) 
Saliva and Urine Sample for 
Viral Shedding 
Refer to Table 4. Viral Shedding, ECG, Immunogenicity, and Biomarker Schedule of 
Assessments (Part 1A) 
Immunogenicity Assessments 
Blood for Serum Sample for 
PF-07263689 
Immunogenicity 
(anti-vaccinia virus 
neutralizing antibody, 
anti-IL-2 antibodies) 
Refer to Table 4. Viral Shedding, ECG, Immunogenicity, and Biomarker Schedule of 
Assessments (Part 1A) 

PF-07263689 
Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
Page 31 
 
 
 
Table 1. 
Schedule of Assessments – Monotherapy (Part 1A) 
 
Visit Identifier 
Abbreviations used in this 
table may be found in 
Appendix 12. 
SCREENIN 
G 
TREATMENT 
NOTES 
Days 
≤28 
1 
2 
3 
4 
8 
9 
10 
15 
22 
29 
43 
• See Table 3 for EOT and 
follow-up visit schedules 
Visit Window 
0 
±4h* 
±4h* 
±4h* 
±1d 
±4h 
* 
±4h 
* 
±1d 
±1d 
±5d 
±5d 
*±4h is relative to the most 
current dosing 
Pharmacodynamic Assessments 
Blood for Germline DNA 
Sequencing 
Refer to Table 4. Viral Shedding, ECG, Immunogenicity, and Biomarker Schedule of 
Assessments (Part 1A) 
Blood for pSTAT5 
Refer to Table 4. Viral Shedding, ECG, Immunogenicity, and Biomarker Schedule of 
Assessments (Part 1A) 
Blood for Serum IL-2gv 
Evaluation (Serum) 
Refer to Table 4. Viral Shedding, ECG, Immunogenicity, and Biomarker Schedule of 
Assessments (Part 1A) 
Treatment Administration 
PF-07263689 
Administration 
X 
X 
X 
X 
• Participants should remain at the 
investigational site for 
observation and labs for at least 
4-hour postdose on D15 and 
D22. Additional monitoring may 
be required based on individual 
toxicities. 
Inpatient Monitoring 
(Hospitalization) 
X 
X 
X 
X 
X 
X 
X 
• Participants will be admitted for 
inpatient monitoring (per local 
standard of practice) CCI 
• Hospitalization period may be 
extended if the participant 
experiences abnormal laboratory 
findings or ongoing AEs that 
require further hospitalization. 

PF-07263689 
Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
Page 32 
 
 
 
Table 1. 
Schedule of Assessments – Monotherapy (Part 1A) 
 
Visit Identifier 
Abbreviations used in this 
table may be found in 
Appendix 12. 
SCREENIN 
G 
TREATMENT 
NOTES 
Days 
≤28 
1 
2 
3 
4 
8 
9 
10 
15 
22 
29 
43 
• See Table 3 for EOT and 
follow-up visit schedules 
Visit Window 
0 
±4h* 
±4h* 
±4h* 
±1d 
±4h 
* 
±4h 
* 
±1d 
±1d 
±5d 
±5d 
*±4h is relative to the most 
current dosing 
Clinical & Radiographic Tumor/Response Assessments 
CT or MRI Scans of Chest, 
Abdomen, Pelvis, Any 
Clinically Indicated Sites of 
Disease, and of Bone 
Lesions; Clinical Evaluation 
of Superficial Disease 
X 
X 
D43 
then 
Q6W 
(±7 
days) 
• If allergic to contrast agents for 
imaging, a non-contrast CT of 
the chest with contrast enhanced 
abdominal and pelvic MRI can 
be used 
• Brain and/or bone scans to be 
performed at screening if disease 
is suspected and during study as 
appropriate. 
• Q6W until disease progression. 
• Confirmatory scan may be done 
4 weeks later if needed. 
Optional Photographs of 
Skin Pox Lesions 
ANYTIME 
• See Section 8.2.11. 
Archival Tumor Tissue 
X 
• See Section 8.7.1. 
De Novo (Fresh) Tumor 
Biopsies 
X 
X 
• See Section 8.7.1. 
Reporting Exposure to PF-07263689 
Exposure of Participant’s 
Close Contact 
ANYTIME 
• See Section 5.3.2. 
Exposure of Subject’s 
Healthcare Provider 
ANYTIME 
• See Section 5.3.2. 

PF-07263689 
Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
Page 33 
 
 
 
Table 2. 
Schedule of Assessments – Combination Therapy (Part 1B and Part 2) 
 
Visit Identifier 
Abbreviations used in 
this table may be found 
in Appendix 12. 
TREATMENT 
NOTES 
SCREENING 
Cycle 1 
(1 cycle = 28 days) 
Cycle ≥2 
Days 
≤28 
1 
2 
3 
4 
8 
9 
10 
15 
22 
1 
• See Table 3 for EOT and 
follow-up visit schedules 
Visit Window 
0 
±4h* 
±4h* 
±4h* 
±1d 
±4h* 
±4h* 
±2d 
±24h 
±2 day 
*±4h is relative to the most 
current dosing 
General Assessments 
Informed Consent 
X 
• Informed consent must be 
obtained prior to undergoing any 
study-specific procedures. 
Registration 
X 
• Participant enrollment number 
and dose level allocation assigned 
by Pfizer Inc. 
Demographics and 
Medical History 
X 
• Includes tumor histology and 
other medical history. 
Complete Physical 
Examination 
X 
• Includes height at screening 
• Includes skin assessments. 
Brief Physical 
Examination 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
• Daily while hospitalized. 
• Includes skin assessments for any 
lesions. 
Overall Skin Monitoring 
X 
X 
X 
X 
X 
X 
• Participants should be monitored 
not only for infusion site reactions 
but also any skin lesions in whole 
body following PF-07268689 
administration (Parts 1B, and 2), 
as well as injection site reactions 
following administration of 
sasanlimab (in Parts 1B and 2). 
• Refer to Section 8.2.3. 
ECOG Performance 
Status 
X 
X 
X 
X 
X 
X 

PF-07263689 
Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
Page 34 
 
 
 
Table 2. 
Schedule of Assessments – Combination Therapy (Part 1B and Part 2) 
 
Visit Identifier 
Abbreviations used in 
this table may be found 
in Appendix 12. 
TREATMENT 
NOTES 
SCREENING 
Cycle 1 
(1 cycle = 28 days) 
Cycle ≥2 
Days 
≤28 
1 
2 
3 
4 
8 
9 
10 
15 
22 
1 
• See Table 3 for EOT and 
follow-up visit schedules 
Visit Window 
0 
±4h* 
±4h* 
±4h* 
±1d 
±4h* 
±4h* 
±2d 
±24h 
±2 day 
*±4h is relative to the most 
current dosing 
Weight 
X 
X 
X 
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
• Measure vitals prior to study 
drug(s) administration on day of 
dosing. 
• Daily while hospitalized; collect 
temperature (oral preferred), pulse 
rate, BP every 6 hrs (± 10 min) 
and as needed during inpatient 
monitoring. 
Pulse Oximetry (SpO2) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Triplicate 12-lead ECGs 
X 
Refer to Table 5. PK, Viral Shedding, ECG, Immunogenicity, and 
Biomarker Schedule of Assessments: PF-07263689 Combination with 
Sasanlimab (Part 1B and Part 2). 
Every other 
cycle 
beginning 
with Cycle 2 
• Perform prior to dosing. 
• Additional triplicate ECGs may 
be performed as clinically 
indicated. 
• See Section 8.2.5. 
Echocardiogram or 
MUGA 
X 
Assess at baseline. Additional testing as clinically indicated. 
• Echocardiogram or MUGA; 
imaging method must be 
consistent throughout the study 
for individual participants. 
AE Assessments 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
• Document AEs as described in 
Section 8.3 and Appendix 3. 
• SAEs identified during LTFU will 
be reported to Pfizer Safety only if 
considered reasonably related to 
study intervention. 

PF-07263689 
Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
Page 35 
 
 
 
Table 2. 
Schedule of Assessments – Combination Therapy (Part 1B and Part 2) 
 
Visit Identifier 
Abbreviations used in 
this table may be found 
in Appendix 12. 
TREATMENT 
NOTES 
SCREENING 
Cycle 1 
(1 cycle = 28 days) 
Cycle ≥2 
Days 
≤28 
1 
2 
3 
4 
8 
9 
10 
15 
22 
1 
• See Table 3 for EOT and 
follow-up visit schedules 
Visit Window 
0 
±4h* 
±4h* 
±4h* 
±1d 
±4h* 
±4h* 
±2d 
±24h 
±2 day 
*±4h is relative to the most 
current dosing 
Concomitant 
Treatment(s) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
• All concomitant treatment and 
Non-Drug Supportive 
Interventions should be recorded 
on the CRF through the treatment 
period. Only subsequent anti- 
cancer therapy initiated after end 
of study treatment(s) will be 
reported at the follow-up visits. 
Laboratory Assessments 
Hematology 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood Chemistry 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation 
X 
X 
X 
X 
X 
X 
• PT or INR and PTT/aPTT. 
Endocrinology 
X 
X 
X 
X 
X 
• TSH, ACTH, Free T4. 
• Every cycle for the first 3 cycles 
followed by every 4 cycles 
starting at Cycle 4 Day 1. 
Cardiac Biomarker 
X 
X 
X 
X 
X 
X 
• CPK and troponin 
Hepatitis Serology 
X 
• HbsAg, anti-HCV antibody. 
• If anti-HCV antibody test is 
positive, HCV RNA test must be 
performed. 

PF-07263689 
Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
Page 36 
 
 
 
Table 2. 
Schedule of Assessments – Combination Therapy (Part 1B and Part 2) 
 
Visit Identifier 
Abbreviations used in 
this table may be found 
in Appendix 12. 
 
 
SCREENING 
TREATMENT 
 
Cycle 1 
(1 cycle = 28 days) 
 
 
Cycle ≥2 
NOTES 
Days 
≤28 
1 
2 
3 
4 
8 
9 
10 
15 
22 
1 
• See Table 3 for EOT and 
follow-up visit schedules 
 
Visit Window 
 
 
CCI 
0 
±4h* 
±4h* 
±4h* 
±1d 
±4h* 
±4h* 
±2d 
±24h 
±2 day 
*±4h is relative to the most 
current dosing 
 
Pregnancy Testing/ 
X 
X 
Contraception Check 
Urinalysis 
X 
X 
• See Section 5.3.1 and 
Section 8.2.8. 
X 
• No need to repeat on Day 1 if 
baseline assessment performed 
within 7 days prior to Day 1. 
• Dipstick is acceptable at minimum 
at screening and EOT. 
• Samples will be analyzed locally. 
Pharmacokinetics and Viral Shedding Assessments 
 
Whole Blood Sample 
for Viral Load Kinetics 
of PF-07263689 
Blood Serum PK 
Sample for Sasanlimab 
Refer to Table 5.PK, Viral Shedding, ECG, Immunogenicity, and Biomarker Schedule 
of Assessments: PF-07263689 Combination with Sasanlimab (Part 1B and Part 2) 
 
Refer to Table 5.PK, Viral Shedding, ECG, Immunogenicity, and Biomarker Schedule 
of Assessments: PF-07263689 Combination with Sasanlimab (Part 1B and Part 2) 
 
Injection Site Swab for 
Viral Shedding 
Refer to Table 5.PK, Viral Shedding, ECG, Immunogenicity, and Biomarker Schedule 
of Assessments: PF-07263689 Combination with Sasanlimab (Part 1B and Part 2) 
 
Saliva and Urine 
Sample for Viral 
Sheddingc 
Refer to Table 5.PK, Viral Shedding, ECG, Immunogenicity, and Biomarker Schedule 
of Assessments: PF-07263689 Combination with Sasanlimab (Part 1B and Part 2) 

PF-07263689 
Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
Page 37 
 
 
 
Table 2. 
Schedule of Assessments – Combination Therapy (Part 1B and Part 2) 
 
Visit Identifier 
Abbreviations used in 
this table may be found 
in Appendix 12. 
TREATMENT 
NOTES 
SCREENING 
Cycle 1 
(1 cycle = 28 days) 
Cycle ≥2 
Days 
≤28 
1 
2 
3 
4 
8 
9 
10 
15 
22 
1 
• See Table 3 for EOT and 
follow-up visit schedules 
Visit Window 
0 
±4h* 
±4h* 
±4h* 
±1d 
±4h* 
±4h* 
±2d 
±24h 
±2 day 
*±4h is relative to the most 
current dosing 
Immunogenicity Assessments 
Blood Serum Sample 
for Sasanlimab 
Immunogenicity 
Refer to Table 5.PK, Viral Shedding, ECG, Immunogenicity, and Biomarker Schedule 
of Assessments: PF-07263689 Combination with Sasanlimab (Part 1B and Part 2) 
Blood Serum Sample 
for PF-07263689 
Immunogenicity 
Anti-VV Neutralizing 
Antibody, Anti-IL-2 
Antibodies 
Refer to Table 5.PK, Viral Shedding, ECG, Immunogenicity, and Biomarker Schedule 
of Assessments: PF-07263689 Combination with Sasanlimab (Part 1B and Part 2) 
Pharmacodynamic Assessments 
Blood for Germline 
DNA Sequencing 
Refer to Table 5.PK, Viral Shedding, ECG, Immunogenicity, and Biomarker Schedule 
of Assessments: PF-07263689 Combination with Sasanlimab (Part 1B and Part 2) 
Blood for Serum IL-2gv 
Evaluation (Serum) 
Refer to Table 5.PK, Viral Shedding, ECG, Immunogenicity, and Biomarker Schedule 
of Assessments: PF-07263689 Combination with Sasanlimab (Part 1B and Part 2) 
Immune Cell Profiling 
and pSTAT5 (Flow 
Cytometry) 
Refer to Table 5.PK, Viral Shedding, ECG, Immunogenicity, and Biomarker Schedule 
of Assessments: PF-07263689 Combination with Sasanlimab (Part 1B and Part 2) 
Treatment Administration 

PF-07263689 
Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
Page 38 
 
 
 
Table 2. 
Schedule of Assessments – Combination Therapy (Part 1B and Part 2) 
 
Visit Identifier 
Abbreviations used in 
this table may be found 
in Appendix 12. 
TREATMENT 
NOTES 
SCREENING 
Cycle 1 
(1 cycle = 28 days) 
Cycle ≥2 
Days 
≤28 
1 
2 
3 
4 
8 
9 
10 
15 
22 
1 
• See Table 3 for EOT and 
follow-up visit schedules 
Visit Window 
0 
±4h* 
±4h* 
±4h* 
±1d 
±4h* 
±4h* 
±2d 
±24h 
±2 day 
*±4h is relative to the most 
current dosing 
PF-07263689 
Administration 
X 
X 
X 
X 
• Participants should remain at the 
investigational site for observation 
and labs for at least 4-hour post 
dose for Day 15 and Day 22. 
• Additional monitoring may be 
required based on individual 
toxicities. 
Sasanlimab 
Administration 
X 
X 
• Must be administered after 
PF-07263689 on Cycle 1 Day 1. 
Inpatient Monitoring 
(Hospitalization) 
X 
X 
X 
X 
X 
X 
X 
• Part 1B participants will be 
admitted for inpatient monitoring 
(per local standard of practice) C 
CI 
• Length of hospitalization will be 
re-assessed based on safety data 
prior to starting Part 2. 
• Hospitalization period may be 
extended if the participant 
experiences abnormal laboratory 
findings or ongoing AEs that 
require further hospitalization. 
Clinical & Radiographic Tumor/Response Assessments 

PF-07263689 
Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
Page 39 
 
 
 
Table 2. 
Schedule of Assessments – Combination Therapy (Part 1B and Part 2) 
 
Visit Identifier 
Abbreviations used in 
this table may be found 
in Appendix 12. 
TREATMENT 
NOTES 
SCREENING 
Cycle 1 
(1 cycle = 28 days) 
Cycle ≥2 
Days 
≤28 
1 
2 
3 
4 
8 
9 
10 
15 
22 
1 
• See Table 3 for EOT and 
follow-up visit schedules 
Visit Window 
0 
±4h* 
±4h* 
±4h* 
±1d 
±4h* 
±4h* 
±2d 
±24h 
±2 day 
*±4h is relative to the most 
current dosing 
CT or MRI Scans of 
Chest, Abdomen, 
Pelvis, Any Clinically 
Indicated Sites of 
Disease, and of Bone 
Lesions; Clinical 
Evaluation of 
Superficial Disease 
X 
Imaging visits will occur Q6W (±7 days) through Week 24 followed by Q12W (±7 
days) until starting new anticancer therapy or at time of radiographic 
progression, whichever is earlier. 
• If allergic to contrast agents for 
imaging, a non-contrast computed 
tomography of the chest with 
contrast enhanced abdominal and 
pelvic MRI can be used. 
• Brain and/or bone scans to be 
performed at screening if disease 
is suspected and during study as 
appropriate to follow disease. 
• Confirmatory scan may be done 4 
weeks later as needed. For 
participants who discontinue 
treatment before confirmed 
disease progression, tumor 
imaging will continue per standard 
of care until progression of 
disease. 
Optional Photographs of 
Skin Pox Lesions 
ANYTIME 
• See Section 8.2.11. 
Archival Tumor Tissue 
X 
• An archival sample collected ≤1 
year prior to study start should be 
submitted per laboratory manual. 
• If archival FFPE ≤1 yr is not 
available a fresh tumor sample 
must be collected at screening. 
• If the archival sample is >1 yr and 
a biopsy during screening cannot 

PF-07263689 
Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
Page 40 
 
 
 
Table 2. 
Schedule of Assessments – Combination Therapy (Part 1B and Part 2) 
 
Visit Identifier 
Abbreviations used in 
this table may be found 
in Appendix 12. 
TREATMENT 
NOTES 
SCREENING 
Cycle 1 
(1 cycle = 28 days) 
Cycle ≥2 
Days 
≤28 
1 
2 
3 
4 
8 
9 
10 
15 
22 
1 
• See Table 3 for EOT and 
follow-up visit schedules 
Visit Window 
0 
±4h* 
±4h* 
±4h* 
±1d 
±4h* 
±4h* 
±2d 
±24h 
±2 day 
*±4h is relative to the most 
current dosing 
be performed safely, the 
investigator must contact the 
sponsor to discuss eligibility prior 
to enrollment. 
De Novo (Fresh) Tumor 
Biopsies 
X 
X 
• Request 5 pre-/on-treatment fresh 
biopsy pairs at or below one dose 
level from MTD in both Part 1A 
monotherapy and Part 1B in 
combination with sasanlimab 
cohorts. 
• Request 5-8 pre-/on-treatment 
fresh biopsy pairs in each arm of 
Part 2 dose expansion study unless 
biopsy cannot be performed 
safely. 
• An archival sample collected prior 
to study start may not be 
substituted for the mandatory 
pre‑treatment paired biopsy in Part 
1 and Part 2. 
• Participants who provide fresh 
pre- and on-treatment tumor 
biopsy pairs may also provide 
archival samples. 
Reporting Exposure to PF-07263689 

PF-07263689 
Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
Page 41 
 
 
 
Table 2. 
Schedule of Assessments – Combination Therapy (Part 1B and Part 2) 
 
Visit Identifier 
Abbreviations used in 
this table may be found 
in Appendix 12. 
TREATMENT 
NOTES 
SCREENING 
Cycle 1 
(1 cycle = 28 days) 
Cycle ≥2 
Days 
≤28 
1 
2 
3 
4 
8 
9 
10 
15 
22 
1 
• See Table 3 for EOT and 
follow-up visit schedules 
Visit Window 
0 
±4h* 
±4h* 
±4h* 
±1d 
±4h* 
±4h* 
±2d 
±24h 
±2 day 
*±4h is relative to the most 
current dosing 
Exposure of 
Participant’s Close 
Contact 
ANYTIME 
• See Section 5.3.2. 
Exposure of Subject’s 
Healthcare Provider 
ANYTIME 
• See Section 5.3.2. 

PF-07263689 
Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
Page 42 
 
 
 
Table 3. 
Schedule of Activities: EOT, Post-Treatment, and Survival Follow-up (Parts 1A, 1B, and 2) 
 
EOT1/ 
Withdrawal 
30 Day 
Follow-up2 
45 Day 
Follow-up3 
60 Day 
Follow-up4 
90 Day 
Follow-up5 
Survival 
Follow-up6 
Notes 
For detailed notes refer to main 
schedule of assessment 
28 days 
after last 
dose 
Every 3 
months 
after 30 
Day 
Follow-up 
Visit Window (days) 
± 7 days 
± 2 days 
± 7 days 
± 7 days 
± 7 days 
Physical Examination 
Complete Physical Examination 
X 
Brief Physical Examination 
X 
ECOG Performance Status 
X 
X 
Vital Signs 
X 
X 
ECG 
X 
Pulse Oximetry 
X 
Echocardiogram or MUGA 
X 
• Assessment of LVEF using 
echocardiogram or MUGA. 
Blood draw for Laboratory 
Assessment 
Hematology 
X 
X 
Blood Chemistry 
X 
X 
Coagulation 
X 
X 
• PT or INR, PTT/aPTT. 
Endocrinology 
X 
X 
• TSH, ACTH, Free T4. 
Cardiac Biomarkers 
X 
X 
• CPK and troponin 
Tumor Markers 
X 
• After EOT, continue to report standard 
or care tumor marker assessments until 
start of new therapy or EOS. 
• CA125 for OvCA; CEA for CRC; 
CA15-3 for BRCA; PSA for prostate 
cancer. 
Pregnancy Test/Contraception 
Check 
X 
• See Section 5.3.1 and Section 8.2.8. 
Urinalysis 
X 
X 
• Dipstick is acceptable at minimum. 
Tumor Response Assessment 

PF-07263689 
Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
Page 43 
 
 
 
Table 3. 
Schedule of Activities: EOT, Post-Treatment, and Survival Follow-up (Parts 1A, 1B, and 2) 
 
EOT1/ 
Withdrawal 
30 Day 
Follow-up2 
45 Day 
Follow-up3 
60 Day 
Follow-up4 
90 Day 
Follow-up5 
Survival 
Follow-up6 
Notes 
For detailed notes refer to main 
schedule of assessment 
28 days 
after last 
dose 
Every 3 
months 
after 30 
Day 
Follow-up 
Visit Window (days) 
± 7 days 
± 2 days 
± 7 days 
± 7 days 
± 7 days 
CT or MRI Scans of Chest, 
Abdomen, Pelvis, Any Clinically 
Indicated Sites of Disease, and of 
Bone Lesions; Clinical Evaluation 
of Superficial Disease 
X 
X 
• Tumor assessment should be repeated 
at the EOT visit if >6 weeks have 
passed since the last evaluation. 
• After EOT, continue to report standard 
of care imaging until start of new 
therapy or EOS. 
Subsequent Anti-cancer Therapy 
X 
X 
AE Assessment 
X 
X 
X 
X 
X 
X 
• All AEs and SAEs must be collected 
until a minimum of 90 days after the 
last administration of the study 
intervention. 
• The SAEs identified during long-term 
follow-up will be reported to Pfizer 
Safety on the CT SAE Report Form 
only if considered reasonably related to 
the study intervention. 
Whole Blood Sample for Viral Load 
Kinetics of PF-07263689 
X 
X 
Blood for Serum Sample for PF- 
07263689 Immunogenicity (anti-VV 
neutralizing antibody, anti-IL-2 
antibodies) 
X 
X 
(if 
suspected 
ADA- 
related 
AE) 
X 
(if 
suspected 
ADA- 
related 
AE) 
Injection Site Swab for Viral Shedding 
X 
X 
Saliva and Urine Sample for Viral 
Shedding 
X 
X 
X 
X 

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Table 3. 
Schedule of Activities: EOT, Post-Treatment, and Survival Follow-up (Parts 1A, 1B, and 2) 
 
EOT1/ 
Withdrawal 
30 Day 
Follow-up2 
45 Day 
Follow-up3 
60 Day 
Follow-up4 
90 Day 
Follow-up5 
Survival 
Follow-up6 
Notes 
For detailed notes refer to main 
schedule of assessment 
28 days 
after last 
dose 
Every 3 
months 
after 30 
Day 
Follow-up 
Visit Window (days) 
± 7 days 
± 2 days 
± 7 days 
± 7 days 
± 7 days 
1. 
EOT/Withdrawal: Visit to be performed as soon as possible but no later than 28 days from the last dose of study intervention and prior to initiation of any new anticancer 
therapy. Obtain these assessments if not completed in the last week (last 6 weeks for tumor assessments). 
2. 
30 Day Follow-up: At least 28 calendar days, and no more than 35 calendar days, after discontinuation of study intervention, participants will return to undergo the 
procedures listed above. If EOT occurs at the same time of the 30 Day Follow-up, then the 30 Day Follow-up do not need to be completed. 
3. 
45 Day Follow-up: 45 days after last dose of PF-07263689. 
4. 
60-Day Follow-up: 60 days after last dose of PF-07263689. 
5. 
90-Day Follow-up: 90 days after last dose of PF-07263689. 
6. 
Survival Follow-up: Subsequent to the 1-month follow-up visit, participants survival status will be collected by telephone every 12 weeks (±7 days) to obtain information 
on subsequent anticancer treatment and overall survival until the end of the study. If the participant is seen in the clinic during the window of time that a scheduled 
telephone call is to be made to collect survival data, then the clinic visit may replace the survival telephone call. Any standard of care tumor response assessments 
including CT/MRI imaging and/or tumor-specific markers (ie, CEA and CA125) obtained between EOT and subsequent anti-cancer therapy will also be collected. 

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Table 4. 
Viral Shedding, ECG, Immunogenicity, and Biomarker Schedule of Assessments (Part 1A) 
 
Visit Identifier 
Screen 
Day 1 
Day 2 Day 3 Day 4 
Day 8 
Day 9
Day 
10 
Day 15 
Day 22e 
(±2 days) 
Pre- 
dose 
0.5h* 1h* 
4h* 
8h* 
24h* 
(±4h) 
48h* 
(±4h) 
72h* 
(±4h) 
Pre- 
dose 
0.5h* 1h* 
4h* 
8h* 
24h* 
(±4h) 
48h* 
(±4h) 
Pre- 
dose 
4h* Pre- 
dose 
4h* 
Whole Blood Sample 
for Viral Load 
Kinetics of PF- 
07263689a 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood for Serum 
Sample for 
PF-07263689 
Immunogenicity (anti- 
Vaccinia Virus 
Neutralizing antibody, 
anti-IL-2 Antibodiesb 
X 
X 
X 
X 
Injection Site Swab 
for Viral Shedding 
X 
X 
X 
X 
Saliva and Urine 
Sample for Viral 
Sheddingc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CCI 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood for Cytokines 
Evaluation (Serum) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Table 4. 
Viral Shedding, ECG, Immunogenicity, and Biomarker Schedule of Assessments (Part 1A) 
 
Visit Identifier 
Screen 
Day 1 
Day 2 Day 3 Day 4 
Day 8 
Day 9 Day 
10 
Day 15 
Day 22e 
(±2 days) 
Pre- 
dose 
0.5h* 1h* 
4h* 
8h* 
24h* 
(±4h) 
48h* 
(±4h) 
72h* 
(±4h) 
Pre- 
dose 
0.5h* 1h* 
4h* 
8h* 
24h* 
(±4h) 
48h* 
(±4h) 
Pre- 
dose 
4h* Pre- 
dose 
4h* 
Triplicate 12-Lead 
ECGf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
* All sampling times are relative to the most recent dose. Samples collected on day of dosing (ie, on Day 1, Day 8, Day 15, and Day 22) will be collected ±10% of nominal 
time. Therefore, 0.5, 1, 4, and 8 hr samples will have a ±3, ±6, ±24, ±48 minutes collection window, respectively. On all other days, sampling windows are indicated ie, 
24 hr ± 4hrs. 
a. 
Blood samples for determination of viral genomes: Blood samples will be collectedly at each time point for determination of viral load kinetics after PF-07263689 
administration. 
b. 
Blood samples for anti-vaccinia virus neutralizing antibody and anti-IL2 IgG measurement: Blood samples will be collected at each time point for neutralizing antibody 
and anti-IL2 IgG assessment. 
c. 
Samples for viral shedding assessment: Indicated samples will be collected at each time point for assessment of viral shedding. Samples will be collected 60 days post 
last dose of PF-07263689 (see Table 3). 
C 
C 
Ie. 
f. 
 
Refer to Table 3 for EOT and follow-up visit schedules. 
Screening ECGs should be performed < 14 days from Day 1. When ECGs are obtained with PK sampling, ECGs must be completed before the PK samples is taken. 

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Table 5. 
PK, Viral Shedding, ECG, Immunogenicity, and Biomarker Schedule of Assessments: PF-07263689 Combination 
with Sasanlimab (Part 1B and Part 2) 
Visit Identifier  Screen 
Day 1 
Day 2 Day 3 Day 4 
Day 8 
Day 9 Day 10 
Day 15 
Day 22 
Cycle 
≥ 2h 
Pre- 
dose* 
0.5h* 1h* 
4h* 
8h* 
24h* 48h* 72h* Pre- 
(±4h) (±4h) (± 4h) dose* 
0.5h* 1h* 
4h* 
8h* 
24h* 
(±4h) 
48h* 
(±4h) 
Pre- 
dose* 
4h* 
Pre- 
dose* 
4h* 
(±3 
days) 
Whole Blood 
Sample for Viral 
Load Kinetics of 
PF-07263689a 
Blood Serum PK 
Sample for 
Sasanlimabd 
Blood Serum 
Sample for 
Sasanlimab 
Immunogenicity 
Blood Serum 
Sample for 
PF-07263689 
Immunogenicity 
Anti-VV 
Neutralizing 
Antibody, Anti- 
IL-2 Antibodies b 
Injection Site 
Swab for Viral 
Shedding 
Saliva and Urine 
Sample for Viral 
Sheddingc 
CCI 
X 
 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
X 
 
 
X 
Xf 
 
 
 
X 
X 
 
 
 
 
 
 
X 
X 
 
 
X 
X 
X 

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Pre- 
dose* 
CCI 
Triplicate 12-lead 
ECGi 
 
 
 
 
 
 
 
 
 
(±3 
days) 
4h* 
Pre- 
dose* 
4h* 
Pre- 
dose* 
48h* 
(±4h) 
Cycle 
≥ 2h 
Day 22 
Day 15 
24h* 
(±4h) 
8h* 
4h* 
1h* 
0.5h* 
Pre- 
dose* 
72h* 
(± 4h) 
48h* 
(±4h) 
24h* 
(±4h) 
8h* 
4h* 
1h* 
0.5h* 
Day 10 
Day 9 
Day 8 
Day 4 
Day 3 
Day 2 
Day 1 
Screen 
Visit Identifier 
 
Table 5. 
PK, Viral Shedding, ECG, Immunogenicity, and Biomarker Schedule of Assessments: PF-07263689 Combination 
with Sasanlimab (Part 1B and Part 2) 
 

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Table 5. 
PK, Viral Shedding, ECG, Immunogenicity, and Biomarker Schedule of Assessments: PF-07263689 Combination 
with Sasanlimab (Part 1B and Part 2) 
 
Visit Identifier Screen 
Day 1 
Day 2 Day 3 Day 4 
Day 8 
Day 9 Day 10 
Day 15 
Day 22 
Cycle 
≥ 2h 
Pre- 
dose* 
0.5h* 1h* 
4h* 
8h* 
24h* 
(±4h) 
48h* 
(±4h) 
72h* 
(± 4h) 
Pre- 
dose* 
0.5h* 1h* 
4h* 
8h* 
24h* 
(±4h) 
48h* 
(±4h) 
Pre- 
dose* 
4h* 
Pre- 
dose* 
4h* 
(±3 
days) 
* All sampling times are related to start of dosing. Samples collected on day of dosing (ie, on Day 1, Day 8, Day 15, and Day 22) will be collected ±10% of nominal time. 
Therefore, 0.5, 1, 4, and 8 hr samples will have a ±3, ±6, ±24, ±48 minutes collection window, respectively. On all other days, sampling windows are indicated ie, 24 hr 
± 4hrs. 
a. 
Blood samples for determination of viral genomes: Blood samples will be collectedly at each time point for determination of viral load kinetics after PF-07263689 
administration. 
b. 
Blood for serum samples for anti-vaccinia virus neutralizing antibody and anti-IL2 measurement: Blood samples will be collected at each time point for anti-VV 
neutralizing antibody assessment. 
c. 
Samples for viral shedding assessment: Indicated samples will be collected at each time point for assessment of viral shedding. Samples will be collected 60 days post 
last dose of PF-07263689 (see Table 3). 
d. 
Blood sample for determination of sasanlimab concentration: Blood samples will be collected at each time point for PK analysis of sasanlimab. 
e. 
Blood sample for sasanlimab immunogenicity: Blood samples will be collected at each time point for ADA/NAb assessment. 
f. 
Blood sample for sasanlimab immunogenicity to be collected every 3rd cycle starting with Cycle 5, as well as 30 days post last dose of sasanlimab. 
C 
C 
Ih. 
i. 
. 
Refer to Table 3 for EOT and follow-up visit schedules. 
Screening ECGs should be performed < 14 days from Day 1. When ECGs are obtained at the same time as a PK sample, the ECGs must be completed before the PK 
samples is taken. 

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2. INTRODUCTION 
PF-07263689 is a genetically engineered oncolytic vaccinia virus being developed for the 
treatment of solid tumors following IV administration. 
 
2.1. Study Rationale 
The purpose of this FIH study is to evaluate the safety, tolerability, viral load kinetics and 
shedding, and PD of repeat IV dosing of PF-07263689 as a monotherapy (Part 1A) and in 
combination with sasanlimab, an investigational anti-PD-1 antibody (Part 1B), in participants 
with locally advanced or metastatic solid tumors who have exhausted all standard of care 
therapy available to them. Participants with any advanced or metastatic solid tumor 
indications known to have approved therapies using immune checkpoint inhibitors or anti- 
vascular endothelial growth factor agents are eligible for Part 1, including but not limited to 
NSCLC, RCC, UC, melanoma, sarcoma, ovarian, and CRC. Part 2 is to evaluate the efficacy 
and safety of PF-07263689 as combination therapy with sasanlimab in selected PDx-naïve or 
refractory solid tumors. 
 
2.2. Background 
2.2.1. Oncolytic Viruses 
OVs have been widely investigated as cancer immunotherapy platforms and are represented 
by a diverse group of DNA and RNA viruses. Almost all OVs have the properties of being 
replication-competent, selectively replicating in tumor cells while sparing normal cells, 
causing tumor-selective cell killing (oncolysis) and tumor debulking, acting as in situ 
vaccines, and inducing both innate and adaptive anti-tumor immune responses (Lawler et al, 
2017; Russell et al, 2012). Most OVs have been genetically engineered for additional tumor 
selectivity, and a common strategy used is to alter or delete viral genes (eg, viral TK-) to 
enhance safety by greatly limiting replication in normal cells by taking advantage of high 
endogenous TK levels in tumors compared with normal resting cells (Twumasi-Boateng et 
al, 2018). In addition to harnessing the oncolytic efficacy of OVs, there are considerable 
efforts and opportunities to “arm” these viruses with transgenes that work to counter the 
immunosuppressive TME allowing for immunogenic tumor cell death, DC recruitment and 
activation, and tumor cell killing mediated by infiltrating tumor antigen specific T cells 
(Bommareddy et al, 2018; Kirn et al, 2009). 
 
Vaccinia viruses are double-stranded DNA viruses and an attractive OV platform because of 
the proven potential for systemic delivery, rapid replication in permissive tissues, broad 
tumor tropism, and robust tumor cell lysis. Additionally, the large DNA genome enables 
insertion of foreign transgenes, including immunomodulatory transgenes, under the control 
of natural or synthetic promoters to better control CCI 
. An example of this 
approach using vaccinia virus is JX-594 or pexastimogene devacirepvec (Pexa-Vec), a TK- 
oncolytic vaccinia virus derived from the Wyeth strain containing GM-CSF and LacZ 
transgene insertions. JX-594 has been evaluated both as an IT injection in HCC (Park et al 
2008; Heo et al 2013) as well as via IV dosing to achieve oncolysis and antitumor responses 
in less accessible primary and/or more widespread metastatic tumors, such as refractory CRC 

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CCI 
(Brietbach et al 2011; Park et al. 2015). JX-594 has also been evaluated in combination with 
sorafenib as well as ongoing trials with immune checkpoint inhibitors. 
 
2.2.2. PF-07263689 
PF-07263689 is an oncolytic vaccinia virus based on VV-Cop that has been genetically 
modified for safety and anti-tumor efficacy following IV administration. Unmodified, 
wild-type VV-Cop was used as a vaccine strain during the smallpox eradication campaign in 
Europe (Kretzschmar et al, 2006). It was selected for its superior oncolytic activity in human 
 
 
 
 
 
PF-07263689 sensitive to readily available antiviral drugs (eg, GCV, ACV) to enable 
treatment of spontaneous skin lesions that can occur in some patients following vaccinia 
virus treatment (Breitbach et al, 2015; Kung et al, 2015) with topical antivirals, thus reducing 
the risk of secondary transmission of infectious virus. A third genetic modification is a 
mutation in the viral A34R gene to encode a K151E variant that enhances release of virus 
from infected cells (Blasco et al, 1993) in the early stages of virus infection, thus expediting 
progeny virus spread and enhancing IV efficacy. 
 
designed to enhance immune-mediated 
tumor cell killing by activation of CD8+ T cells and NK cells, while avoiding the activation 
and immunosuppressive effects of Treg cells and the systemic toxicities associated with 
clinical use of recombinant wild-type IL-2. 
 
IL-2 is a potent cytokine and an approved immunotherapy for the treatment of metastatic 
RCC and metastatic melanoma (Proleukin® USPI). While very effective, the high doses of 
recombinant IL-2 required to achieve antitumor efficacy are associated with significant but 
reversible systemic toxicities (eg, capillary leak syndrome) as a result of IL2Rα receptor 
binding on vascular endothelial cells (Rosenberg, 2014). Researchers have sought to develop 
IL-2 variants with modified receptor binding properties in an effort to avoid these 
IL2Rα-mediated toxicities and bias activity of the IL-2 variant towards immunostimulatory 
activity (via the IL2Rβ/ɣ present on CD8+ T cells and NK cells) and away from 
immunosuppressive activity (via the α/β/ɣ receptor complex present on Treg cells). 
Examples of such IL-2 variants that have advanced to Phase 2/3 clinical studies and shown 
promising anti-tumor activity and safety in multiple indications include NKTR-214 
tumor cell lines compared to other strains (eg, Wyeth, WR; Ricordel et al, 2018). C 
CI 
A foreign transgene encoding a variant of herpes simplex 
virus type 1 TK (HSV TK.007, Preuss et al, 2010) CCI 
(Bentebibel et al, 2019) and FAP-IL-2v (Soerensen et al, 2018). CCI 

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CCI 
2.2.3. Sasanlimab 
Sasanlimab is a humanized, hinge region-stabilized IgG4 monoclonal antibody, with 
antagonistic activities specific for human PD-1. PD-1 is a member of the CD-28 superfamily 
that is mainly, but not exclusively, expressed on activated T-cells. Engagement of PD-1 with 
its ligands, PD-L1 and PD-L2, delivers negative signals that limit T-cell proliferation and 
cytokine production; thereby, regulating peripheral immune tolerance. Activation of PD-1 
also attenuates tumor immunity and facilitates tumor progression. Therefore, inhibition of 
PD-1 signaling reveals a mechanism of action that may enhance tumor immune surveillance 
and anti-tumor immune responses (Francisco et al, 2010; Jin et al, 2011; Pico de Coaña et al, 
2015). Agents targeting PD-1 and PD-L1 specifically are currently showing promise in 
multiple tumor types, including Opdivo® (nivolumab), Keytruda® (pembrolizumab), 
Imfinzi® (durvalumab), Tecentriq® (atezolizumab), Bavencio® (avelumab), and Libtayo® 
(cemiplimab) (Opdivdo package insert, 2018; Keytruda package insert, 2018). 
 
Sasanlimab can selectively and reversibly bind to human PD-1 and block the interaction 
between PD-1 and PD-L1/PD-L2. Sasanlimab has shown to increase human T-cell 
proliferation and cytokine secretion (IFN-g and IL-2), when PD-L1 is highly expressed in 
both in-vitro and in-vivo systems. Sasanlimab blockade of the interaction between PD-1 on 
T-cells and its ligands on tumor cells is expected to restore antitumor immunity and form the 
basis for an immunotherapeutic approach to treat cancer. 
 
2.2.3.1. Sasanlimab, an Anti-PD-1 Antibody: Clinical Experience in Study B8011001 
(NCT02573259) 
B8011001 is an ongoing Phase 1, open-label, multicenter, 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 1) phase and a dose expansion (Part 2) phase. 
Study enrollment was completed and a total of CCI 
. The available 
clinical data indicate sasanlimab has an acceptable safety profile and evidence of efficacy, 
both highly consistent with other approved PD-1 agents. Refer to Appendix 14 for 
Preliminary Clinical Summary and the sasanlimab IB for more details. 
 
2.2.4. Nonclinical Pharmacology 
2.2.4.1. In vitro and In vivo Pharmacology 
 
 
 
 
 
studies demonstrate the in vitro and in vivo oncolytic mechanism of action of PF-07263689 
in human tumor models. VV-Cop, and by inference PF-07263689, demonstrated stronger 
activity in a human tumor cell line xenograft tumor model than VV-Wyeth. 
CCI 
. These nonclinica

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. 
 
 
 
 
 
CCI 

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2.2.5. Nonclinical Pharmacokinetics and Metabolism 
No nonclinical methods of analysis, absorption, PK, toxicokinetic, metabolism, excretion, or 
drug interaction studies have been conducted for PF-07263689. Traditional pharmacokinetic 
studies are not considered relevant for oncolytic viruses/cancer vaccines (WHO, 2005). 
Nonclinical biodistribution study results are discussed in Section 2.2.4. 
 
2.2.6. Nonclinical Safety 
Toxicity studies of PF-07263689 were conducted in cynomolgus monkeys, which were 
 
 
Overall, the nonclinical profile of PF-07263689 has been adequately characterized and 
supports its exploration in patients with advanced cancer. 
 
2.2.7. Clinical Overview 
This is a FIH study for PF-07263689; therefore, no clinical data are available. 
 
This study will be conducted in solid tumor indications known to have approved therapies 
using immune checkpoint inhibitors or anti-vascular endothelial growth factor agents, or 
known to be susceptible to oncolytic virus. The study will enroll participants with locally 
advanced or metastatic solid tumors who have exhausted all relevant standard of care therapy 
including PDx treatment if approved or accepted per local standard for such indications. 
Therefore, the target populations represent unmet needs having no or very limited alternative 
therapeutic options for their advanced disease. 
 
2.3. Benefit/Risk Assessment 
Since this is the FIH study for selected disease indications where participants in late line 
settings have exhausted standard of care treatment options, the benefit/risk relationship has 
been considered in the planning of this study based on preclinical efficacy data, toxicology 
studies, and nonclinical safety profiles of PF-07263689. 
 
Safety findings that were observed in the nonclinical studies with PF-07263689 include: 
CCI 
, and 
administered CCI 

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CCI 
. The potential overlapping toxicities with the combination therapy based on 
clinical data with sasanlimab to date include CCI 
. Injection site 
reactions and skin changes with sasanlimab SC administration may affect or impact 
spontaneous skin lesions with PF-07263689. In this Phase 1 study, risks are being mitigated 
through eligibility criteria and clinical assessments via appropriate and frequent safety 
monitoring (see Section 2.3.1). Notably, participants in dose escalation will be hospitalized 
for at least CCI 
In Part 1A monotherapy, the dosing CCI 
to mitigate against 
unexpected immune-related adverse reactions. In Part 1B (combination with sasanlimab), the 
CCI 
 to mitigate against possible overlapping 
adverse reactions. There is no formal staggering for subsequent participants in each dose 
cohort. The requirements of inpatient hospitalization and stagger will be re-evaluated based 
on totality of the safety data prior to initiating dose expansion cohorts. 
 
Combination treatment with sasanlimab, which belongs to a class of drugs where the 
benefit/risk ratio is well known as a single agent, is also expected to have a favorable 
benefit/risk ratio. Sasanlimab may potentiate the effects of oncolytic vaccinia virus (Liu et al, 
2017) without significant overlapping toxicity, resulting in a similar or better benefit/risk 
profile compared with PF-07263689 as a monotherapy. 
 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of PF-07263689 and sasanlimab may be found in the respective IBs, which are 
the SRSDs for this study. 

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2.3.1. Risk Assessment 
 
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Study Intervention with PF-07263689 
Skin lesions 
The potential risks are based on non-clinical 
studies for PF-07263689. 
Skin Lesions: Supportive care including non-occlusive 
dressing or bandage and topical treatment will be applied to 
the skin lesions. Refer to Section 5.3.2 and Section 6.8.3.1. 
CCI 
 
Study Intervention with PF-07263689 and Sasanlimab 
irAE 
The potential overlapping risks are based on the 
investigator’s brochure for sasanlimab and 
nonclinical studies for PF-07263689. 
Guidelines for treatment interruption and discontinuation in 
case toxicities, and guidelines for steroid treatment 
implementation are incorporated in Appendix 3. 
 
Participants must have a LVEF ≥50% by echocardiogram or 
MUGA to be eligible. Cardiac biomarkers such as troponin 
and CPK will be performed throughout the study. Participants 
with active ILD/pneumonitis or history of ILD/pneumonitis 
requiring systemic steroids are excluded. Participants with a 
baseline pulse oximetry of < 92% “on Room air” are 
excluded. CCI 

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Study Procedures 
De novo (fresh) tumor biopsy 
• Mandatory pre-/on-treatment paired 
biopsies for at least 5 participants at or 
below 1 dose level from MTD in Part 
1A, Part 1B, and in Part 2 dose 
expansion (~5-8 participants in each 
arm unless biopsy cannot be 
performed safely) 
There is a risk associated with any tumor biopsy: 
• Stinging pain from injection of local anesthetic; 
• Pain or discomfort from the biopsy procedure; 
• Discomfort from lying still for an extended 
time; 
• Bleeding, swelling, scarring, soreness, or 
bruising at the biopsy site; 
• Infection of wound; 
• Contamination of cancer cells to unaffected 
tissue when removing biopsy needle. 
• Local anesthetic will be administered. 
• Sterile techniques will be used. 
• Procedures will be performed by qualified medical 
practitioners. 
• Participants should not be subjected to a significant risk 
procedure to obtain the biopsies (ie, the absolute risk of 
mortality or major morbidity in the participant’s clinical 
setting and at the institution completing the procedure 
should be <2%). 
CT or MRI procedures for tumor 
assessments 
CT scans expose the participant to a small dose of 
radiation. The contrast dye used with the CT scan 
may cause pain or burning when injected. The 
dye may worsen kidney function for those with 
kidney disease or are dehydrated. The dye may 
cause an allergic reaction. MRI risks include 
possible reactions to metals due to magnets, loud 
noises from the machine causing hearing issues, 
increase in body temperature during long MRIs, 
and claustrophobia. 
• Only experienced professionals will conduct the CT or MRI 
procedures. The participant will be asked about allergies to the 
contrast dye. Medical history will be reviewed for kidney disease, 
and information will be provided to minimize dehydration. If 
possible, an open MRI can be used for those experiencing 
claustrophobia. The participant may be offered earplugs and/or 
headphones to minimize the noise. 
Potential Risk of Clinical Significance 
Participants should be monitored not only for infusion site 
reactions but also any skin lesions in whole body following 
PF-07263689 administration (Parts 1A, 1B, and 2), as well as 
injection site reactions following administration of sasanlimab 
(in Parts 1B and 2). Refer to Section 5.3.2, Section 6.8.3.1 and 
Section 8.2.3. 
Injection site reactions and skin changes 
Mitigation Strategy 
Summary of Data/Rationale for Risk 
CCI 

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2.3.2. Benefit Assessment 
In the animal studies, toxicity from PF-07263689 has been observed only at a much higher 
dose per weight or body surface area in the mouse than the equivalent maximum dose that 
will be tested in humans in the Phase 1 study. As a class, vaccinia viruses have been safely 
administered to humans across vaccine and oncology studies, and there is a potential for 
therapeutic benefit to the administration of PF-07263689 given the antitumor effects seen in 
preclinical data, even with single-agent PF-07263689. Given that the prognosis in metastatic 
cancers is quite poor following standard of care therapies in solid tumor malignancies in 
general, and given that patients in this study do not have alternative treatment options with 
proven efficacy, the benefit/risk remains favorable for clinical evaluation of PF-07263689 in 
the proposed setting. Combination treatment with sasanlimab, a PD-1 inhibitor, which as a 
class has an established and favorable benefit/risk ratio in multiple tumor types and in 
addition may potentiate the effects of oncolytic vaccinia virus (Liu et al, 2017), is also 
expected to have a favorable benefit/risk ratio. 
 
Close medical monitoring will occur during the participant’s time on study, including 
identification of AEs through evaluations and assessments by the site and sponsor teams, 
which will further mitigate participant risk. 
 
2.3.3. Overall Benefit/Risk Conclusion 
Taking into account the measures taken to minimize risk to study participants, the potential 
risks identified in association with PF-07263689 and sasanlimab are justified by the 
anticipated benefits that may be afforded to participants with locally advanced or metastatic 
solid tumors who have exhausted all standard of care therapy. 
 
3. OBJECTIVES, ENDPOINTS, AND ESTIMANDS 
3.1. Dose Escalation (Part 1) 
 
Objectives 
Endpoints 
Estimands 
Primary: 
• 
Part 1A: To assess safety and 
tolerability at increasing dose 
levels of PF-07263689 in 
successive cohorts of participants 
with select locally 
advanced/metastatic solid tumors, 
until the MTD is estimated or the 
MFD dose is reached. 
• 
Part 1B: To assess safety and 
tolerability PF-07263689 in 
combination with sasanlimab in 
successive cohorts of participants 
with select locally 
advanced/metastatic solid tumors, 
• 
First cycle DLTs. 
• 
AEs as characterized by type, 
frequency, severity (as graded by NCI 
CTCAE version 5.0, except CRS, which 
will be graded by ASTCT criteria), 
timing, seriousness, and relationship to 
study treatment. 
• 
Laboratory abnormalities as 
characterized by type, frequency, 
severity (as graded by NCI CTCAE 
version 5.0), and timing. 
• The primary estimand for 
incidence of DLTs in Part 1 is 
DLT rate estimated based on 
data from DLT-evaluable 
participants during the DLT 
evaluation period, which is the 
first 28 days after the first dose 
of study intervention. The 
attributes of this estimand are 
provided in Section 9. 

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Objectives 
Endpoints 
Estimands 
in order to estimate and select the 
combination RP2D/schedule. 
Secondary: 
• 
To evaluate preliminary 
antitumor activity. 
• 
ORR, as assessed using the RECIST 
version 1.1. 
• 
Time to event endpoints: DOR, PFS, 
TTP by RECIST 1.1. 
• The key secondary estimand in 
Part 1 is to evaluate the 
treatment effect of PF-07263689 
assessed by ORR, based on 
investigator assessment per 
RECIST 1.1, in the response 
evaluable analysis population. 
The attributes of this estimand 
are provided in Section 9. 
• 
To evaluate the viral load kinetics 
following first and second dose of 
PF-07263689. 
• To collect sasanlimab drug 
concentration data in Part 1B 
for evaluation of sasanlimab 
PK. 
• 
Viral load kinetics parameters of PF- 
07263689 in blood, including Cmax, 
Tmax and AUClast. 
• Trough concentrations of 
sasanlimab for selected cycles 
• NA 
• 
To characterize the viral shedding 
of PF-07263689. 
• 
Viral titers during 30, 45, and 60 days 
after the last PF-07263689 dose. 
• NA 
• 
To evaluate the immunogenicity 
of PF-07263689 and sasanlimab 
following monotherapy and 
combination administration. 
• 
Incidence and titers of ADA against 
PF-07263689 and sasanlimab. 
• 
Incidence and titers of anti-IL2 
antibodies. 
• NA 
CCI 
• 
To assess viral replication and 
transgene expression of 
PF-07263689 in both tumors and 
blood of participants. 
• CCI 
• NA 
• 
To explore the pharmacodynamic 
effect of PF-07263689 in both 
tumor and blood of participants. 
• CCI 
• NA 

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Objectives 
Endpoints 
Estimands 
• CCI 
• 
To explore additional biomarkers 
associated with clinical response 
and to elucidate the potential 
MOA and mechanism of 
resistance to PF-07263689. 
• CCI 
• 
NA 
3.2. Dose Expansion (Part 2) 
 
Objectives 
Endpoints 
Estimands 
Primary: 
• 
To confirm safety and tolerability of 
PF-07263689 at the RP2D in 
combination therapy in participants 
with selected tumor types. 
• 
To evaluate preliminary evidence of 
antitumor activity of PF-07263689 in 
combination therapy in participants 
with selected tumor types. 
• 
AEs as characterized by type, 
frequency, severity (as graded by 
NCI CTCAE version 5.0, except 
CRS, which will be graded by 
ASTCT criteria), timing, seriousness, 
and relationship to study therapy. 
• 
Laboratory abnormalities as 
characterized by type, frequency, 
severity (as graded by NCI CTCAE 
version 5.0), and timing. 
• 
ORR as determined by RECIST 
version 1.1. 
• The primary estimand in Part 2 
is to evaluate the treatment 
effect of PF-07263689 in 
combination with 
PF-06801591 assessed by the 
ORR, based on investigator 
assessment per RECIST 1.1, in 
the response evaluable analysis 
population. The attributes of 
this estimand are provided in 
Section 9. 
Secondary: 
• 
To further evaluate the viral load 
kinetics following PF-07263689 
administration. 
• 
To collect sasanlimab drug 
concentration data in Part 2 for 
evaluation of sasanlimab PK. 
• 
Viral load kinetics parameters of PF- 
07263689 in blood, including Cmax, 
Tmax, and AUClast. 
• 
Trough concentrations of sasanlimab 
for selected cycles. 
• NA 
• 
To characterize the viral shedding of 
PF-07263689. 
• 
Viral titers during 30, 45, and 60 
days after the last PF-07263689 dose. 
• NA 
• 
To further evaluate the 
immunogenicity of PF-07263689 
and sasanlimab. 
• 
Incidence and titers of ADA against 
PF-07263689 and sasanlimab. 
• 
Incidence and titers of anti- IL-2 
antibodies. 
• NA 

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Objectives 
Endpoints 
Estimands 
• 
To evaluate preliminary antitumor 
activity through time to event time 
points. 
• 
DCR, DOR, PFS, and TTP by 
RECIST version 1.1. 
• NA 
• 
To assess overall survival of 
participants treated with 
PF-07263689. 
• 
Overall survival 
• NA 
CCI 
• 
To assess viral replication and 
transgene expression of 
PF-07263689 in tumors of 
participants. 
• 
To explore the pharmacodynamic 
effect of PF-07263689 in both tumor 
and blood. 
• 
To explore additional biomarkers 
associated with clinical response and 
to elucidate the potential mode of 
action and mechanism of resistance 
to PF-07263689. 
• CCI 
• NA 
4. STUDY DESIGN 
4.1. Overall Design 
The proposed Phase 1, open-label, multicenter, multiple dose, dose escalation, and dose 
expansion study will evaluate the safety, tolerability, viral load kinetics and shedding, PD, 
and antitumor activity of PF-07263689, either alone or in combination with sasanlimab (an 
investigational anti-PD-1 antibody), in participants with locally advanced or metastatic solid 
tumors who have exhausted all standard of care therapies available to them. The study 
consists of 2 parts: Part 1 dose escalation for PF-07263689 monotherapy (Part 1A) and 
combination with sasanlimab (Part 1B) and Part 2 dose expansion for the combination 
therapy. 
 
The study will evaluate weekly IV dosing of PF-07263689 for 4 total doses, either as a 
monotherapy or in combination with sasanlimab administered at 300 mg SC Q4W. In the 
combination therapy arm, administration of sasanlimab will start concurrently with 
PF-07263689 and continue beyond the end of the PF-07263689 treatment course until 
disease progression, intolerable toxicity, withdrawal of consent, or until the study is 

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Participants will be hospitalized for at least CCI 
monotherapy, the dosing of the first CCI 
. In Part 1A 
to mitigate against unexpected immune-related adverse reactions. In 
Part 1B (PF-07263689 in combination with sasanlimab), the dosing of the first CCI 
to mitigate against possible overlapping adverse reactions. 
CCI 
completed. Alternative PF-07263689 regimens may be evaluated if supported by emerging 
data. 
 
Approximately 120 participants are expected to be enrolled in the study overall, including 
approximately 40 DLT evaluable participants for Part 1 and approximately 80 participants 
(15 to 20 per cohort) for Part 2. 
 
For Part 1A, participants will be assessed for radiological response on Day 43 (±5 days). 
Additional scans may be performed every 6 weeks (±7 days) following Day 43. For Part 1B 
and Part 2, all participants will be assessed for radiographic response every 6 weeks 
(±7 days) for up to 6 months followed by every 12 weeks (±7 days) until starting new 
anticancer therapy or at time of radiographic progression, whichever is earlier. Urine, saliva, 
and infusion site swabs will be collected to assess viral shedding during treatment and up to 
60 days after last dose of PF-07263689 as indicated in the SoA. Any skin lesions that appear 
will be swabbed to assess for virus shedding. Additionally, survival follow-up will occur by 
telephone Q12W (±7 days). Participants will continue to be followed for survival and long- 
term safety until death, withdrawal of consent, or the end of the entire study (see 
Section 4.3). 
 
4.1.1. Dose Escalation (Part 1) 
Participants with any advanced or metastatic solid tumor indications known to have approved 
therapies using immune checkpoint inhibitors or anti-vascular endothelial growth factor 
agents are eligible for Part 1. Participants must have exhausted all standard of care therapy 
for the primary tumor type available to them. Participants with immune checkpoint inhibitor- 
sensitive tumor types (eg, NSCLC, RCC, UC, melanoma) are expected to be treated in a 
post-anti-PD-1/PD-L1 (hereafter referred to as anti-PDx) failure setting in Part 1. Tumor 
types in which anti-PDx antibody therapy is not indicated, such as ovarian and MSS CRC, 
may be treated in any post-standard of care setting. 
 
 
 
There is no formal staggering for subsequent participants in each dose cohort. 
 
Part 1A Monotherapy Dose Escalation: A BLRM along with EWOC will be utilized to guide 
dose escalation and to determine the monotherapy MTD if MFD is not reached. Dose 
escalation from the determined starting dose (at one log level 
 
After the last participant at the MTD or the MFD has finished all doses of PF-07263689, the 
monotherapy RP2D will be determined based on all available safety, efficacy, and viral load 
kinetics and shedding data. During the dose escalation process, intermediate doses may be 
tested based on BLRM. 

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Part 1B Combination Dose Escalation: Dose escalation of PF-07263689 in combination with 
sasanlimab will start at equal to or one dose level lower than the monotherapy MTD of 
PF-07263689, or any intermediate dose between MTD and the next lower dose of MTD, as 
guided by the BLRM and EWOC criteria. If started below the monotherapy MTD, 
PF-07263689 may be escalated to MTD or the MFD in the combination. After completing 
PF-07263689 dosing, participants will remain on sasanlimab 300 mg SC Q4W until disease 
progression, intolerable toxicity, withdrawal of consent, or until the study is completed. The 
combination therapy RP2D will be determined based on all available safety, efficacy, and 
PK/PD data during the combination dose escalation process. 
 
4.1.2. Dose Expansion (Part 2) 
Part 2 will further evaluate PF-07263689 in combination with sasanlimab at the preliminary 
combination RP2D from Part 1B. Sasanlimab will be administered at 300 mg SC Q4W in 
tumor-specific arms of post-PDx failure NSCLC (Arm A), post-PDx failure RCC (Arm B), 
post-PDx failure melanoma (Arm C), and PDx-naïve refractory CRC (Arm D), at 
approximately 15 to 20 participants per arm. Initially, 3 tumor-specific arms will commence 
based on preliminary data from Part 1, with the option to subsequently open the fourth arm 
based on emerging data. For the post-PDx indications, Arms A, B, and C may be limited to 
participants with primary or secondary resistance to PDx inhibitors after discussion with 
investigators. 
 
4.2. Scientific Rationale for Study Design 
PF-07263689 is an oncolytic virus that selectively grows in and kills cancer cells. In addition 
to its direct cytolytic activity, it has the capability to stimulate innate and adaptive immune 
reactions against tumor cells. PF-07263689 is also genetically engineered to express an 
IL-2gv therapeutic payload as a strategy to alter the tumor immune microenvironment to 
potentially reverse checkpoint refractoriness and induce killing of uninfected bystander 
tumor cells. It is delivered systemically for infection of disseminated disease that can 
stimulate systemic antitumor immune responses in patients with or without prior anti-PDx 
therapies. As demonstrated in preclinical studies with PF-07263689 in which antitumor 
efficacy was further enhanced by coadministration of an anti-PD-1 antibody, combination 
therapy of sasanlimab with PF-07263689 is expected to maintain the oncolytic virus induced 
antitumor T-cell immune response long-term. 
 
4.2.1. Dose Level Review Committee 
This study will not use a DMC. However, a DLRM will convene for dose escalation 
decisions. The actual dose selected at each dose decision may be at or below the statistical 
model’s (ie, BLRM) recommended dose as determined by the members of the DLRM after 
considering all safety information. The review team will be composed of investigator(s), 
Pfizer GCL, Pfizer Study Clinician, and Pfizer Study Manager. Additional members may be 
added as needed (eg, Clinical Pharmacology Lead, Translational Oncology, Safety Risk Lead 
or designee, and Pfizer Biostatistics representative). A quorum, defined as >50% of the 
participating investigators or their qualified designee (ie, subinvestigator or research nurse or 
study coordinator possessing hard copy documentation [eg, email] of the investigator’s vote 

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CCI 
CCI 
CCI 
regarding the dose level review), must be in attendance for the DLRM. Participating 
investigators are defined as those whose sites have been initiated for screening and 
enrollment of patients. The DLRM will be rescheduled if a quorum is not reached. 
 
Voting members of the DLRM will include the Pfizer Medical Monitor and all participating 
investigators or their qualified medical doctor designee(s). The team may recommend 
escalation to the next planned dose, escalation to an intermediate dose (a dose lower than the 
next planned dose), continuation or delay in dosing, repetition or expansion or a cohort, 
de-escalation at a lower dose, or termination of the study. 
 
All available study data including demographics, medical history (including tumor history), 
concomitant medications, AEs, ECGs, vital signs, laboratory results, and emerging PK or PD 
data will be reviewed. 
 
4.2.2. Choice of Contraception/Barrier Requirements 
Studies to evaluate the development toxicity of PF-07263689 and sasanlimab have not been 
conducted. On the basis of the mechanism of action of sasanlimab and data from approved 
drugs of the same class, sasanlimab may cause a risk for severe manifestations of 
developmental toxicity in humans. Therefore, the use of a highly effective method of 
contraception is required (see Appendix 4). 
 
4.2.3. Collection of Retained Research Samples 
Retained Research Samples will be collected and stored for further analyses which may, for 
example, provide greater understanding of the study intervention. 
 
4.3. Justification of Dose 
The selection of starting dose and regimen for this FIH study was based on the nonclinical 
toxicology and pharmacology studies. Results from nonclinical toxicological studies indicate 
that monkey is the most relevant species. In the pivotal GLP toxicological study in monkeys, 
the CCI 
. The key findings in this study were the 
expected skin lesions and immune system findings consistent with viral infection. The human 
equivalent dose for the HNSTD/NOAEL dose 
 
The proposed starting dose CCI 
 is one log level below the human equivalent dose 
of NOAEL in monkey, and is predicted to be in the lower range of biologically active dose 
based on preclinical data. In nonclinical pharmacology studies 
of PF-07263689 CCI 
, a 
was shown to 
be effective in tumor growth inhibition. This dose is CCI 
 
 
(assuming a 60 kg body weight) and represents a conservative biologic active dose based on 
the preclinical data. 
 
PF-07263689 will be administered using flat dosing. Both flat dosing and body weight-based 
dosing have been employed in clinical trials with other oncolytic viruses with lack of 

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C 
C 
I 
Dose (PFU) 
Dose Level/Cohort 
evidence favoring body weight-based dosing (Streby et al, 2019; García M et al, 2018; Small 
et al, 2006; Mell et al, 2017; Downs-Canner et al, 2016; Freeman et al, 2006; Comins et al, 
2010; Rudin et al, 2011; Breitbach et al, 2011; Karapanagiotou et al, 2012; Kolb et al, 2015; 
Park et al, 2015; Machiels et al, 2019). In addition, flat dosing would be more convenient and 
could reduce potential dosing errors associated with body weight-based dosing. 
 
Doses presented are projected based on nonclinical data and may be modified based on 
emerging safety, tolerability, and viral load kinetic data. 
 
4.3.1. Starting Dose 
The starting dose for Part 1A will CCI 
 given once weekly for 4 weeks. 
4.3.2. Criteria for Dose Escalation 
The objective of Part 1 of the study is to establish the MTD before the pre-specified MFD 
using the BLRM approach and the EWOC principle. The use of the EWOC principle limits 
the risk that a potential next dose will be toxic. A 2-parameter BLRM will be used to guide 
the dose escalation process of the monotherapy of PF-07263689, and a 5-parameter BLRM 
will be used to guide the dose escalation of PF-07263689 in combination with sasanlimab. 
See Section 9.3.2 and Appendix 9 for more details on the Bayesian logistic regression model. 
Using DLT data at all tested dose levels and pre-specified prior distribution of model 
parameters, posterior probabilities of probability of having a DLT falling into 3 dosing 
intervals (underdosing, target dosing, overdosing) will be calculated for all dose levels. A 
dose may only be used for newly enrolled participants if the risk of excessive toxicity, ie, 
toxicity higher than 0.33 at that dose is less than 25%. 
 
The provisional maximum dose for each dose level to be evaluated are listed in Table 6. 
 
Table 6. 
Provisional Dose Levels in Dose Escalation 
 
 
 
Intermediate doses that may be explored will be within the dose range listed in the table 
above. The CCI 
required to CCI 
significant microbial and safety risks. 
; the dose preparation and handling time 
DP presentation would present 
 
Dose escalation will stop when stopping criteria are met (see Section 9.3.2). 

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4.3.3. DLT Definition 
In Part 1A and Part 1B , a participant is classified as DLT evaluable if he/she either 1) 
receives 3 of the 4 doses of PF-07263689 and has completed the scheduled safety 
assessments during the DLT observation period or 2) has experienced a DLT. Participants 
may miss a single dose, but the first dose and the last dose must occur within the 22-day 
window. Participants who withdraw from the study during the DLT evaluable period for 
reasons other than a DLT may be replaced with a new participant at the same dose level. The 
sole exception to criterion 1) is if the participant has missed a minority of safety assessments 
due to emergency situations (eg, site accessibility issues, inability to go to an external lab, 
etc.). In such cases, the DLRM Committee may judge the participant evaluable, depending 
on the abundance of the available data. Participants that experience any DLT at any dose 
level in Part 1 and Part 2 of the study will not be replaced. 
 
For the purpose of dose escalation, the DLT observation period will be during the first cycle 
(28 days after the start of PF-07263689 monotherapy [Part 1A] and PF-07263689 
combination with sasanlimab [Part 1B]) in each participant. 
 
Significant AEs considered to be related to study intervention that occur after the DLT 
observation period will be reviewed in context of all safety data available. That review may 
result in re-evaluation of the dosing level or regimen. Severity of AEs will be graded 
according to CTCAE version 5.0 except CRS, which will be graded by ASTCT criteria. 
 
For the purpose of dose escalation, any of the following AEs occurring in the DLT 
observation period that are considered at least possibly related to PF-07263689 and/or 
sasanlimab will be classified as DLTs: 
 
4.3.3.1 Hematological DLTs 
• Grade 4 neutropenia lasting >5 days from initiation of granulocyte-colony 
stimulating factor; 
 
• Febrile neutropenia defined as ANC <1000/mm3 with a single temperature of 
>38.3°C (101°F), or a sustained temperature of >38°C (100.4°F) for more than 1 
hour; 
 
• Grade 3 neutropenia with infection; 
• Grade 3 thrombocytopenia with any bleeding; 
• Grade 4 thrombocytopenia. 
4.3.3.2. Non-Hematologic DLTs 
• Any treatment-related Grade ≥3 non-hematologic toxicity (see below for 
specifications applying to special circumstances); 

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• Clinical events consistent with Hy’s Law; 
• Any Grade 3 CRS as per ASTCT that does not improve to Grade ≤2 within 72 
hours despite medical management; 
 
• Any Grade 4 CRS; 
• Grade ≥3 toxicity of any duration affecting vital organs (eg, heart, lung and CNS) 
should also be considered as DLT and be reviewed with the Sponsor. 
 
• Grade 4 vaccinia infection lasting ≥6 days; 
• Grade ≥3 nausea, vomiting, diarrhea, or fatigue that cannot be controlled to 
Grade ≤2 with or without medical therapy within 3 days; 
 
• Grade ≥3 rash that does not resolve to Grade ≤2 within 21 days with supportive 
measures (including anti-viral therapy); 
 
• Grade ≥3 laboratory abnormalities with a clinical correlate that cannot be 
controlled to Grade ≤2 with or without appropriate medical management within 3 
days; 
 
• A treatment-related AE inducing a delay by 2 weeks in receiving the next 
scheduled dose due to persisting toxicities attributable to study drug will be 
considered a DLT; 
 
• Clinically important or persistent toxicities (eg, toxicities responsible for 
significant dose delay or missed doses) that are not included in the above criteria 
may also be considered a DLT following review by the investigators and the 
sponsor. 
 
4.3.3.3. Other DLTs (Part 1B Only) 
In addition, for combination therapy, irAEs that meet the following criteria will be 
considered DLTs: 
 
• Grade 4 irAE regardless of duration (for laboratory abnormalities without clinical 
correlate and do not require medical intervention please refer to criteria above); 
 
• Grade ≥3 colitis regardless of duration (must be supported by diagnostic testing); 
• Grade ≥3 non-infectious pneumonitis regardless of duration; 
• Grade 2 non-infectious pneumonitis that does not resolve to Grade 1 or less 
within 3 days of the initiation of maximal supportive care; 

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• Any grade immune-mediated myocarditis. Participants with Grade ≥3 myocarditis 
will be permanently discontinued; 
 
• Grade 3 irAE, excluding colitis and pneumonitis, that does not improve to Grade 
≤2 within 3 days after onset of the AE despite maximal supportive care including 
systemic corticosteroids or downgrade to ≤ Grade 1 or baseline within 14 days; 
 
• Grade ≥3 immune-related endocrinopathies (eg, thyroid disorders, diabetes 
mellitus, adrenal insufficiency) that require treatment discontinuation or are not 
managed successfully with hormonal replacement therapy. 
 
The following AEs will not be adjudicated as DLTs in Part 1A or Part 1B: 
 
• Grade 3 IRR, allergic reaction, or anaphylaxis will not be considered as DLTs but 
may be a reason for study discontinuation and will be reviewed with the sponsor. 
 
4.3.4. Late Toxicity Definition and Management 
Significant AEs considered to be related to the PF-07263689 as monotherapy or in 
combination treatment under investigation that occur after the DLT observation period will 
be reviewed in the context of all available safety data. That review may result in re- 
evaluation of the dosing level or regimen. 
 
The details of the potential late onset toxicity will be reviewed during dose level review 
meetings to inform decisions about enrollment and dosing (eg, dose level increments, 
determination of the dose(s) used beyond dose escalation, regimen). Late onset toxicities that 
meet the definition of DLT will be considered in the evaluation of the MTD, Phase 1 
Expansion Dose, and/or RP2D, as appropriate. 
 
All participants will be monitored for at least 90 days after treatment discontinuation for 
immune-related toxicities. 
 
4.3.5. MTD Definition 
MTD is defined as the highest dose with true DLT rate within the target toxicity interval. The 
target interval for the DLT rate is defined as [0.16, 0.33]. 
 
The safety of each cohort will be assessed by a Dose Level Review Committee, which is 
composed of Sponsor representatives and the Investigators. The Committee will consider all 
relevant clinical data, including safety, PK, efficacy, and PD in making decisions such as 
whether to dose escalate, dose de-escalate, dose level increments, expand 
cohorts, and declare MTD. 
 
4.3.6. Recommended Phase 2 Dose Definition 
The MTD is identified based on acute toxicities observed during the DLT evaluation period 
and defines the limit of acceptable dose escalation in a small sample size. The RP2D, on the 

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other hand, identifies a dose that can be used in further large-scale testing and its 
determination is based on an overall assessment of feasibility, tolerability, and perhaps 
efficacy, based on a larger patient exposure to the agent, both in number and duration, and 
may be the same as the MTD or the MFD, or may be lower. The RP2D will be determined in 
this study after the expansion cohort(s) have provided sufficient data on which to make such 
a determination. The final determination of the RP2D will be made by the sponsor based on a 
recommendation from the investigators and study team. 
 
The dose(s) selected for use in the expansion cohorts will be referred to as the Phase 1 
Expansion Dose(s). Participants enrolled to Part 1B dosed at the same dose(s) selected for the 
expansion cohorts and meeting the same requirements will be counted toward such data 
analyses. 
4.4. End of Study Definition 
The end of the study will be the date of the last visit of the last participant or 2 years after the 
last participant receives their first dose (whichever occurs first). The study may also be 
terminated at any time at the discretion of the sponsor. Any additional treatment beyond 
2 years shall be discussed and approved by the sponsor. 
 
A participant is considered to have completed the study if he/she has completed all phases of 
the study including the EOT visit. 
 
5. STUDY POPULATION 
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 
protocol. 
 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
 
5.1. Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
 
Age and Sex: 
 
1. Participants age ≥18 years. 
 
• Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female 
(Section 10.4.2) participants. 

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Type of Participant and Disease Characteristics: 
 
2. Histological or cytological diagnosis of locally advanced/metastatic solid tumor 
indications known to have approved therapies using immune checkpoint inhibitors or 
anti-vascular endothelial growth factor agents. 
 
3. Participants should have exhausted all available standard of care therapy or for whom 
no standard therapy is available for their tumor type. Participants who have actively 
declined available standard of care therapies are eligible upon documentation of 
refusal. 
 
4. Participants with solid tumors with FDA-approved anti-PDx antibody therapy should 
have received at least 1 prior anti-PDx therapy. 
 
5. Participants with prior anti-PDx therapy must have documentation of primary or 
secondary resistance to last prior anti-PDx therapy according to Society for 
Immunotherapy of Cancer Immunotherapy Resistance Taskforce (Kluger et al, 2020) 
as follows: 
 
a. Primary resistance: drug exposure for at least 6 weeks with best response of PD, 
or SD for < 6 months (including PD at any time after stopping PDx for any reason 
unrelated to toxicity if best response while receiving anti-PDx therapy was PD or 
SD < 6 months). 
 
b. Secondary resistance: drug exposure for at least 6 months with best response of 
CR or PR or SD for ≥ 6 months. If prior PDx was stopped prior to PD, PD must 
have occurred within 12 weeks after the last dose of PDx. 
 
6. Participants entering the study in the expansion cohort have at least 1 measurable 
lesion as defined by RECIST version 1.1 that has not been previously irradiated. 
 
7. Dose Escalation (Part 1A and 1B): Participants with any advanced or metastatic solid 
tumor indications known to have approved therapies using immune checkpoint 
inhibitors or anti-vascular endothelial growth factor agents. 
 
8. Dose Expansion (Part 2): Participants with the following indications must have 
exhausted all relevant available standard of care or have documented intolerability to 
such therapies. 
 
a. NSCLC (≥2L): Participants with NSCLC must have received prior anti-PDx 
therapies. NSCLC participants with driver mutation(s) must have received prior 
available targeted therapy(ies) (eg, participant with BRAF V600E mutation must 
have also received BRAF inhibitor with or without MEK inhibitor) or have 
documented intolerability. 

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b. RCC (≥2L): Participants with RCC must have received prior anti-PDx therapies. 
RCC participants must also have received prior anti-VEGF therapy. 
 
c. Melanoma (≥2L): Participants with melanoma must have received prior anti-PDx 
therapy with or without anti-CTLA-4. Melanoma participants with driver 
mutations must have received prior available targeted therapies. 
 
d. MSS CRC: Participants with CRC must have received regimen containing 
combinations of pyrimidine analog-containing combination chemotherapy with 
anti-VEGF (as appropriate), anti-EGFR (as appropriate if RAS wild-type), and/or 
encorafenib (if BRAF V600E). 
 
9. Participants must have recently obtained (≤1 year prior to Day 1) archival FFPE 
tumor tissue sample available; details are provided in the Laboratory Manual. If 
archival FFPE ≤1 year is not available a fresh tumor sample must be collected at 
screening. If the archival sample is older than 1 year and a biopsy during screening 
cannot be performed safely, the investigator must contact the sponsor to discuss 
eligibility prior to enrollment. 
 
Informed Consent: 
 
10. Capable of giving signed informed consent as described in Appendix 1, which 
includes compliance with the requirements and restrictions listed in the ICD and in 
this protocol. 
 
Other Inclusion Criteria: 
 
11. ECOG PS 0 or 1. 
 
12. Adequate Bone Marrow Function within 14 days of the planned first dose, defined as: 
 
• ANC ≥1,250/mm3 or 125 x 109/L; 
• Platelets ≥75,000/mm3 or 75 x109/L; 
• Hemoglobin ≥9 g/dL. Limited transfusions to reach this value are allowed, after 
discussion with the sponsor’s medical monitor. There should not be a chronic 
need for transfusions (>1 per month) in the recent (approximately 3 months) past. 
 
13. Adequate Renal Function within 14 days of the planned first dose, defined as an 
estimated creatinine clearance ≥60 mL/min (≥30 mL/min for RCC participants) as 
calculated by Cockcroft-Gault method. In equivocal cases, a 24-hour urine collection 
test can be used to estimate the creatinine clearance more accurately. 

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14. Adequate Liver Function within 14 days of the planned first dose, defined as: 
 
• Total bilirubin ≤1.5 x ULN unless the participant has documented Gilbert’s 
syndrome; 
 
• AST and ALT ≤2.5 x ULN; ≤5.0 x ULN if there is liver involvement by the 
tumor; 
 
• AP ≤2.5 x ULN (≤5 x ULN in case of bone metastasis or liver metastasis). 
15. Participants with brain metastases must meet all the following conditions: 
 
• Have completed their planned course of local treatment; 
• Have recovered from the acute effects of radiation therapy or surgery prior to 
planned first dose; 
 
• Have discontinued corticosteroid treatment for these metastases for at least 
4 weeks; 
 
• Have been on stable doses of anti-seizure medications (if applicable) for at least 
3 months. Antiseizure medications must meet any eligibility criteria outlined for 
concomitant medications. 
 
• Are neurologically stable for 3 months since the conclusion of therapy, as 
documented by both neurologic and MRI examinations. 
 
• Participants who are diagnosed with a CNS metastasis during the screening period 
must also meet these criteria. 
 
16. Resolution of acute effects of any prior therapy to either baseline severity or 
CTCAE version 5 Grade ≤1 (except for AEs not constituting a safety risk in the 
investigator’s judgment unless the AEs represent persistent non-hematological 
toxicities of Grade ≥3). 
 
17. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations, and other study procedures. 
 
5.2. Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
 
Medical Conditions: 
 
1. Participants with any other active malignancy within 3 years prior to planned first 
dose, except for adequately treated basal cell or squamous cell skin cancer, or 

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carcinoma in situ of the cervix, Bowen’s disease. Other indolent, secondary cancers 
may be permitted after discussion with sponsor. 
 
2. Participants sustaining recent major surgery defined as a complex procedure 
performed under regional or general anesthesia with a recovery period of at least 
4 weeks prior to planned first dose. Exceptions include: 
 
• Minor surgical procedures require at least 1-week period prior to planned first 
dose. 
• Participants having an implantable port placed can enter the study 1 week 
after the port is placed, assuming no complications have occurred, and the port 
is functioning normally. 
3. Participants with persistent non-hematological toxicities of ≥ Grade 3 (NCI-CTCAE 
v5.0), including symptoms and objective findings from treatment such as 
chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation, or 
surgery. 
 
4. Participants with a history of myocarditis or congestive heart failure (as defined by 
New York Heart Association (NYHA) Functional Classification III or IV), as well as 
unstable angina, serious uncontrolled cardiac arrhythmia, or myocardial infarction 6 
months prior to study entry. 
 
5. Clinically important (eg, uncontrolled) hypertension that cannot be controlled by 
medications (approximately above 150/90 mmHg) despite optimal medical therapy. 
Equivocal cases should be discussed with the sponsor prior to study entry. 
 
6. Known or suspected hypersensitivity to, allergic history of, or prior treatment within 
the past 10 years on any vaccinia oncolytic, pox virus, or antiviral agents. 
 
7. Known or suspected hypersensitivity to any anti-PDx antibody if planned to receive 
combination therapy with sasanlimab. 
 
8. History of Grade ≥3 immune mediated AE (including AST/ALT elevations that were 
considered drug-related and cytokine release syndrome) that was considered related 
to prior immune modulatory therapy (eg, immune checkpoint inhibitors, 
costimulatory agents, etc.) and required immunosuppressive therapy. 
 
9. Has a diagnosis of severe immunodeficiencies immunosuppression (eg, history of 
leukemia, lymphoma, solid organ transplantation, hematopoietic stem cell transplant 
recipients who are <24 months posttransplant, and hematopoietic stem cell transplant 
recipients who are >24 months posttransplant but who have graft-versus-host disease, 
and humoral or cellular immunity disorders such as T-cell and NK cell dysfunction 
(ex, Chediak-Higashi syndrome, Leukocyte Adhesion Deficiency, and 
myeloperoxidase deficiency). 

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10. Participants with known symptomatic brain metastases requiring steroids. 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 (requires MRI 
confirmation). 
 
11. Participants with active ILD/pneumonitis or a history of ILD/pneumonitis requiring 
treatment with systemic steroids. 
 
12. History of or ongoing severe immune response or inflammatory skin condition such 
as severe eczema (as determined by the investigator) requiring medical treatment. 
 
13. Any prior or planned organ transplant. 
 
14. Known history of immune-mediated colitis, inflammatory bowel disease, 
pneumonitis, or pulmonary fibrosis. 
 
15. Ongoing bowel perforation or presence of bowel fistula or abscess or history of small 
or large bowel obstruction within 3 months of planned first dose, including 
participants with palliative gastric drainage catheters. Participants with palliative 
diverting ileostomy or colostomy are allowed if they have been symptom-free for 
more than 3 months. 
 
16. Active bleeding disorder, including gastrointestinal bleeding, as evidenced by 
hematemesis, significant hemoptysis or melena in the past 6 months. 
 
17. Presence of any open, active wound requiring treatment for proper healing. 
 
18. Other medical or psychiatric condition including recent (within the past year) or 
active suicidal ideation/behavior or laboratory abnormality that may increase the risk 
of study participation or, in the investigator’s judgment, make the participant 
inappropriate for the study. 
 
Prior/Concomitant Therapy: 
 
19. Current use of any prohibited concomitant medication(s) or those unwilling/unable to 
use a permitted concomitant medication(s) (refer to Section 6.8). 
 
20. Radiation therapy within 4 weeks prior to planned first dose. Exceptions include: 
 
• Limited, focal radiation therapy (including Gamma-Knife) require only a 
3-day period before planned first dose and the absence of any radiation- 
induced complications. 
• Palliative radiation therapy within 2 weeks of planned first dose and the 
absence of any radiation-induced complications. 

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21. Vaccination with a live virus (eg, measles, mumps, rubella) within 4 weeks prior to 
planned first dose. 
 
22. Participants requiring chronic systemic immunosuppressants. 
 
23. Anticoagulation with vitamin K antagonists or factor Xa inhibitors is not allowed. 
Anticoagulation with subcutaneous heparin is allowed. Equivocal cases should be 
discussed with the sponsor prior to study entry. 
 
24. Systemic anticancer therapy and chemotherapy within 4 weeks prior to planned first 
dose (6 weeks for mitomycin C or nitrosoureas). Prior targeted or endocrine therapy 
require an interval of 2 weeks or 5 half-lives (whichever is shorter) prior to planned 
first dose. If the last immediate anticancer treatment contained an antibody-based 
agent(s) (approved or investigational), then an interval of 4 weeks or 5 half-lives 
(whichever is shorter) of the agent(s) prior to receiving the study intervention 
treatment is required. With last prior anti-PDx therapy, the washout period may be 
extended based on emerging clinical data. 
 
Blood Product Support: 
 
25. Recent transfusion of RBCs or platelets within 4 weeks prior may be exclusionary. 
Discuss with the sponsor if participant had recent transfusion(s). 
 
Prior/Concurrent Clinical Study Experience: 
 
26. Participation in other studies involving investigational drug(s) within 4 weeks or 
5 half-lives prior to planned first dose. A participant may be eligible if a long-term 
follow-up from prior investigational studies has been met. Cases must be discussed 
with sponsor’s medical monitor to judge eligibility. 
 
Diagnostic Assessments: 
 
27. Serum pregnancy test (for females of childbearing potential) positive at screening. 
 
28. Participants with active, uncontrolled bacterial, fungal, or viral infection, including 
(but not limited to) HBV, HCV, and known HIV or AIDS-related illness. 
 
a. COVID-19/SARS-CoV2 (Participants enrolled in Part 1A, Part 1B and Part 2): 
This protocol excludes participants with active infections, as noted above. While 
SARS-CoV2 testing is not mandated for entry into this protocol, testing should 
follow local clinical practice standards. If a participant has a positive test result 
indicating active SARS-CoV2 infection, is known to have active asymptomatic 
infection or is suspected of having active SARS-CoV2, he/she is excluded. 
Participants with a prior positive test who subsequently test negative may be 
eligible with prior sponsor approval. 

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b. HIV (Participants enrolled in Part 2 Only): In equivocal cases, participants whose 
viral load is negative may be eligible. HIV seropositive participants who are 
otherwise healthy and at low risk for AIDS-related outcomes may qualify for 
inclusion in the study after discussion with the sponsor, but AIDS is exclusionary. 
The following criteria for immune status and HIV ongoing therapy must be met 
for a HIV seropositive participant to be eligible for the study: 
 
• Immune status criteria: 
• CD4+ T-cell counts ≥500 cells/μL at the study start; 
• No history of AIDS-defining opportunistic infections; 
• In general, patients should be eligible if they have not had an opportunistic 
infection within the past 12 months. 
 
• Ongoing HIV therapy criteria: 
• Must be receiving recommended concurrent ART treatment according to 
the guidelines (AIDSinfo, 2020); 
 
• 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). 
 
c. HBV/HCV: Relevant laboratory tests should be performed at screening and added 
to the table in Appendix 2 Clinical Laboratory Tests. Refer to CDC website 
(https://www.cdc.gov/hepatitis/index.htm) for further details. 
 
• Participants enrolled in Part 1A and Part 1B – History of chronic hepatitis as 
evidenced by the following: Any positive test results for hepatitis B virus or 
hepatitis C virus indicating presence of virus (eg, hepatitis B surface antigen 
positive), or hepatitis C antibody positive (except if hepatitis C ribonucleic 
acid [RNA] negative). 
 
• HBV (Participants enrolled in Part 2 Only): 
• This criterion excludes participants with a positive HBsAg (ie, either acute 
or chronic active hepatitis). 
 
• However, participants with HBV antibody positivity indicating immunity, 
either due to vaccination or prior natural infection, are eligible. 

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• Participants with positive anti-HBcAb but negative HBsAg and anti- 
HBsAb profile may, depending on clinical circumstances, be eligible. 
Discussion with the sponsor is indicated. 
 
• HCV (Participants enrolled in Part 2 only): 
• Positive HCV antibody is indicative of infection but may not necessarily 
render a potential candidate ineligible, depending on clinical 
circumstances. 
 
29. Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may 
affect participant safety or interpretation of study results (eg, baseline QTc interval 
>470 msec, complete LBBB, signs of an acute or indeterminate age myocardial 
infarction, ST T interval changes suggestive of active myocardial ischemia, second 
or third degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If the 
baseline uncorrected QT interval is >470 msec, this interval should be rate corrected 
using the Fridericia method and the resulting QTcF should be used for decision 
making and reporting. If QTc exceeds 470 msec, or QRS exceeds 120 msec, the ECG 
should be repeated 2 more times and the average of the 3 QTc or QRS values should 
be used to determine the participant’s eligibility. Computer interpreted ECGs should 
be overread by a physician experienced in reading ECGs before excluding 
participants. Cases must be discussed in detail with sponsor’s medical monitor to 
judge eligibility. 
 
30. Participants with an LVEF <50% by echocardiogram or MUGA. 
 
31. Participants whose baseline pulse oximetry ≤ 92% “on Room air”. 
 
Other Exclusions: 
 
32. Investigator site staff or Pfizer employees directly involved in the conduct of the 
study, site staff otherwise supervised by the investigator, and their respective family 
members. 
 
5.3. Lifestyle Considerations 
5.3.1. Contraception 
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 
Appendix 4) and will confirm that the participant has been instructed in its consistent and 
correct use. At time points indicated in the schedule of activities (SoA), the investigator or 
designee will inform the participant of the need to use highly effective contraception 
consistently and correctly and document the conversation and the participant’s affirmation in 
the participant’s chart (participants need to affirm their consistent and correct use of at least 1 
of the selected methods of contraception) considering that their risk for pregnancy may have 

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changed since the last visit. 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. 
 
Shedding From Sperm or Vaginal Secretion 
 
Participants and/or sexual partners must practice sexual abstinence or use of condoms due to 
possible viral shedding from sperm or vaginal secretion. Please refer to Section 10.4. 
 
5.3.2. Accidental Exposures and Viral Shedding Considerations 
Guidelines for preventive/containment measures to limit spread of the shed product beyond 
the treated individual to minimize exposure of third parties are provided, as accidental 
exposure may lead to transmission of vaccinia virus and infection. In most cases, the 
potential for transmission to untreated individuals is extremely low when the oncolytic 
product is shed because of the derivation methods and modifications that are designed to 
attenuate the product when compared to the parent strain of virus (FDA Guidance for 
Industry – Design and Analysis of Shedding Studies for Virus or Bacteria-Based Gene 
Therapy and Oncolytic Products (p.16) August 2015). As peak shedding occurs soon after 
treatment when the participant is monitored in a health-care setting, the possibility of 
transmission is mainly confined to HCPs within the clinical site such as the pharmacist or 
nursing staff handling the drug, and to a lesser extent, individuals that come into close 
contact with the participant. A second peak of shedding in the days following discharge of a 
participant from a health care setting in not expected, therefore there is limited possibility of 
transmission to contacts beyond the health care and home setting. 
 
Treated participants should avoid touching or scratching infusion sites, spontaneous lesions, 
or their occlusive dressings, as doing so could lead to inadvertent transfer of PF-07263689 to 
other areas of the body. 
 
HCPs, participant close contacts (household members, caregivers, sex partners, or perhaps 
sharing the same bed), pregnant women, newborns and neonates, elderly, and 
immunocompromised contacts should avoid direct contact with infusion site, dressings, or 
body fluids of treated patients. Caregivers should wear protective gloves when applying or 
changing occlusive dressings and observe safety precautions for disposal of used dressings, 
gloves, and cleaning materials. 
 
In the event of an accidental exposure to PF-07263689 by needle stick, exposed individuals 
should clean the affected area thoroughly with soap and water and/or a disinfectant, 
following local institutional biosafety guidelines and procedures, such as cover the site of 
skin puncture with occlusive dressing along with dressing change at least twice a day, obtain 
blood test for measuring vaccinia virus titer level, and contact the Principal Investigator, the 
institution’s Biosafety Specialists, and/or physician knowledgeable in the care of individuals 
experienced with vaccinia infection. If signs or symptoms of pox infection develop, apply 
topical anti-viral therapy (ie, ganciclovir), cover the lesion with occlusive dressing along with 
dressing change at least to match timing of topical anti-viral application, and contact 

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appropriate investigator for medical advice. Systemic toxicity from accidental needle stick is 
expected to be low due to the likely minimal exposure to the attenuated oncolytic vaccinia 
virus product in situations of a needle stick. Signs of systemic toxicity may include but are 
not limited to fever, regional lymphadenopathy, remote skin lesions. Accidental needle stick 
in HCPs and other accidental exposures during drug preparation and administration of PF- 
07263689 should be reported according to Section 8.3.5.3. 
 
Shedding via Direct Contact or Respiratory Route 
 
Appropriate infection control measures should be implemented to minimize the 
environmental risk, eg: 
 
• Recommendations of good hygiene practices to participants/caregivers: 
o Cover mouth and nose while coughing or sneezing with a single-use tissue and 
dispose dirty tissues after use; 
o Frequent washing of hands with soap and water or use of alcohol-based products. 
• Clothes, household linens, including cleaning cloths, should be washed at least at 60°C 
on a regular basis. The home should be cleaned regularly with standard household 
cleaners. 
• Measures of social distancing should be considered, in particular with regard to 
immunocompromised persons or vulnerable populations (avoid touching, kissing or 
hugging, avoid sharing of eating utensils or drinking glasses). 
• Participants with respiratory symptoms (e.g. running nose, coughing) should avoid 
crowded or poorly ventilated public places and, where applicable, avoid contact to 
susceptible animals or pets. 
Shedding From Urine/Stools 
 
Instructions on hygiene procedures should be provided to participants/caregivers (eg, hand 
washing, cleaning of surfaces that were in contact with bodily fluids, use of separate toilet (if 
possible), adding bleach or equivalent products to toilet after each use, no sharing of towels). 
 
Shedding From Saliva 
 
Participants should minimize exposure to others by refraining from kissing, sharing of eating 
utensils or drinking glasses. 
 
5.3.2.1. Contacts Exhibiting Symptoms of Viral Infections 
If a contact of a participant treated with PF-07263689 report symptoms of a possible 
PF-07263689 related toxicity: 
 
1. Immediately notify the institution’s Biosafety Specialist as applicable 

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Study Interventions(s) 
Intervention Name 
ARM Name 
(group of patients 
receiving a specific 
treatment (or no 
treatment) 
Type 
Dose Formulation 
PF-07263689 
All 
Sasanlimab 
Part 1B and Part 2 
Biologic 
CCI 
Biologic 
Unit Dose Strength(s) 
CCI 
2. The individual should be referred to and medically monitored by a physician 
knowledgeable in the care and treatment of patients with vaccinia infections 
 
3. Report the event to Pfizer Safety within 24 hours of the investigator’s awareness by 
completing and submitting a CT SAE Report Form (refer to Section 8.3) regardless of 
whether there is an associated SAE. Follow all instructions on the form regarding 
avoidance of excluded individuals, considerations (in conjunctions with consultation 
with infectious disease expert and the Sponsor) of antiviral treatment if warranted 
(refer to Section 6.8.1), obtaining clinical samples if applicable according to local 
guidelines, monitoring the individual for response to treatment (if any), and resolution 
of symptoms. 
 
5.4. Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently enrolled in the study. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants to meet the CONSORT 
publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details, eligibility criteria, and any SAE. 
 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened, up to a limit of 2 times. Rescreened participants should be assigned a new 
participant number as for the initial screening. 
 
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, medical device(s), or study procedure(s) intended to be administered to a study 
participant according to the study protocol. 
 
For the purposes of this protocol, study intervention refers to PF-07263689 and sasanlimab. 
 
6.1. Study Intervention(s) Administered 
 

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Study Interventions(s) 
(vial is labeled and dosed with the batch- 
specific measured release concentration) 
Dosage Level(s) 
Q1W for 4 weeks 
300 mg Q4W 
Route of Administration 
IV push 
Subcutaneous 
Use 
Experimental 
Experimental 
IMP or NIMP 
IMP 
IMP 
Sourcing 
Provided centrally by the sponsor 
(manufactured by Pfizer). 
Refer to the IP Manual. 
Provided centrally by the sponsor 
(manufactured by Pfizer). 
Refer to the IP Manual. 
Packaging and Labeling 
Study intervention will be provided in 
vials. Each vial will be labeled as 
required per country requirement. 
Study intervention will be provided 
in vials for 300 mg dose . Each 
prefilled syringe or vials will be 
labeled as required per country 
requirement. 
Current/Former 
Name(s) or Alias(es) 
PF-07263689, OBIR-2, VV110 
Sasanlimab, PF-06801591, RN888 
 
 
6.1.1. Administration 
No premedication will be administered with the first dose. Based on emerging data, 
premedication may be permitted for subsequent doses for all participants, consistent with 
institutional guidelines, and may include an antihistamine, anti-inflammatory agent, or pain 
reliever. Oral or parenteral steroids are not allowed during PF-07263689 treatment period, 
and for 1 week prior to and 2 weeks after PF-07263689 treatment. Please refer to Section 6.8 
regarding concomitant therapy. 
 
A cycle is defined as 28 days, regardless of missed doses or dose delays. 
 
6.1.1.1. PF-07263689 
PF-07263689 will be administered once weekly for 4 weeks as an IV push without 
adjustment for body size at every cycle. The infusion will occur over 10 minutes (for IV 
push) or up to 20 minutes (for syringe pump). Since PF-07263689 will be given every week 
for 4 weeks, no dose modifications are allowed in this study. If participants do not complete 
at least 3 of 4 scheduled doses of PF-07263689 due to toxicity related to study drug, then 
study treatment should be permanently discontinued. If an infusion cannot be completed 
within the time specified, the participant will be discontinued from study treatment and may 
be replaced. 
 
Study staff should refer to the IP Manual for specific instructions on the handling and 
preparation of the study intervention. 
 
Participants will be admitted for inpatient monitoring (per local standard of practice) during 
and for CCI 
 following the first dose of PF-07263689 and CCI 
 
following the second dose of PF-07263689 for monitoring. Hospitalization period may be 
extended if the participant experiences abnormal laboratory findings or ongoing AEs that 

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require further hospitalization. For Day 15 and Day 22, participants will remain at the clinical 
site for up to 4 hours for observation and for labs. Additional monitoring may be required 
based on individual toxicities. 
 
6.1.1.2. Sasanlimab 
Sasanlimab will be administered at a fixed dose of 300 mg SC Q4W starting on Day 1. 
Sasanlimab must be administered after PF-07263689 on Cycle 1 Day 1. 
 
Injections to the abdomen are preferred. If SC injections in the abdominal location are not 
possible, SC injections can be administered in a distributed manner in the thighs. SC 
injections in the upper extremities (eg, deltoid, upper and lower arm) are not permitted. The 
maximum number of injections per participant CCI 
. Refer to Appendix 13 for 
details on administration of multiple injections to the abdomen. 
 
Study staff should refer to the IP Manual for specific instructions on the handling and 
preparation of the study intervention. 
 
A cycle is defined as the time from Day 1 dose to the next Day 1 dose. Participants will 
receive a single dose of sasanlimab on Day 1 of each cycle. A cycle will be 28 days (±2 days) 
for SC administration. Each participant may receive sasanlimab until completion of study 
treatment, progression of disease, unacceptable toxicity, withdrawal of consent, participant 
no longer willing to participate in study, end of study, or study termination. 
 
6.1.2. Order of Administration (Part 1B and Part 2) 
On the days of scheduled administration of both PF-07263689 and sasanlimab, PF-07263689 
IV push should be administered first, followed by SC injection of sasanlimab. Please refer to 
the IP Manual for specific instructions. 
 
6.2. Preparation, Handling, Storage and Accountability 
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study interventions received and any 
discrepancies are reported and resolved before use of the study intervention. 
 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study 
interventions must be stored in a secure, environmentally controlled, and monitored 
(manual or automated recording) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff. At a 
minimum, daily minimum and maximum temperatures for all site storage locations 
must be documented and available upon request. Data for nonworking days must 
indicate the minimum and maximum temperatures since previously documented for 
all site storage locations upon return to business. 

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3. Any excursions from the study intervention label storage conditions should be 
reported to Pfizer upon discovery along with any actions taken. The site should 
actively pursue options for returning the study intervention to the storage conditions 
described in the labeling, as soon as possible. Once an excursion is identified, the 
study intervention must be quarantined and not used until Pfizer provides permission 
to use the study intervention. Specific details regarding the definition of an excursion 
and information the site should report for each excursion will be provided to the site 
in the IP manual. 
 
4. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the label. 
 
5. Study interventions should be stored in their original containers. 
 
6. See the IP manual for storage conditions of the study intervention once reconstituted 
and/or diluted. 
 
7. The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record 
maintenance (ie, receipt, reconciliation, and final disposition records), such as the 
IPAL or sponsor-approved equivalent. All study interventions will be accounted for 
using a study intervention accountability form/record. 
 
8. Further guidance and information for the final disposition of unused study 
interventions are provided in the IP manual. All destruction must be adequately 
documented. 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. 
 
Upon identification of a product complaint, notify the sponsor within 1 business day of 
discovery as described in the IP manual. 
 
6.2.1. Preparation and Dispensing 
See the IP manual for instructions on how to prepare each study intervention for 
administration. Study intervention 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. A second staff member will verify the dispensing. 
 
Vials are for single-use only. 
 
Preparation of PF-07263689 will be carried out in accordance with local regulatory 
requirements for Biosafety/Containment level (Level 1 or Level 2 depending on countries) in 
pharmacy or laboratory, according to site’s SOPs and all applicable laws and regulations. 

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CCI 
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. 
 
6.2.2. Additional Instructions for PF-07263689 
6.2.2.1. Special Handling of PF-07263689 
Depending on the country, 
All applicable infection control policies should be consulted 
and followed. Refer to the current PF-07263689 IB and PF-07263689 Safety Data Sheet for 
recommendations on handling PF-07263689. 
 
For more information regarding biohazard risk group classification and biohazard safety 
levels see The NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic 
Acid Molecules (NIH Guidelines), April 2019: https://osp.od.nih.gov/biotechnology/nih- 
guidelines/ and CDC Biosafety in Microbiological and Biomedical Laboratories (BMBL) 6th 
Edition: https://www.cdc.gov/labs/pdf/SF  19_308133-A_BMBL6_00-BOOK-WEB-final- 
3.pdf or https://www.cdc.gov/labs/BMBL.html. 
 
6.2.2.2. Transport of PF-07263689 
6.2.2.2.1. Interstate Transport 
PF-07263689 will be shipped interstate as a “Biological Substance, Category B” in 
compliance with International Air Transportation Association and Department of 
Transportation regulations and other local regulations. 
 
6.2.2.2.2. Transport within the Clinic 
PF-07263689 should be transported within a sealed plastic transport bag or other sealed, 
leak-proof secondary container displaying a clearly marked biohazard symbol. Refer to the 
IP manual for further instructions. 
 
6.2.2.3. Handling and Thawing 
BSL-2 infection control policies should be utilized for preparation, transport, and disposal of 
PF-07263689. Appropriate gowns, gloves, safety glasses with side shields or face shields 
should be worn at all times during handling. Refer to the IP manual for detailed instructions 
about preparation and storage of the investigational product. 
 
6.2.2.4. Cleaning/Disinfection and Disposal 
Standard institutional policies should be followed for cleaning and decontamination while 
handling vaccinia virus-based products. Hospital-grade chemical disinfectants containing 
bleach (with at least 0.6% of active chlorine), alcohols (≥60%), aldehydes, hydrogen 
peroxide (3%), iodophor (75 ppm), phenols or quaternary ammonium compounds are 
adequate for routine cleaning and disinfection of work area after PF-07263689 handling. The 

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manufacturer’s instructions should be followed to ensure adequate contact time and confirm 
the ability of the equipment to withstand the disinfectant used. 
 
All contaminated material (eg, syringes, catheters, needles, tubing, gloves, used or unused 
vials, containers, bandages, etc.) should be disposed of in a clearly-marked biomedical waste 
container and discarded according to regular institution procedure for infections waste ie, 
autoclaving, incineration, or treatment with sodium hypochlorite solution. Biomedical waste 
will not be left unattended in a public area; autoclaved medical waste must not be disposed of 
as regular trash. 
 
Textiles and fabrics can be laundered in hot water (71°F) with detergent and hot air drying. 
 
6.2.2.5. Spills or Environmental Contamination 
In the event of a spill, people in the immediate area will be alerted and other institutional 
personnel will be notified as required by institutional policies. Refer to PF-07263689 IB and 
Safety Data Sheet, for detailed instructions. 
 
Spills and accidents that result in overt exposures to infectious material will be reported 
according to Section 8.3.4 and as required by local institutional policies. 
 
6.3. Measures to Minimize Bias: Randomization and Blinding 
This is an open-label study. 
 
6.3.1. Allocation to Study Intervention 
This is an open-label study that will not be randomized. The investigator’s knowledge of the 
treatment should not influence the decision to enroll a particular participant or affect the 
order in which participants are enrolled. 
 
Study intervention will be dispensed at the study visits summarized in the SoA. 
Returned study intervention must not be redispensed to the participants. 
Allocation of participants to treatment groups in Part 2 will proceed through the use of an 
IRT system (IWR). The site personnel (study coordinator or specified designee) will be 
required to enter or select information including but not limited to the user’s ID and 
password, the protocol number, and the participant number. The site personnel will then be 
provided with a treatment assignment, randomization number, and DU or container number 
when study intervention is being supplied via the IRT system. The IRT system will provide a 
confirmation report containing the participant number, randomization number, and DU or 
container number assigned. The confirmation report must be stored in the site’s files. 
 
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system. 

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6.4. Study Intervention Compliance 
When participants are dosed at the site, they will receive study intervention directly from the 
investigator or designee, under medical supervision. The date and time of each dose 
administered in the clinic will be recorded in the source documents and recorded in the CRF. 
The dose of study intervention and study participant identification will be confirmed at the 
time of dosing by a member of the study site staff other than the person administering the 
study intervention. 
 
The site will complete the required dosage Preparation Record located in the IP 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 sponsor and/or designee. 
 
6.5. Dose Modification 
Every effort should be made to administer study intervention on the planned dose and 
schedule. Dose modification is limited to interruption or skipping a dose based on outlined 
criteria (see Section 6.5.1 and Section 6.5.2). No dose reductions are allowed. In the event of 
significant toxicity, dosing may be delayed as described below. In the event of multiple 
toxicities, dose modification should be based on the worst toxicity observed and attribution 
for the combination treatment (for combination therapy). Participants are to be instructed to 
notify investigators at the first occurrence of any adverse symptom. In addition to dose 
interruption or skipping a dose, investigators are encouraged to employ best supportive care 
according to local institutional clinical practices. 
 
Selected toxicities that do not resolve or worsen following supportive care and dose 
modifications and with a clinical presentation consistent with a potential irAE without a clear 
alternative explanation, may require treatment with corticosteroids or other 
immunosuppressants and should be managed according to the management of irAEs as 
described in Appendix 3. 
 
6.5.1. PF-07263689 
No dose reductions or delays are permitted. PF-07263689 must be administered ± 1 day of 
the scheduled dose. There are no planned delays outside of this window. If for any reason 
PF-07263689 is not given within the allowed treatment window, it will be cancelled. If 
participants do not complete at least 3 of 4 scheduled doses of PF-07263689 due to toxicity 
related to study drug, then study treatment should be permanently discontinued. 
6.5.2. Sasanlimab 
No dose reductions are permitted, but the next dosing of sasanlimab may be delayed or 
skipped for the cycle based on persisting toxicity (see Table 7). 

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Dose modifications may occur in one of 2 ways: 
 
• Within a cycle: dosing interruption until adequate recovery, 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. 
 
Events including, but not limited to, pneumonitis, colitis, creatinine and LFT elevation 
should be monitored carefully with this class of agents. 
 
Table 7. 
Sasanlimab Recommended Treatment Modifications for Drug-Related 
Toxicity (Excluding irAEs) 
 
Hematologic toxicities 
Grade 1 and Grade 2 
• 
Continue as per schedule. 
• 
Anemia Grade ≥3 
(hemoglobin <8 g/dL) 
• 
Hold sasanlimab and monitor weekly until resolution to Grade ≤1 or baseline. 
• 
Resume sasanlimab at the next scheduled dose after recovery to Grade ≤1 or 
baseline. 
• 
Permanently discontinue sasanlimab if anemia does not resolve to Grade ≤1 or 
baseline within 12 weeks or if the same Grade 3 toxicity recurs. 
• 
Neutropenia Grade ≥3 
(ANC <1000/µL) 
• 
Hold sasanlimab and monitor weekly until resolution to Grade ≤1 or baseline. 
• 
Resume sasanlimab at the next scheduled dose after recovery to Grade ≤1 or 
baseline. 
• 
Permanently discontinue sasanlimab if neutropenia does not resolve to Grade ≤1 
or baseline within 12 weeks or if the same Grade 3 toxicity recurs. 
• 
Thrombocytopenia 
Grade ≥3 (platelets 
<50,000/µL) 
• 
Hold sasanlimab and monitor weekly until resolution to Grade ≤1 or baseline. 
• 
Resume sasanlimab at the next scheduled dose after recovery to Grade ≤1 or 
baseline. 
• 
Permanently discontinue sasanlimab if thrombocytopenia does not resolve to 
Grade ≤1 or baseline within 12 weeks or if the same Grade 3 toxicity recurs. 
Non-hematologic toxicities 
Grade 1 and Grade 2 
• 
Continue as per schedule. 

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Table 7. 
Sasanlimab Recommended Treatment Modifications for Drug-Related 
Toxicity (Excluding irAEs) 
 
Grade 3 
• 
Hold sasanlimab. 
• 
Resume sasanlimab at the next scheduled dose after recovery to Grade ≤1 or 
baseline. 
• 
Permanently discontinue if toxicity does not resolve to Grade ≤1 or baseline 
within 12 weeks or if the same Grade 3 toxicity recurs. 
• 
Exceptions are: laboratory values that do not have any clinical correlate. 
• 
For suspected immune-related toxicity follow guidance in Appendix 3. 
Grade 4 
• 
Permanently discontinue sasanlimab. 
• 
Exceptions are: laboratory values that do not have any clinical correlate. 
• 
For suspected immune-related toxicity follow guidance in Appendix 3. 
 
To facilitate the early recognition and prompt intervention in the event of clinically 
meaningful sasanlimab-related AEs, management algorithms have been developed for 
suspected pulmonary, GI, liver, endocrine, skin, neurological and renal toxicities (see 
Appendix 3). 
 
6.6. Continued Access to Study Intervention After the End of the Study 
As this is a FIH clinical study, no post-trial study intervention is currently planned to be 
provided to study participants at the end of the study. Depending on the overall development 
path, the sponsor will make an effort to provide post-trial study intervention to appropriate 
participants who are tolerating treatment and continuing to experience clinical benefit. 
 
6.7. Treatment of Overdose 
For this study, any dose of PF-07263689 or sasanlimab greater than the assigned dose level at 
any scheduled administration visit will be considered an overdose. 
 
Sponsor does not recommend specific treatment for an overdose. 
 
In the event of an overdose, the investigator/treating physician should: 
 
1. Contact the sponsor’s medical monitor within 24 hours. 
 
2. Closely monitor the participant for any AEs/SAEs and laboratory abnormalities for at 
least 6 months after the overdose of study intervention (whichever is longer). 

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3. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF. 
 
4. Overdose is reportable to Pfizer Safety only when associated with an SAE. 
 
5. Obtain a blood sample for PK analysis with clear documentation of the time it is 
collected relative to the date of the last dose of study intervention if requested by the 
sponsor’s medical monitor (determined on a case-by-case basis). 
 
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant. 
 
6.8. Concomitant Therapy 
All prior and concomitant treatments, received by participants from screening and up to 
30 days after the last dose of study treatment, or up to the start of new anti-cancer therapy, 
including supportive care drugs (eg, anti-emetic treatment and prophylaxis), drugs used to 
treat AEs or chronic diseases, and non-drug supportive interventions (eg, transfusions) will 
be recorded on the CRF. Concomitant medications for AEs and SAEs should follow 
respective guidance for the AE and SAE reporting period. Only subsequent anti-cancer 
therapy initiated after end of study treatment(s) will be reported at the follow-up visits. 
 
Hormonal contraceptives that meet the requirements of this study are allowed to be used in 
participants who are WOCBP (see Appendix 4). 
 
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 EOT visit will be recorded on the CRF. 
 
Prohibited therapies and concomitant therapy instructions during the study are listed in this 
section and in the sub-study appendices. If there is a clinical indication for 1 of the 
medications specifically prohibited during the study, discontinuation from the study 
treatment may be required. Participants may receive other medications that the investigator 
deems to be medically necessary. The final decision on any supportive therapy rests with the 
Investigator and/or the participant’s primary physician. The decision to continue the 
participant in the study requires mutual agreement of the investigator, the sponsor and the 
participant. 
 
Any questions regarding administration of concomitant medications should be directed to the 
sponsor. 

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6.8.1. Other Prohibited and/or Limited use of Anti-tumor/Anti-Cancer or Experimental 
Drugs, or Procedures 
No additional anti-tumor treatment will be permitted while participants are receiving study 
treatment. Additionally, the concurrent use of select vitamins or herbal supplements for an 
anticancer treatment is not permitted. 
 
In view of the current lack of data about the interaction of PF-07263689 with radiotherapy, 
palliative radiotherapy on study is permitted for the treatment of painful bony lesions 
provided that 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. 
Palliative radiotherapy should be delayed until completion of PF-07263689 treatment. 
 
6.8.2. Agents with Potential Inhibitory Activity Against Vaccinia Viruses 
In the extremely unlikely case of generalized vaccinia virus infection, encephalitis or another 
clinically-significant, progressive toxicity that, in the opinion of the Investigator could be 
related to PF-0726389 replication. Investigators may consider the use of agents with vaccinia 
inhibitory activity, if available in their country for such clinical use. Such agents may 
include anti-vaccinia immune globulin (VIG), cidofovir, and/or Arestvyr. In addition, based 
on limited preclinical data, interferon, ribavirin, ganciclovir, and sorafenib may have anti- 
vaccinia activity. 
 
None of these agents have been used or approved for this purpose to date. Since these agents 
have not been used in PF-07263689 treated participant, clinical judgement should be used 
when determining optimal regiment and duration of treatment. 
 
The availability of these or similar antiviral products is country-dependent; options will be 
investigated and a plan for response to infection-related toxicities will be documented and 
communicated to study staff prior to initiation of the clinical trial. 
 
6.8.3. Supportive Care 
Palliative and supportive care for disease related symptoms may be administered at the 
investigator’s discretion and according to the specific supportive care product Prescribing 
Information or the current ASCO guidelines (Schiffer et al, 2018). 
 
6.8.3.1. Supportive Care for Superficial Skin Lesion(s) 
A small (< 1 cm) superficial skin or oral mucous membrane lesion containing PF-07263689 
may develop after PF-07263689 treatment. If lesions develop, they do so typically within 1 
week after the first administration. These lesions generally resolve within approximately the 
following 2-3 weeks, a time course that is consistent with the usual course following 
intentional vaccination with non-attenuated vaccinia vaccine. Lesions may resolve without 
complications or the need for specific anti-viral treatment. 

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Participants will be recommended to treat any skin pox lesion(s) possibly related to virus 
with topical acyclovir/ganciclovir 5% six times per day for at least 7 days until lesion(s) have 
disappeared, and cover the lesion(s) with occlusive dressing or bandage. 
 
6.8.3.2. Supportive Care for Infusion Related Reactions 
In the event of infusion-related reactions, Investigators should institute treatment measures 
according to best medical and nursing practice. 
 
If chills and fever (>100.4°F/38.0°C) or hypotension occur, the infusion should be 
interrupted. Participants should be treated symptomatically according to best medical and 
nursing practice and the infusion should be restarted at 50% of the original rate. 
 
If infusion reactions, characterized by fever and chills, and less commonly hypotension, are 
experienced either by an individual participant or in other participants, pretreatment 
medication may be administered prior to subsequent doses to reduce the incidence and 
severity. The following pretreatment regimen is suggested, although a different regimen 
based on local standard of care is permitted: 
 
• Participants should be pretreated with acetaminophen and diphenhydramine (or other 
antihistamine) approximately 0.5 to 2 hours before each study drug administration. 
Pretreatment medications will not be supplied by Pfizer. Suggested starting doses are 
650 to 1000 mg acetaminophen and 50 mg diphenhydramine (or equivalent of other 
antihistamine) IV or oral. Two (2) additional doses of acetaminophen may be 
administered approximately every 4 to 6 hours after the initial pretreatment or as 
needed. 
 
6.8.3.3. Supportive Care for CRS 
Symptoms associated with CRS vary greatly and may be difficult to distinguish from other 
conditions. The more common symptoms include fever, nausea, headache, tachycardia, 
hypotension, rash, and shortness of breath. The severity of symptoms can be mild to 
life-threatening and thus there should be a high suspicion for CRS if these symptoms occur. 
The severity of CRS will be assessed according to the ASTCT modified grading (Lee et al, 
2019). A suggested treatment algorithm for the management of CRS is provided in 
Appendix 11; however, if local standard of care is a different regimen, this should be utilized. 
 
Depending upon study findings, a decision might be made to incorporate pre medication 
(ie, corticosteroids and other anti-inflammatory agents) for CRS prophylaxis in study 
participants. This decision would only occur following discussions between the sponsor and 
the investigators. Any pretreatment medication will not be supplied by Pfizer. 

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Potential medications to use in the supportive care of CRS, including active therapy and 
possibly prophylactic use, include these agents combined in a single regimen: 
 
• Acetaminophen 650 mg PO 
• Diphenhydramine 25 mg PO or IV 
• Dexamethasone 20 mg PO or IV 
• Corticosteroids (refer to Section 6.8.6) 
In cases of suspected CRS, additional unscheduled blood samples will be collected for 
cytokine release assay analysis at the time of the event and every 2 to 3 days after at the 
discretion of the investigator (if there are no collections normally scheduled). 
 
6.8.3.4. Supportive Care for Hypersensitivity Reactions Types 1 and 3 
Type 1 hypersensitivity or allergic (eg, shortness of breath, urticaria, anaphylaxis, 
angioedema) reactions are theoretically possible in response to any injected protein. Immune 
complex mediated Type 3 hypersensitivity reactions are similar to the AEs of Type 1 
reactions but are likely to be delayed from the time of infusion and may include symptoms 
such as rash, urticaria, polyarthritis, myalgia, polysynovitis, fever, and, if severe, 
glomerulonephritis. 
 
All participants should be closely observed while receiving study intervention infusions and 
monitoring for clinical signs of a systemic reaction will continue thereafter for clinical signs 
of allergic reactions/hypersensitivity. 
 
In the case of a hypersensitivity reaction, the participant will be treated symptomatically with 
supportive care, further monitoring, and treatment with anti-histamines and/or 
corticosteroids. Study infusions may be stopped and the participant will be followed until the 
end of the study. 
 
Detailed guidance on treatment, dose interruptions and potential retreatment is provided in 
Section 6.5. 
 
6.8.3.5. Supportive Care for Immune-Related Adverse Events 
While theoretically any immune checkpoint–blockade toxicity can occur at any time, certain 
toxicities have been reported earlier in the treatment course, while others develop as later 
complications. Commonly encountered irAEs include rash/dermatitis, diarrhea/colitis, 
hepatitis, and endocrinopathies. Algorithms for the clinical management of these events are 
provided in Section 10.3.5. 
 
Prior to administration of the next dose of sasanlimab, the investigator should perform a 
comprehensive review of systems with specific focus on common and serious toxicities, such 
as skin changes, diarrhea and abdominal pain, headache, fever, shortness of breath, cough, 

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and neurologic changes. Routine laboratory testing, including hematologic profile, 
comprehensive metabolic panel, and TSH level, should be reviewed. Any new symptoms or 
abnormalities in examination or laboratory test results should be evaluated prior to 
administration of the next dose of sasanlimab. 
 
6.8.4. Hematopoietic Growth Factors 
Primary prophylactic use of colony stimulating factors is not permitted during the first 
14 days of Cycle 1 Part 1, but they may be used to treat treatment emergent neutropenia as 
indicated by the current ASCO guidelines (Schiffer et al, 2018). During the screening 
window, granulocyte colony stimulating factors are not permitted to qualify a participant 
with low WBC counts. 
 
Erythropoietin may be used at the investigator’s discretion for the supportive treatment of 
anemia. Erythropoietin is not approved in some countries for anemia caused by cancer 
treatment. 
 
6.8.5. Antidiarrheal, Antiemetic Therapy 
Primary prophylaxis beyond the first cycle is at the investigator’s discretion. The choice of 
the prophylactic drug as well as the duration of treatment is up to the investigator with 
sponsor approval assuming there is no known or expected drug-drug interaction and 
assuming the drug is not included in the Concomitant Therapy section (Section 6.8). 
 
6.8.6. Corticosteroids 
Oral or parenteral steroids are not permitted during PF-07263689 treatment period, and for 1 
week prior to and 2 weeks after PF-07263689 treatment. Chronic systemic corticosteroid use 
(prednisone >10 mg/day or equivalents) for palliative or supportive purposes is not 
permitted. Acute emergency administration, topical applications, inhaled sprays, eye drops, 
or local injections of corticosteroids are allowed. 
 
If immune-related AEs occur, immune suppressive treatment should be administered 
according to local standards or practice. 
 
The use of steroids during this study is restricted as follows: 
 
a) Therapeutic use: for the treatment of infusion-related reactions and short-term 
treatment of irAEs, steroids are permitted according to the modalities indicated in the 
respective sub-study appendices. 
 
b) Physiologic use: replacement for adrenal insufficiency at doses equivalent to ≤10 mg 
prednisone daily is acceptable. 
 
c) Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular 
injection) are permitted. 
 
Any other use of corticosteroids should be discussed with the sponsor before implementation. 

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6.8.7. 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 Therapy section (Section 6.8). 
 
6.8.8. Vaccines Administration 
No vaccines (licensed or investigational) other than study vaccine, influenza, and 
pneumococcal vaccines should be given during the study. Other vaccines may be 
administered only if medically necessary (eg, tetanus post exposure prophylaxis). COVID-19 
vaccine should not be administered during the first 28 days of treatment (Cycle 1). 
 
For participants who receive sasanlimab, live attenuated vaccines should not be administered 
within 30 days prior to or after dosing with sasanlimab. The administration of inactivated 
vaccines are allowed. 
 
6.8.9. Surgery 
Caution is advised for any surgical procedures during the study. The appropriate interval of 
time between surgery and PF-07263689 and sasanlimab required to minimize the risk of 
impaired wound healing and bleeding has not been determined. Stopping study intervention 
is recommended at least 7 days prior to surgery. Postoperatively, the decision to reinitiate 
study intervention treatment should be based on a clinical assessment of satisfactory wound 
healing and recovery from surgery 
 
6.8.10. Radiation Therapy 
Palliative radiotherapy to a limited field but not to a target lesion(s) is allowed after 
consultation with the sponsor’s medical monitor during study participation, unless clearly 
indicative of disease progression. Due to lack of data regarding the interaction of 
PF‑07263689 with radiotherapy, PF-07263689 should be interrupted 7 days prior to the start 
of radiotherapy and resumed after the participant has returned to baseline. If the effects of 
palliative radiotherapy cannot be distinguished from the effects of PF-07263689 on antitumor 
efficacy, response assessments should be considered as non-evaluable. 
 
6.8.11. Rescue Medicine 
Standard medical supportive care must be provided to manage the AEs. 
 
Although the use of rescue medications is allowable at any time during the study, the use of 
rescue medications should be delayed, if possible, for at least 5 days following the 
administration of study intervention. The date and time of rescue medication administration 
as well as the name and dosage regimen of the rescue medication must be recorded. 
 
Refer to Section 6.8.1 for agents with potential inhibitory activity against vaccinia viruses. 

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7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1. Discontinuation of Study Intervention 
It may be necessary for a participant to permanently discontinue study intervention. Reasons 
for permanent discontinuation of study intervention may include the following: 
 
• 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. 
NOTE: In Part 1B and Part 2 where participants are treated with PF-07263689 in 
combination with sasanlimab, participants will be allowed to continue study treatment 
beyond progression, if the treating physician feels that it is in the participant’s best interest in 
the case of radiological progression, and the absence of clear clinical progression. 
 
Note that discontinuation of study intervention does not represent withdrawal from the study. 
If study intervention is permanently discontinued, the participant will remain in the study to 
be evaluated for at least 90 days after discontinuation of study intervention. See the SoA for 
data to be collected at the time of discontinuation of study intervention and follow-up for any 
further evaluations that need to be completed. 
 
In the event of discontinuation of study intervention, it must be documented on the 
appropriate CRF/in the medical records whether the participant is discontinuing further 
receipt of study intervention or also from study procedures, posttreatment study follow-up, 
and/or future collection of additional information. 
 
Follow-Up: 
 
Participants will attend a follow-up visit 28 to 90 days after discontinuation of study 
intervention and survival follow-up visits Q12W (±7 days) until study discontinuation; the 
procedures for these visits are listed in the SoA. 

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7.1.1. Potential Cases of Acute Kidney Injury 
Abnormal values in SCr concurrent with presence or absence of increase in BUN that meet 
the criteria below, in the absence of other causes of kidney injury, are considered potential 
cases of acute kidney injury and should be considered important medical events. 
 
An increase of ≥0.3 mg/dL (or ≥26.5 µmol/L) in SCr level relative to the participant’s own 
baseline measurement should trigger another assessment of SCr as soon as practically 
feasible, preferably within 48 hours from awareness. 
 
If the second assessment (after the first observations of ≥0.3 mg/dL [or ≥26.5 µmol/L] in SCr 
relative to the participant’s own baseline measurement) is ≥0.4 mg/dL (or ≥35.4 µmol/L), the 
participant should be discontinued from the study and adequate, immediate, supportive 
measures taken to correct apparent acute kidney injury. 
 
Participants should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the second assessment confirming abnormal 
SCr result. This evaluation should include laboratory tests, detailed history, and physical 
assessment. In addition to repeating SCr, laboratory tests should include serum BUN, serum 
creatine kinase, and serum electrolytes (including at a minimum potassium, sodium, 
phosphate/phosphorus, and calcium), in addition to urinary dipstick, urine microscopic 
examination, and urinary indices. All cases confirmed on repeat testing as meeting the 
laboratory criteria for acute kidney injury, with no other cause(s) of laboratory abnormalities 
identified, should be considered potential cases of drug-induced kidney injury irrespective of 
availability of all the results of the investigations performed to determine etiology of the 
abnormal SCr. If ≥2 participants in a given period are noted to have 2 consecutive SCr 
results of ≥0.3 mg/dL (or ≥26.5 µmol/L), an assessment of whether the finding may be 
considered an adverse drug reaction should be undertaken. 
 
7.1.2. ECG Changes 
A participant who meets either of the following criteria based on the average of triplicate 
ECG readings will be withdrawn from the study intervention: 
 
• QTcF >500 msec. 
• Change from baseline: QTcF >60 msec. 
If a clinically significant finding is identified (including, but not limited to, changes from 
baseline in QTcF after enrollment), the investigator or qualified designee will determine if 
the participant can continue in the study and if any change in participant management is 
needed. This review of the ECG printed at the time of collection must be documented. Any 
new clinically relevant finding should be reported as an AE. 

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7.1.3. Cardiac Adverse Events 
Any participant who has an occurrence of Grade ≥3 myocarditis will be permanently 
discontinued from the study. 
 
7.2. Participant Discontinuation/Withdrawal From the Study 
A participant may withdraw from the study at any time at their own request. Reasons for 
discontinuation from the study may include: 
 
• Refused further study procedures; 
• Lost to followup; 
• Treatment interruption; 
• Death; 
• Study terminated by sponsor. 
At the time of discontinuing from the study, if possible, an early discontinuation visit should 
be conducted. See the SoA for assessments to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
 
If a participant withdraws from the study, he/she may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly. 
 
If the participant withdraws from the study and also withdraws consent (see Section 7.2.1) 
for disclosure of future information, no further 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. 
 
7.2.1. Withdrawal of Consent 
Participants who request to discontinue receipt of study intervention 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 him or her 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 study intervention or also from study procedures and/or 
posttreatment study follow-up, and entered on the appropriate CRF page. In the event that 
vital status (whether the participant is alive or dead) is being measured, publicly available 
information should be used to determine vital status only as appropriately directed in 
accordance with local law. 

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7.3. Lost to Follow-Up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
 
The following actions must be taken if a participant fails to return to the clinic for/attend a 
required study visit: 
 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible. Counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to and/or 
should continue in the study. 
 
• Before a participant is deemed lost to followup, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 
telephone calls and, if necessary, a certified letter to the participant’s last known 
mailing address or local equivalent methods). These contact attempts should be 
documented in the participant’s medical record. 
 
• Should the participant continue to be unreachable, he/she will be considered to 
have withdrawn from the study. 
 
8. STUDY ASSESSMENTS AND PROCEDURES 
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures. 
 
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed. 
 
Safety issues should be discussed with the sponsor immediately upon occurrence or 
awareness to determine whether the participant should continue or discontinue study 
intervention. 
 
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. 
 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
 
Procedures conducted as part of the participant’s routine clinical management (eg, blood 
count) and obtained before signing of the ICD may be utilized for screening or baseline 
purposes provided the procedures met the protocol-specified criteria and were performed 
within the time frame defined in the SoA. 

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Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside 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 the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible. The study team must be informed of these incidents in a timely manner. 
 
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study. 
 
The total blood sampling volume for individual participants in this study is approximately 
500 mL. The actual collection times of blood sampling may change. Additional blood 
samples may be taken for safety assessments at times specified by Pfizer, provided the total 
volume taken during the study does not exceed 550 mL during any period of 56 consecutive 
days. 
 
8.1. Efficacy Assessments 
8.1.1. Tumor Response Assessments 
Tumor assessments will include all known or suspected disease sites. Imaging will include 
contrast enhanced chest, abdomen and pelvis computed tomography or MRI scans; brain 
computed tomography or MRI scan for participants with known or suspected brain 
metastases; bone scan and/or bone x-rays for participants with known or suspected bone 
metastases. For participants with known computed tomography contrast allergy, a 
non-contrast computed tomography of the chest with contrast enhanced abdominal and pelvic 
MRI can be used. The same imaging technique used to characterize each identified and 
reported lesion at baseline will be employed in the following tumor assessments. 
 
Antitumor activity will be assessed through radiological tumor assessments conducted at 
baseline, during treatment as specified in the , whenever disease progression is suspected (eg, 
symptomatic deterioration), and at the time of withdrawal from treatment (if not done in the 
previous 4 weeks). Tumor response assessment will be performed locally. Assessment of 
response will be made using RECIST version 1.1 (see Appendix 10). 
 
All participants’ files and radiologic images must be available for source verification and for 
potential peer review. 
 
For Part 1A, participants will be assessed for radiological response on Day 43 (±5 day 
window). Additional scans may be performed Q6W (±7 days) following Day 43. For Part 1B 
and Part 2, all participants will be assessed for radiographic response Q6W (±7 day window) 
through Week 24 followed by Q12W (±7 days) until starting new anticancer therapy or at 
time of radiographic progression, whichever is earlier. 

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For Part 2 Dose Expansion, radiographic imaging scans may be submitted to a central 
imaging core laboratory for the purpose of holding for possible future central review if 
deemed necessary. In the event that central review is conducted, it would not be a complete 
medical review of participant and non-incidental findings will be shared with the PI, site 
staff, or participant. All safety reviews will be the sole responsibility of the site staff. 
 
8.2. Safety Assessments 
Planned time points for all safety assessments are provided in SoA. Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety issues. 
 
Safety assessments will include collection of AEs, SAEs, vital signs and physical 
examinations, ECG (12-lead), dermatologic examinations, laboratory assessments, including 
pregnancy tests and verification of concomitant treatments. 
 
8.2.1. Participant Demographics and Other Baseline Characteristics 
Demographic data and general medical history will be collected at screening by the 
investigator or qualified designee and will include relevant medical and surgical history 
within the last 10 years and current illnesses. 
 
A disease-targeted medical and treatment history will be collected at screening. Details 
regarding the participant’s malignancy under study, including date and stage at initial 
diagnosis, date and extent of metastatic disease at study entry, tumor histology and known 
gene alterations, relevant disease characteristics and prior anti-cancer treatments, including 
systemic, radiation and surgical procedures, will be recorded. 
 
8.2.2. Physical Examinations 
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 will include, at a minimum, assessments of the skin, 
cardiovascular, respiratory, gastrointestinal, and neurological systems. 
 
A brief physical examination will include, at a minimum, assessments of skin, lungs, 
cardiovascular system, and abdomen (liver and spleen). 
 
Investigators should pay special attention to clinical signs related to previous serious 
illnesses. As superficial skin lesions or oral mucous membrane lesion may develop after 
PF-07263689 treatment, investigators should report any clinical findings. 
 
Physical examinations may be conducted by a physician, trained physician's assistant, or 
nurse practitioner as acceptable according to local regulation. 
 
Height and weight will also be measured and recorded as per the SoA. For measuring weight, 
a scale with appropriate range and resolution is used and must be placed on a stable, flat 

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surface. Participants must remove shoes, bulky layers of clothing, and jackets so that only 
light clothing remains. They must also remove the contents of their pockets and remain still 
during measurement of weight. 
 
Physical examination findings collected during the study will be considered source data and 
will not be required to be reported, unless otherwise noted. Any untoward physical 
examination findings that are identified during the active collection period and meet the 
definition of an AE or SAE (Appendix 3) must be reported according to the processes in 
Sections 8.3.1 to 8.3.3. 
 
8.2.3. Skin Monitoring 
Participants should be monitored not only for infusion site reactions but also any skin lesions 
in whole body following PF-7263689 administration (Parts 1A, 1B, and 2), as well as 
injection site reactions following administration of sasanlimab (in Parts 1B and 2). Record 
the location of the infusion and skin lesions found other than infusion site, and, for 
combination treatment with sasanlimab, record the injection site location, time of each 
injection and any injection site reactions in the participant’s source records and study CRF. 
 
8.2.4. Vital Signs 
BP and pulse rate measurements will be assessed either in the sitting position with feet 
supported (ie, not dangling) or the supine position. It is recommended that the same position 
be used consistently throughout the study duration unless circumstances, eg, hospitalization, 
dictate otherwise. BP should be obtained using the auscultatory method or via an automated 
BP device, ensuring use of an appropriately sized cuff on the bare arm and consistent 
technique of measurement (eg, using the same arm each time). Care should be taken to use 
the appropriate size BP cuff for the participant’s arm circumference as incorrect cuff sizes 
can lead to falsely elevated BP measurements. 
 
Abnormal readings should be repeated and confirmed. 
 
Pulse rate preferably should be obtained using a pulse oximeter, automated BP device, or 
other pulse measurement device. Temperature may be determined using oral, tympanic, 
axillary, or temporal (ie, forehead scan) methods of measurement, as long as the chosen 
method is used consistently (oral preferred). 
 
During inpatient monitoring, temperature, pulse rate, and BP will be collected every 6 hours 
(±10 min) and as needed. 
 
Pulse oximetry (SpO2) will also be measured as described on SoA. 
 
8.2.5. Electrocardiograms 
Standard 12-lead ECGs utilizing limb leads (with a 10-second rhythm strip) should be 
collected at times specified in the SoA using an ECG machine that automatically calculates 
the heart rate and measures PR, QT, and QTc intervals and QRS complex. Alternative lead 

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placement methodology using torso leads (eg, Mason-Likar) should not be used given the 
potential risk of discrepancies with ECGs acquired using standard limb lead placement. All 
scheduled ECGs should be performed after the participant has rested quietly for at least 
5 minutes in a supine position. 
 
Triple 12-lead ECGs should be performed approximately 1 to 4 minutes apart to determine 
mean QTcF interval. 
 
If a) a postdose QTcF interval remains ≥60 msec from the baseline and is >450 msec; or b) 
an absolute QT value is ≥500 msec for any scheduled ECG for greater than 4 hours (or 
sooner, at the discretion of the investigator); or c) QTcF intervals get progressively longer, 
the participant should undergo continuous ECG monitoring. A cardiologist should be 
consulted if QTcF intervals do not return to less than the criteria listed above after 8 hours of 
monitoring (or sooner, at the discretion of the investigator). 
 
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality. It is important that leads be placed in the 
same positions each time in order to achieve precise ECG recordings. If a machine-read QTc 
value is prolonged, as defined above, repeat measurements may not be necessary if a 
qualified medical provider’s interpretation determines that the QTcF values are in the 
acceptable range. 
 
ECG values of potential clinical concern are listed in Appendix 7. 
 
8.2.6. Echocardiogram or MUGA 
Participants must be in supine position in a rested and calm state for at least 5 minutes before 
LVEF assessment is conducted. If the participant is unable to be in the supine position, the 
participant should be in the most recumbent position possible. 
 
The investigator or designated site physician will review all echocardiograms. Once signed, 
the original echocardiogram will be retained with the participant’s source documents. At the 
request of the sponsor, a copy of the original echocardiogram will be made available to 
Pfizer. Standard echocardiogram machines should be used for all study-related 
echocardiogram requirements. 
 
Echocardiogram or MUGA will be measured at time point(s) specified in the SoA or if 
clinically warranted. Imaging method must be consistent throughout the study for individual 
participants. 
 
8.2.7. Clinical Safety Laboratory Assessments 
See Appendix 2 for the list of clinical safety laboratory tests to be performed and the SoA for 
the timing and frequency. All protocol-required laboratory assessments, as defined in 
Appendix 2, must be conducted in accordance with the laboratory manual and the SoA. 
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety issues. 

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The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. 
Clinically significant abnormal laboratory findings are those which are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant's condition. 
 
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 90 (±7) days after the last dose of study intervention 
should be repeated until the values return to normal or baseline or are no longer considered 
clinically significant by the investigator or medical monitor. 
 
If such values do not return to normal/baseline within a period of time judged reasonable by 
the investigator, the etiology should be identified and the sponsor notified. 
 
See Appendix 6 for suggested actions and follow-up assessments in the event of potential 
drug-induced liver injury. 
 
No need to repeat a clinical laboratory assessments on Cycle 1 Day 1 if the baseline 
assessment was performed within 14 days prior to that date. 
 
8.2.8. Pregnancy Testing 
Pregnancy tests may be urine or serum tests, but must have a sensitivity of at least 
25 mIU/mL. Pregnancy tests will be performed in WOCBP at the times listed in the SoA. 
Following a negative pregnancy test result at screening, appropriate contraception must be 
commenced and a second negative pregnancy test result will be required at the baseline visit 
prior to the participant’s receiving the study treatment. Pregnancy tests will also be done 
whenever 1 menstrual cycle is missed during the active treatment period (or when potential 
pregnancy is otherwise suspected) and at the 30-day follow-up visit. Pregnancy tests may 
also be repeated if requested by IRBs/ECs or if required by local regulations. If a urine test 
cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is 
required. In such cases, the participant must be excluded if the serum pregnancy result is 
positive. 
 
If a participant requiring pregnancy testing cannot visit a local laboratory, a home urine 
pregnancy testing kit with a sensitivity of at least 25 mIU/mL may be used by the participant 
to perform the test at home, if compliant with local regulatory requirements. The pregnancy 
test outcome should be documented in the participant’s source documents/medical records 
and relevant data recorded on the CRF. Confirm that the participant is adhering to the 
contraception method(s) required in the protocol. 
 
8.2.9. Vector Shedding Kinetics and Infectivity Assessments: 
Whole blood will be collected for viral load kinetics of PF-07263689 according to the SoA 
table. 

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In addition, saliva, urine, injection site swabs, and swabs from any spontaneous skin lesions 
will be collected for vector shedding according to the SoA table. 
 
Samples, except blood, that are positive for viral DNA in qPCR shedding assay at levels 
above the LLOQ of the infectivity will be analyzed for infectious virus. Instructions for the 
collection and handling of biological samples will be provided in the laboratory manual or by 
the sponsor. 
 
The actual date and time (24-hour clock time) of each sample will be recorded. All efforts 
will be made to obtain the samples at the exact nominal time relative to dosing. Collection of 
samples within the sampling time window specified in Table 4 and Table 5 (collection of 
samples within 10% of the nominal time relative to dosing [eg, within 6 minutes of a 
60-minute sample]) will not be captured as a protocol deviation, as long as the exact time of 
the collection is noted on the source document and 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, patient, and sponsor. 
 
Samples collected for analyses of PF-07263689 in whole blood, saliva, urine, injections site 
swabs, and swabs from any spontaneous skin lesions, may also be used to evaluate safety or 
efficacy aspects related to concerns arising during or after the study, for evaluation of the 
bioanalytical method, or for other internal exploratory purposes. 
 
Samples collected for measurement of viral load kinetics in whole blood, vector shedding in 
saliva, urine, injection site swabs, and swabs from spontaneous skin lesions will be analyzed 
using a validated analytical method in compliance with applicable SOPs. 
 
Viral load kinetics and vector and shedding 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 and shedding 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 changes in the timing or addition of time points for any planned study assessments must 
be documented and approved by the relevant study team member and then archived in the 
sponsor and site study files, but will not constitute a protocol amendment. The IRB/EC will 
be informed of any safety issues that require alteration of the safety monitoring scheme or 
amendment of the ICD. 
 
8.2.10. Mouth Swab and Urine Specimens 
Mouth swabs should be collected as described in the Laboratory Manual. 
 
Participant will collect a mid-stream urine sample of approximately 50 mL. Urine samples 
will be processed according to the Laboratory Manual. 

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Specimens will be collected as specified in the SOA. If the specimen is positive on Day 22 
then follow-up specimen collection will be performed on Day 29 (C2D1) and also potentially 
on Day 43 if the Day 29 (C2D1) sample is positive. 
 
8.2.11. Photographs of Skin Lesions 
Documentation by color photography, including a ruler (or caliper) to estimate the size of the 
lesion, is recommended. Photographs of visible skin lesions may be taken at any time during 
the study period, or copies of pre-existing photographs may be collected if available. Whole 
limb photographs may be taken at baseline, as appropriate, to document overall disease status 
and to document responses. If any clinically notable visible phenomenon appears at any time, 
this should be photographed and followed up by photography at each subsequent visit until it 
resolves. The sponsor may use, copy and/or distribute the photographs for educational 
purposes, in scientific lectures, journal articles, and textbooks. The sponsor may also use the 
photographs for general commercial purposes and may have the photographs published, 
circulated, or presented in any way either alone or with other written, printed, graphic, or 
audio matter to members of the medical, nursing, pharmaceutical and related progressions, as 
well as to the public at large. The participants’ identity will not be disclosed in any 
photographs. Written authorization must be obtained from the participants and IRB/IEC/REB 
prior to the release of such information. 
8.3. Adverse Events, Serious Adverse Events, and Other Safety Reporting 
The definitions of an AE and an SAE can be found in Appendix 3. 
 
AEs may arise from symptoms or other complaints reported to the investigator by the 
participant (or, when appropriate, by a caregiver, surrogate, or the participant's legally 
authorized representative), or they may arise from clinical findings of the Investigator or 
other healthcare providers (clinical signs, test results, etc.). 
 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (see Section 7.1). 
 
During the active collection period as described in Section 8.3.1, each participant/parent/legal 
guardian/legally authorized representative will be questioned about the occurrence of AEs in 
a nonleading manner. 
 
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion. 
 
8.3.1. Time Period and Frequency for Collecting AE and 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 

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any study related procedure and/or receiving study intervention), through and including a 
minimum of 90 calendar days, except as indicated below, after the last administration of the 
study intervention. 
 
Follow-up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator. 
 
For participants who are screen failures, the active collection period ends when screen failure 
status is determined. 
 
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn. 
 
If a participant permanently discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the CT SAE Report Form. 
 
Investigators are not obligated to actively seek information on AEs or SAEs after the 
participant has concluded study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has completed the study, and he/she 
considers the event to be reasonably related to the study intervention, the investigator must 
promptly report the SAE to Pfizer using the CT SAE Report Form. The SAEs identified 
during long-term follow-up will be reported to Pfizer Safety on the CT SAE Report Form 
only if considered reasonably related to the study intervention. 
 
8.3.1.1. Reporting SAEs to Pfizer Safety 
All SAEs occurring in a participant during the active collection period as described in 
Section 8.3.1 are reported to Pfizer Safety on the CT SAE Report Form immediately upon 
awareness and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3. The investigator will submit any updated SAE data to the sponsor within 
24 hours of it being available. 
 
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. Note that a switch to a commercially available version of the study intervention is 
considered as a new anticancer therapy for purposes of SAE reporting. 
 
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF 
All nonserious AEs and SAEs occurring in a participant during the active collection period 
which begins after obtaining informed consent as described in Section 8.3.1, will be recorded 
on the AE section of the CRF. 
 
The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant. 

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If a participant begins a new anticancer therapy, the recording period for nonserious 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. Note that a switch to a 
commercially available version of the study intervention is considered as a new anticancer 
therapy for the purposes of SAE reporting. 
 
8.3.2. Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3. 
 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
 
8.3.3. Follow-Up of AEs and SAEs 
After the initial AE or SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3). 
 
In general, follow-up information 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. 
 
Further information on follow-up procedures is given in Appendix 3. 
 
8.3.4. Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a 
study intervention under clinical investigation are met. 
 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators. 
 
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary. 
 
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate according to local requirements. 

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8.3.5. Environmental Exposure, Exposure During Pregnancy or Breastfeeding, and 
Occupational Exposure 
Environmental exposure occurs when a person not enrolled in the study as a participant 
receives unplanned direct contact with or exposure to the study intervention. Such exposure 
may or may not lead to the occurrence of an AE or SAE. Persons at risk for environmental 
exposure include healthcare providers, family members, and others who may be exposed. An 
environmental exposure may include exposure during pregnancy, exposure during 
breastfeeding, and occupational exposure. 
 
Any such exposure to the study intervention under study are reportable to Pfizer Safety 
within 24 hours of investigator awareness. 
 
If an accidental human exposure to PF-07263689 occurs, the following is recommended: 
 
• Implementation of local, institutional needle stick, or other exposure guidelines. 
• Wash area thoroughly with soap and water. 
• Cover area with non-occlusive dressing and provide local wound care (as needed) 
until complete resolution. 
 
Refer to Section 5.3 for additional details and management guidance. 
 
The investigator must report any instance of environmental exposure 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 about the environmental exposure 
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 Form must be maintained in the 
investigator site file. If applicable, the institution’s Biosafety Specialist should be informed. 
 
8.3.5.1. Exposure During Pregnancy 
An exposure during pregnancy (EDP) occurs if: 
 
• A female participant is found to be pregnant while receiving or after discontinuing 
study intervention. 
 
• A male participant who is receiving or has discontinued study intervention 
exposes a female partner prior to or around the time of conception. 

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• A female is found to be pregnant while being exposed or having been exposed to 
study intervention due to environmental exposure. Below are examples of 
environmental EDP: 
 
• A female family member or healthcare provider reports that she is pregnant 
after having been exposed to the study intervention by semen, inhalation, or 
skin contact. 
 
• A male family member or healthcare provider who has been exposed to the 
study intervention by semen, inhalation, or skin contact then exposes his 
female partner prior to or around the time of conception. 
 
The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
termination of pregnancy). 
 
• If EDP occurs in a participant or a participant’s partner, 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. Details of the 
pregnancy will be collected after the start of study intervention and until 6 months 
after the last dose. 
 
• If EDP occurs in the setting of environmental exposure, the investigator must 
report information to Pfizer Safety using the CT SAE Report Form and EDP 
Supplemental Form. Since the exposure information does not pertain to the 
participant enrolled in the study, the information is not recorded on a CRF; 
however, a copy of the completed CT SAE Report Form is maintained in the 
investigator site file. 
 
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 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedural test findings are conclusive for a congenital anomaly and the findings are 
reported). 

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Abnormal pregnancy outcomes are considered SAEs. 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 including 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 study intervention. 
 
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. 
 
8.3.5.2. Exposure During Breastfeeding 
An exposure during breastfeeding occurs if: 
 
• A female participant is found to be breastfeeding while receiving or after 
discontinuing study intervention. 
 
• A female is found to be breastfeeding while being exposed or having been 
exposed to study intervention (ie, environmental exposure). An example of 
environmental exposure during breastfeeding is a female family member or 
healthcare provider who reports that she is breastfeeding after having been 
exposed to the study intervention by semen, inhalation, or skin contact. 
 
The investigator must report exposure during breastfeeding to Pfizer Safety within 24 hours 
of the investigator’s awareness, irrespective of whether an SAE has occurred. The 
information must be reported using the CT SAE Report Form. When exposure during 
breastfeeding occurs in the setting of environmental exposure, the exposure information does 
not pertain to the participant enrolled in the study, so the information is not recorded on a 
CRF. However, a copy of the completed CT SAE Report Form is maintained in the 
investigator site file. 
 
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 

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authorized use. However, if the infant experiences an SAE associated with such a drug, the 
SAE is reported together with the exposure during breastfeeding. 
 
8.3.5.3. Occupational Exposure 
The investigator must report any instance of occupational exposure 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 about the occupational exposure 
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 Form must be maintained in the 
investigator site file. If applicable, the institution’s Biosafety Specialist should also be 
informed. Refer to Section 5.3.2 for additional details. 
 
8.3.6. Cardiovascular and Death Events 
Not applicable. 
 
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs 
Not applicable. 
 
8.3.8. Adverse Events of Special Interest 
Based on the GLP nonclinical studies, the key toxicities of potential clinical importance that 
should be classified as AESIs CCI 
 
, which may manifest at any time 
during treatment. Such events include but are not limited pneumonitis, myocarditis, hepatitis, 
colitis, endocrinopathies, and rash. As a routine precaution, participants will be admitted for 
inpatient monitoring for CCI 
 following the first dose of PF-07263689 and aCCI  
following the second dose of PF-07263689. For subsequent doses (Day 15 and Day 
22), all participants must be observed for 4 hour post infusion. 
 
Adverse events of special interest (AESIs) are examined as part of routine safety data review 
procedures throughout the clinical trial and as part of signal detection processes. 
 
All AESIs must be reported as an AE or SAE following the procedures described in 
Sections 8.3.1 through 8.3.4. An AESI is to be recorded as an AE or SAE on the CRF. In 
addition, an AESI that is also an SAE must be reported using the CT SAE Report Form. An 
AESI is to be recorded as an AE or SAE on the CRF. In addition, an AESI that is also an 
SAE must be reported using the CT SAE Report Form. 
 
8.3.8.1. Lack of Efficacy 
This study is primarily designed to investigate the safety of PF-07263689; thus, this does not 
apply. 
 
8.3.9. Medical Device Deficiencies 
Not applicable. 

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8.3.10. Medication Errors 
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength. 
 
Exposures to the study intervention under study may occur in clinical trial settings, such as 
medication errors. 
 
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 
 
Medication errors include, but are not limited to: 
 
• Medication errors involving participant exposure to the study intervention; 
• Potential medication errors or uses outside of what is foreseen in the protocol that 
do or do not involve the study participant. 
 
• The administration of expired study intervention; 
• The administration of an incorrect study intervention; 
• The administration of an incorrect dosage; 
• The administration of study intervention that has undergone temperature 
excursion from the specified storage range, unless it is determined by the sponsor 
that the study intervention under question is acceptable for use. 
 
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 a 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 nonserious, are recorded on the 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. 

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8.4. Pharmacokinetics 
PK samples will be collected for sasanlimab only. Traditional PK analysis is not considered 
relevant for oncolytic viruses/cancer vaccines (FDA, 2013; WHO, 2005). 
 
Blood samples (approximately 3 mL) to provide serum for the analysis of sasanlimab 
concentrations will be collected, in Parts 1B and Part 2 of the study as outlined in the SoA. 
 
The actual date and time (24-hour clock time) of each sample will be recorded. In addition to 
samples collected at the scheduled times, an additional blood sample should be collected 
from participants experiencing unexpected and/or serious AE’s and the date and time of 
blood sample collection and of last dosing prior to PK collection documented in the CRF. 
 
Samples collected for analyses of sasanlimab serum concentration may also be used to 
evaluate safety or efficacy aspects related to concerns arising during or after the study, for 
evaluation of the bioanalytical method, or for other internal exploratory purposes. 
 
Genetic analyses will not be performed on these serum samples (unless consent for this was 
included in the informed consent). Participant confidentiality will be maintained. 
 
Samples collected for measurement of serum concentrations of sasanlimab will be analyzed 
using a validated analytical method in compliance with applicable 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. 
 
8.5. Genetics 
8.5.1. Specified Genetics 
Not applicable. 
 
8.5.2. Retained Research Samples for Genetics 
A 4-mL blood sample optimized for DNA isolation Prep D1 will be collected according to 
the SoA, as local regulations and IRBs/ECs allow. 
 
Retained Research Samples may be used for research related to the study intervention(s) and 
the cancer under study. Genes and other analytes (eg, proteins, RNA, nondrug metabolites) 
may be studied using the banked samples. 
 
See Appendix 5 for information regarding genetic research. Details on processes for 
collection and shipment of these samples can be found in the Laboratory Manual. 

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8.6. Biomarkers 
Collection of samples for biomarker research is also part of this study. 
 
The following samples for biomarker research are required and will be collected from all 
participants in this study as specified in the SoA: 
 
• 
 
 
 
 
 
 
Optional samples for biomarker research that should be collected from participants in the 
study as appropriate are the following: 
 
• 
 
 
Biospecimens collected for target engagement, pharmacodynamic and other biomarker 
assessments will include peripheral blood and tumor tissues which will be used to (1) detect 
virus/transgene, and (2) analyze DNA, RNA, and proteins, for achieving planned biomarker 
objectives. Refer to the SoA for sample collection time points and Study/Laboratory Manual 
for sample processing and shipping. The following biospecimen types are planned to be 
collected in support of study objectives. Additional biospecimens collected over the course of 
participant disease management may be submitted for biomarker analyses. 
 
8.6.1. Tumor Biopsies 
Tumor biospecimens from archival, de novo pretreatment, and on-treatment biopsies will be 
used to analyze candidate nucleic acid and protein biomarkers for their ability to (1) 
demonstrate the presence of virus and transgene expression in tumor post-treatment, and (2) 
identify those participants who are most likely to benefit from treatment with the study drugs. 
Biomarkers may include, but are not limited to, nucleic acid and protein analyses, as well as 
cell types and constituents of the TME. De novo tumor biopsies obtained upon disease 
progression may be used to investigate target engagement, pharmacodynamic activities, 
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mode of action and acquired mechanisms of resistance ie, presence of virus/transgene, 
evaluating immune cells by quantifying intra-tumoral CD8+ T cells, regulatory T cells, NK 
cells or dendritic cells in on-treatment versus baseline TME. Additional information on tissue 
collection procedures can be found in the Laboratory/Study Manual. 
 
Pre-treatment archival FFPE material containing tumor that is of diagnostic quality and 
representative of the diagnosed malignancy collected ≤1 year prior to study start is required 
of all participants, and if not available, a pre-treatment de novo (fresh) tumor biopsy will be 
required. If the archived sample is older than 1 year and a biopsy during screening cannot be 
performed, the investigator must contact the sponsor to discuss eligibility prior to enrollment. 
 
Participants should not be subjected to a significant risk procedure to obtain the biopsies 
(ie, the absolute risk of mortality or major morbidity in the participant’s clinical setting and at 
the institution completing the procedure should be <2%). Additional information on tissue 
collection procedures can be found in the Laboratory Manual. 
 
CCI 
 
 

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8.6.2. Whole Blood, Plasma, Serum 
 
 
4 ml of blood samples for exploratory molecular analysis and biobanking will be collected at 
the time specified in the SoA. Instructions for sample collection, processing, storage 
shipment and detailed panels of cytokine/chemokine and immunophenotyping markers will 
be provided in the laboratory manual. 
 
8.6.3. Retained Research Samples for Biomarkers 
Retained Research Samples for Biomarkers will not be collected in this study. 
 
8.7. Immunogenicity Assessments 
8.7.1. PF-07263689 Immunogenicity Assessments 
Blood samples of approximately 4 mL will be collected to provide serum for analyses of 
anti-IL-2 antibodies and detection of anti-VV NAb into appropriately labeled tubes, in Part 
1A, Part 1B, Part 2 of the study, at times as specified in the SoA. Instructions for the 
collection and handling of biological samples will be provided in the laboratory manual or by 
the sponsor. The actual date and time (24-hour clock time) of each sample will be recorded. 

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Samples collected for determination of ADA and NAb may also be used for additional 
characterization of the immune response and/or evaluation of the bioanalytical method, or for 
other internal exploratory purposes. These data will be used for internal exploratory 
purposes. 
 
Genetic analyses will not be performed on these plasma/serum/whole blood samples unless 
consent for this was included in the informed consent. Participant confidentiality will be 
maintained. 
 
Samples will be analyzed using a validated analytical method in compliance with applicable 
SOPs. 
 
8.7.2. Sasanlimab Immunogenicity Assessments 
Blood samples of approximately 4 mL, to provide serum for detection of ADA and NAb 
against sasanlimab will be collected into appropriately labeled tubes, in combinations 
portions of Part 1B and Part 2 of the study, at times as specified in the SoA. Instructions for 
the collection and handling of biological samples will be provided in the laboratory manual 
or by the sponsor. The actual date and time (24-hour clock time) of each sample will be 
recorded. 
 
Samples will be analyzed using a validated analytical method in compliance with applicable 
SOPs. 
 
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. 
 
8.8. Health Economics 
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study. 
 
9. STATISTICAL CONSIDERATIONS 
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a 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. Statistical Hypotheses 
There is no formal hypothesis testing in this study. 

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9.2. Analysis Sets 
For purposes of analysis, the following analysis sets are defined. 
 
Participant Analysis Set 
Description 
Full Analysis Set (FAS) 
All enrolled participants. 
Enrolled denotes a participant's, or his or her legally authorized 
representative’s, agreement to participate in a clinical study following 
completion of the informed consent process. Potential participants who are 
screened for the purpose of determining eligibility for the study, but do not 
participate in the study, are not considered enrolled, unless otherwise 
specified by the protocol. 
Safety Analysis Set (SAS) 
All enrolled participants who receive at least 1 dose of study intervention. 
Unless otherwise specified the safety analysis set will be the default analysis 
set used for all analyses. 
DLT Evaluable Set 
This is defined for the DLT observation period only. A participant is 
classified as DLT evaluable if they either 1.) receives at least 3 of 4 doses of 
PF 07263689, did not miss the first and the last dose, and has completed the 
safety assessments during the DLT observation period or 2) has experienced a 
DLT. If a participant withdraws from the study during the DLT observation 
period, they may be replaced by a participant at the same dose. The sole 
exception to criterion 1.) is if the participant has missed a minority of safety 
assessments due to emergency situations (eg, site accessibility issues, 
inability to go to an external lab, etc.). In such cases, the DLRM may judge 
the participant evaluable, depending on the abundance of the available data. 
Blood viral load Kinetics 
Parameter Set 
All enrolled participants treated who do not have protocol deviations 
influencing viral load kinetics assessment, and have sufficient information to 
estimate at least 1 of the parameters of interest. 
Vector Shedding Analysis 
Set 
All enrolled participants who are treated and have at least 1 analyte 
concentration above the lower limit of quantitation. 
Response Evaluable Set 
All enrolled participants who received at least one dose of study treatment 
and had adequate baseline disease assessment and at least one post baseline 
disease assessment. Patients who discontinued early or died will be included. 
Pharmacodynamic/ 
Biomarker Analysis Set(s) 
The Pharmacodynamic/Biomarker analysis population is defined as all 
enrolled participants with at least 1 of the Pharmacodynamic/Biomarkers 
evaluated at pre and/or post dose. 
Immunogenicity Analysis 
Set 
The immunogenicity analysis set includes all enrolled participants who 
received at least one dose of study treatment and have at least one sample 
tested for ADA. 
 
9.3. Statistical Analyses 
The SAP will be developed and finalized before any analyses are performed and will 
describe the analyses and procedures for accounting for missing, unused, and spurious data. 
This section is a summary of the planned statistical analyses of the primary and secondary 
endpoints. 

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9.3.1. General Considerations 
9.3.2. Primary Endpoint(s)/Estimand(s)/Analysis 
For Part 1, determination of MTD is achieved prior to the MFD will be performed using the 
DLT Evaluable set. 
 
The dose escalation in the Part 1 of the study will be guided by a Bayesian analysis of DLT 
data for PF-07263689 using a 2-parameter BLRM (Part 1A) or for the combination of 
PF-07263689 and sasanlimab using a 5-parameter BLRM (Part 1B). Weakly informative 
prior distributions based on preclinical/expert opinion information will be chosen for the 
logistic parameters in Part 1A; the observed DLT data in Part 1A and DLT data of 
sasanlimab will be used to form prior distribution for the BLRM in Part 1B (see Appendix 9). 
 
After each cohort of participants, the posterior distribution for the risk of DLT for new 
participants at different doses of interest for PF-07263689 will be evaluated. The posterior 
distributions will be summarized to provide the posterior probability that the risk of DLT lies 
within the following intervals: 
 
Under-dosing: 
[0, 0.16] 
Targeted dosing: 
[0.16, 0.33] 
Overdosing: 
[0.33, 1] 
 
Dosing decisions are guided by the EWOC principle (Rogatko 2007). A dose may only be 
used for newly enrolled participants if the risk of excessive toxicity at that dose is less than 
25%. Initially, dose escalation increases will be limited to no more than a half log increase 
from the previous dose level, which is a common approach for biologic compounds (Saber et 
al. 2017; Saber et al. 2016). Following the observation of a DLT in the current cohort, 
subsequent dose escalation increases will be limited to no more than 100%. A return to half 
log dose increases may be permitted at the discretion of the sponsor if no DLT are seen at the 
following dose level. 
Stopping criteria 
 
The dose escalation will be stopped when the following criteria are met: 
 
• At least 6 participants have been treated at the recommended MTD or at the MFD. 
• The dose satisfies 1 of the following conditions: 
• The probability of target toxicity at dose exceeds 50%, ie, Pr(0.16 ≤0.33)≥50%. 
• A minimum of 15 participants have been treated in the study. 
In case all doses explored appear to be overly toxic and the MTD cannot be determined, the 
overall study will stop. 

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Dose escalation will stop when stopping criteria are met (see DLT Definition). 
 
Additionally, when any of the following safety criteria are met, enrollment and study 
intervention administration will be paused, all available clinical safety data will be reviewed 
by the Sponsor together with the Investigators prior to determining next steps: 
 
• Any death that is not related to disease progression occurring within 30 days of 
receiving IP or does not have a determined alternative etiology. 
 
• Occurrence of 2 Grade ≥4 DLTs in 2 study participants at the starting dose. 
• For subsequent dose levels after the starting dose, a criterion guiding pause on 
enrollment at the current cohort is defined based on Bayesian posterior 
probabilities using a non-informative Beta (0.5, 0.5) prior distribution. The 
probabilities will be calculated for total number of participants in the current 
cohort. The safety criterion is met if the number of evaluable participants 
observed to have a DLT due to Grade 4 or higher AE results in a posterior 
probability that the true rate of such event exceeding 30% is ≥0.80. 
 
• Any Grade 4 hypersensitivity reaction/anaphylaxis observed. 
 
which satisfies the EWOC criterion. A full assessment 
of the prior risk to participants is given in Appendix 9. 
 
To mitigate the risk of misclassifying DLTs, a sensitivity that uses weighted DLT/AE data 
(in equivocal cases) within the BLRM may be performed. If all investigators and the sponsor 
agree on the equivocal DLT/AE data, the DLT weighting approach could be the primary dose 
escalation method. 
 
For Part 2, ORR will be a primary endpoint, along with safety and tolerability assessment. 
ORR evaluation, as well as other secondary efficacy endpoints, are described in 
Section 9.3.3. 
 
9.3.3. Secondary Endpoint(s)/Estimands Analysis 
9.3.3.1. Efficacy Endpoint(s) 
Response evaluable set will be used for all response related analysis including ORR and 
DOR. Tumor response will be presented in the form of participant data listings that include, 
but are not limited to, tumor type, dose on Day 1, tumor response at each visit, and best 
overall response. In addition, progression date, death date, date of first response and last 
assessment date, and date of last contact will be listed. A summary of tumor response and 
best overall response based on RECIST 1.1 will also be presented. 
 
The Kaplan-Meier method will be used for time-to-event type of efficacy endpoint. 

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The efficacy endpoints that will be analyzed in this study are defined as follows: 
 
• ORR is defined as the percentage of participants with a best overall response of 
CR or PR relative to the appropriate analysis set. 
 
• DOR is defined as the time from first documentation of CR or PR to date of first 
documentation of PD or death due to any cause. 
 
• PFS is defined as time from start date of treatment to the date of first 
documentation of PD or death due to any cause. 
 
• TTP is defined as the time from start date of treatment to the date of the first 
documentation of PD. 
 
• OS is the time from start date of treatment to the date of death due to any cause. 
The detailed analyses will be described in the SAP. 
9.3.3.2. Sasanlimab Pharmacokinetic Analysis 
The concentration-time data of sasanlimab will be summarized by descriptive statistics (n, 
mean, standard deviation, coefficient of variation, median, minimum, maximum, and 
geometric mean) according to dosing cohort and time for each part of the study. 
 
9.3.3.3. Viral Load Kinetics and Vector Shedding Analysis 
Viral load kinetics in whole blood: Individual participant whole blood viral titer-time data 
after first dose and after second dose will be analyzed using noncompartmental methods to 
determine relevant parameters. The parameters will include whole blood Cmax, whole blood 
Tmax, and AUC from time 0 to the last quantifiable time point (AUClast). 
 
Vector shedding in saliva, urine and skin swabs: Viral titers in each matrix will be 
summarized descriptively (n, mean, standard deviation, coefficient of variation, median, 
minimum, maximum, geometric mean and its associated coefficient of variation) by dose, 
day and nominal time. 
 
Peak viral titer levels from shedding qPCR assay in saliva, and urine will also be summarized 
descriptively by dose cohort and study visit separately if sufficient data is available. Further, 
duration of shedding may be reported if sufficient data is available. For samples that are 
tested for infectious virus, descriptive statistics will be provided for each matrix by dose, day, 
and nominal time. 
9.3.3.4. Analysis of Immunogenicity Data 
For the PF-07263689 immunogenicity data, the percentage of participants with anti-vaccinia 
virus neutralizing antibodies and positive anti-IL2 antibodies will be summarized. 

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For sasanlimab immunogenicity data, the percentage of participants with positive ADA and 
neutralizing antibodies will be summarized. For participants with positive ADA or 
neutralizing antibodies, the magnitude (titre), time of onset, and duration of ADA or 
neutralizing antibodies response will also be described, if data permit. 
 
9.3.4. Tertiary/Exploratory Endpoints 
For the tertiary and exploratory endpoints as described in Section 3, summary statistics will 
be presented. For each pair of specimens, the percent change from baseline will be 
calculated. 
 
Results from tertiary/exploratory analyses will be reported in the CSR where possible. 
However, given the exploratory nature of exploratory objectives and endpoints, the analyses 
may not be complete at the time of the CSR. Results from exploratory analyses that are not 
included in the CSR will be shared with the scientific community through publication at a 
scientific conference and/or in a peer-reviewed scientific journal. Detailed analysis for the 
tertiary and exploratory endpoints will be specified in a separate technical document outside 
of the SAP. 
9.3.5. Other Safety Analyses 
All safety analyses will be performed on the safety population. 
 
AEs, ECGs, BP, pulse rate, cardiac monitoring results, and safety laboratory data will be 
reviewed and summarized on an ongoing basis during the study to evaluate the safety of 
participants. Any clinical laboratory, ECG, BP, and PR abnormalities of potential clinical 
concern will be described. Safety data will be presented in tabular and/or graphical format 
and summarized descriptively, where appropriate. 
 
Medical history and physical examination and neurological examination information, as 
applicable, collected during the course of the study will be considered source data and will 
not be required to be reported, unless otherwise noted. However, any untoward findings 
identified on physical and/or neurological examinations conducted during the active 
collection period will be captured as AEs if those findings meet the definition of an AE. Data 
collected at screening that are used for inclusion/exclusion criteria, such as laboratory data, 
ECGs, and vital signs, will be considered source data, and will not be required to be reported, 
unless otherwise noted. Demographic data collected at screening will be reported. 
 
9.3.5.1. Electrocardiogram Analyses 
Changes from baseline for the ECG parameters QT interval, heart rate, QTcF, PR interval, 
and QRS complex will be summarized by treatment and time. 

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The number (%) of participants with maximum postdose QTcF values and maximum 
increases from baseline in the following categories (see Table 9) will be tabulated by 
treatment: 
 
Table 9.  Safety QTcF Assessment 
 
Degree of Prolongation 
Mild (ms) 
Moderate (ms) 
Severe (ms) 
Absolute value 
>450-480 
>480-500 
>500 
Increase from baseline 
30-60 
>60 
 
If more than 1 ECG is collected at a nominal time after dose administration (for example, 
triplicate ECGs), the mean of the replicate measurements will be used to represent a single 
observation at that time point. If any of the 3 individual ECG tracings has a QTcF value 
>500 ms, but the mean of the triplicates is not >500 ms, the data from the participant’s 
individual tracing will be described in a safety section of the CSR in order to place the 
>500 ms value in appropriate clinical context. However, values from individual tracings 
within triplicate measurements that are >500 ms will not be included in the categorical 
analysis unless the average from the triplicate measurements is also >500 ms. Changes from 
baseline will be defined as the change between the postdose QTcF value and the average of 
the time-matched baseline triplicate values on Day -1, or the average of the predose triplicate 
values on Day 1. 
 
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 most recent ECG 
measurements prior to the cycle 1 day 1 dosing. 
 
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 
analysis (categorical analysis) as individual values obtained at unscheduled time points. 
 
QT intervals will be corrected for HR (QTcF) using standard correction factors 
(ie, Fridericia’s (default correction), Bazett’s, and possibly a study-specific factor, as 
appropriate). Data will be summarized and listed for QT interval, HR, RR interval, PR 
interval, QRS complex, QTcF (and other correction factors, eg, QTcB as appropriate), and by 
dose. Individual QT (all evaluated corrections) intervals will be listed by time and dose. The 
most appropriate correction factor will be selected and used for the following analyses of 
central tendency and outliers and used for the study conclusions. Descriptive statistics (n, 
mean, median, standard deviation, minimum, and maximum) will be used to summarize the 
absolute value of the corrected QT interval and changes from baseline in corrected QT after 
treatment by dose and time point. Details of additional analysis (if any) will be specified in 
SAP. 

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9.3.5.2. AEs 
AEs will be graded by the investigator according to the CTCAE version 5.0 and coded using 
MedDRA. AE data will be reported in tables and listings. Summaries of AE by appropriate 
MedDRA terms, toxicity grade, and seriousness and relationship to study treatment will be 
presented, as well as summaries of AEs leading to death and premature withdrawal from 
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 and by cycle 
(Cycle 1 and Cycles beyond 1). Listings of DLTs and deaths will be provided. 
 
9.3.5.3. Laboratory Test Abnormalities 
The number and percentage of participants who experienced laboratory test abnormalities 
will be summarized according to worst toxicity grade observed for each laboratory assay. 
The analyses will summarize laboratory tests both on the entire study period and by cycle 
(Cycle 1 and Cycles beyond 1). For laboratory tests without CTCAE grade definitions, 
results will be categorized as normal, abnormal, or not done. 
 
 
 
 
 
9.4. Interim Analyses 
No formal interim analysis will be conducted for this study. As this is an open-label study, 
the sponsor may conduct unblinded reviews of the data during the course of the study for the 
purpose of safety assessment, facilitating dose escalation decisions, facilitating PK/PD 
modeling, and/or supporting clinical development. 
 
 
 

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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations 
10.1.1. Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
 
• Consensus ethical principles derived from international guidelines, including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines; 
 
• Applicable ICH GCP guidelines; 
• Applicable laws and regulations, including applicable privacy laws. 
The protocol, protocol amendments, ICD, SRSD(s), and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor, submitted to an IRB/EC 
by the investigator, and reviewed and approved by the IRB/EC before the study is initiated. 
 
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants. 
 
Protocols and any substantial amendments to the protocol will require health authority 
approval prior to initiation except for changes necessary to eliminate an immediate hazard to 
study participants. 
 
The investigator will be responsible for the following: 
 
• Providing written summaries of the status of the study to the IRB/EC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC. 
 
• Notifying the IRB/EC of SAEs or other significant safety findings as required by 
IRB/EC procedures. 
 
• Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH GCP guidelines, the IRB/EC, European regulation 
536/2014 for clinical studies (if applicable), European Medical Device Regulation 
2017/745 for clinical device research (if applicable), and all other applicable local 
regulations. 
 
10.1.1.1. 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 study 
intervention, Pfizer should be informed immediately. 

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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 
of any serious breaches of this protocol or of the ICH GCP that the investigator becomes 
aware of. 
 
10.1.2. Financial Disclosure 
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study. 
 
10.1.3. Informed Consent Process 
The investigator or his/her representative will explain the nature of the study, including the 
risks and benefits, to the participant or his/her legally authorized representative and answer 
all questions regarding the study. The participant or his/her legally authorized representative 
should be given sufficient time and opportunity to ask questions and to decide whether or not 
to participate in the trial. 
 
Participants must be informed that their participation is voluntary. Participants or their 
legally authorized representative will be required to sign a statement of informed consent that 
meets the requirements of 21 CFR 50, local regulations, ICH GCP guidelines, privacy and 
data protection requirements, where applicable, and the IRB/EC or study center. 
 
The investigator must ensure that each study participant or his or her legally authorized 
representative is fully informed about the nature and objectives of the study, the sharing of 
data related to the study, and possible risks associated with participation, including the risks 
associated with the processing of the participant’s personal data. 
 
The participant or his or her legally authorized representative must be informed that his/her 
personal study-related data will be used by the sponsor in accordance with local data 
protection law. The level of disclosure must also be explained to the participant or his or her 
legally authorized representative. 
 
The participant or his or her legally authorized representative must be informed that his/her 
medical records may be examined by Clinical Quality Assurance auditors or other authorized 
personnel appointed by the sponsor, by appropriate IRB/EC members, and by inspectors 
from regulatory authorities. 
 
The investigator further must ensure that each study participant or his or her legally 
authorized representative 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. 

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The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date on which the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICD. 
 
Participants or his or her legally authorized representative must be reconsented to the most 
current version of the ICD(s) during their participation in the study. 
 
A copy of the ICD(s) must be provided to the participant or the participant’s legally 
authorized representative. 
 
A participant who is rescreened is not required to sign another ICD if the rescreening occurs 
within 60 days from the previous ICD signature date. 
 
10.1.4. Data Protection 
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data. 
 
Participants’ 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 will 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 participants with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code. Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred. All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code. The study 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 and medical record ID. In case of 
data transfer, the sponsor will protect the confidentiality of participants’ personal data 
consistent with the clinical study agreement and applicable privacy laws. 
 
10.1.5. Committees Structure 
10.1.5.1. Data Monitoring Committee 
This study will not use a DMC. 
 
10.1.6. Dissemination of Clinical Study Data 
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the EudraCT, and/or 
www.pfizer.com, and other public registries in accordance with applicable local 

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laws/regulations. In addition, Pfizer reports study results outside of the requirements of local 
laws/regulations pursuant to its SOPs. 
 
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 results on www.clinicaltrials.gov for Pfizer-sponsored interventional 
studies (conducted in participants) that evaluate the safety and/or efficacy of a product, 
regardless of the geographical location in which the study is conducted. These results are 
submitted for posting in accordance with the format and timelines set forth by US law. 
 
EudraCT 
 
Pfizer posts clinical trial results on EudraCT for Pfizer-sponsored interventional studies in 
accordance with the format and timelines set forth by EU requirements. 
 
www.pfizer.com 
 
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used 
to identify individual participants have been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the corresponding study results are 
posted to www.clinicaltrials.gov. 
 
Documents within marketing authorization packages/submissions 
 
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the EMA website. Clinical data, under Phase 1 of this policy, includes clinical 
overviews, clinical summaries, CSRs, and appendices containing the protocol and protocol 
amendments, sample CRFs, and statistical methods. Clinical data, under Phase 2 of this 
policy, includes the publishing of individual participant data. Policy 0070 applies to new 
marketing authorization applications submitted via the centralized procedure since 
01 January 2015 and applications for line extensions and for new indications submitted via 
the centralized procedure since 01 July 2015. 
 
Data sharing 
 
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contributes to the scientific understanding of the 
disease, target, or compound class. Pfizer will make data available from these trials 
24 months after study completion. Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations. CSRs will have personally identifiable information 
redacted. 

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Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes. 
 
10.1.7. Data Quality Assurance 
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF. 
 
Guidance on completion of CRFs will be provided in the CRF Completion Requirements 
document. 
 
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password-protected or secured in a locked room to 
prevent access by unauthorized third parties. 
 
QTLs are predefined parameters that are monitored during the study. Important deviations 
from the QTLs and any remedial actions taken will be summarized in the clinical study 
report. 
 
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents. This 
verification may also occur after study completion. 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. 
 
Monitoring details describing strategy, including the definition of study critical data items 
and processes (eg, risk-based initiatives in operations and quality, such as risk management 
and mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques 
(central, virtual, or on-site monitoring), are provided in the contract. 
 
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data. 
 
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained. 

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When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems. 
 
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study. Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor 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 the sponsor or its agent. Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings. 
 
10.1.8. Source Documents 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator site. 
 
Data reported on the CRF or entered in the eCRF that are from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available. 
 
Definition of what constitutes source data and its origin can be found in the Study 
Management Plan which is maintained by the sponsor. 
 
Description of the use of the computerized system is documented in CRF Guidelines, which 
is maintained by the sponsor. 
 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
 
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, the ICH GCP guidelines, and all applicable regulatory requirements. 
 
10.1.9. Study and Site Start and Closure 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
 
The first act of recruitment is the date of the first participant’s first visit and will be the study 
start date. 

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The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed. 
 
The investigator may initiate study-site closure at any time upon notification to the sponsor 
or designee/CRO if requested to do so by the responsible IRB/EC or if such termination is 
required to protect the health of study participants. 
 
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to: 
 
• Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or the ICH GCP 
guidelines; 
 
• Inadequate recruitment of participants by the investigator; 
• Discontinuation of further study intervention development. 
• Sites in a specific country may be closed early if enrollment is complete in that 
country but is ongoing in other countries to meet a required number of 
participants. 
 
• Sites may be closed early if they are unable to continue to enroll participants if a 
treatment arm is discontinued, as described in Section 9.4. 
 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up. 
 
Study termination is also provided for in the clinical study agreement. If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights. 
 
10.1.10. Publication Policy 
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after the end of the study 
(or study termination), whichever comes first. 
 
The investigator agrees to refer to the primary publication in any subsequent publications, 
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 
30 days before submission. This allows the sponsor to protect proprietary information and to 
provide comments, and the investigator will, on request, remove any previously undisclosed 

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confidential information before disclosure, except for any study- or Pfizer 
intervention-related information necessary for the appropriate scientific presentation or 
understanding of the study results. 
 
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors. 
 
The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites. In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data. In this case, a coordinating investigator will be designated by mutual 
agreement. 
 
Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements. 
 
If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply. 
 
10.1.11. 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 
documentation/study portal or other electronic system. 
 
To facilitate access to appropriately qualified medical personnel for study-related medical 
questions or problems, participants are provided with an Emergency Contact Card (ECC) at 
the time of informed consent. The ECC contains, at a minimum, (a) protocol and study 
intervention identifiers, (b) participant’s study identification number, (c) site emergency 
phone number active 24 hours/day, 7 days per week, and (d) Pfizer Call Center number. 
 
The ECC is intended to augment, not replace, the established communication pathways 
between the investigator, site staff, and study team. The ECC is to be used by healthcare 
professionals not involved in the research study only, as a means of reaching the investigator 
or site staff related to the care of a participant. The Pfizer Call Center number should only be 
used when the investigator and site staff cannot be reached. The Pfizer Call Center number is 
not intended for use by the participant directly; if a participant calls that number directly, he 
or she will be directed back to the investigator site. 

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10.2. Appendix 2: Clinical Laboratory Assessments 
The following laboratory tests will be performed at times defined in the SoA section of this 
protocol (see Table 10). Additional laboratory results may be reported on these samples as a 
result of the method of analysis or the type of analyzer used by the clinical laboratory, or as 
derived from calculated values. These additional tests would not require additional collection 
of blood. Unscheduled clinical laboratory measurements may be obtained at any time during 
the study to assess any perceived safety issues. 
 
Table 10. Laboratory Tests 
 
Phase 1 
Notes 
Hematology 
Database should be constructed to allow capture of 
differential counts as percent and absolute values but only 
one or the other should be used by the site to collect data. 
Results will be reported as absolute values after 
conversion and graded according to the CTCAE criteria 
Hemoglobin 
Platelets 
WBC 
Absolute Neutrophils 
Absolute Lymphocytes 
Absolute Monocytes 
Absolute Eosinophils 
Absolute Basophils 
Chemistry 
ALT 
AST 
AP 
Sodium 
Potassium 
Ad hoc Central Lab Cytokine Analysesa 
Magnesium 
IL-6 
Chloride 
IL-10 
Total Calcium 
IL-1β 
Total Bilirubin*** 
IL-2 
BUN or Urea 
sIL2R 
Creatinine 
IL-15 
Uric Acid 
IL-17 
Glucose (non-fasted) 
IL-1b 
Albumin 
IL-8 
Phosphorus or Phosphate 
IFNγ 
MCP-1 
Coagulation 
IP10 
PT or INR 
TNF-α 
PTT/aPTT 
Other cytokines 
Urinalysis 
Urine dipstick for urine protein: If positive collect 24-hr and 
microscopic (Reflex Testing) 
Urine dipstick for urine blood: if positive collect 
microscopic (Reflex Testing) 
Pregnancy Test 
For female participants of childbearing potential, on serum 
or urine (to be specified in the protocol) 
Hepatitis Serology 
Cardiac Biomarkers 
HBsAg 
CPK (CK-MP) 

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Table 10. Laboratory Tests 
 
anti-HCV antibody or HCV RNA 
Troponin I and/or Troponin T 
Endocrinology 
ACTH 
TSH 
Free T4 
Tumor Biomarkers 
CA125 for OvCA 
CEA for CRC 
CA15-3 for BRCA 
PSA for prostate cancer 
***For Hy’s law potential cases, in addition to repeating AST and ALT, laboratory tests should include 
albumin, creatine kinase, total bilirubin, direct and indirect bilirubin, gamma-glutamyl transferase, PT/INR, 
and alkaline phosphatase. 
a. 
Cytokines for central lab evaluation will be collected if CRS is suspected. Local lab evaluation of 
cytokine is only required if the site requires this information for participant management. 
 
 
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. 

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10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting 
10.3.1. Definition of AE 
 
AE Definition 
• An AE is any untoward medical occurrence in a patient or clinical study 
participant, temporally associated with the use of study intervention, whether or not 
considered related to the study intervention. 
• Note: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of study intervention. 
 
 
Events Meeting the AE Definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (eg, ECG, radiological scans, vital sign measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator. Any abnormal laboratory test 
results that meet any of the conditions below must be recorded as an AE: 
• Is associated with accompanying symptoms; 
• Requires additional diagnostic testing or medical/surgical intervention; 
• 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. 
• Exacerbation of a chronic or intermittent preexisting condition, including either an 
increase in frequency and/or intensity of the condition. 
• New condition detected or diagnosed after study intervention administration, even 
though it may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE or SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent. Such overdoses should be reported regardless of 
sequelae. 

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Events NOT Meeting the AE Definition 
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition. 
• Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present 
or detected at the start of the study that do not worsen. 
• 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 malignant lesions on radiographs or other methods 
should not be reported as AEs. 
10.3.2. Definition of an SAE 
 
An SAE is defined as any untoward medical occurrence that, at any dose, meets 1 or 
more of the criteria listed below: 
a.  Results in death. 
b.  Is life-threatening. 
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event that 
hypothetically might have caused death if it were more severe. 
c.  Requires inpatient hospitalization or prolongation of existing hospitalization. 
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during hospitalization are AEs. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 

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serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious. 
Hospitalization for elective treatment of a preexisting condition that did not worsen from 
baseline is not considered an AE. 
d. Results in persistent or significant disability/incapacity. 
• The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. 
• This definition is not intended to include experiences of relatively minor 
medical significance, such as uncomplicated headache, nausea, vomiting, 
diarrhea, influenza, and accidental trauma (eg, sprained ankle), that may 
interfere with or prevent everyday life functions but do not constitute a 
substantial disruption. 
e.  Is a congenital anomaly/birth defect. 
f. Is a suspected transmission via a Pfizer product of an infectious agent, pathogenic 
or non-pathogenic, is considered serious. 
The event may be suspected from clinical symptoms or laboratory findings indicating an 
infection in a participant exposed to a Pfizer product. The terms “suspected transmission” 
and “transmission” are considered synonymous. These cases are considered unexpected 
and handled as serious expedited cases by pharmacovigilance personnel. Such cases are 
also considered for reporting as product defects, if appropriate. 
g. Other situations: 
• Medical or scientific judgment should be exercised by the investigator in 
deciding whether SAE reporting is appropriate in other situations, such as 
significant medical events that but may jeopardize the participant or may 
require medical or surgical intervention to prevent one of the other outcomes 
listed in the above definition. These events should usually be considered 
serious. 
• Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development 
of drug dependency or drug abuse. 
• 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 

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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 CTCAE Grade 5 (see the Assessment of Severity section). 
 
 
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During the Active 
Collection Period 
 
AE and SAE Recording/Reporting 
The table below summarizes the requirements for recording AEs on the CRF and for 
reporting SAEs on the CT SAE Report Form to Pfizer Safety throughout the active 
collection period. These requirements are delineated for 3 types of events: (1) SAEs; (2) 
nonserious AEs; and (3) exposure to the study intervention under study during pregnancy 
or breastfeeding, and occupational exposure. 
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. 
Safety Event 
Recorded on the CRF 
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness 
SAE 
All 
All 
Nonserious AE 
All 
None 
Exposure to the study 
intervention under study 
during pregnancy or 
breastfeeding 
All AEs/SAEs associated 
with exposure during 
pregnancy or breastfeeding 
Note: Instances of EDP or 
EDB not associated with an 
AE or SAE are not captured 
in the CRF. 
All instances of EDP are 
reported (whether or not 
there is an associated SAE)* 
All instances of EDB are 
reported (whether or not 
there is an associated SAE). 
** 

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Environmental or 
occupational exposure 
to the product under 
study to a non-participant 
(not involving EDP or 
EDB). 
None. Exposure to a study 
non-participant is not 
collected on the CRF. 
The exposure (whether or 
not there is an associated 
AE or SAE) must be 
reported.*** 
* EDP (with or without an associated AE or SAE): any pregnancy information is 
reported to Pfizer Safety using CT SAE Report Form and EDP Supplemental 
Form; if the EDP is associated with an SAE, then the SAE is reported to Pfizer 
Safety using the CT SAE Report Form. 
** EDB is reported to Pfizer Safety using the CT SAE Report Form which would 
also include details of any SAE that might be associated with the EDB. 
***Environmental or Occupational exposure: AEs or SAEs associated with 
occupational exposure are reported to Pfizer Safety using the CT SAE Report Form. 
When an AE or SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic reports) 
related to the event. 
The investigator will then record all relevant AE or SAE information in the CRF. 
It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Pfizer Safety in lieu of completion of the CT SAE Report Form/AE or SAE 
CRF page. 
There may be instances when copies of medical records for certain cases are requested by 
Pfizer Safety. In this case, all participant identifiers, with the exception of the participant 
number, will be redacted on the copies of the medical records before submission to Pfizer 
Safety. 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE or SAE. 

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Assessment of Severity 
• The investigator will make an assessment of severity for each AE reported during the 
study and assign it to 1 of the categories listed below (as defined by the NCI CTCAE 
system). An event is defined as “serious” when it meets at least 1 of the predefined 
outcomes as described in the definition of an SAE, NOT when it is rated as severe. 
GRADE Clinical Description of Severity 
1 
MILD AE 
2 
MODERATE AE 
3 
SEVERE AE 
4 
LIFE-THREATENING; urgent intervention indicated 
5 
DEATH RELATED TO AE 
 
 
Assessment of Causality 
• The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE or SAE. The investigator will use clinical 
judgment to determine the relationship. 
• A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration, will be considered and investigated. 
• The investigator will also consult the IB and/or product information, for marketed 
products, in his/her assessment. 
• For each AE or SAE, the investigator must document in the medical notes that 
he/she has reviewed the AE or SAE and has provided an assessment of causality. 
• There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor. However, it is 
very important that the investigator always make an assessment of causality 
for every event before the initial transmission of the SAE data to the sponsor. 
• The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 

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• The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
• If the investigator does not know whether or not the study intervention caused the 
event, then the event will be handled as “related to study intervention” for reporting 
purposes, as defined by the sponsor. 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. 
 
 
Follow-Up of AEs and SAEs 
• The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations, as medically indicated or as requested by the 
sponsor, to elucidate the nature and/or causality of the AE or SAE as fully as 
possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare providers. 
• New or updated information will be recorded in the originally submitted 
documents. 
• The investigator will submit any updated SAE data to the sponsor within 24 hours 
of receipt of the information. 
10.3.4. Reporting of SAEs 
 
SAE Reporting to Pfizer Safety via CT SAE Report Form 
• Facsimile transmission of the CT SAE Report Form is the preferred method to 
transmit this information to Pfizer Safety. 
• In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the CT SAE Report Form sent by overnight mail or 
courier service. 
• Initial notification via telephone does not replace the need for the investigator to 
complete and sign the CT SAE Report Form pages within the designated reporting 
time frames. 

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10.3.5. Guidance for Immune-Related Adverse Events 
 
Table 11. Management of Immune-Related Adverse Events 
 
Grade 
Management 
Follow-Up 
Gastrointestinal 
Grade 1 
Symptomatic treatment 
Continue study intervention therapy 
irAEs 
Diarrhea: <4 stools/day 
over baseline; 
Colitis: asymptomatic 
Grade 2 
Withhold study intervention 
If improves to Grade 1: 
Diarrhea: 4 to 6 stools 
therapy 
Resume study intervention therapy. 
per day over baseline; 
Symptomatic treatment 
If persists >5-7 days or recur: 
IV fluids indicated <24 
0.5 to 1.0 mg/kg/day 
hours; not interfering 
methylprednisolone or equivalent. 
with ADL 
When symptoms improve to 
Colitis: abdominal pain; 
Grade 1, taper steroids over at least 
blood in stool 
1 month, consider prophylactic 
antibiotics for opportunistic 
infections, and resume study 
intervention therapy per protocol. 
If worsens or persists >3 to 5 days 
with oral steroids: 
Treat as Grade 3 to 4. 
Grade 3 to 4 
Discontinue study intervention 
If improves: 
Diarrhea (Grade 3): ≥7 
therapy. 
Continue steroids until Grade 1, 
stools per day over 
1.0 to 2.0 mg/kg/day 
then taper over at least 1 month. 
baseline; incontinence; 
methylprednisolone IV or 
If persists >3 to 5 days, or recur 
IV fluids ≥24 hrs.; 
equivalent. 
after improvement: 
interfering with ADL 
Add prophylactic antibiotics 
Add infliximab 5 mg/kg (if no 
Colitis (Grade 3): severe 
for opportunistic infections 
contraindication), Note: Infliximab 
abdominal pain, medical 
Consider endoscopy. 
should not be used in cases of 
intervention indicated, 
perforation or sepsis. 
peritoneal signs 
Dermatitis irAE 
Grade 1 to 2 
Symptomatic therapy 
If persists >1 to 2 weeks or recurs: 
Covering ≤30% body 
(eg, antihistamines, topical 
Consider skin biopsy 
surface area 
steroids) Continue study 
Withhold study intervention 
intervention therapy. 
therapy. 
Consider 0.5 to 1.0 mg/kg/day 
methylprednisolone IV or oral 
equivalent. Once improving, taper 
steroids over at least 1 month, 
consider prophylactic antibiotics for 
opportunistic infections, and resume 
study intervention therapy 
If worsens: 
Treat as Grade 3 to 4. 
Grade 3 to 4 
Withhold or discontinue study 
If improves to Grade 1: 
Covering >30% body 
intervention therapy Consider 
Taper steroids over at least 1 month 
surface area; life 
skin biopsy Dermatology 
and add prophylactic antibiotics for 
threatening 
consult 
opportunistic infections. 
consequences 
1.0 to 2.0 mg/kg/day 
Resume study intervention therapy. 
methylprednisolone IV or IV 
equivalent. 

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Table 11. Management of Immune-Related Adverse Events 
 
Grade 
Management 
Follow-Up 
Pneumonitis 
irAEs 
Grade 1 
Radiographic changes 
only 
Consider delay of study 
intervention therapy 
Monitor for symptoms every 2 
to 3 days 
Consider Pulmonary and 
Infectious Disease consults. 
Re-image 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 intervention 
therapy 
Pulmonary and Infectious 
Disease consults 
Monitor symptoms daily, 
consider hospitalization 
1.0 mg/kg/day 
methyl-prednisolone IV or oral 
equivalent 
Consider bronchoscopy, lung 
biopsy. 
Re-image every 1 to 3 days 
If improves: 
When symptoms return to near 
baseline, taper steroids over at least 
1 month and then resume study 
intervention therapy and consider 
prophylactic antibiotics If not 
improving after 2 weeks or 
worsening: 
Treat as Grade 3 to 4. 
Grade 3 to 4 
Severe new symptoms; 
New/worsening hypoxia; 
life-threatening 
Discontinue study intervention 
therapy 
Hospitalize 
Pulmonary and Infectious 
Disease consults 
2 to 4 mg/kg/day 
methylprednisolone IV or IV 
equivalent 
Add prophylactic antibiotics 
for opportunistic infections 
Consider bronchoscopy, lung 
biopsy 
If improves to baseline: 
Taper steroids over at least 6 weeks. 
If not improving after 48 hours or 
worsening: 
Add additional immunosuppression 
(eg, infliximab, cyclophosphamide, 
intravenous immunoglobulin, or 
mycophenolate mofetil). 
Hepatitis irAEs 
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 intervention 
therapy. 
Continue liver function monitoring 
If worsens, treat as Grade 2 or 3 to 
4. 
Grade 2 
AST or ALT >3.0 to ≤5 
x ULN and/or total 
bilirubin >1.5 to ≤3 x 
ULN 
Withhold study intervention 
therapy 
Increase frequency of 
monitoring to every 3 days. 
If returns to baseline: 
Resume routine monitoring, resume 
study intervention therapy. 
If elevations persist >5 to 7 days or 
worsen: 
0.5 to 1 mg/kg/day 
methylprednisolone or oral 
equivalent and when LFT returns to 
Grade 1 or baseline, taper steroids 
over at least 1 month, consider 
prophylactic antibiotics for 
opportunistic infections, and resume 
study intervention therapy. 
Grade 3 to 4 
AST or ALT >5 x ULN 
and /or total bilirubin >3 
x ULN 
Discontinue study intervention 
therapy. 
Increase frequency of 
monitoring to every 1 to 2 
days. 
If returns to Grade 2: 
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. 

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Table 11. Management of Immune-Related Adverse Events 
 
Grade 
Management 
Follow-Up 
1.0 to 2.0 mg/kg/day 
methylprednisolone IV or IV 
equivalent. 
Add prophylactic antibiotics 
for opportunistic infections. 
Consult gastroenterologist. 
Consider obtaining MRI/ 
computed tomography scan of 
liver and liver biopsy if 
clinically warranted. 
If no response within an additional 3 
to 5 days, consider other 
immunosuppressants per local 
guidelines. 
Endocrine irAEs 
Asymptomatic TSH 
abnormality 
Continue study intervention 
therapy. 
If TSH <0.5 x LLN, or TSH >2 x 
ULN, or consistently out of range in 
2 subsequent measurements: include 
free T4 at subsequent cycles as 
clinically indicated; consider 
endocrinology consult. 
Symptomatic 
endocrinopathy 
Evaluate endocrine function 
Consider pituitary MRI scan. 
If symptomatic with abnormal 
lab/pituitary scan: 
Withhold study intervention 
therapy: 
1 to 2 mg/kg/day 
methylprednisolone IV or oral 
equivalent. 
Initiate appropriate hormone 
replacement therapy. 
If normal lab/pituitary MRI 
scan but symptoms persist: 
Repeat labs in 1 to 3 
weeks/MRI in 1 month. 
If improves (with or without 
hormone replacement): 
Taper steroids over at least 1 month 
and consider prophylactic antibiotics 
for opportunistic infections. 
Resume study intervention therapy. 
Participants with adrenal 
insufficiency may need to continue 
steroids with mineralocorticoid 
component. 
Suspicion of adrenal 
crisis (eg, severe 
dehydration, 
hypotension, shock out 
of proportion to current 
illness) 
Withhold or discontinue study 
intervention therapy. 
Rule out sepsis 
Stress dose of IV steroids with 
mineralocorticoid activity IV 
fluids. 
Consult endocrinologist 
If adrenal crisis ruled out, then 
treat as above for symptomatic 
endocrinopathy. 
Grade 1 or Grade 2 
endocrinopathies 
(hypothyroidism, 
hyperthyroidism, adrenal 
insufficiency, type I 
diabetes mellitus) 
Continue study treatment 
Endocrinology consult if 
needed 
Start thyroid hormone 
replacement therapy (for 
hypothyroidism), 
anti-thyroid treatment (for 
hyperthyroidism), 
corticosteroids (for adrenal 
insufficiency) or insulin (for 
Type I diabetes mellitus) as 
appropriate 
Continue hormone 
replacement/suppression and 
monitoring of endocrine function as 
appropriate. 

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Table 11. Management of Immune-Related Adverse Events 
 
Grade 
Management 
Follow-Up 
Rule-out secondary 
endocrinopathies (ie, 
hypopituitarism / hypophysitis) 
Grade 3 or Grade 4 
endocrinopathies 
(hypothyroidism, 
hyperthyroidism, adrenal 
insufficiency, type I 
diabetes mellitus) 
Withhold study treatment 
Consider hospitalization ----- 
Endocrinology consult 
Start thyroid hormone 
replacement therapy (for 
hypothyroidism), anti-thyroid 
treatment (for 
hyperthyroidism), 
corticosteroids (for adrenal 
insufficiency) or insulin (for 
type I diabetes mellitus) as 
appropriate. 
Rule-out secondary 
endocrinopathies (ie, 
hypopituitarism / hypophysitis) 
Resume study treatment once 
symptoms and/or laboratory tests 
improve to Grade ≤ 1 (with or 
without hormone 
replacement/suppression). 
Continue hormone 
replacement/suppression and 
monitoring of endocrine function as 
appropriate. 
Hypopituitarism/ 
Hypophysitis (secondary 
endocrinopathies) 
If secondary thyroid and/or 
adrenal insufficiency is 
confirmed (ie, subnormal 
serum FT4 with inappropriately 
low TSH and/or low serum 
cortisol with inappropriately 
low ACTH) : 
-Refer to endocrinologist for 
dynamic testing as indicated 
and measurement of other 
hormones (FSH, LH, 
GH/IGF-1, PRL, 
testosterone in men, 
estrogens in women) 
-Hormone 
replacement/suppressive 
therapy as appropriate 
-Perform pituitary MRI and 
visual field examination as 
indicated 
If hypophysitis is confirmed: 
-Continue study treatment if 
mild symptoms with normal 
MRI. Repeat the MRI in 1 
month 
-Withhold study treatment if 
moderate, severe or life- 
threatening symptoms of 
hypophysitis and/or abnormal 
MRI. Consider 
hospitalization. Initiate 
corticosteroids (1 to 2 
mg/kg/day prednisone or 
equivalent) followed by 
corticosteroids taper during at 
least 1 month. 
Resume study treatment once 
symptoms and hormone tests 
improve to Grade ≤ 1 (with or 
without hormone replacement). 
In addition, for hypophysitis with 
abnormal MRI, resume study 
treatment only once shrinkage of the 
pituitary gland on MRI/CT scan is 
documented. 
Continue hormone 
replacement/suppression therapy as 
appropriate. 

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Table 11. Management of Immune-Related Adverse Events 
 
Grade 
Management 
Follow-Up 
Add prophylactic antibiotics 
for opportunistic infections. 
Renal irAEs 
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. 
Cardiac irAEs 
Myocarditis 
New onset of cardiac 
signs or symptoms and / 
or new laboratory 
cardiac biomarker 
elevations (e.g. troponin 
I, 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 (e.g. 
azathioprine, cyclosporine A, 
abatacept). 
Other irAEs (not 
described 
above)** 
Grade 2 or Grade 3 
clinical signs or 
symptoms suggestive of 
a potential irAE 
Withhold study treatment 
pending clinical investigation 
If irAE is ruled out, manage as 
appropriate according to the 
diagnosis and consider re-starting 
study treatment 

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Table 11. Management of Immune-Related Adverse Events 
 
Grade 
Management 
Follow-Up 
If irAE is confirmed, treat as Grade 
2 or 3 irAE. 
Grade 2 irAE or first 
occurrence of Grade 3 
irAE 
Withhold study treatment 1.0 to 
2.0 mg/kg/day prednisone or 
equivalent. Add prophylactic 
antibiotics for opportunistic 
infections 
Specialty consult as appropriate 
If improves to Grade ≤ 1: 
Taper steroids over at least 1 month 
and resume study treatment 
following steroids taper. 
Recurrence of same 
Grade 3 irAEs 
Permanently discontinue study 
treatment 
1.0 to 2.0 mg/kg/day 
prednisone or equivalent 
Add prophylactic antibiotics 
for opportunistic infections 
Specialty consult as appropriate 
If improves to Grade ≤ 1: 
Taper steroids over at least 1 month. 
Grade 4 
Permanently discontinue study 
treatment 
1.0 to 2.0 mg/kg/day 
prednisone or equivalent and/or 
other immunosuppressant as 
needed 
Add prophylactic antibiotics 
for opportunistic infections 
Specialty consult. 
If improves to Grade ≤ 1: 
Taper steroids over at least 1 month 
Requirement for 10 mg 
per day or greater 
prednisone or equivalent 
for more than 12 weeks 
for reasons other than 
hormonal replacement 
for adrenal insufficiency 
Persistent Grade 2 or 3 
irAE lasting 12 weeks or 
longer 
Permanently discontinue study 
treatment 
Specialty consult 
*Local guidelines, or eg. ESC or AHA guidelines 
ESC guidelines website https://www.escardio.org/Guidelines/Clinical-Practice- 
Guidelines 
AHA guidelines website: https://www.heart.org/en/professional/quality-improvement 
**For other irAEs not specifically covered in this table (such as uveitis), refer to the NCCN Management of 
Immunotherapy-Related Toxicities for detailed guidance: 
https://www.nccn.org/guidelines/guidelines-detail?category=3&id=1486 

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10.4. Appendix 4: Contraceptive and Barrier Guidance 
10.4.1. Male Participant Reproductive Inclusion Criteria 
Male participants are eligible to participate if they agree to the following requirements during 
the intervention period and for at least 90 days after the last dose of study intervention, which 
corresponds to the time needed to eliminate reproductive safety risk of the study 
intervention(s): 
 
• Refrain from donating sperm. 
PLUS either: 
• Be abstinent from heterosexual intercourse with a female of childbearing potential 
as their preferred and usual lifestyle (abstinent on a long-term and persistent 
basis) and agree to remain abstinent. 
 
OR 
 
• Must agree to use contraception/barrier as detailed below: 
• Agree to use a male condom and should also be advised of the benefit for a 
female partner to use a highly effective method of contraception as a condom 
may break or leak when having sexual intercourse with a woman of 
childbearing potential who is not currently pregnant. 
 
• In addition to male condom use, a highly effective method of contraception may 
be considered in WOCBP partners of male participants (refer to the list of highly 
effective methods below in Section 10.4.4). 
 
10.4.2. Female Participant Reproductive Inclusion Criteria 
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at 
least 1 of the following conditions applies: 
 
• Is not a WOCBP (see definitions below in Section 10.4.3). 
OR 
• Is a WOCBP and using a contraceptive method that is highly effective (with a failure 
rate of <1% per year), preferably with low user dependency, as described below 
during the intervention period and for at least 90 days after the last dose of study 
intervention, which corresponds to the time needed to eliminate any reproductive 
safety risk of the study intervention(s). The investigator should evaluate the 
effectiveness of the contraceptive method in relationship to the first dose of study 
intervention. 

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• Is a WOCBP and using a contraceptive method that is highly effective (with a failure 
rate of <1% per year), with high user dependency, as described below during the 
intervention period and for at least 90 days after the last dose of study intervention, 
which corresponds to the time needed to eliminate any reproductive safety risk of the 
study intervention(s). In addition, a second effective method of contraception, as 
described below, must be used. The investigator should evaluate the effectiveness of 
the contraceptive method in relationship to the first dose of study intervention. 
 
The investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy. 
 
10.4.3. Woman of Childbearing and Non-Childbearing Potential 
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below). 
 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before the first dose of study intervention, additional evaluation should be 
considered. 
 
Women in the following categories are not considered WOCBP: 
 
1. Premenopausal female with 1 of the following: 
 
• Documented hysterectomy; 
• Documented bilateral salpingectomy; 
• Documented bilateral oophorectomy. 
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry. 
 
Note: Documentation for any of the above categories can come from the site personnel’s 
review of the participant’s medical records, medical examination, or medical history 
interview. The method of documentation should be recorded in the participant’s medical 
record for the study. 

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2. Postmenopausal female: 
 
• A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. In addition, 
 
• A high FSH level in the postmenopausal range must be used to confirm a 
postmenopausal state in women under 60 years of age and not using hormonal 
contraception or HRT. 
 
• A female on HRT and whose menopausal status is in doubt will be required to 
use one of the nonestrogen hormonal highly effective contraception methods 
if they wish to continue their HRT during the study. Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment. 
 
10.4.4. Contraception Methods 
Contraceptive use by men or women should be consistent with local availability/regulations 
regarding the use of contraceptive methods for those participating in clinical trials. 
 
Highly Effective Methods That Have Low User Dependency 
 
1. Implantable progestogen only hormone contraception associated with inhibition of 
ovulation. 
 
2. Intrauterine device. 
 
3. Intrauterine hormone-releasing system. 
 
4. Bilateral tubal occlusion. [eg, bilateral tubal ligation] 
 
5. Vasectomized partner. 
 
• A vasectomized partner is a highly effective contraceptive method provided that 
the partner is the sole sexual partner of the WOCBP and the absence of sperm has 
been confirmed. If not, an additional highly effective method of contraception 
should be used. The spermatogenesis cycle is approximately 90 days. 
 
Highly Effective Methods That Are User Dependent 
 
6. Combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation: 
 
• Oral; 
• Intravaginal; 

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• Transdermal; 
7. Progestogen-only hormone contraception associated with inhibition of ovulation: 
 
• Oral; 
• Injectable. 
8. Sexual abstinence: 
 
• Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention. The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual 
lifestyle of the participant. 
 
One of the following effective barrier methods must be used in addition to the highly 
effective methods listed above that are user dependent: 
 
• Male or female condom with or without spermicide; 
• Cervical cap, diaphragm, or sponge with spermicide; 
• A combination of male condom with either cervical cap, diaphragm, or sponge 
with spermicide (double-barrier methods). 

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CCI 

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10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-Up Assessments and 
Study Intervention Rechallenge Guidelines 
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 DILI. 
Participants who experience a transaminase elevation above 3 × ULN should be monitored 
more frequently to determine if they are “adaptors” or are “susceptible.” 
 
LFTs are not required as a routine safety monitoring procedure in this study. However, 
should an investigator deem it necessary to assess LFTs because a participant presents with 
clinical signs/symptoms, such LFT results should be managed and followed as described 
below. 
 
In the majority of DILI cases, elevations in AST and/or ALT precede 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 laboratory 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 
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). 

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• 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. 
 
In addition to repeating measurements of AST and ALT and TBili for suspected Hy’s law 
cases, additional laboratory tests should include albumin, CK, direct and indirect bilirubin, 
GGT, PT/INR, total bile acids, and alkaline phosphatase. 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/paracetamol (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, or 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, liver imaging (eg, biliary tract), and collection of serum 
samples for acetaminophen/paracetamol drug and/or protein adduct levels 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) 
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. 

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10.7. Appendix 7: ECG Findings of Potential Clinical Concern 
 
ECG Findings That May Qualify as AE 
• Marked sinus bradycardia (rate <40 bpm) lasting minutes. 
• New PR interval prolongation >280 msec. 
• New prolongation of QTcB or QTcF to >480 msec (absolute) or by ≥60 msec from 
baseline. 
• New-onset atrial flutter or fibrillation, with controlled ventricular response rate: 
ie, rate <120 bpm. 
• New-onset type I second-degree (Wenckebach) AV block of >30 seconds’ duration. 
• Frequent PVCs, triplets, or short intervals (<30 seconds) of consecutive ventricular 
complexes. 
ECG Findings That May Qualify as Serious AE 
• QTcF prolongation >500 ms. 
• New ST-T changes suggestive of myocardial ischemia. 
• New-onset left bundle branch block (QRS >120 ms). 
• New-onset right bundle branch block (QRS >120 ms). 
• Symptomatic bradycardia. 
• Asystole: 
• In awake, symptom-free participants in sinus rhythm, with documented periods of 
asystole ≥3.0 seconds or any escape rate <40 bpm, or with an escape rhythm that is 
below the AV node. 
• In awake, symptom-free participants with atrial fibrillation and bradycardia with 1 or 
more pauses of at least 5 seconds or longer. 
• Atrial flutter or fibrillation, with rapid ventricular response rate: rapid = rate 
>120 bpm. 
• Sustained supraventricular tachycardia (rate >120 bpm) (“sustained” = short duration 
with relevant symptoms or lasting >1 minute). 

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• Ventricular rhythms >30 seconds’ duration, including idioventricular rhythm (heart 
rate <40 bpm), accelerated idioventricular rhythm (HR >40 bpm to <100 bpm), and 
monomorphic/polymorphic ventricular tachycardia (HR >100 bpm (such as torsades 
de pointes)). 
• Type II second-degree (Mobitz II) AV block. 
• Complete (third-degree) heart block. 
ECG Findings That Qualify as SAE 
• Change in pattern suggestive of new myocardial infarction. 
• Sustained ventricular tachyarrhythmias (>30 seconds’ duration). 
• Second- or third-degree AV block requiring pacemaker placement. 
• Asystolic pauses requiring pacemaker placement. 
• Atrial flutter or fibrillation with rapid ventricular response requiring cardioversion. 
• Ventricular fibrillation/flutter. 
• At the discretion of the investigator, any arrhythmia classified as an adverse 
experience. 
The enumerated list of major events of potential clinical concern are recommended as “alerts” or 
notifications from the core ECG laboratory to the investigator and Pfizer study team, and not to be 
considered as all inclusive of what to be reported as AEs/SAEs. 

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10.8. Appendix 8: 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 globally 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). 
 
10.8.1. 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 #28. When the infection resolves, the participant may 
be considered for rescreening. 
 
10.8.2. Telehealth Visits 
In the event that in-clinic study visits cannot be conducted, every effort should be made to 
follow up on the safety of study participants at scheduled visits per the Schedule of 
Activities or unscheduled visits. Telehealth visits may be used to continue to assess 
participant safety and collect data points. Telehealth includes the exchange of healthcare 
information and services via telecommunication technologies (eg, audio, video, video- 
conferencing software) remotely, allowing the participant and the investigator to 
communicate on aspects of clinical care, including medical advice, reminders, education, and 
safety monitoring. The following assessments must be performed during a telehealth visit: 
 
• Review and record study intervention(s), including compliance and missed doses. 
• Review and record any AEs and SAEs since the last contact. Refer to Section 8.3. 
• Review and record any new concomitant medications or changes in concomitant 
medications since the last contact. 
 
• Review and record contraceptive method and results of pregnancy testing. Confirm that 
the participant is adhering to the contraception method(s) required in the protocol. Refer 
to Appendix 4 and Section 10.8.3.1 of this appendix regarding pregnancy tests. 
 
Study participants must be reminded to promptly notify site staff about any change in their 
health status. 

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10.8.3. Alternative Facilities for Safety Assessments 
10.8.3.1. 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 
following safety laboratory evaluations may be performed at a local laboratory: 
 
• All safety laboratory tests (Table 10) 
If a local laboratory is used, qualified study site personnel must order, receive, and review 
results. 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. 
 
If a participant requiring pregnancy testing cannot visit a local laboratory for pregnancy 
testing, a home urine pregnancy testing kit with a sensitivity of at least 25 mIU/mL may be 
used by the participant to perform the test at home, if compliant with local regulatory 
requirements. The pregnancy test outcome should be documented in the participant’s source 
documents/medical records and relevant data recorded on the CRF. Confirm that the 
participant is adhering to the contraception method(s) required in the protocol. 
 
10.8.3.2. Imaging 
If the participant is unable to visit the study site for safety imaging assessment(s), the 
participant may visit an alternative facility to have the safety imaging assessment(s) 
performed. Qualified study site personnel must order, receive, and review results. 
 
10.8.3.3. Electrocardiograms 
If the participant is unable to visit the study site for ECGs, the participant may visit an 
alternative facility to have the ECGs performed. Qualified study site personnel must order, 
receive, and review results. 
 
10.8.3.4. Echocardiogram or MUGA 
If the participant is unable to visit the study site for Echocardiogram or MUGA, the 
participant may visit an alternative facility to have the Echocardiogram or MUGA 
performed. Qualified study site personnel must order, receive, and review results. 
 
10.8.4. 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 administration of study intervention 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 6.8 
for any concomitant medication administered for treatment of SARS-CoV2 
infection. 
 
10.8.5. Home Health Visits 
A home health care service may be utilized to facilitate scheduled visits per the SoA. Home 
health visits include a healthcare provider conducting an in-person study visit at the 
participant’s location, rather than an in-person study visit at the site. The following may be 
performed during a home health visit: 
 
• Review and record study intervention(s), including compliance and missed doses. 
• Review and record any AEs and SAEs since the last contact. Refer to Section 8.5. 
• Review and record any new concomitant medications or changes in concomitant 
medications since the last contact. 
 
• Review and record contraceptive method and results of pregnancy testing. 
Confirm that the participant is adhering to the contraception method(s) required in 
the protocol. Refer to Appendix 4 and Section 10.8.3.1 of this appendix regarding 
pregnancy tests. 
 
10.8.6. Adverse Events and Serious Adverse Events 
If a participant has COVID-19 during the study, this should be reported as an adverse event 
(AE) or serious adverse events (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. 

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10.8.7. Efficacy Assessments 
If the participant is unable to visit the study site for CT or MRI scan, the participant may visit 
an alternative facility to have the CT or MRI scan performed. Qualified study site personnel 
must order, receive, and review results. 
 
10.8.8. Independent Oversight Committees 
No IOCs will be used in this study. 
 
10.9. Appendix 9: Detailed Dose Escalation/De-Escalation Scheme for BLRM Design 
This appendix provides the details of the statistical model, the general description of the prior 
distribution of the model parameters, and the sensitivity analysis. The BLRM will be set up 
separately for the dose-toxicity relationship when PF-07263689 when administered as 
monotherapy (Part 1A) and in combination with sasanlimab (Part 1B). The derivation of 
prior distributions for the model parameters is detailed in a separate Technical Supplement to 
this appendix. The results of the Bayesian analyses and respective dosing decisions for some 
hypothetical data scenarios, and a simulation study of the operating characteristics of the 
model are also presented in the separate Technical Supplement. 
 
10.9.1. Statistical Model for Monotherapy 
Let rr (d ) be the risk of DLT for PF-07263689 given as a single agent at dose d. The 
dose-DLT model is logistic: 
 
Logit (rr (d )) = log(a ) + [3 log(d ⁄ d ∗ ) 
d ∗ is the reference dose in the model and will be used to scale the doses of PF-07263689. 
Hence, α (>0) are the PF-07263689 odds of a DLT at d ∗; and β (>0) is the increase in the 
log-odds of a DLT by a unit increase in log-dose. 
 
The Bayesian approach requires the specification of prior distributions for all model 
parameters, which include the parameters log(α) and log(β). A weakly informative prior will 
be used as there are no relevant human historical DLT data available for PF-07263689. It is 
assumed that model parameters will follow a bivariate normal (BVN) distribution. 
 
(log(a), log([3 ) ) ~ N_2 (m, S) 
with prior means m = (m_1, m_2 ), and prior covariance matrix S composed of standard 
deviations and the correlation. The specifications of these parameters, and the operating 
characteristics of the BLRM are detailed in the separate Technical Supplement document. 

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d
d
d
10.9.2. Statistical Model for Combination with Sasanlimab 
In dose finding Part 1B, the dose/DLT relationship will be described by a 5-parameter 
BLRM for the combination of PF-07263689 with sasanlimab, formulated as follows: 
 
• PF-07263689 single agent toxicity, represented by parameters α1, and β1. 
 
( 
) 
( 
) 
d1 
logit(π1 d1 ) = log α1 + β1 log ( ∗) 
d1 
• The single agent toxicity of sasanlimab, represented by parameters α2, and β2. 
 
 
logit(π2 (d2 )) = log(α2) 
d2 
+ β2 log ( ∗ ) 
2 
 
where π1(d1) and π2(d2) are the probability that a participant experiences a DLT during the 
first cycle of combination treatment with PF-07263689 and sasanlimab at dose d1 and d2 
respectively and where d∗ and d∗ are the PF-07263689 and sasanlimab reference doses. 
1 
2 
 
Then, the dose-DLT relationship of the combination is defined as: 
 
 
Odds(rr12 (d1 
 
, d2 )) =  rr12(d1, d2) 
 
1 − rr12(d1, d2) 
= exp(η 
d1 d2) [rr1(d1) + rr2(d2) − rr1(d1)rr2(d2)] 
12  ∗ 
∗ 
1 
2 
(1 − rr1(d1))(1 − rr2(d2)) 
 
where η12 is the interaction parameter between PF-07263689 and sasanlimab. The interaction 
parameter is set up depending on the assumption that the drug combination may produce a 
toxic effect whose magnitude is less than (protective, η12 <0), equal to (no interaction, η12 = 
0), or greater than (synergistic, η12 >0) that obtained by the treatments acting independently. 
 
The Bayesian approach requires the specification of prior distributions for the model 
parameters log(a1), log([31), log(a2), log([32) and the interaction parameter η12. The prior 
for log(a1), log([31) will be based on emerging DLT data from PF-07263689 in Part 1A. The 
prior for log(a2), log([32) will be based on safety data available in the literature for 
Palbociclib. A weakly informative prior for the interaction parameter η12 will be used 
reflecting the current uncertainty about the interaction. 
 
Meta-Analytic-Predictive Priors Approach 
 
A MAP prior may be used to define the prior for any or all of the treatment in the dose 
escalation in order to account for heterogeneity between the available safety data and the 
actual study protocol population and treatment regimen/schedule. A MAP prior may be used 
instead of, or in addition to a weakly informative prior to form a weighted mixture prior and 
account for uncertainty. A mixture prior can take the form 

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p × BVNMAP + (1 − p) × BVNWeak 
The weights of the mixture prior are driven by clinical judgement. The aim of the MAP prior 
approach for treatment is to derive a prior distribution for the logistic parameters 
(log(a∗), log([3∗)) using prior DLT data, available from previously conducted trial, or from 
i 
i 
the same study but with another regimen. 
 
Let ri and ni be the number of participants with a DLT, and the total number of participants 
at dose di in the DLT data available from the historical trial. The corresponding probability 
of a DLT is rrdi. The model specifications are as follows: 
ri | rrdi ~ Bin(rrdi, ni) 
logit(rrdi) = log(ai) + [3i log(di/d∗) 
(log(ai), log([31)) I µ, 1/ ~ BVN(µi, 1/i) 
(log(a∗), log([3∗)) I µ, 1/ ~ BVN(µi, 1/i) 
i 
i 
 
The parameter µi = (µi1, µi2) is the mean for the logistic parameters, and 1/i is the 
between-regimen/study covariance matrix. Covariance matrix 1/i is defined by the standard 
deviations (ti1, ti2), and correlation ri. 
The following priors will be used for these parameters: 
 
• Normal priors for µi1 and µi2; 
• Log-normal priors for ti1 and ti2; and 
• A uniform prior for ri. 
To further specify the details of these distributions the principles described in 
Neuenschwander et.al., 2014 will be followed. The MAP prior for model parameters of 
PF-07263689, (log(a∗), log([3∗)), is the predictive distribution. 
i 
i 
 
(log(a∗), log([3∗)) I (ri, ni) 
i 
i 
 
Since the predictive distribution is not available analytically, the MCMC method is used to 
simulate values from this distribution. This is implemented using JAGS version 4.10. 
 
10.9.3. Sensitivity Analysis 
Despite being prespecified in the protocol, some AEs that fall into the category of DLTs may 
need to be considered differently. Conversely, some AEs that are not defined as a DLT per 
protocol should be considered by the dose escalation algorithm. Accordingly, the new 

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concept of an “equivocal” DLT or AE is introduced: most AE/DLTs are considered 
“unequivocal,” but certain types of AEs/DLTs are considered to be “equivocal.” 
 
To mitigate the risk of dichotomizing and misclassifying DLTs, the sensitivity analysis that 
uses those weighted equivocal DLT/AE data into the BLRM model estimation will also be 
performed. The BLRM model uses all the equivocal and unequivocal AE/DLT data, but the 
variability associated with equivocal AEs/DLTs (less interpretable) is increased. So, the 
model recommendations are more heavily weighted towards unequivocal data. See below for 
the posterior distribution of the BLRM model parameters based on the theory of power prior. 
 
Suppose n participants treated at dose with m unequivocal DLTs and r equivocal DLTs/AEs, 
and the weight w for the equivocal data, then based on the power prior, 
 
Posterior(a, β | d, m, r, w) ∝ L (m | a, β, d, w) × L (r | a, β, d, w) w × prior (a, β) 
 
∝ p (a, β, d) m ×[1- p (a, β, d)] n-r-m× p (a, β, d) rw× prior (a, β), 
where L is the likelihood of the observed DLT data, and p (a, β, d) is the probability of DLT 
at dose d that is modeled by logistic regression in BLRM. To achieve the equality sign, 
appropriate normalizing constant is required. 
 
The contribution of equivocal AEs/DLTs to the data (likelihood) and the Bayesian posterior 
estimation of the MTD are weighted; the weight parameter controls the influence and can be 
interpreted as a precision parameter for the equivocal AE/DLT data, similar to the scale 
parameter in the power prior for the Bayesian historical borrowing. 
 
The weight for an equivocal DLT is decreased (eg, 1 decreased to 0.5) and the weight for an 
equivocal AE (non-DLT by protocol) is increased (eg, 0 increased to 0.5). To maintain the 
integrity of a trial, the weight is pre-specified as 0.5 in the analysis. If all the investigators 
and the sponsor agree on the equivocal DLT/AE data, the DLT weighting approach could be 
the primary dose escalation method. This DLT weighting approach provides a flexible and 
powerful tool that may incorporate the clinician’s valuable experience with some specific 
DLTs/AEs and improve MTD estimation in dose escalation trials. 

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10.10. Appendix 10: RECIST (Response Evaluation Criteria In Solid Tumors) version 
1.1 Guidelines 
Adapted from Eisenhauer EA, et al (2009). 
 
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 CRF (eg, ‘multiple enlarged pelvic lymph nodes’ or ‘multiple liver 
metastases’). 
 
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. 

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Target disease 
• Complete response: 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: 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: 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. 
 
• PD: Unequivocal progression of pre-existing lesions. Generally the overall tumor 
burden must increase sufficiently to merit discontinuation of therapy. In the 
presence of SD or PR in target disease, progression due to unequivocal increase in 
non-target disease should be rare. 

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• 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 
Patients 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 EOT 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. 
 
Table 12. 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 

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If the protocol allows enrollment of patients with only non-target disease, the following 
Table 13 will be used: 
 
Table 13. Objective Response Status at each Evaluation for Patients 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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10.11. Appendix 11: CRS Mitigation and Management 
CRS is a non-antigen-specific cytokine-associated toxicity that occurs as a result of 
high-level immune activation. CRS is a potentially life-threatening toxicity that has been 
observed following administration of immune-base therapies for cancer (antibodies and 
adoptive T cell therapies). CRS is likely to be a common toxicity that can be managed 
through supportive care and anti-cytokine interventions. 
 
In cases of suspected CRS, a serum sample should be provided for cytokine release assay 
analysis by the local laboratory (see Section 6.8.3.3) provided the sampling does not interfere 
with the medical treatment of the participant. 
 
Early intervention should be undertaken at the first sign of CRS; signs may include pyrexia, 
tachycardia, tachypnea and/or hypotension and are temporally related to PF-07263689 in the 
absence of alternative etiologies. 
 
The ASTCT CRS criteria proposed by Lee et al. as presented in Table 14 will be used for the 
assessment of the CRS severity grade which will be captured on the AE CRF and on the CRS 
CRF (Lee et al, 2019). 
 
Table 14.  ASTCT CRS Revised Grading System 
 
CRS parameter: 
Fever* 
With Hypotension 
And/or† Hypoxia 
Grade 1 
Temp. ≥38°C 
None 
None 
Grade 2 
Temp. ≥38°C 
Not requiring vasopressors 
Requiring low-flow‡ nasal cannula, 
low-flow‡ facemask or blow-by 
Grade 3 
Temp. ≥38°C 
Requiring a vasopressor with or 
without vasopressin 
Requiring high-flow‡ nasal cannula, 
high-flow‡ facemask, nonrebreather 
mask, or Venturi mask 
Grade 4 
Temp. ≥38°C 
Requiring multiple vasopressors 
(excluding vasopressin) 
Requiring positive pressure (eg, 
CPAP, BiPAP, intubation and 
mechanical ventilation) 
Organ toxicities associated with CRS should still be graded according to CTCAE v 5.0 and do not influence CRS 
grading. 
* Fever is defined as temperature ≥38°C and not attributable to any other cause. In participants who have CRS then 
receive antipyretic or anticytokine therapy such as tocilizumab or steroids, fever is no longer required to grade 
subsequent CRS severity. In this case, CRS grading is driven by hypotension and/or hypoxia. 
† CRS grade is determined by the more severe event: hypotension or hypoxia not attributable to any other cause. For 
example, a patient with temperature of 39.5°C hypotension requiring 1 vasopressor, and hypoxia requiring low-flow 
nasal cannula is classified as Grade 3 CRS. 
‡ Low-flow nasal cannula or facemask is defined as oxygen delivered at ≤6 L/min. Low flow also includes blow-by 
oxygen delivery, sometimes used in pediatrics. High-flow nasal cannula or facemask is defined as oxygen delivered at >6 
L/min. This is modified from original ASTCT criteria to differentiate between low-flow and high-flow facemask. 

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The definitions for high-dose vasopressors are shown in Table 15. 
 
Table 15. Definition of High Dose Vasopressor 
 
Pressor 
High Dose 
(doses less than these would be considered low) 
Norepinephrine monotherapy 
20 g/min 
Dopamine monotherapy 
10 g/kg/min 
Phenylephrine monotherapy 
200 g/min 
Epinephrine monotherapy 
10 g/min 
If on vasopressin 
Vasopressin + norepinephrine 
equivalent of 10 g/min* 
If on combination vasopressors 
(not vasopressin) 
Norepinephrine equivalent of 
20 g/min* 
* VASST Trial vasopressor equivalent equation: norepinephrine equivalent dose = [norepinephrine ( g/min)] + 
[dopamine ( g/kg/min) ÷ 2] + [epinephrine ( g/min)] + [phenylephrine ( g/min) ÷10 
 
 
 
CRS Management Guidelines (Lee et al, 2019). 
 
These may be modified as needed by the responsible Investigator according to the best 
practices at their institute. 
 
ASTCT Grade 1 CRS: 
 
• Monitor vital signs for worsening of condition. 
Fever 
 
• Acetaminophen/paracetamol and hypothermia blanket for the treatment of fever. 
• Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen can be used as 
second treatment option for fever if not contraindicated. 
 
• Assess for infection using blood and urine cultures, and chest radiography. 
• Empiric broad-spectrum antibiotics and filgrastim if neutropenic. 

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• Maintenance IV fluids for hydration. 
• Symptomatic management of constitutional symptoms or organ toxicity. 
• Consider tocilizumab 8 mg/kg* IV or siltuximab 11 mg/kg IV for persistent (lasting 
>3 days) and refractory fever. 
 
ASTCT Grade 2 CRS: 
 
• Monitor vital signs every 4 hours for worsening of condition. 
Fever 
 
• Manage as in Grade 1 CRS. 
Hypotension 
 
• IV fluid bolus of 500-1000 ml of normal saline. Can give second IV fluid bolus if 
systolic blood pressure remains <90 mmHg. 
 
• Consider tocilizumab 8 mg/kg (maximum dose 800 mg) IV or siltuximab 11 mg/kg 
IV for treatment of hypotension refractory to fluid boluses; tocilizumab can be 
repeated after 6 h if needed. 
 
• If hypotension persists after 2 fluid boluses and anti-IL-6 therapy, start vasopressors, 
consider transfer to ICU, obtain ECHO, and initiate other methods of hemodynamic 
monitoring. 
 
• In participants at high-risk (bulky disease, older age or comorbidities) or if 
hypotension persists after 1-2 doses of anti-IL-6 therapy, dexamethasone can be used 
at 10 mg IV every 6 hrs. 
 
Hypoxia 
 
• Supplemental oxygen. 
• Tocilizumab or siltuximab ± corticosteroids and supportive care, as indicated for 
hypotension. 
 
ASTCT Grade 3 CRS: 
 
• Monitor patient (including continuous ECG monitoring) in an ICU and obtain ECHO 
if not done already. 

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Fever 
 
• Manage as in Grade 1 CRS. 
Hypotension 
 
• IV boluses, as needed, as recommended for Grade 2 CRS. 
• Tocilizumab and siltuximab as recommended for Grade 2 CRS if not administered 
previously. 
 
• Vasopressors as needed. 
• Dexamethasone 10 mg IV every 6 hrs; if refractory, increase to 20 mg IV every 6 hrs. 
Hypoxia 
 
• Supplemental oxygen including high-flow oxygen delivery. 
• Tocilizumab or siltuximab plus corticosteroids and supportive care, as described 
above. 
 
ASTCT Grade 4 CRS: 
 
• Monitor patient (including continuous ECG monitoring) in an ICU and obtain ECHO 
if not done already. 
 
Fever 
 
• Manage as in Grade 1 CRS. 
Hypotension 
 
• IV boluses, anti-IL-6 therapy, vasopressors, and hemodynamic monitoring as 
recommended for grade 3 CRS. 
 
• Methylprednisolone 1 g/day IV. 
Hypoxia 
 
• Supplemental oxygen via positive pressure/mechanical ventilation. 
• Tocilizumab or siltuximab plus corticosteroids and supportive care, as described 
above. 

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10.12. Appendix 12: 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. 
Source: Oken M et al. 1982. 

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10.13. Appendix 13: Sasanlimab Subcutaneous Injection Site Location Diagram 
 
Injection site locations include a maximum of 8 unique administration sites distributed across 
4 abdominal quadrants with a possibility of up to 2 injection locations per quadrant. Location 
1 is proximal to the umbilicus and Location 2 is distal to the umbilicus. 
 
Administer the required number of injections in the following order: 
 
o Lower Left Quadrant Location 1. 
o Lower Right Quadrant Location 1. 
o Lower Left Quadrant Location 2. 
o Lower Right Quadrant Location 2. 
o Upper Right Quadrant Location 1. 
o Upper Left Quadrant Location 1. 
o Upper Right Quadrant Location 2. 
o Upper Left Quadrant Location 2. 
Injections to the abdomen are preferred. If SC injections in the abdominal location are not 
possible, SC injections can be administered in a distributed manner in the thighs. 
SC injections in the upper extremities (eg, deltoid, upper and lower arm) are not permitted. 
 
Track the participant’s injection site(s) sequentially on this diagram with a red pen and mark 
the injection sites on the participant’s abdomen according to your clinic’s standard practice. 

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Record the location, time of each injection and any injection site reactions in the participant’s 
source records and study CRF. Complete 1 CRF per injection. 

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10.14. Appendix 14: Preliminary Clinical Summary for Study B8011001 Phase 1 FIH 
(PF-06801591) 
Data Cutoff Date: 03 August 2020. 
 
10.14.1. Study Design 
B8011001 is an ongoing Phase 1, open-label, multicenter, multiple dose, dose escalation and 
expansion study of PF-06801591 in patients with locally advanced or metastatic melanoma, 
HNSCC, ovarian cancer, sarcoma, NSCLC, urothelial carcinoma or other solid tumors. The 
primary purpose of this study is to evaluate safety and early signs of efficacy of 
PF-06801591. This clinical study is divided into a dose escalation (Part 1) phase, and a dose 
expansion (Part 2) phase. 
 
Part 1 Dose Escalation 
Part 1 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 patients with locally advanced or metastatic 
melanoma, HNSCC, ovarian cancer, sarcoma, small cell lung cancer (SCLC), 
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 
standard of care therapy; were not previously treated with an anti-PDx agent; and 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 1 with 
25 participants total enrolled into the IV dose cohorts and 15 participants enrolled into the SC 
dose cohort. 
 
Part 2 Dose Expansion 
 
The 300 mg SC dose was evaluated in an expanded population of 106 participants. This 
included 68 participants with locally advanced or metastatic NSCLC and 38 participants with 
locally advanced or metastatic UC who were anti-PDx 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 EGFR-activating mutation or an 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 PF-06801591 SC every 
4 weeks. 
 
10.14.2. Exposure 
As of 03 August 2020, 146 participants have been dosed on the study as shown in Table 16. 

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CCI 
 
Table 16. Part 1 and Part 2 Cohort Enrollment Details 
 
Cohort 
Route of Administration 
N Treated 
0.5 mg/kg 
IV 
2 
1 mg/kg 
IV 
8 
3 mg/kg 
IV 
8 
10 mg/kg 
IV 
7 
300 mg Part 1 
SC 
15 
300 mg Part 2 NSCLC 
SC 
68 
300 mg Part 2 UC 
SC 
38 
Total 
IV and SC 
146 
10.14.3. Summary of Safety 
10.14.3.1. Dose Limiting Toxicities (DLTs) 
No dose limiting toxicities were observed and thus, there was no maximum tolerated dose 
identified. 
 
10.14.3.2. Adverse Events 
 
Part 1, IV administration (n = 25) 
 
Information about AEs in the IV dose levels can be found in the PF-06801591 IB. 
 
Part 1, SC administration (n = 15) 
 
 

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CCI 
CCI 
Part 2, SC administration (n = 106) in participants with NSCLC and UC 
 
 
10.14.3.3. Serious Adverse Events (SAEs) 
 

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As of 27 July 2020, efficacy of Study B8011001 was evaluated CCI 
 
 
 
10.14.4. Summary of Efficacy 
Part 1 Dose Escalation 
 
 
Part 2 Dose Expansion 
Safety and clinical activity of SC administered anti-PD-1 antibody PF-06801591 in Phase 1 
dose expansion cohorts of locally advanced or metastatic NSCLC and UC were reported in 
ESMO of 2019 (Cho et al, 2019). 
 
The efficacy analyses were performed with 68 participants with NSCLC and 38 participants 
with UC that were evaluable for efficacy. As of 27 July 2020, the observed ORR in the 
NSCLC cohort was 20.6% (95% CI: 11.7, 32.1%) with 14 confirmed PR, and 24 (35.3%) 
participants with NSCLC achieved a BOR of SD. In the UC cohort the ORR was 21.1% 
(95% CI 9.6, 37.3%) with 8 confirmed PR and 12 (31.6%) participants had SD. In the 
NSCLC cohort, median duration of response was 230 (57–445) days. In the UC cohort, 
median duration of response was 183 (23–371) days (Cho et al, 2020). 
 
Updated results of SC (PD-1) receptor antibody PF-06801591 for locally advanced or 
metastatic NSCLC or UC were reported in September of 2020. These details are provided in 
the full citation from ESMO 2020. 
 
10.14.5. Summary of Clinical Pharmacology 
PF-06801591 demonstrated pharmacokinetic (PK) characteristics typical of IgG4 monoclonal 
 
 
10.14.6. Conclusions 
Based on the available safety and efficacy data for PF-06801591, the benefit risk profile of 
PF-06801591 is expected to be favorable. 
CCI 
antibodies. CCI 

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10.15. Appendix 15: Abbreviations 
The following is a list of abbreviations that may be used in the protocol. 
 
Abbreviation 
Term 
Ab 
antibody 
ACTH 
adrenocorticotropic hormone 
ACV 
acyclovir 
ADA 
antidrug antibodies 
ADL 
activities of daily living 
AE 
adverse event 
AESI 
adverse events of special interest 
AIDS 
acquired immunodeficiency syndrome 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
AP 
alkaline phosphatase 
aPTT 
activated partial thromboplastin time 
ASCO 
American Society of Clinical Oncology 
AST 
aspartate aminotransferase 
ASTCT 
American Society for Transplantation and Cellular Therapy 
AUC 
area under the curve 
AUClast 
area under the plasma concentration-time curve from time 0 to time 
of last measurable concentration 
AV 
atrioventricular 
BLRM 
Bayesian logistic regression model 
BP 
blood pressure 
Bpm 
beats per minute 
BNP 
B-type natriuretic peptide 
BOR 
best overall response 
BRCA 
breast cancer 
BUN 
blood urea nitrogen 
CA 
cancer antigen 
CD 
cluster of differentiation 
CEA 
carcinoembryonic antigen 
cfDNA 
circulating free DNA 
CFR 
Code of Federal Regulations 
CHF 
congestive heart failure 
CI 
confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
CK 
creatine kinase 
CK-MB 
creatine kinase MB 
Cmax 
maximum observed concentration 
CPAP 
Continuous positive airway pressure 
CNS 
central nervous system 

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Abbreviation 
Term 
CONSORT 
Consolidated Standards of Reporting Trials 
COVID-19 
coronavirus disease 2019 
CR 
complete response 
CRC 
colorectal cancer 
CRF 
case report form 
CRO 
contract research organization 
CRS 
cytokine release syndrome 
CSR 
clinical study report 
CT 
clinical trial/computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTLA-4 
cytotoxic T-lymphocyte-associated protein 4 
CxDx 
cycle x day x 
DC 
dendritic cell 
DCR 
disease control rate 
DILI 
drug-induced liver injury 
DLRM 
dose level review meeting 
DLT 
dose-limiting toxicity 
DMC 
data monitoring committee 
DOR 
duration of response 
DU 
dispensable unit 
EC 
ethics committee 
ECC 
emergency contact card 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDB 
exposure during breastfeeding 
EDP 
exposure during pregnancy 
EGFR 
epidermal growth factor receptor 
EMA 
European Medicines Agency 
EOS 
end of study 
EOT 
end of treatment 
ESMO 
European Society for Medical Oncology 
EU 
European Union 
EudraCT 
European Clinical Trials Database 
EWOC 
escalation with overdose control 
FAP 
fibroblast activation protein 
FAS 
full analysis set 
FDA 
Food and Drug Administration (United States) 
FFPE 
formalin-fixed paraffin-embedded 
FIH 
first-in-human 
FSH 
follicle-stimulating hormone 
GCL 
Global Clinical Lead 

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Abbreviation 
Term 
GCP 
Good Clinical Practice 
GCV 
ganciclovir 
GGT 
gamma-glutamyl transferase 
GH 
growth hormone 
GI 
gastrointestinal 
GLP 
Good laboratory practice 
GM-CSF 
granulocyte-macrophage colony stimulating factor 
gv 
glycovariant 
HBV 
hepatitis B virus 
HCC 
hepatocellular carcinoma 
HCP 
health care provider 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
HNSCC 
head and neck squamous cell carcinoma 
HNSTD 
highest non-severe toxic dose 
HR 
heart rate 
HRT 
hormone replacement therapy 
HSV 
herpes simplex virus 
IB 
investigator’s brochure 
ICD 
informed consent document 
ICH 
International Council for Harmonisation 
ICU 
intensive care unit 
ID 
identification 
IFN-γ 
interferon-gamma 
IgG 
Immunoglobulin gamma 
IHC 
immunohistochemistry 
C 
CI 
ILD 
interstitial lung disease 
IMP 
investigational medicinal product 
IND 
investigational new drug 
INR 
international normalized ratio 
IP manual 
investigational product manual 
IPAL 
Investigational Product Accountability Log 
irAE 
immune-related adverse events 
IRB 
institutional review board 
IRC 
internal review committee 
IRR 
infusion related reaction 
IRT 
interactive response technology 
IT 
intratumoral 

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Abbreviation 
Term 
IV 
Intravenous(ly) 
IWR 
interactive Web-based response 
LBBB 
left bundle branch block 
LFT 
liver function test 
LH 
luteinizing hormone 
LLOQ 
lower limit of quantitation 
LLN 
lower limit of normal 
LTFU 
long-term follow-up 
LVEF 
left ventricular ejection fraction 
MAP 
meta-analytic-predictive 
MedDRA 
Medical Dictionary for Regulatory Activities 
MEK 
mitogen-activated protein kinase 
MFD 
maximum feasible dose 
mIL-2v 
Mouse interleukin 2 variant 
MOA 
mechanism of action 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
MSS 
microsatellite stable 
MUGA 
multiple-gated acquisition 
NA 
not applicable 
NAb 
neutralizing antibodies 
NCI 
National Cancer Institute 
NCCN 
National Comprehensive Cancer Network 
NIMP 
non-investigational medicinal product 
NK 
natural killer 
NOAEL 
no-observed-adverse-effect level 
NSAID 
nonsteroidal anti-inflammatory drug 
NSCLC 
non-small-cell lung carcinoma 
NZW 
New Zealand white 
ORR 
objective response rate 
OS 
overall survival 
OV 
oncolytic virus 
OvCA 
ovarian cancer 
PD 
pharmacodynamics(s); progressive disease 
PD-1 
programmed cell death protein 1 
PD-L1 
programmed death ligand 1 
PDx 
programmed cell death protein 1/programmed death ligand 1 
PET 
positron emission tomography 
PFS 
progression-free survival 
PFU 
plaque-forming unit 
PI 
principal investigator 
PK 
pharmacokinetic(s) 

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Abbreviation 
Term 
PR 
partial response; pulse rate 
PRL 
prolactin 
PS 
performance status 
PSA 
prostate-specific antigen 
CCI 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
PVC 
premature ventricular contraction/complex 
QxW 
every x week 
QTc 
corrected QT 
QTcB 
corrected QT (Bazett method) 
QTcF 
corrected QT (Fridericia method) 
QTL 
quality tolerance limit 
RBC 
red blood cell 
RCC 
renal cell carcinoma 
REB 
Research Ethics Board 
RECIST 
Response Evaluation Criteria in Solid Tumors 
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(ly) 
SCLC 
small cell lung cancer 
SCr 
serum Creatinine 
SD 
stable disease 
SoA 
schedule of activities 
SOP 
standard operating procedure 
SpO2 
oxygen saturation 
SRSD 
single reference safety document 
SUSAR 
suspected unexpected serious adverse reaction 
T4 
thyroxine 
TBili 
total bilirubin 
TCR 
T-cell receptor 
TGI 
tumor growth inhibition 
TEAE 
treatment emergent adverse event(s) 
TETRAE 
treatment-related adverse events 
TK 
thymidine kinase 
TK- 
thymidine kinase deletion 
Tmax 
time to maximum concentration 
TME 
tumor microenvironment 
TNF 
tumor necrosis factor 

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Abbreviation 
Term 
TSH 
thyroid-stimulating hormone 
TTP 
time to progression 
UC 
urothelial carcinoma 
ULN 
upper limit of normal 
US 
United States 
USPI 
United States Prescribing Information 
VIG 
Vaccinia immune globin 
VEGF 
vascular endothelial growth factor 
VV 
Vaccinia virus 
VV-Cop 
Vaccinia virus Copenhagen strain 
VV-WR 
Vaccinia virus Western Reserve strain 
WBC 
white blood cell 
WHO 
World Health Organization 
WOCBP 
woman/women of childbearing potential 

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11. REFERENCES 
AIDSinfo. Interim Guidance for COVID-19 and Persons with HIV. 2020. 
https://aidsinfo.nih.gov/guidelines/html/8/covid-19-and-persons-with-hiv--interim-guidance- 
/0. Accessed 29 Jun 2020. 
 
Bentebibel S, Hurwitz ME, Bernatchez C, et al. A first-in-human study and biomarker 
analysis of NKTR-124, a novel IL2Rβγ-biased cytokine, in patients with advanced or 
metastatic solid tumors. Cancer Discov. 2019;9(6):711-21. 
 
Blasco R, Sisler JR, Moss B, et al. Dissociation of progeny vaccinia virus from the cell 
membrane is regulated by a viral envelope glycoprotein: effect of a point mutation in the 
lectin homology domain of the A34R gene. J Virol. 1993;67:3319-25. 
 
Bommareddy P, Shettigar M, Kaufman H. Integrating oncolytic viruses in combination 
cancer immunotherapy. Nat Rev Immunol 2018; 18(8):498-513. 
 
Breitbach CJ, Burke J, Jonker D, et al. Intravenous delivery of a multi-mechanistic cancer- 
targeted oncolytic poxvirus in humans. Nature. 2011;477(7362):99-102. 
 
The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for 
Diagnosis of Diseases of the Heart and Great Vessels. 9th ed. Boston, Mass: Little, Brown & 
Co; 1994:253-256. 
 
Cho BC, Penkov K, Bondarenko I, et al. Safety and clinical activity of subcutaneously 
administered anti-PD-1 antibody PF-06801591 in Phase 1 1 dose-expansion cohorts of 
locally advanced or metastatic non-small-cell lung cancer (NSCLC) and urothelial carcinoma 
(UC). Annals of Oncology. 2019;30(suppl_5):v475-v532. 
 
Cho BC, Penkov K, Bondarenko I, et al. Updated results of subcutaneous anti-programmed 
cell death 1 receptor antibody sasanlimab (PF-06801591) for locally advanced or metastatic 
non–small cell lung cancer or urothelial carcinoma. ESMO 2020_Sasanlimab Ph1 Exp 
Updated Poster. Available at: esmo2020 european society of medical oncology 660 rn888 
cho 2297. 
 
Comins C, Spicer J, Protheroe A, et al. REO-10: a phase I study of intravenous reovirus and 
docetaxel in patients with advanced cancer. Clin Cancer Res. 2010;16(22):5564-72. 
 
Defining cancer. National Cancer Institute, updated February 9, 2015. 
http://www.cancer.gov/cancertopics/what-is-cancer. 
 
Downs-Canner S, Guo ZS, Ravindranathan R, et al. Phase 1 study of intravenous oncolytic 
poxvirus (vvDD) in patients with advanced solid cancers. Mol Ther. 2016;24(8):1492-501. 
 
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid 
tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-47. 

PF-07263689 
Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
Page 188 
 
 
Francisco LM, Sage PT, Sharpe AH. The PD-1 pathway in tolerance and autoimmunity. 
Immunol Rev. 2010;236:219-42. 
 
Freeman AI, Zakay-Rones Z, Gomori JM, et al. Phase I/II trial of intravenous NDV-HUJ 
oncolytic virus in recurrent glioblastoma multiforme. Mol Ther. 2006;13(1):221-8. 
 
García M, Moreno R, Gil-Martin M, et al. A Phase 1 Trial of Oncolytic Adenovirus 
ICOVIR-5 Administered Intravenously to Cutaneous and Uveal Melanoma Patients. Hum 
Gene Ther. 2019;30(3):352-64. 
 
Heo J, Reid T, Ruo L, et al. Randomized dose-finding clinical trial of oncolytic 
immunotherapeutic vaccinia JX-594 in liver cancer. Nat Med 2013;19(3):329-36. 
 
Jin HT, Ahmed R, Okazaki T. Role of PD-1 in regulating T-cell immunity. Curr Top 
Microbiol Immunol. 2011;350:17-37. 
 
Karapanagiotou EM, Roulstone V, Twigger K, et al. Phase I/II trial of carboplatin and 
paclitaxel chemotherapy in combination with intravenous oncolytic reovirus in patients with 
advanced malignancies. Clin Cancer Res. 2012;18(7):2080-9. 
 
Kirn D, Thorne SH. Targeted and armed oncolytic poxviruses: a novel multi-mechanistic 
therapeutic class for cancer. Nat Rev Cancer 2009; 9(1):64-71 
 
KEYTRUDA® (pembrolizumab lyophilized powder; intravenous infusion) [package insert]. 
Whitehouse Station (NJ): Merck & Co, Inc; 2018. 
 
Kluger HM, Tawbi HA, Ascierto ML, et al. Defining tumor resistance to PD-1 pathway 
blockade: recommendations from the first meeting of the SITC Immuotherapy Resistance 
Taskfore. J Immunother Cancer. 2020;8(1):e000398. 
 
Kolb EA, Sampson V, Stabley D, et al. A phase I trial and viral clearance study of reovirus 
(Reolysin) in children with relapsed or refractory extra-cranial solid tumors: a Children's 
Oncology Group Phase I Consortium report. Pediatr Blood Cancer. 2015;62(5):751-8. 
 
Kretzschmar M, Wallinga J, Teunis P, et al. Frequency of adverse events after vaccination 
with different vaccinia strains. PLOS Medicine. 2006;3(8):e272. 
 
Kung C-H, Kuo S-C, Chen Te-Li, et al. Isolation of vaccinia JX594 from pustules following 
therapy for hepatocellular carcinoma. BMC Cancer. 2015;15:704. 
 
Lauer UM, Schell M, Beil J, et al. Phase I study of oncolytic vaccinia virus GL-ONC1 in 
patients with peritoneal carcinomatosis. Clin Cancer Res. 2018;24(18):4388-98. 
 
Lawler S, Speranza M, Cho C, et al. Oncolytic Viruses in Cancer Treatment: A 
Review. JAMA Oncol 2017; 3(6):841-9. 

PF-07263689 
Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
Page 189 
 
 
Lee DW, Santomass BD, Locke FL, et al. ASTCT consensus grading for cytokine release 
syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow 
Transplant. 2019;25(4):625-38. 
 
Liu Z, Ravindranathan R, Kalinski P, et al. Rational combination of oncolytic vaccinia virus 
and PD-L1 blockade works synergistically to enhance therapeutic efficacy. Nat Commun. 
2017;8:14754. 
 
Machiels JP, Salazar R, Rottey S, et al. A phase 1 dose escalation study of the oncolytic 
adenovirus enadenotucirev, administered intravenously to patients with epithelial solid 
tumors (EVOLVE). J Immunother Cancer. 2019;7(1):20. 
 
Mell LK, Brumund KT, Daniels GA, et al. Phase I Trial of Intravenous Oncolytic Vaccinia 
Virus (GL-ONC1) with Cisplatin and Radiotherapy in Patients with Locoregionally 
Advanced Head and Neck Carcinoma. Clin Cancer Res. 2017;23(19):5696-702. 
 
Neuenschwander PF, Matano A, Tang Z, et al. A Bayesian Industry Approach to Phase I 
Combination Trials in Oncology. In: Zhao W, Yang H, editors. Statistical Methods in Drug 
Combination Studies. Chapman & Hall/CRC; 2014:95-135. 
 
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern 
Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649-55. 
 
OPDIVO® (nivolumab solution; intravenous infusion) [package insert]. Princeton (NJ): 
Bristol-Myers Squibb Company; 2018. 
 
Park BH, Hwang T, Liu TC, et al. Use of a targeted oncolytic poxvirus, JX-594, in patients 
with refractory primary or metastatic liver cancer: a phase I trial. Lancet Oncol 
2008;9(6):533-42. 
 
Park SH, Breitbach CJ, Lee J, et al. Phase 1b Trial of Biweekly Intravenous Pexa-Vec (JX- 
594), an Oncolytic and Immunotherapeutic Vaccinia Virus in Colorectal Cancer. Mol Ther. 
2015;23(9):1532-40. 
 
Pecora AL, Rizvi N, Cohen GI, et al. Phase I trial of intravenous administration of PV701, an 
oncolytic virus, in patients with advanced solid cancers. J Clin Oncol. 2002 May 
1;20(9):2251-66. 
 
Pico de Coaña Y, Choudhury A, Kiessling R. Checkpoint blockade for cancer therapy: 
revitalizing a suppressed immune system. Trends Mol Med. 2015;21(8):482-91. 
 
Preuss E, Treschow A, Newrzela S, et al. TK.007: a novel, codon-optimized HSVtk(A168H) 
mutant for suicide gene therapy. Hum Gene Ther. 2010;21(8):929-41. 
 
Rosenberg SA. IL-2: the first effective immunotherapy for human cancer. J Immunol. 
2014;192(12):5451-8. 

PF-07263689 
Protocol C4651001 
Final Protocol, Amendment 1, 20 July 2021 
PFIZER CONFIDENTIAL 
Page 190 
 
 
Ricordel M, Foloppe J, Antoine D, et al. Vaccinia virus shuffling: deVV5, a novel chimeric 
poxvirus with improved oncolytic potency. Cancers (Basel). 2018;10(7):231. 
 
Rudin CM, Poirier JT, Senzer NN, et al. Phase I clinical study of Seneca Valley Virus (SVV- 
001), a replication-competent picornavirus, in advanced solid tumors with neuroendocrine 
features. Clin Cancer Res. 2011;17(4):888-95. 
 
Russell S, Peng K, Bell J. Oncolytic virotherapy. Nat Biotechnol 2012;30(7):658-70. 
 
Schiffer CA, Bohlke K, Delaney M, et al. Platelet transfusion for patients with cancer: 
American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 
2018;36(3):283-99. 
 
Small EJ, Carducci MA, Burke JM, et al. A phase I trial of intravenous CG7870, a 
replication-selective, prostate-specific antigen-targeted oncolytic adenovirus, for the 
treatment of hormone-refractory, metastatic prostate cancer. Mol Ther. 2006;14(1):107-17. 
 
Soerensen MM, Ros W, Rodriguez-Ruiz ME, et al. Safety, PK/PD, and antitumor activity of 
RO6874281, an engineered variant of interleukin-2 (IL-2v) targeted to tumor-associated 
fibroblasts via binding to fibroblast activation protein (FAP). 2018;36(15_suppl):e15155. 
 
Streby KA, Currier MA, Triplet M, et al. First-in-human intravenous seprehvir in young 
cancer patients: a Phase 1 clinical trial. Mol Ther. 2019;27(11):1930-8. 
 
Twumasi-Boateng K, Pettigrew J, Kwok YYE, et al. Bell JC. 2018. Oncolytic viruses as 
engineering platforms for combination immunotherapy. Nat Rev Cancer 2018; 18(7):419-32. 
 
WHO guidelines on nonclinical evaluation of vaccines. Geneva, World Health Organization, 
2005 (WHO Technical Report Series, No 927, Annex 1.