A Phase 1b/2 Open Label Umbrella Study of Sasanlimab Combined With Anti-Cancer Therapies Targeting Multiple Molecular Mechanisms in Participants With Non-Small Cell Lung Cancer (NSCLC)
Phase: PHASE1
Conditions: Carcinoma, Non-Small-Cell Lung
Sponsor: Pfizer

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 1
Title page
A Phase 1b/2 Open Label Umbrella Study of Sasanlimab Combined with Anti-Cancer 
Therapies Targeting Multiple Molecular Mechanisms in Participants with Non-Small 
Cell Lung Cancer (NSCLC)
Compound: Sasanlimab (PF-06801591)
Regulatory Agency Identifier Number(s)
Registry
ID
IND
EudraCT
2020-002829-28
Protocol Number: B8011011
Amendment Number: 4
Phase: Phase 1b/Phase 2
Short Title: Umbrella Study of Sasanlimab in Participants with NSCLC 
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.
CCI

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 2
Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary and Rationale for Changes
Original protocol
18 June 2020
Protocol 
Amendment 1
04 August 2020
Protocol 
Amendment 2
07 December 2020 
Protocol 
Amendment 3
28 April 2021 
Protocol 
Amendment #4 
21 October 2021

Master protocol exclusion criterion 
#13 was clarified to indicate HIV 
testing if required locally 
(Section 5.2).

For Sub-Study A, added extra 
information and concomitant 
therapy caution for BCRP 
substrates, P-gp substrates, 
UGT1A1 inducers, and UGT1A1 
inhibitors (Sections 10.13 and
12.6.5.1).    

Sub-Study A exclusion criterion 
#19 and Sub-Study B exclusion 
criterion #17 were updated to 
clarify that EGFR mutation status 
must be known, and that only 
activating mutations are excluded 
(Sections 12.5.2 and 13.5.2, 
respectively).

For Sub-Study A, added that blood 
samples collected at Screening may 
be used for development of a 
medical device/diagnostic test for 
the BRAFV600 mutation 
(Section 12.1 and 12.8.4).

For Sub-Study A and B, added cf
DNA blood draw and removed 
blood draws for specified gene 
expression (RNA) and specified 
protein and metabolic research to 
prioritize exploratory analysis of 
ctDNA as a biomarker for outcome 
(Sections 12.1 and 13.1).

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 3
Document History
Document
Version Date
Summary and Rationale for Changes

Added a Pre-Screening period in 
the SoA for Sub-Study B to allow 
extra time for sites to obtain results 
of local PD-L1 and/or genetic 
testing that are required for 
eligibility; a corresponding row for 
Eligibility Review was also added 
(Section 13.1).

Added coagulation testing at Cycle 
5 in the SoA for Sub-Study B, as it
was inadvertently omitted 
(Section 13.1).

Added newly obtained information
for the monotherapy dose-
escalation of SEA-TGT from the 
FIH study (study SGNTGT-001)
(Section 13.2.2.3.2).

Added the SEA-TGT doses in Sub-
Study B based on new findings
from the FIH study
(Sections 13.4.1, 13.4.4.1, 13.6).

For Sub-Study B, reduced 
frequency of troponin clinical 
laboratory testing from every visit 
to Screening/C1D1 and when 
clinically indicated, because routine 
monitoring of troponin is not 
indicated for axitinib or approved 
immune checkpoint inhibitors 
(Section 13.10.1).

Injectables were removed from the 
list of combined hormonal birth 
control methods that are highly 
effective and user dependent per 
new Pfizer standard because there 
are no approved injectable agents 
in this category (Sections 12.10.2.4   
and 13.10.2.4.)

Moved rationale for Protocol 
Amendments prior to the current 
amendment to new Section 10.14 in 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 4
Document History
Document
Version Date
Summary and Rationale for Changes
accordance with the new Pfizer 
template.

Administrative changes were made 
to improve readability and 
consistency of structure and 
wording across the sub-studies and 
master protocol.
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 letters.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 5
TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................16
LIST OF FIGURES .................................................................................................................17
1. PROTOCOL SUMMARY...................................................................................................18
1.1. Synopsis ..................................................................................................................18
1.2. Schema ....................................................................................................................21
1.3. Schedule of Activities (SoA)...................................................................................21
2. INTRODUCTION ...............................................................................................................22
2.1. Study Rationale .......................................................................................................22
2.2. Background .............................................................................................................24
2.2.1. Nonclinical Overview.................................................................................25
2.2.1.1. Nonclinical Pharmacology........................................................25
2.2.1.2. Nonclinical Pharmacokinetics and Metabolism........................25
2.2.1.3. Nonclinical Safety.....................................................................26
2.2.2. Clinical Overview.......................................................................................26
2.3. Benefit/Risk Assessment.........................................................................................27
3. OBJECTIVES AND ENDPOINTS.....................................................................................28
4. STUDY DESIGN.................................................................................................................28
4.1. Overall Design.........................................................................................................28
4.2. Scientific Rationale for Study Design.....................................................................29
4.3. Justification for Dose ..............................................................................................29
4.3.1. Starting Dose for Phase 1b .........................................................................29
4.3.2. Criteria for Dose Escalation/De-Escalation................................................29
4.3.3. Dose Limiting Toxicity (DLT) Definition..................................................29
4.3.4. Maximum Tolerated Dose (MTD) Definition............................................31
4.3.5. Recommended Phase 2 Dose (RP2D) Definition.......................................31
4.4. End of Study Definition ..........................................................................................31
5. STUDY POPULATION......................................................................................................31
5.1. Inclusion Criteria.....................................................................................................32
5.2. Exclusion Criteria....................................................................................................33
5.3. Lifestyle Considerations..........................................................................................35
5.3.1. Contraception..............................................................................................35

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 6
5.4. Screen Failures ........................................................................................................35
6. STUDY INTERVENTION..................................................................................................36
6.1. Study Intervention(s) Administered........................................................................36
6.1.1. Administration of Sasanlimab ....................................................................37
6.1.2. Medical Devices .........................................................................................38
6.2. Preparation/Handling/Storage/Accountability of All IP .........................................38
6.2.1. Preparation and Dispensing of All IP .........................................................39
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................39
6.3.1. Allocation to Study Intervention ................................................................39
6.4. Study Intervention Compliance...............................................................................40
6.5. Concomitant Therapy..............................................................................................40
6.5.1. Other Anti-tumor/Anti-cancer or Experimental Treatments ......................41
6.5.2. Supportive Care ..........................................................................................41
6.5.3. Hematopoietic Growth Factors...................................................................41
6.5.4. Anti-Diarrheal, Anti-Emetic Therapy.........................................................42
6.5.5. Anti-Inflammatory Therapy........................................................................42
6.5.6. Corticosteroids............................................................................................42
6.5.7. Surgery........................................................................................................42
6.5.8. Rescue Medicine.........................................................................................42
6.5.9. Proton-Pump Inhibitors ..............................................................................43
6.5.10. Antacids or H2-Receptor Antagonists......................................................43
6.5.11. Vaccines Administration ..........................................................................43
6.6. Dose Modification...................................................................................................43
6.6.1. Management of Treatment-Related Adverse Events..................................45
6.7. Intervention After the End of the Study..................................................................46
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................46
7.1. Discontinuation of Study Intervention ....................................................................46
7.1.1. Treatment after Initial Evidence of Radiological Disease Progression......47
7.1.2. Rechallenge.................................................................................................47
7.2. Participant Discontinuation/Withdrawal From the Study.......................................48
7.2.1. Withdrawal of Consent...............................................................................48

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 7
7.3. Lost to Follow-up....................................................................................................48
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................49
8.1. Efficacy Assessments..............................................................................................50
8.1.1. Tumor Response Assessment .....................................................................50
8.1.2. Tumor Markers...........................................................................................52
8.1.3. Overall Survival..........................................................................................52
8.2. Safety Assessments .................................................................................................52
8.2.1. Physical Examinations................................................................................52
8.2.2. Vital Signs ..................................................................................................53
8.2.3. Electrocardiograms.....................................................................................53
8.2.4. Clinical Safety Laboratory Assessments ....................................................54
8.2.5. Pregnancy Testing ......................................................................................54
8.2.6. ECOG Performance Status .........................................................................54
8.2.7. Local Site Injection Tolerability Assessment.............................................55
8.2.8. 30/60/90/180 Day Follow-Up Visits ..........................................................55
8.3. Adverse Events and Serious Adverse Events..........................................................56
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......56
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................57
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................57
8.3.2. Method of Detecting AEs and SAEs ..........................................................57
8.3.3. Follow-up of AEs and SAEs.......................................................................57
8.3.4. Regulatory Reporting Requirements for SAEs...........................................58
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................58
8.3.5.1. Exposure During Pregnancy......................................................58
8.3.5.2. Exposure During Breastfeeding ................................................60
8.3.5.3. Occupational Exposure .............................................................61
8.3.6. Cardiovascular and Death Events...............................................................61
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................61
8.3.8. Adverse Events of Special Interest.............................................................61
8.3.8.1. Lack of Efficacy........................................................................61
8.3.9. Medical Device Deficiencies......................................................................61

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 8
8.3.9.1. Time Period for Detecting Medical Device Deficiencies .........62
8.3.9.2. Follow-up of Medical Device Deficiencies...............................62
8.3.9.3. Prompt Reporting of Medical Device Deficiencies to 
Sponsor..............................................................................................62
8.3.9.4. Regulatory Reporting Requirements for Device 
Deficiencies .......................................................................................62
8.3.10. Medication Errors.....................................................................................63
8.4. Treatment of Overdose............................................................................................63
8.5. Pharmacokinetics ....................................................................................................64
8.5.1. Blood for PK Analysis of Sasanlimab........................................................65
8.5.2. Blood for PK Analysis of Combination Target Agents..............................65
8.6. Pharmacodynamics..................................................................................................65
8.7. Genetics...................................................................................................................65
8.7.1. Specified Genetics ......................................................................................65
8.7.2. Banked Biospecimens for Genetics............................................................66
8.8. Biomarkers ..............................................................................................................66
8.8.1. Specified Gene Expression (RNA) Research .............................................67
8.8.2. Specified Protein Research.........................................................................68
8.8.3. Specified Metabolomic Research ...............................................................68
8.9. Immunogenicity Assessments.................................................................................68
8.9.1. Immunogenicity Assessment of Sasanlimab ..............................................68
8.10. Health Economics .................................................................................................68
8.11. End of Treatment (EOT) Visit ..............................................................................69
9. STATISTICAL CONSIDERATIONS ................................................................................69
9.1. Estimands and Statistical Hypotheses.....................................................................69
9.1.1. Estimands....................................................................................................69
9.2. Sample Size Determination.....................................................................................69
9.2.1. Phase 1b Dose Finding ...............................................................................69
9.2.2. Phase 2 Dose...............................................................................................69
9.3. Analysis Set.............................................................................................................70
9.4. Statistical Analyses .................................................................................................71
9.4.1. General Considerations...............................................................................71
9.4.2. Primary Endpoint(s)....................................................................................71

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 9
9.4.3. Secondary Endpoints ..................................................................................71
9.4.3.1. Efficacy Analysis ......................................................................71
9.4.3.2. Safety Analyses.........................................................................71
9.4.3.3. PK Analyses of Sasanlimab ......................................................72
9.4.3.4. Analysis of Immunogenicity Data of Sasanlimab.....................72
9.4.4. Exploratory Endpoints................................................................................72
9.4.4.1. Analyses of Biomarker Endpoints.............................................72
9.4.5. Other Safety Analyses ................................................................................73
9.4.5.1. Electrocardiogram Analyses......................................................73
9.4.6. Other Analyses............................................................................................73
9.5. Interim Analyses .....................................................................................................73
9.6. Data Monitoring Committee or Other Independent Oversight Committee.............73
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................75
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............75
10.1.1. Regulatory and Ethical Considerations ....................................................75
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................75
10.1.2. Financial Disclosure .................................................................................76
10.1.3. Informed Consent Process ........................................................................76
10.1.4. Data Protection .........................................................................................77
10.1.5. Dissemination of Clinical Study Data ......................................................77
10.1.6. Data Quality Assurance ............................................................................79
10.1.7. Source Documents....................................................................................80
10.1.8. Study and Site Start and Closure ..............................................................80
10.1.9. Publication Policy.....................................................................................81
10.1.10. Sponsor’s Qualified Medical Personnel .................................................82
10.2. Appendix 2: Clinical Laboratory Tests .................................................................83
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ......................................................................84
10.3.1. Definition of AE .......................................................................................84
10.3.2. Definition of SAE.....................................................................................85
10.3.3. Recording/Reporting and Follow up of AEs and/or SAEs.......................87

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 10
10.3.4. Reporting of SAEs....................................................................................90
10.4. Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information................................................................................................................91
10.5. Appendix 5: Genetics............................................................................................92
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments ........93
10.7. Appendix 7: ECG Findings of Potential Clinical Concern ...................................95
10.8. Appendix 8: Medical Device Adverse Events, Adverse Device Effects, 
Serious Adverse Events, and Device Deficiencies: Definition and Procedures 
for Recording, Evaluating, Follow-up, and Reporting..............................................97
10.8.1. Definition of AE and ADE .......................................................................97
10.8.2. Definition of SAE, SADE, and Unanticipated Serious Adverse 
Device Effect ...................................................................................................97
10.8.3. Definition of Device Deficiency...............................................................98
10.8.4. Recording/Reporting and Follow-up of AEs and/or SAEs and 
Device Deficiencies .........................................................................................98
10.8.5. Reporting of SAEs..................................................................................100
10.8.6. Reporting of SADEs...............................................................................100
10.9. Appendix 9: RECIST (Response Evaluation Criteria In Solid Tumors) 
version 1.1 Guidelines.............................................................................................102
10.10. Appendix 10: Management of Immune-Related Adverse Events (irAEs) 
for Sasanlimab.........................................................................................................102
10.11. Appendix 11: Abbreviations .............................................................................116
10.12. Appendix 12: Alternative Measures During Public Emergencies.....................122
10.12.1. Eligibility..............................................................................................122
10.12.2. Telehealth Visits  ..................................................................................122
10.12.3. Alternative Facilities for Safety Assessments ......................................122
10.12.3.1. Laboratory Testing ..............................................................123
10.12.3.2. Electrocardiograms, MUGA/Echocardiograms, Visual 
Acuity Exams (when required per the SOA)...................................123
10.12.4. Study Intervention ................................................................................124
10.12.5. Home Health Visits ..............................................................................124
10.12.6. Adverse Events and Serious Adverse Events.......................................125
10.12.7. Efficacy Assessments ...........................................................................125
10.13. Appendix 13: Potential Drug-Drug Interactions ...............................................125

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 11
10.14. Protocol Amendment History............................................................................129
11. REFERENCES ................................................................................................................137
12. APPENDIX A: SUB-STUDY A: SASANLIMAB + ENCORAFENIB + 
BINIMETINIB..................................................................................................................142
12.1. Schedule of Activities (SoA): Sub-Study A........................................................142
12.2. Introduction for Sub-Study A..............................................................................150
12.2.1. Study Rationale.......................................................................................150
12.2.2. Background.............................................................................................150
12.2.2.1. Clinical Overview: Clinical Safety of Encorafenib in 
Combination with Binimetinib........................................................151
12.2.3. Benefit/Risk Assessment ........................................................................152
12.3. Objectives, Endpoints, and Estimands for Sub-Study A.....................................153
12.4. Study Design for Sub-Study A............................................................................156
12.4.1. Phase 1b Design......................................................................................157
12.4.2. Phase 2 Design........................................................................................158
12.4.3. Rationale for the Sub-Study A Combination..........................................158
12.4.4. Justification for Dose in Sub-Study A....................................................159
12.4.4.1. Starting Dose for Phase 1b....................................................159
12.4.4.2. Criteria for Dose Escalation/De-Escalation ..........................159
12.4.5. Dose Limiting Toxicity...........................................................................159
12.4.6. Maximum Tolerated Dose......................................................................159
12.4.7. Recommended Phase 2 Dose (RP2D) Definition...................................159
12.5. Study Population for Sub-Study A......................................................................160
12.5.1. Inclusion Criteria for Sub-Study A.........................................................160
12.5.2. Exclusion Criteria for Sub-Study A........................................................160
12.6. Study Intervention for Sub-Study A....................................................................161
12.6.1. Administration of Encorafenib and Binimetinib ....................................162
12.6.2. Preparation, Handling, Storage, Accountability, and Dispensing ..........163
12.6.3. Measures to Minimize Bias: Randomization and Blinding....................163
12.6.3.1. Allocation to Study Intervention...........................................163
12.6.4. Study Intervention Compliance..............................................................163
12.6.5. Concomitant Therapy for Sub-Study A..................................................163

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 12
12.6.5.1. Permitted Concomitant Therapy Requiring Caution 
and/or Action...................................................................................163
12.6.5.2. CYP3A Inducers ...................................................................165
12.6.6. Dose Interruptions and Modifications for Sub-Study A.........................165
12.6.6.1. Dose Interruptions.................................................................165
12.6.6.2. Dose Modifications ...............................................................166
12.7. Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal....................................................................................167
12.8. Study Assessments and Procedures for Sub-Study A .........................................167
12.8.1. Efficacy Assessments .............................................................................167
12.8.1.1. Tumor Response Assessments ..............................................167
12.8.2. Safety Assessments.................................................................................167
12.8.2.1. Echocardiogram/ Multigated Acquisition Scan (MUGA) ....167
12.8.2.2. Dermatologic Examination ...................................................168
12.8.2.3. Ophthalmic and Visual Acuity Examinations.......................168
12.8.3. Treatment of Overdose ...........................................................................169
12.8.4. Genetics ..................................................................................................169
12.8.5. Patient Reported Outcomes ....................................................................169
12.9. Statistical Considerations for Sub-Study A.........................................................170
12.9.1. Estimands and Statistical Hypotheses ....................................................170
12.9.1.1. Estimands ..............................................................................170
12.9.1.2. Statistical Consideration for Phase 1b...................................170
12.9.1.3. Sample Size Determination...................................................172
12.9.1.4. Analysis Set...........................................................................172
12.9.1.5. General Considerations .........................................................172
12.10. Supporting Documentation and Operational Considerations for Sub-
Study A....................................................................................................................175
12.10.1. Clinical Laboratory Tests for Sub-Study A..........................................175
12.10.2. Contraceptive Guidance for Sub-Study A ............................................176
12.10.2.1. Male Participant Reproductive Inclusion Criteria...............176
12.10.2.2. Female Participant Reproductive Inclusion Criteria ...........176
12.10.2.3. Woman of Childbearing Potential (WOCBP).....................177
12.10.2.4. Contraception Methods .......................................................178

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 13
12.10.3. Examples of Strong and Moderate CYP3A4 Inhibitors .......................179
12.10.4. Recommended Dose Modifications for Encorafenib-related* 
Adverse Events and Overlapping Toxicities with Sasanlimab**..................179
12.10.5. Recommended Dose Modifications for Binimetinib-related* 
Adverse Events and Overlapping Toxicities with Sasanlimab**..................184
12.10.6. Detailed Dose Escalation /De-escalation Scheme for BLRM 
Design for Sasanlimab + Encorafenib + Binimetinib....................................188
13. APPENDIX B: SUB-STUDY B: SASANLIMAB + AXITINIB + SEA-TGT...............199
13.1. Schedule of Activities (SoA): Sub-Study B........................................................199
13.2. Introduction for Sub-Study B..............................................................................206
13.2.1. Study Rationale.......................................................................................206
13.2.2. Background.............................................................................................206
13.2.2.1. Background for Axitinib .......................................................206
13.2.2.2. Background for SEA-TGT....................................................206
13.2.2.3. Clinical Overview of Sub-Study B Investigational 
Products ...........................................................................................207
13.2.3. Benefit/Risk Assessment ........................................................................211
13.3. Objectives, Endpoints, and Estimands for Sub-Study B.....................................212
13.4. Study Design for Sub-Study B............................................................................215
13.4.1. Phase 1b Design......................................................................................216
13.4.2. Phase 2 Design........................................................................................217
13.4.3. Rationale for the Sub-Study B Combination..........................................218
13.4.4. Justification for Dose in Sub-Study B ....................................................219
13.4.4.1. Starting Dose for Phase 1b....................................................219
13.4.4.2. Criteria for Dose Escalation/De-Escalation ..........................220
13.4.5. Dose Limiting Toxicity...........................................................................220
13.4.6. Maximum Tolerated Dose......................................................................220
13.4.7. Recommended Phase 2 Dose (RP2D) Definition...................................220
13.5. Study Population for Sub-Study B......................................................................220
13.5.1. Inclusion Criteria for Sub-Study B.........................................................220
13.5.2. Exclusion Criteria for Sub-Study B........................................................222
13.6. Study Intervention for Sub-Study B....................................................................223
13.6.1. Administration of Sub-Study B Investigational Products ......................224

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 14
13.6.1.1. Administration of Axitinib....................................................224
13.6.1.2. Administration of SEA-TGT.................................................225
13.6.2. Preparation, Handling, Storage, Accountability, and Dispensing ..........226
13.6.3. Measures to Minimize Bias: Randomization and Blinding....................226
13.6.3.1. Allocation to Study Intervention...........................................226
13.6.4. Study Intervention Compliance..............................................................226
13.6.5. Concomitant Therapy for Sub-Study B ..................................................226
13.6.5.1. Permitted Concomitant Therapy Requiring Caution 
and/or Action...................................................................................226
13.6.5.2. CYP3A Inducers ...................................................................227
13.6.5.3. Supportive Care.....................................................................227
13.6.5.4. Surgery ..................................................................................227
13.6.6. Dose Interruptions and Modifications for Sub-Study B.........................227
13.6.6.1. SEA-TGT Dose Modifications..............................................228
13.6.6.2. Axitinib Dose Modifications.................................................229
13.7. Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal....................................................................................230
13.8. Study Assessments and Procedures for Sub-Study B .........................................230
13.8.1. Efficacy Assessments .............................................................................230
13.8.1.1. Tumor Response Assessments ..............................................230
13.8.2. Safety Assessments.................................................................................230
13.8.2.1. Home Blood Pressure Monitoring (Vital Signs)...................230
13.8.2.2. Echocardiogram/ Multigated Acquisition Scan (MUGA) ....230
13.8.3. Treatment of Overdose for Sub-Study B................................................230
13.8.3.1. Treatment of Overdose for Axitinib......................................230
13.8.3.2. Treatment of Overdose for SEA-TGT...................................231
13.8.4. Biomarkers..............................................................................................231
13.9. Statistical Considerations for Sub-Study B.........................................................231
13.9.1. Estimands and Statistical Hypotheses ....................................................231
13.9.1.1. Estimands ..............................................................................231
13.9.1.2. Statistical Consideration for Phase 1b...................................232
13.9.1.3. Sample Size Determination...................................................232
13.9.1.4. Analysis Set...........................................................................233

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 15
13.9.1.5. General Considerations .........................................................233
13.10. Supporting Documentation and Operational Considerations for Sub-
Study B ....................................................................................................................235
13.10.1. Clinical Laboratory Tests for Sub-Study B ..........................................235
13.10.2. Contraceptive Guidance for Sub-Study B ............................................235
13.10.2.1. Male Participant Reproductive Inclusion Criteria...............235
13.10.2.2. Female Participant Reproductive Inclusion Criteria ...........236
13.10.2.3. Woman of Childbearing Potential (WOCBP).....................236
13.10.2.4. Contraception Methods .......................................................237
13.10.3. Examples of Strong and Moderate CYP3A4 Inhibitors .......................238
13.10.4. Recommended Dose Modification and Management of SEA-TGT-
related Adverse Events ..................................................................................239
13.10.5. Recommended Dose Modifications for Axitinib-related Adverse 
Events.............................................................................................................241
13.10.6. Detailed Dose Escalation /De-escalation Scheme for mTPI Design 
for Sasanlimab + Axitinib + SEA-TGT.........................................................243

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 16
LIST OF TABLES
Table 1.
Study Intervention Sasanlimab.................................................................37
Table 2.
Sasanlimab Recommended Treatment Modifications for Study 
Intervention-Related Toxicity (Excluding Immune-Related AEs)...........45
Table 3.
ECOG Performance Status .......................................................................55
Table 4.
Master Protocol-Required Safety Laboratory Assessments .....................83
Table 5.
Schedule of Activities Sub-Study A Phase 1b and Phase 2....................143
Table 6.
Sub-Study A Objectives and Endpoints .................................................153
Table 7.
Sub-Study A Combination:  Sasanlimab + Encorafenib + 
Binimetinib – Available Dose Levels.....................................................158
Table 8.
Study Interventions: Sub Study A (Sasanlimab + Encorafenib + 
Binimetinib)............................................................................................162
Table 9.
Dose Reductions for Encorafenib for Toxicity Management.................166
Table 10.
Dose Reductions for Binimetinib for Toxicity Management .................167
Table 11.
Clinical Laboratory Tests Added for Sub-Study A ................................175
Table 12.
Historical Dose Limiting Toxicity data from study 
CLGX818X2101.....................................................................................191
Table 13.
Prior Distributions for the Parameters of the MAP Model Used to 
Derive the Prior for the Single-Agent Encorafenib Model 
Parameters...............................................................................................191
Table 14.
Historical Dose Limiting Toxicity Data from Study Array-162-111 
and Study CMEK162X1101...................................................................192
Table 15.
Prior Distributions for the Parameters of the MAP Model Used to 
Derive the Prior for the Single-Agent Binimetinib Model 
Parameters...............................................................................................192
Table 16.
Historical Dose Limiting Toxicity data from Study B8011001 .............193
Table 17.
Prior Distributions for the Parameters of the MAP Model Used to 
Derive the Prior for the Single-Agent Sasanlimab Model 
Parameters...............................................................................................193
Table 18.
Prior Distribution for the Model Parameters ..........................................194
Table 19.
Summary of Prior Distribution of DLT Rates for the Triplet 
Combination of Encorafenib in Combination with Binimetinib and 
Sasanlimab..............................................................................................195
Table 20.
Next Dose Recommendation and the Interval probability of Target 
Toxicity and Overdosing at Next Dose ..................................................195

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 17
Table 21.
Combination A: Dose Limiting Toxicity Rate Scenarios (Fixed 
Sasanlimab Dose 300 mg Once Per Cycle) ............................................196
Table 22.
Combination A: Operating Characteristics.............................................197
Table 23.
Schedule of Activities Sub-Study B Phase 1b & Phase 2 ......................200
Table 24.
Sub-Study B Objectives and Endpoints..................................................212
Table 25.
Sub-Study B Phase 1b, Doublet Cohorts Dose Levels...........................216
Table 26.
Sub-Study B, Phase 1b, Triplet Cohorts Dose Levels............................216
Table 27.
Study Interventions: Sub-Study B (Sasanlimab + Axitinib + SEA-
TGT) .......................................................................................................224
Table 28.
Dose Reductions for Axitinib for Toxicity Management.......................229
Table 29.
Clinical Laboratory Tests Added for Sub-Study B.................................235
Table 30.
Dose Finding Rules.................................................................................244
LIST OF FIGURES
Figure 1 
Master Protocol Study Schematic.............................................................21
Figure 2.
Sub-Study A Design ...............................................................................157
Figure 3.
Sub-Study B Design ...............................................................................215

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 18
1. PROTOCOL SUMMARY
1.1. Synopsis
Protocol Title: A Phase 1b/2 Open Label Umbrella Study of Sasanlimab Combined with 
Anti-Cancer Therapies Targeting Multiple Molecular Mechanisms in Participants with 
Non-Small Cell Lung Cancer (NSCLC)
Short Title: Umbrella Study of Sasanlimab in Participants with NSCLC
Rationale:
Master Protocol Rationale
The central scientific theme of the master protocol is that NSCLC is a disease that can be 
controlled by anti-tumor immunity.  Agents that target molecular alterations in these tumors 
with the potential to increase tumor immunogenicity or agents that target specific pathways 
of immune resistance in the tumor microenvironment may activate anti-tumor immunity. 
Once anti-tumor immunity is activated, it is expected that immune checkpoints will be 
induced as a result of normal homeostatic control of the immune system.  The PD-1/PD-L1 
interaction has emerged as the most important immune checkpoint limiting anti-tumor 
immunity in humans.  Sasanlimab has shown anti-tumor activity in patients with 
advanced/metastatic NSCLC comparable to other anti-PD-1/PD-L1 inhibitor monoclonal 
antibodies.  Therefore, blockade of PD-1/PD-L1 interactions through sasanlimab-mediated 
binding to PD-1 will be the backbone therapy for combination with other agents that may 
have the ability to induce anti-tumor immunity.  Such combination therapies have the 
potential to induce and sustain long-term disease control in this patient population. 
The mechanisms by which anti-tumor immunity becomes established include presentation of 
tumor antigens within tumor draining lymph nodes and expansion of effector T cells that then 
traffic to tumors and mediate tumor cell killing.  Down-modulatory interactions between 
such T cells and tumor cells can be induced in the presence of inflammatory cytokines at 
multiple levels either simultaneously or in series.  PD-L1 can be induced on non-immune 
cells, including tumor cells, in the presence of IFN-, a key inflammatory cytokine produced 
by activated T-cells.  PD-L1-mediated down-modulation of T cell activity via engagement of 
PD-1 on the T-cell surface represents a mechanism to restore immune homeostasis in tissues.   
The inhibition of PD-L1 interaction with PD-1 in tissue distinguishes the mechanism of 
anti-PD-1/PD-L1 antibodies from other checkpoint inhibitors such as anti-CTLA-4 
antibodies, which primarily act in the context of hematopoietic cells expressing CTLA-4 
ligands.  As such, single-agent anti-PD-1/PD-L1 antibodies are more effective compared 
with CTLA-4 blocking antibodies in the treatment of NSCLC, supporting the use of a PD-1 
blocking antibody (sasanlimab) as the backbone agent to be used in this master protocol.
Patients with advanced/metastatic NSCLC who experience disease progression while on a 
first-line PD-1/PD-L1-containing therapy represent an increasing unmet need for more 
effective therapies.  Combinations of agents which can address mechanisms of disease 
progression and increase the potency of anti-tumor responses could lead to greater depth and 
durability of anti-tumor responses in tumors that are sensitive to PD-1/PD-L1 therapy.  

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 19
In addition, for tumors that become resistant to PD-1/PD-L1 therapy, there is a need for new 
agents that can overcome resistance mechanisms, which could then lead to activation or 
reactivation of anti-tumor immunity.  Nonclinical data suggest that once anti-tumor immunity 
is re-established in such settings that blockade of the PD-1/PD-L1 pathway will still be 
needed.  Therefore, this master protocol will focus on combinations of sasanlimab with 
molecularly-targeted agents that have the potential to either restore anti-tumor immunity or 
inhibit mechanisms of resistance to PD-1/PD-L1 therapy. 
The scientific rationale for each of the agents combined with sasanlimab in this study is 
based on the potential to stimulate anti-tumor immunity and/or increase tumor susceptibility 
to immune attack.  Each sub-study will be comprised of a Phase 1b component to evaluate 
initial safety and a Phase 2 component to evaluate anti-tumor activity and additional safety.  
It is initially anticipated that 5 combinations will be explored in this umbrella protocol to 
provide scientific focus (Figure 1).  It is also anticipated that data from this study may be 
used to inform the design of additional clinical trials.
Participant subgroups will be prioritized for treatment with a given combination based on 
available data regarding the ability of the combination to prevent, bypass, or reverse 
resistance to PD-1/PD-L1 therapy.  Prospective biomarker testing will be employed in 
settings where safety and efficacy are known to be contingent on a particular biomarker test 
result.  In settings where the relationships between safety, efficacy, and biomarker test results 
are either unknown or may be different from the relationships observed for the single-agent 
components, enrollment may not be based on a test result but retrospective analysis will be 
used to assess the level of heterogeneity in biomarker-defined subgroups.  If such 
retrospective analysis suggests that the target benefit is only seen in a defined subpopulation, 
then enrollment into future cohorts could be based on prospective confirmation that 
participants are members of that subpopulation. These new cohorts will be included in the 
study via protocol amendment.  Control arms may be included within sub-studies to this 
master study and may be applied to specific treatment settings, where an understanding of the 
contribution of the individual components of a higher order combination is needed.
Please refer to the sub-study appendices for the rationale of each sub-study. 
Objectives and Endpoints 
Please refer to the sub-study appendices for the objectives and endpoints of each sub-study. 
Estimands
Please refer to the sub-study appendices for the rationale of each sub-study. 
Overall Design
This is a prospective, open-label, multi-center, parallel group, Phase 1b/2 umbrella study to 
evaluate safety, efficacy, pharmacokinetics, and/or pharmacodynamics of sasanlimab in 
combination with targeted agents that increase anti-tumor immunity and activity in adult 
participants with locally advanced or metastatic NSCLC.  Each sub-study may be conducted 
in parallel, as new agents are included to begin a sub-study within the framework of the 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 20
master protocol.  Each sub-study will specify the treatment setting.  Participants will receive 
study interventions until permanent treatment discontinuation criteria are met as defined in 
Section 7.1.  
The combination arms will be assessed individually in 2 parts: 
1. A Phase 1b part to evaluate the safety of the combination and select an RP2D dose level 
for the combination.
2. A Phase 2 part to evaluate the activity and further evaluate the safety of the RP2D from 
the Phase 1b part in pre-specified participant populations.
Phase 1b Design:
The sasanlimab dose will remain fixed (at either 300 mg SC Q4W or 
) for 
all cohorts in the Phase 1b part of each sub-study.
Guidance for the Phase 1b dosing (dose level to be evaluated in the next cohort) and 
enrollment decisions (number of participants to be enrolled in the next cohort) will be based 
on methods described in the appendix for each sub-study.  
Phase 2 Design:
Once the Phase 1b is completed for a sub-study and the combination RP2D has been 
determined, Phase 2 for the sub-study may be initiated to further evaluate the safety and 
anti-tumor activity.  The Phase 2 design will be detailed in the appendix for the respective 
sub-study.
Number of Participants:
Approximately 375 participants are expected to be assigned to study intervention based on 
eligibility, assuming the initial plan that 5 combinations will be explored in the umbrella 
study; refer to the respective sub-study appendix for the sample size determination for each 
sub-study.
Intervention Groups and Duration:
Study Interventions:
Sasanlimab SC (either 300 mg Q4W or 
) will be administered in all sub-studies 
and additional agents will be administered as described in the respective sub-study 
appendices. 
Phase 2 Dose Levels: 
RP2D/MTD of sasanlimab + other study drugs 
Data Monitoring Committee:
No
CCI
CCI

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 21
Statistical Methods:
The statistical methods will be specified in the respective sub-study appendices.
1.2. Schema
In Sub-Study A, the target population will be participants who have BRAFV600E mutations 
and the investigational products administered will be sasanlimab, encorafenib, and 
binimetinib as a triplet therapy. In Sub-Study B, the target population in Phase 2 will be 
participants without oncogene drivers who have PD-L1- positive tumors (TPS ≥ 1%), and are 
either treatment-naïve or whose disease has progressed on prior immune checkpoint 
inhibitor-containing therapy; the investigational products administered will be sasanlimab, 
axitinib, and SEA-TGT as a triplet therapy.
Figure 1
Master Protocol Study Schematic
1.3. Schedule of Activities (SoA)
The SoA table provides an overview of the protocol visits and procedures.  
Refer to the SoA of Sub-Study A in Section 12.1 and the SoA of Sub-Study B in 
Section 13.1.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 22
2. INTRODUCTION
Study B8011011 is a master protocol for the treatment of participants with locally 
advanced/metastatic (Stage IIIB-IV) NSCLC, incorporating an anti-PD-1 mAb (sasanlimab, 
also known as PF-06801591) as the backbone therapy for combinations with different 
molecularly targeted agents.  B8011011 is primarily designed as an exploratory study.
Sasanlimab is a clinically active, humanized, hinge region stabilized immunoglobulin G4 
mAb specific for human PD-1 that can selectively bind to human PD-1 and block the 
interaction between PD-1 and PD-L1/PD-L2.1  First-in-human studies of sasanlimab show 
that it has the ability to be administered via SC administration.  The convenience of 
administration coupled with a low rate of injection-related reactions may provide a 
significant benefit to participants, especially when combined with other anti-cancer agents.1-4
The use of PD-1 blocking antibodies alone or in combination with chemotherapy has become 
a standard-of-care first-line therapy for locally advanced/metastatic NSCLC, with response 
rates approaching 50%.2  However, the mPFS of 7.1 months for single-agent pembrolizumab 
in patients with ≥50% tumor PD-L1 expression3 and the mPFS of 8.8 months in a broader 
population of patients treated with chemotherapy/pembrolizumab2 indicates that the majority 
of patients will experience disease progression and require a subsequent therapy within their 
first year of treatment.  For patients who experience disease progression on chemotherapy-
containing regimens in the first-line setting, the prognosis remains poor for salvage 
chemotherapy with a mPFS of 4.0 months and an mOS of 8.5 months.5  In this 
resistant/refractory setting, single-agent PD-1/PD-L1 inhibitory agents are not therapeutically 
effective.  Therefore, there is an unmet need for more effective therapies for locally 
advanced/metastatic NSCLC, especially after disease progression on PD-1/PD-L1 inhibitor-
containing therapies, where there are limited effective treatment options. 
In addition, patients with NSCLC treated with targeted agents will frequently develop 
resistance to the agents.  In settings where there is evidence that the targeted agents trigger an 
anti-tumor immune response and/or settings where a tumor molecular alteration is associated 
with active anti-tumor immunity, increased clinical benefit might be experienced by 
combining tumor-targeted agents with a PD-1 agent, such as sasanlimab.5
Combinations of sasanlimab, as a backbone therapy, with new agents will be included in the 
protocol as sub-studies within appendices.  The sub-studies will include the key protocol 
elements based on the chosen clinical setting, including objectives and endpoints.
2.1. Study Rationale
The central scientific theme of the master protocol is that NSCLC is a disease that can be 
controlled by anti-tumor immunity.  Agents that target molecular alterations in these tumors 
with the potential to increase tumor immunogenicity or agents that target specific pathways 
of immune resistance in the tumor microenvironment may activate anti-tumor immunity. 
Once anti-tumor immunity is activated, it is expected that immune checkpoints will be 
induced as a result of normal homeostatic control of the immune system.  The PD-1/PD-L1 
interaction has emerged as the most important immune checkpoint limiting anti-tumor 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 23
immunity in humans.  Sasanlimab has shown anti-tumor activity in patients with 
advanced/metastatic NSCLC comparable to other anti-PD-1/PD-L1 inhibitor monoclonal 
antibodies.  Therefore, blockade of PD-1/PD-L1 interactions through sasanlimab-mediated 
binding to PD-1 will be the backbone therapy for combination with other agents that may 
have the ability to induce anti-tumor immunity.  Such combination therapies have the 
potential to induce and sustain long-term disease control in this patient population. 
The mechanisms by which anti-tumor immunity becomes established include presentation of 
tumor antigens within tumor draining lymph nodes and expansion of effector T cells that then 
traffic to tumors and mediate tumor cell killing.  Down-modulatory interactions between 
such T cells and tumor cells can be induced in the presence of inflammatory cytokines at 
multiple levels either simultaneously or in series.  PD-L1 can be induced on non-immune 
cells, including tumor cells, in the presence of IFN-, a key inflammatory cytokine produced 
by activated T-cells.  PD-L1-mediated down-modulation of T cell activity via engagement of 
PD-1 on the T-cell surface represents a mechanism to restore immune homeostasis in tissues.   
The inhibition of PD-L1 interaction with PD-1 in tissue distinguishes the mechanism of 
anti-PD-1/PD-L1 antibodies from other checkpoint inhibitors such as anti-CTLA-4 
antibodies, which primarily act in the context of hematopoietic cells expressing CTLA-4 
ligands.  As such, single-agent anti-PD-1/PD-L1 antibodies are more effective compared 
with CTLA-4 blocking antibodies in the treatment of NSCLC, supporting the use of a PD-1 
blocking antibody (sasanlimab) as the backbone agent to be used in this master protocol.
Patients with advanced/metastatic NSCLC who experience disease progression while on a 
first-line PD-1/PD-L1-containing therapy represent an increasing unmet need for more 
effective therapies.  Combinations of agents which can address mechanisms of disease 
progression and increase the potency of anti-tumor responses could lead to greater depth and 
durability of anti-tumor responses in tumors that are sensitive to PD-1/PD-L1 therapy.  
In addition, for tumors that become resistant to PD-1/PD-L1 therapy, there is a need for new 
agents that can overcome resistance mechanisms, which could then lead to activation or 
reactivation of anti-tumor immunity.  Nonclinical data suggest that once anti-tumor immunity 
is re-established in such settings that blockade of the PD-1/PD-L1 pathway will still be 
needed.  Therefore, this master protocol will focus on combinations of sasanlimab with 
molecularly-targeted agents that have the potential to either restore anti-tumor immunity or 
inhibit mechanisms of resistance to PD-1/PD-L1 therapy. 
The scientific rationale for each of the agents combined with sasanlimab in this study is 
based on the potential to stimulate anti-tumor immunity and/or increase tumor susceptibility 
to immune attack.  Each sub-study will be comprised of a Phase 1b component to evaluate 
initial safety and a Phase 2 component to evaluate anti-tumor activity and additional safety. It 
is initially anticipated that 5 combinations will be explored in this umbrella protocol to 
provide scientific focus.  It is also anticipated that data from this study may be used to inform 
the design of additional clinical trials.
Participant subgroups will be prioritized for treatment with a given combination based on 
available data regarding the ability of the combination to prevent, bypass, or reverse 
resistance to PD-1/PD-L1 therapy.  Prospective biomarker testing will be employed in 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 24
settings where safety and efficacy are known to be contingent on a particular biomarker test 
result.  In settings where the relationships between safety, efficacy, and biomarker test results 
are either unknown or may be different from the relationships observed for the single-agent 
components, enrollment may not be based on a test result but retrospective analysis will be 
used to assess the level of heterogeneity in biomarker-defined subgroups.  If such 
retrospective analysis suggests that the target benefit is only seen in a defined subpopulation, 
then enrollment into future cohorts could be based on prospective confirmation that 
participants are members of that subpopulation. These new cohorts will be included in the 
study via protocol amendment.  Control arms may be included within sub-studies to this 
master study and may be applied to specific treatment settings, where an understanding of the 
contribution of the individual components of a higher order combination is needed. 
2.2. Background
NSCLC is a disease which is responsive to immune-checkpoint inhibition.  In the first-line 
advanced NSCLC setting, PD-1/PD-L1 inhibitors as single agents are effective in tumors 
with strong anti-tumor T cell activity which has been down-modulated by tumor-associated 
PD-L1 expression.  High PD-L1 expression is observed in approximately 50% of advanced 
NSCLC PD-L1-positive cases.  For the majority of patients with NSCLC, the use of 
PD-1/PD-L1 inhibitors as single agents is insufficient to control disease progression.3
For patients with advanced NSCLC in the first-line setting, combinations of PD-1/PD-L1 
agents with chemotherapy are the most common standard-of-care regimens for those patients 
who can tolerate chemotherapy and who do not have known targetable aberrations.  Upon 
progression, patients treated with chemotherapy/PD-1/PD-L1 combinations have limited 
effective treatment options and may be treated with other chemotherapy-containing 
regimens, which are not highly effective in providing participants with long-term benefit and 
for docetaxel, the product label contains a black-box warning for severe toxicities.5-7
Mechanisms of resistance to PD-1/PD-L1 therapies have been proposed to include 
2-microglobulin/MHC Class I down-modulation, insufficient amount of tumor antigens 
recognizable by T cells, and upregulation of alternative immune suppressive mechanisms 
(eg, TGFpathway upregulation, alternative immune checkpoints, PTEN loss).8-10
Combinations of targeted therapies having the capability of stimulating anti-tumor immunity 
with PD-1/PD-L1 agents have shown improved clinical activity compared with targeted 
agents alone.  Examples include triplet combinations that show activity in patients with 
metastatic melanoma.  Triplet combinations of PD-1/PD-L1 inhibitors with a BRAF inhibitor 
and MEK inhibitor have shown activity, including a) pembrolizumab with 
dabrafenib/trametinib or b) atezolizumab with vemurafenib/cobimetinib.  In these clinical 
studies, the addition of the PD-1/PD-L1 inhibitor resulted in an improvement in the durability 
of responses and trends toward improvement in PFS and OS.  ORR was comparable between 
the targeted agents alone and the triplets.11,12
Combinations of sasanlimab with targeted therapy are designed to leverage the relatively 
rapid reduction in tumor burden possible with targeted therapy and the relatively prolonged 
tumor control produced by an effective immune response.  This hypothesis predicts that the 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 25
effect of the targeted therapy will be reflected in the ORR, whereas the effect of sasanlimab 
will be manifest as extensions of DR, PFS, and OS.   
It has been observed in multiple clinical trials of a PD-1/PD-L1 agent with other therapies in 
NSCLC that due to the kinetics of immune-associated anti-tumor activity, neither the ORR 
nor mPFS are reliable predictors of OS.  In fact, what has been observed with these 
combinations is that a greater durability of disease control in the intent-to-treat patient 
population and high maximum depth of the anti-tumor response correlates with an 
improvement in OS.13 Accordingly, durable response will be either a primary endpoint or 
co-primary endpoint with OR, depending on the design of each sub-study. 
To summarize, the central goal of this study is to identify combinations that lead to improved 
anti-tumor activity by activating and sustaining anti-tumor immunity.
2.2.1. Nonclinical Overview
2.2.1.1. Nonclinical Pharmacology
Results from sasanlimab nonclinical pharmacology studies are consistent with the expected 
effects of blocking the PD-1 pathway and demonstrate the potential to enhance tumor 
immuno-surveillance and anti-tumor immune responses.
Sasanlimab binds to human PD-1 with high affinity to both recombinant PD-1 protein and 
cell surface expressed PD-1. Binding affinity to cynomolgus monkey PD-1 was similar to 
human PD-1. The ability of sasanlimab to block the PD-1 pathway, as measured on primary 
human and primary cynomolgus monkey T cells, was shown by increased T cell proliferation 
and cytokine secretion in both of these systems.
See Section 5.1 of the sasanlimab (PF-06801591) IB14 for detailed information on in vitro 
and in vivo nonclinical studies.
2.2.1.2. Nonclinical Pharmacokinetics and Metabolism
Single- and repeat-dose PK were assessed after IV and SC dosing of sasanlimab in 
cynomolgus monkeys.  In the GLP toxicity studies, systemic exposure was higher with 
increasing dose after repeat dosing, and there were no sex-related differences observed in 
exposure.  ADA was observed after repeat IV dosing in monkeys.
Sasanlimab has been shown to induce cytokine production (IFNγ, TNFα, IL-2). However, 
cytokine-mediated drug interactions observed in the clinic for other anti-PD-1 agents have 
been modest, resulting in less than 2-fold changes in the exposure of a co-administered small 
molecule drug.
See Section 5.2  of the sasanlimab (PF-06801591) IB14 for detailed information on 
nonclinical studies.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 26
2.2.1.3. Nonclinical Safety
The nonclinical safety profile of sasanlimab has been well-characterized in repeat-dose 
toxicity studies in cynomolgus monkeys up to 1 month in duration.  The IV and SC routes of 
exposure were assessed as these are the intended routes of administration in initial clinical 
studies.
In repeat-dose toxicity studies up to 1-month duration in which sasanlimab was administered 
via the IV or SC routes, no direct target organ toxicities were observed.  The key changes 
associated with sasanlimab treatment of cynomolgus monkeys was minimal to mild 
mononuclear cellular infiltration of various tissues that persisted and were likely a result of 
prolonged exposure to sasanlimab throughout the entire recovery phase.  These findings are 
both consistent with expected pharmacology, and previously described in monkey toxicity 
studies with similar compounds targeting the PD-1 receptor.
See Section 5.3 of the sasanlimab (PF-06801591) IB14 for detailed information regarding 
nonclinical toxicology studies.
2.2.2. Clinical Overview
Sasanlimab is being evaluated as a single-agent in Study B8011001 (146 participants  with 
locally advanced or metastatic melanoma, squamous cell carcinoma of the head and neck, 
ovarian cancer, sarcoma, NSCLC, UC, or other solid tumors); as a single-agent in Study 
B8011007 (8 participants with advanced malignancies); and in combination with BCG in 
Study B8011006 (20 participants with high risk non muscle invasive bladder cancer).14  
Anti-tumor activity of single-agent sasanlimab has been demonstrated in Study B8011001. 
As of the data cutoff of 01 November 2019, efficacy has been evaluated in 67 participants 
with NSCLC and 38 participants with UC who were administered sasanlimab 300 mg SC 
Q4W. The ORR (95% Exact CI) was 20.9% (11.9%-32.6%) in the NSCLC cohort and 21.1% 
(9.6%-37.3%) in the UC cohort. Median (range) duration of partial response was 230 days 
(57-445 days) in the NSCLC cohort and 183 days (23-371 days) in the UC cohort.15
A total of 60 of 106 participants who were administered sasanlimab 300 mg SC experienced 
at least 1 treatment-related AE.  Most commonly (>5%) reported treatment-related AEs were 
hyperthyroidism (10.4%), pruritus (7.5%), lipase increased (6.6%), and ALT increased, AST 
increased,  amylase increased, hypothyroidism, rash, and anemia (5.7% each).15  
Sixteen (15.1%) participants reported ≥ Grade 3 treatment related AEs. Grade 3 treatment-
related AEs included lipase increased, amylase increased, and blood alkaline phosphatase 
increased (1.9% each); decreased appetite, hypermagnesemia, pneumonitis, ageusia, 
anosmia, jaundice, blood potassium increased, transaminases increased, lymphocyte count 
decreased, asthenia, fatigue, cognitive disorder, and hypotension (0.9% each).  Grade 4 
treatment-related AEs included lipase increased, neutrophil count decreased, and white blood 
cell count decreased (0.9% each). Grade 5 treatment-related AE included arrhythmia (n = 1, 
0.9%).14  

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 27
Injection site reactions were infrequent, occurring in <5% of patients. Because monoclonal 
antibodies may cause reactions such as pain or erythema at the injection site, local 
tolerability to sasanlimab injections will be assessed.   The irAE profile of sasanlimab is 
mostly consistent with the known safety profile of anti-PD-1 treatment. Treatment-related 
irAEs commonly identified for sasanlimab include hypothyroidism, hyperthyroidism, and
pneumonitis; these have been categorized as ADRs for sasanlimab.
Detailed safety information from clinical studies, as well as nonclinical information, can be 
found in the sasanlimab (PF-06801591) IB.14
Please see Section 12.2.2.1 for a discussion of the clinical overview of investigational 
products used in combination with sasanlimab in Sub-study A, and Section 13.2.2.3 for 
agents used in Sub-Study B.
2.3. Benefit/Risk Assessment
Based on data from Study B8011001, there is significant clinical benefit in terms of OR and 
disease control for participants with advanced/metastatic solid tumors treated with single-
agent sasanlimab.  These results are consistent with the ORR and DCR in the same tumor 
types reported for other agents of the same class. Sasanlimab is well tolerated and with a low 
frequency of treatment-related SAEs.
The benefit risk relationship has been carefully considered in the planning of this study. 
Sasanlimab administered at 300 mg SC every 4 weeks has been evaluated in the Phase 1 
Study B8011001 in participants with advanced solid tumors as described in Section 2.2.2.
The clinical safety data available to date with single-agent sasanlimab suggest an acceptable 
safety profile with most of the observed AEs in line with those expected in patients with 
advanced solid tumors or with similar class effects of mAbs blocking the PD-1/PD-L1 axis. 
Immune-related AEs have been identified as important risks for sasanlimab and risk 
mitigation measures have been implemented in all ongoing clinical studies, including this 
study. These measures include guidelines for treatment interruption and discontinuation in 
case of toxicities, and guidelines for steroid treatment implementation. In the same study 
sasanlimab has shown evidence of clinical activity aligned to other anti-PD-1/PD-L1 single 
agents in participants with advanced/metastatic NSCLC.
The fact that PD-1 antagonists are known to be combinable with many other agents is also 
important to consider. There are exceptional cases where combinations were not tolerated 
and combinations with agents of the same class will not be conducted in this study. Agents 
combined with sasanlimab will have a single-agent MTD and/or a RP2D determined in other 
studies as a basis for the design of the Phase 1b safety cohorts in this study.  A safe dose 
level for each combination will be determined in Phase 1b of this study before proceeding to 
a Phase 2 expansion cohort.
Based on the above considerations, the benefit/risk assessment for the initiation of Phase 1b 
safety cohorts for combinations with other agents is favorable. 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 28
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of sasanlimab may be found in the IB,14 which is the SRSD for sasanlimab for 
this study.
For the benefit/risk assessment of sasanlimab in combination with the targeted agents, see the 
respective sub-studies (Section 12.2.3 for Sub-Study A; Section 13.2.3 for Sub-Study B). 
3. OBJECTIVES AND ENDPOINTS
For sub-study specific objectives and endpoints, refer to each respective sub-study appendix.  
For Sub-Study A, refer to Section 12.3; for Sub-Study B, refer to Section 13.3.
4. STUDY DESIGN
4.1. Overall Design
The sub-study design specific details are further described in Section 12.4 (for Sub-Study A) 
and in Section 13.4 (for Sub-Study B).
This is a prospective, open-label, multi-center, parallel group, Phase 1b/2 umbrella study to 
evaluate safety, efficacy, pharmacokinetics, and/or pharmacodynamics of sasanlimab in 
combination with targeted agents that increase anti-tumor immunity and activity in adult 
participants with locally advanced or metastatic NSCLC.  Each sub-study may be conducted 
in parallel, as new agents are included to begin a sub-study within the framework of this 
master protocol.  Each sub-study will specify the treatment setting.  Participants will receive 
study drugs until permanent treatment discontinuation criteria are met as defined in 
Section 7.1.
The combination arms will be assessed individually in 2 parts: 
1. A Phase 1b part to evaluate the safety of the combination and select an RP2D dose level 
for the combination.
2. A Phase 2 part to evaluate the activity and further evaluate the safety of the RP2D from 
the Phase 1b part in pre-specified participant populations.
Phase 1b Design:
The sasanlimab dose will remain fixed (at either 300 mg SC Q4W or 
) for 
all cohorts in the Phase 1b part of each sub-study.
Guidance for the Phase 1b dosing (dose level to be evaluated in the next cohort) and 
enrollment decisions (number of participants to be enrolled in the next cohort) will be based 
on methods described in the appendix for each sub-study.  
Phase 2 Design:
Once the Phase 1b is completed for a sub-study and the combination RP2D has been 
determined, Phase 2 for the sub-study may be initiated to further evaluate the safety and 
CCI

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 29
anti-tumor activity.  The Phase 2 design will be detailed in the appendix for the respective 
sub-study (see Section 12.4.2 for sasanlimab in combination with encorafenib and 
binimetinib and Section 13.4.2 for sasanlimab in combination with axitinib and SEA-TGT).
For Regulatory, Ethical, and Study Oversight Considerations, refer to Appendix 1: 
Regulatory, Ethical, and Study Oversight Considerations (Section 10.1).
4.2. Scientific Rationale for Study Design
Refer to Section 2.1 for the master protocol study rationale.
See the sub-study appendices for the rationales supporting individual combinations.  
Banked Biospecimens will be collected and stored for further analyses which may, for 
example, provide greater understanding of the study intervention.
4.3. Justification for Dose
4.3.1. Starting Dose for Phase 1b
Sasanlimab will be given subcutaneously at either 300 mg Q4W or 
.  The 
starting dose for sasanlimab and the combination agents is specified in the respective 
sub-study appendices. 
The sasanlimab dose of 300 mg SC Q4W was selected with considerations of the nonclinical 
safety data of sasanlimab and the clinical safety and tolerability data from the IV and SC 
administration cohorts in Study B8011001, along with considerations related to injection 
volume feasibility of the current formulation.
The sasanlimab dose 
 was selected for sub-studies in which the 
combination product is dosed on a 3-week cycle. The dose of 
 yields the 
same dose intensity as that of 300 mg SC Q4W. It is expected that a similar AUC and a 
smaller Cmax/Cmin fluctuation of sasanlimab will be achieved at steady state after 
 
dosing compared with 300 mg SC Q4W dosing. 
4.3.2. Criteria for Dose Escalation/De-Escalation
The criteria for dose escalation/de-escalation will be specified for each combination in the 
respective appendix.  For the Sub-Study A combination, refer to Section 12.4.4.2; for the 
Sub-Study B combination, refer to Section 13.4.4.2.
4.3.3. Dose Limiting Toxicity (DLT) Definition
The DLT observation period will be specified for each sub-study.  For Phase 1b, any of the 
following AEs occurring during the DLT observation period which are attributable to 1 or 
more of the study interventions in the combination will be classified as DLTs.  
CCI
CCI
CCI
CCI

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 30
Hematologic:
1. Grade 4 neutropenia (ANC <500/mm3 or <0.5 × 109/L).
2. 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.
3. Neutropenic infection (ANC <1,000/mm3 or <1.0 x 109/L, and Grade >3 infection).
4. Grade 3 thrombocytopenia (platelet count <50,000-25,000/mm3 or <50.0-25.0 ×
109/L) with bleeding.
5. Grade 4 thrombocytopenia (platelet count <25,000/mm3 or <25.0 x 109/L).
6. Grade 4 anemia (Life-threatening consequences; urgent intervention indicated).
Non-Hematologic:
7. Any Grade ≥3 toxicity, except for any of the following:
a.
Transient (≤24 hours) Grade 3 fatigue, local reactions, or headache that 
resolves to Grade ≤1 or baseline status
b. Grade 3 nausea and vomiting controlled by optimal medical therapy within 
72 hours;
c.
Grade 3 hypertension controlled by medical therapy
d. Grade 3 diarrhea that improves to Grade ≤2 within 72 hours after medical 
management has been initiated
e.
Grade 3 skin toxicity that resolves to Grade ≤1 in less than 7 days after 
medical management (eg, immunosuppressant treatment) has been initiated
f.
Grade 3 endocrinopathies controlled with medical therapy
g. Tumors flare phenomenon defined as local pain, irritation, or rash localized at 
sites of known or suspected tumor
8. Non-hematologic Grade 3 laboratory abnormality if medical intervention or 
hospitalization is required, or any Grade 4 lab abnormality.
9. ALT or AST >3 × ULN (if normal at baseline) or >3 × ULN and doubling the 
baseline (if > ULN at baseline) and associated with total bilirubin >2 × ULN; or ALT/ 
AST >5 × ULN; or total bilirubin >3 × ULN.
Non-Adherence to Treatment Schedule:
10. Failure to receive at least 75% of the planned doses of each of the investigational 
products during the DLT observation period due to treatment-related toxicities

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 31
Other criteria:
11. An AE not listed above, or an AE meeting the DLT criteria above but occurring 
outside of the DLT observation period may be defined as a DLT after consultation 
between sponsor and investigator, based on the emerging safety profile.
The following AEs will not be considered as DLTs:
Single laboratory test values out of normal range that do not have any clinical correlate and 
resolve to Grade ≤1 or baseline within 7 days with adequate medical management are not to 
be considered DLTs. 
Grade 3 IRR, allergic reaction or anaphylaxis will not be considered as DLTs but may be a 
reason for permanent treatment discontinuation and will be reviewed with the sponsor.
4.3.4. Maximum Tolerated Dose (MTD) Definition
The maximum tolerated dose will be defined for each sub-study dependent on the dose 
finding method.
4.3.5. Recommended Phase 2 Dose (RP2D) Definition
The RP2D is the dose level of the combination that will be chosen for further development 
and evaluation in Phase 2.
The RP2D may be determined based on other safety, clinical activity, PK, and
pharmacodynamic data and may be the MTD, a dose below the MTD or highest studied dose 
if the MTD is not reached at the highest studied dose.
4.4. End of Study Definition
The end of the study is defined as the date of study completion for the last participant in the 
trial globally, at sponsor discretion if the data support ending the study, or 3 years after first 
dose of the last participant, whichever is earlier.
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 
master protocol and sub-studies. 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also
known as protocol waivers or exemptions, is not permitted.
Pfizer will review eligibility criteria verified by the investigator or qualified designee to 
confirm that participants meet study eligibility criteria before they are enrolled into the study.  
The enrollment approval process will be initiated for a participant after an informed consent 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 32
document has been signed and the investigator or qualified designee has assessed the 
participant as eligible.  The enrollment approval will be based on review of CRF/system data 
or other site documentation.
5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following master 
protocol criteria apply, as well as sub-study specific inclusion criteria provided in the 
respective sub-study appendices:
Phase 1b and Phase 2 For All Sub-Studies:
Informed Consent:
1. Capable of giving signed informed consent as described in Section 10.1.3, which includes 
compliance with requirements and restrictions listed in the ICD and in this protocol.
2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and 
other study procedures
Age and Sex:
3. Male or female participants age ≥18 years at Screening (except in Japan, where 
participants must be ≥20 years).
4. Male and female participants must agree to contraceptive use according to reproductive 
criteria described in Appendix 4.
5. Female participants of childbearing potential must have negative serum pregnancy or 
urine pregnancy test at Screening.
Type of Participant and Disease Characteristics:
6. Documented histologically or cytologically confirmed locally advanced/metastatic (Stage 
IIIB-IV) NSCLC, per AJCC/ International Union for Cancer Control TNM system, 
7th edition.16  For Stage IIIB disease relapse during treatment or within 6 months 
following adjuvant therapy will be considered metastatic disease.  In addition, for Stage 
IIIB, must not be amenable for definitive therapy (eg, surgery or chemoradiation).
7. At least 1 measurable lesion per RECIST v1.1 at Screening.
8. ECOG Performance Status 0 or 1.
9. Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1, 
unless otherwise specified.
10. Life expectancy ≥3 months as assessed by the investigator for previously treated 
participants or ≥12 months for first-line untreated participants.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 33
11. Adequate bone marrow function (without hematopoietic growth factor or transfusion 
support within 14 days prior to first dose of study intervention), including:
a.
Absolute neutrophil count ≥1500/mm3 or ≥1.5 × 109/L;
b. Platelets ≥100,000/mm3 or ≥100 × 109/L;
c.
Hemoglobin ≥9 g/dL (may have been transfused).
12. Adequate renal function, defined by:
Estimated creatinine clearance ≥30 mL/min according to the Cockcroft-Gault formula or 
by 24-hour urine collection for creatinine clearance, or according to local institutional 
standard method.
13. Adequate liver function, including:
a.
Total serum bilirubin ≤1.5 × ULN unless the participant has documented Gilbert 
syndrome; 
b. AST and ALT ≤2.5 × ULN; ≤5.0 × ULN if there is liver involvement by the tumor;
c.
Alkaline phosphatase ≤2.5 × ULN (≤5 × ULN in case of bone metastasis).
5.2. Exclusion Criteria 
Participants are excluded from the study if any of the following master protocol criteria 
apply, as well as sub-study specific exclusion criteria provided in the respective sub-study 
appendices:
Medical Conditions:
1. Active or prior autoimmune disease that might deteriorate when receiving an 
immunostimulatory agent.  Participants with diabetes type I, vitiligo, psoriasis, or 
hypothyroid or hyperthyroid disease not requiring immunosuppressive treatment are 
eligible.
2. Previous Grade ≥3 irAE; or unresolved irAEs prior to first dose of study intervention.
3. Active non-infectious pneumonitis, pulmonary fibrosis, or known history of immune-
mediated pneumonitis.
4. Active infection requiring systemic therapy.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 34
5. Clinically significant cardiovascular diseases, including any of the following:
a) History of acute myocardial infarction, acute coronary syndromes (including unstable 
angina, coronary artery bypass graft, coronary angioplasty or stenting)
≤6 months prior to start of study treatment;
b) Congestive heart failure requiring treatment (New York Heart Association Class ≥2); 
c) Uncontrolled hypertension defined as persistent systolic blood pressure ≥150 mmHg 
or diastolic blood pressure ≥100 mmHg despite optimal therapy;
d) History or presence of clinically significant or uncontrolled sustained cardiac 
arrhythmias (including uncontrolled atrial fibrillation or uncontrolled paroxysmal 
supraventricular tachycardia);
e) History of thromboembolic or cerebrovascular events ≤3 months prior to the first 
dose of study treatment.  Examples include transient ischemic attacks, 
cerebrovascular accidents, hemodynamically significant (ie, massive or sub-massive) 
deep vein thrombosis or pulmonary emboli.
Note: Participants with either deep vein thrombosis or pulmonary emboli that do not 
result in hemodynamic instability are allowed to enroll as long as they are stable, 
asymptomatic and on stable anticoagulants for at least 2 weeks.
Note: Participants with thromboembolic events related to indwelling catheters or 
other procedures may be enrolled.
6. Other malignancy within 2 years prior to the first dose of study intervention, except for 
adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the 
breast or of the cervix, or low-grade (Gleason 6 or below) prostate cancer on surveillance 
without any plans for treatment intervention (eg, surgery, radiation, or castration) or other 
concurrent malignancy investigator feels has a very low likelihood to become metastatic.
7. Clinically significant multiple or severe drug allergies, intolerance to topical 
corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not 
limited to, erythema multiforme major, linear immunoglobulin A [IgA] dermatosis, toxic 
epidermal necrolysis, and exfoliative dermatitis.
8. Symptomatic brain metastasis: participants previously treated for this condition or 
untreated with brain metastases <10 mm without associated edema, who are 
asymptomatic in the absence of corticosteroid therapy are allowed.
9. Leptomeningeal disease.
10. Known history of acute or chronic pancreatitis.
11. Concurrent neuromuscular disorder that is associated with the potential of elevated CK 
(eg, inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal 
muscular atrophy).  

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 35
12. 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.
13. Participants with active, uncontrolled bacterial, fungal, or viral infection, including HBV, 
HCV, or known HIV infection. If HIV infection status is unknown, testing for HIV must 
be performed at sites where mandated locally.
Prior/Concomitant Therapy:
14. Live attenuated vaccines within 4 weeks prior to first dose of study intervention and 
while on study treatment. 
15. Major surgery or received radiation therapy within 2 weeks prior to first dose of study 
intervention.
Other Exclusions:
16. 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 partners from the permitted list of contraception methods (see the 
respective sub-study appendix) and will confirm that the participant has been instructed in its 
consistent and correct use.  At time points indicated in the SoA, the investigator or designee 
will inform the participant of the need to use protocol-specified 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 the selected 
methods of contraception).  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.
Contraception details will not be entered in a CRF.
5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
do not subsequently receive study treatment.  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.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 36
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened. Rescreened participants should be assigned a new participant number .
6. STUDY INTERVENTION
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.
Sasanlimab is 1 of the study interventions and will be provided in a prefilled syringe or vial 
for SC injection.  The prefilled syringe is a medical device.  Additional study interventions 
will be detailed in their respective sub-study appendices.
6.1. Study Intervention(s) Administered
Sasanlimab will be administered in all sub-studies and additional agents will be administered 
as described in the respective appendices.  Study intervention of sasanlimab is administered 
as shown in Table 1.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 37
Table 1.
Study Intervention Sasanlimab
Intervention Name
sasanlimab
Type 
Biologic Product 
Dose Formulation
Solution for Injection
Unit Dose Strength(s)
150 mg/mL, 2 mL (300 mg total) prefilled syringe
Or
50 mg/mL, 2 mL (100 mg total) vial
Dosage Level(s)
300 mg Q4W or 
Route of Administration
Subcutaneous
Use
Experimental
IMP or NIMP 
IMP
Sourcing
Provided centrally by the sponsor (manufactured by 
Pfizer)
Packaging and Labeling
Study intervention will be provided in either a 
prefilled syringe or vials for the 300 mg dose; study 
intervention will be provided in vials for the 
 
.  Each prefilled syringe or vial will be 
labeled as required per country requirement.
6.1.1. Administration of Sasanlimab
Qualified and trained investigator site personnel will administer sasanlimab at a fixed dose of 
300 mg once every 4 weeks 
 by SC injection to the abdomen 
of participants ; see the respective sub-study appendix for the dose of sasanlimab to be 
administered in each sub-study.  The 300 mg Q4W dose will be administered by either 1 
prefilled syringe or, if provided in vials, 3 SC injections will be administered. For the 
 
 dose, vials will be provided and 3 SC injections will be administered; the maximum 
volume per injection should be 2 mL.  See Section 8.2.7 for local site injection tolerability 
assessment. 
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.
CCI
CCI
CCI
CCI

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 38
Study staff should refer to the IP Manual for specific instructions on the preparation, 
handling, and administration 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.    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 trial, end of study or 
study termination.
6.1.2. Medical Devices
This section is applicable only to sub-studies using the pre-filled syringe for sasanlimab 
administration, not for sub-studies using the vial formulation. 
1. The medical device used to deliver sasanlimab is a prefilled syringe.
2. Instructions for medical device use are provided in the investigational product manual.
3. Medical device deficiencies (including malfunction, use error, and inadequate labeling) 
must be detected, documented, and reported by the investigator throughout the clinical 
investigation and appropriately managed by the sponsor (see Section 8.3.9).
6.2. Preparation/Handling/Storage/Accountability of All IP
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.
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.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 39
5. Study interventions should be stored in their original containers.
6. Site staff will instruct participants on the proper storage requirements for take-home 
study intervention, when applicable.
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.  When applicable, all study interventions that are 
taken home by the participant, both used and unused, must be returned to the investigator 
by the participant.  Returned study intervention must not be redispensed to the 
participants.
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 of All IP
See the IP manual for instructions on how to prepare the 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.
6.3. Measures to Minimize Bias: Randomization and Blinding
Refer to the respective sub-study (See Section 12.6.3 for Sub-Study A and Section 13.6.3 for 
Sub-Study B).
6.3.1. Allocation to Study Intervention
Once a participant has signed consent, the site staff will complete registration in the IRT 
system.  The IRT will assign a participant identification number and supply this number to 
the site.  The participant identification number will be used on all study-related 
documentation at the site.
Allocation of participants to treatment groups will proceed using an IRT system (IWR).  
Specification of the dose level for each participant in Phase 1b will also be provided by the 
IRT.  Allocation of participants will be approved only after all entry criteria have been 
reviewed by the sponsor, and no earlier than 3 days prior to C1D1 dosing.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 40
The site personnel (study coordinator or specified designee) will be required to have an 
active or valid account and password with the IRT system, enter or select information 
including but not limited to the protocol number, specific protocol entrance criteria indicated 
in the system and the screening number.  The site personnel will then be provided with, at a 
minimum, a treatment assignment, 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, allocation number and DU or container number assigned.  
The confirmation report must be stored in the site’s files.  Study intervention will be 
dispensed at the study visits as summarized in the SoA.  Returned study intervention must 
not be redispensed to the participants.
The study-specific IRT reference manual will provide the contact information and further 
details on the use of the IRT system.
For additional details on the allocation of study intervention, refer to the respective sub-study 
appendix.
6.4. Study Intervention Compliance
Sasanlimab will be administered by the appropriately designated study staff at the 
investigational site and compliance will be documented.  Deviation(s) from the prescribed 
dosage regimen should be recorded in the eCRF.
For study interventions that are administered at home as described in each sub-study, 
participant compliance with study intervention will be assessed at each visit. In order to 
document and assess participant compliance with study interventions administered at home, 
participants will record each self-administration of study intervention using a diary.  Data 
entered in the diary will be compared with drug accountability done at the site (ie, counting 
returned capsules/tablets vs dispensed capsules/tablets) prior to dispensing additional study 
treatment.
When applicable and as instructed in the IP manual, 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. 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.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 41
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.
6.5.1. Other Anti-tumor/Anti-cancer or Experimental Treatments
No additional anti-tumor treatment will be permitted while participants are receiving study 
treatment.  No other investigational drugs and devices are permitted while receiving study 
treatment.
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.  
The participant must have clear measurable disease outside the radiated field.  
In view of the current lack of data about the interaction of investigational products with 
radiotherapy, study treatment should be interrupted during palliative radiotherapy, stopping 
7 days before and resuming study treatment after recovery of any radiotherapy associated 
signs and symptoms to baseline.
Radiotherapy to a target lesion during the study will result in a subsequent unevaluable 
responses per RECIST v1.1 (Section 10.9).
6.5.2. 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.
6.5.3. Hematopoietic Growth Factors
Granulocyte-colony stimulating factors may be used for treatment-emergent neutropenia as 
indicated within the current ASCO guidelines.17  Primary prophylactic use of 
granulocyte-colony stimulating factors is not permitted. 
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.  For those countries where the indication and dosage of G-CSF compounds may
differ from ASCO guidelines, refer to local package insert or follow clinical practice in their 
countries.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 42
6.5.4. Anti-Diarrheal, Anti-Emetic Therapy
Primary prophylaxis is not required. If required for individual participant, the decision to 
incorporate pre-medication will be made following discussions between the sponsor and the 
investigator.
6.5.5. Anti-Inflammatory Therapy
Anti-inflammatory or narcotic analgesic may be offered as needed assuming there is no 
known or expected drug-drug interaction.
6.5.6. Corticosteroids
Chronic, systemic corticosteroid use (prednisone >10 mg/day or equivalents) for palliative or
supportive purpose is not permitted.  Acute emergency and short-term administration of 
corticosteroids are allowed.  If immune-related AEs occur, immune suppressive treatment 
should be administered according to local standards or practice. Sasanlimab will not be 
resumed while a participant is receiving immunosuppressive doses of corticosteroids.
The use of steroids during this trial is restricted as follows:
a) Therapeutic use: for the treatment of infusion-related reactions, short-term treatment 
of irAEs, and other drug-related AEs, steroids are permitted according to the 
modalities indicated in the respective toxicity management 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, eye drops, or local steroid injections (eg, intra-
articular injection) are permitted.
Any other use of corticosteroids should be discussed with the sponsor before implementation.
6.5.7. Surgery
Caution is advised on theoretical grounds for any surgical procedures during the study.  The 
appropriate interval of time between surgery and study intervention 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.
Surgery to a target lesion during the study will result in subsequent unevaluable responses 
per RECIST v1.1 (Section 10.9).
6.5.8. Rescue Medicine
There is no rescue therapy to reverse the AEs observed with sasanlimab; standard medical 
supportive care must be provided to manage the AEs. 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 43
6.5.9. Proton-Pump Inhibitors
No restrictions unless specified in sub-studies.
6.5.10. Antacids or H2-Receptor Antagonists
No restrictions unless specified in Sub-Studies.
6.5.11. Vaccines Administration
Live attenuated vaccines within 4 weeks prior to the first dose of sasanlimab and through 
30 days following the last dose of sasanlimab are not allowed. Examples of live vaccines 
include, but are not limited to, the following: measles, mumps, rubella, chickenpox, yellow 
fever, rabies, BCG, and oral typhoid vaccine. Seasonal influenza vaccines for injection are 
generally inactivated virus vaccines and are allowed; however intranasal influenza vaccines 
(eg, FluMist®) are live attenuated vaccines, and are not allowed.
6.6. Dose Modification
Sasanlimab
Every effort should be made to administer study intervention on the planned dose and 
schedule.  In the event of significant toxicity, dosing may be delayed and/or skipped as 
described below; no dose reductions are permitted for sasanlimab.  Dose reductions may be 
allowed for other study treatments administered in combination with sasanlimab and will be 
specified in their respective sub-study appendix.  In the event of multiple toxicities, dose 
modification should be based on the worst toxicity observed (and attribution for the 
combination treatment).  Participants are to be instructed to notify investigators at the first 
occurrence of any adverse symptom.  The following treatment modifications will be allowed 
as described in Table 2 and Section 10.10:
Dose Interruption/Delay:  If a participant develops a treatment related AE meeting withhold 
the treatment criteria, the treatment administration should be immediately stopped and should 
not be resumed until the criteria to restart treatment are met.
If any treatment-related AE is not resolved by the next scheduled dosing, the dosing should 
be delayed until the criteria to restart treatment are met.
Missed Dose:  The next dosing of sasanlimab may be skipped for the cycle based on 
persisting toxicity.
Permanent Treatment Discontinuation: If a participant develops a treatment-related AE 
meeting permanent discontinuation criteria as defined in Section 7.1, all the treatments 
considered related to the AE should be discontinued.  The treatments not considered related 
to the AE can be continued.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 44
General Treatment Modification Guidelines: 
Treatment modifications, delays, interruptions or discontinuations should be assigned to each 
product based on the causality assessment, when possible. 
Appropriate follow-up assessments should be done until adequate recovery occurs as 
assessed by the investigator. If a treatment delay results from worsening of hematologic or 
biochemical parameters, the frequency of relevant blood tests should be increased as 
clinically indicated.
In the event of a treatment interruption for reasons other than treatment-related toxicity (eg, 
elective surgery) lasting >4 weeks, treatment resumption will be decided in consultation with 
the sponsor.
All treatment modifications should be based on recommendations described in Table 2 and 
the respective sub-study appendix, unless expressly agreed otherwise following discussion 
between the investigator and the sponsor. 
All treatment modifications/adjustments must be clearly documented in the participant's 
source notes and CRF. 
Depending on when the AE resolved, a treatment interruption may lead to delay of the 
initiation of the subsequent cycle.
The treatment modification guidelines for the drugs to be administered in combination with 
sasanlimab will be specified in the respective sub-study appendices.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 45
Table 2.
Sasanlimab Recommended Treatment Modifications for Study 
Intervention-Related Toxicity (Excluding Immune-Related AEs)
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
Continue as per schedule.
Grade 2
First occurrence: continue per schedule.
Follow modifications for Grade 3 event if Grade 2 AE is considered 
intolerable and recurrent based on medical judgment.
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 Section 10.10.
Grade 4
Permanently discontinue sasanlimab.
Exceptions are: laboratory values that do not have any clinical correlate.
For suspected immune-related toxicity follow guidance in Section 10.10.
6.6.1. Management of Treatment-Related Adverse Events
Since inhibition of PD-1 stimulates the immune system, irAEs may occur.  Treatment of 
irAEs is mainly dependent upon severity as outlined in Section 10.10 for the management of 
irAEs related to sasanlimab.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 46
For any irAE of any grade, the investigator may consider consulting with the sponsor’s
medical monitor if deemed necessary.
Treatment of irAEs should follow guidelines set forth in Section 10.10.
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 administration and may include 
symptoms such as rash, urticaria, polyarthritis, myalgias, polysynovitis, fever, and if severe, 
glomerulonephritis.
All participants should be closely observed while receiving sasanlimab.  Monitoring for 
clinical signs of a systemic reaction should continue thereafter for clinical signs of allergic 
reactions/hypersensitivity.
In case of a hypersensitivity reaction, the participant will be treated symptomatically, with 
supportive care and further monitoring until the end of the study.  Guidance on dose 
interruptions and potential retreatment is detailed in Table 2.
6.7. Intervention After the End of the Study
No intervention will be provided to study participants after the end of the study.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
See the respective sub-study SoA for data to be collected at the time of study treatment 
discontinuation (End of Treatment (EOT) visit assessments) and follow-up and for any 
further evaluations that need to be completed.
In rare instances, it may be necessary for a participant to permanently discontinue study 
intervention (definitive discontinuation). Reasons for definitive discontinuation of study 
intervention may include:

Objective disease progression; 

Global deterioration of health status requiring discontinuation;

Unacceptable toxicity;

Pregnancy;

Significant protocol violation;

Lost to follow-up;

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 47

Participant refused further treatment;

Study terminated by sponsor;

Death.
The discontinuation of study intervention is defined as the discontinuation of all the assigned 
study drugs.
Note that discontinuation of study intervention does not represent withdrawal from the study.  
If study intervention is definitively discontinued, the participant will remain in the study to 
be evaluated for survival.  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.
7.1.1. Treatment after Initial Evidence of Radiological Disease Progression
Immunotherapeutic agents, such as sasanlimab, may produce anti-tumor effects by 
potentiating endogenous cancer specific immune responses.  The response patterns seen with 
such an approach may extend beyond the typical time course of responses seen with 
cytotoxic agents and can manifest as a clinical response after an initial increase in tumor 
burden or even the appearance of new lesions. 
If radiologic imaging shows disease progression after dosing with the investigational 
product(s), participants may continue to receive investigational products, at the investigator’s 
discretion if the following criteria are met:  

Absence of clinical signs and symptoms (including worsening of laboratory values) 
of disease progression;

No decline in ECOG performance status;

Absence of rapid progression of disease by radiographic imaging;

Absence of progressive tumor at critical anatomical sites (eg, cord compression) 
requiring urgent alternative medical intervention.
If the participant is subsequently found to have further disease progression at a subsequent 
tumor assessment, either radiologically according to RECIST v1.1 or clinically, then 
treatment with investigational products should be permanently discontinued.
7.1.2. Rechallenge
Retreatment within the study after permanent discontinuation of treatment is not allowed.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 48
7.2. Participant Discontinuation/Withdrawal From the Study
A participant may withdraw from the study at any time at his/her own request. 
Reasons for discontinuation from the study may include:

Refused further follow-up;

Lost to follow-up;

Death;

Study terminated by sponsor;.
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 for disclosure of 
future information (see Section 7.2.1), 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.
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved.
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.
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.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 49
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:
The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the participant wishes to and/or should continue in the 
study;
Before a participant is deemed lost to follow-up, 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. 
Discontinuation of specific sites or of the study is handled as part of Section 10.1.
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 respective sub-study 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 and applicable Cycle 1 Day 1 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.
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 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 50
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. Guidance 
for handling protocol-required tests and procedures in public emergencies is provided in 
Section 10.12.
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.
8.1. Efficacy Assessments
8.1.1. Tumor Response Assessment
RECIST version 1.1 (see Section 10.9) will be applied by the site as the primary measure of 
tumor assessment and response and as the basis for protocol guidelines related to disease 
status (eg, discontinuation of study treatment).  
Radiological scans of all suspected sites of disease will be performed utilizing the same 
method and technique throughout the study. Target lesions should demonstrate the 
participant’s baseline tumor burden and will be selected based on size (i.e., lesions with the 
longest diameter), and suitability for accurate repeat assessment.
The following should be performed at Screening/baseline:

Chest, abdomen, and pelvis CT or MRI scans are required for all participants at 
Screening. 

An MRI of the brain is also required for all participants at Screening.  A CT scan of the
brain, preferably with IV contrast, may be performed if MRI is contraindicated. 
Additional imaging of anatomical sites (eg, head, neck, etc.) should be performed as 
applicable based on location of disease sites.  

Bone imaging using bone scan (bone scintigraphy), 18F-FDG-PET, MRI, or other 
methods considered standard of care locally is required at baseline only if bone 
metastases are known or suspected outside the body areas scanned using other 
techniques.

Radiographic assessments obtained per the participant’s standard of care prior to 
enrollment into the study do not need to be repeated and are acceptable to be used as the 
Screening/baseline evaluation, if, (1) obtained within 28 days prior to first dose of study 
treatment, (2) performed using the method requirements (ie, RECIST v. 1.1 ), (3) the 
same technique/modality can be used to follow identified lesions throughout the trial for 
a given participant, and (4) appropriate documentation indicating that these radiographic 
tumor assessments were performed as standard of care is available in the participant’s 
source notes.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 51
The following should be performed during the study/postbaseline:

During the study chest, abdomen, and pelvis CT or MRI scans are required for all 
participants. Additional imaging of anatomical sites (eg, head, neck, etc.) should be 
performed as applicable based on location of disease sites. 

Subsequent MRIs of the brain will only be performed if there were lesions present at 
baseline or if new brain metastases are suspected. 

If bone lesions are present at baseline, bone imaging should be performed every 12 weeks 
for the first year and every 24 weeks thereafter. Bone imaging is also required at the time 
of confirmation of CR for participants who have bone metastases. Otherwise, bone 
imaging is required only if new bone metastases are suspected. 

Additional imaging evaluations may be performed at any time if there is symptomatic 
evidence suggesting the possibility of disease progression based on clinical symptoms or 
physical examination. 
Chest X-ray or ultrasound should not be used for tumor response assessments in this study.
While 18F-FDG-PET scans are not required for this study, sites may perform combined 
PET/CT scans per their local standard of care, provided the CT is of similar diagnostic 
quality as CT performed without PET, including the use of oral and IV contrast media. If 
acquired according to local standard of care 18F-FDG-PET may be relied upon to document 
PD in accordance with RECIST.
For participants with known CT contrast allergy, a non-contrast CT 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 
subsequent tumor assessments. If the imaging technique is changed due to unavoidable 
circumstances, as assessed by radiologist/investigator, and a comparable measurement of 
lesion is feasible then the tumor measurement should be reported, otherwise the lesion should 
be reported as non-evaluable.
CT or MRI scans must be completed before tumor biopsy samples are collected.  
Anti-tumor activity will be assessed through radiological tumor assessments conducted at 
following occasions:

At timepoints specified in the SoA.

Whenever disease progression is suspected (eg, symptomatic deterioration). 

After first occurrence of PR or CR is observed according to RECIST v1.1, repeat 
imaging at least 4 weeks after initial documentation.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 52

At the time of withdrawal from treatment if not done in the previous 8 weeks and 
prior response if other than PD.
Measurable or evaluable lesions that have been previously irradiated will not be considered 
target lesions unless increase in size has been observed following completion of radiation 
therapy. 
All participants’ files and radiologic images must be available for source verification and for 
potential peer review.  Radiologic images must be made available to a central vendor, if  
specified in the respective sub-study appendix, for potential central imaging reading.
For participants who did not end treatment due to disease progression, or withdrawal of 
consent, a tumor assessment will be performed as per SoA, post the EOT visit, until disease 
progression by RECIST v1.1, or initiation of a new anti-cancer treatment, or end of study, 
whichever is first.
8.1.2. Tumor Markers
No tumor markers will be collected for efficacy assessment.
8.1.3. Overall Survival
Following completion of the 180-day follow-up period all participants who receive study 
drug in Phase 2 will be followed for survival status (independent of time of disease 
progression) and subsequent anti-cancer treatments.  The assessment can be conducted by 
telephone every 12 weeks (±7 days) until death, lost-to-follow-up, study discontinued by 
sponsor, end of study, or participant withdrawal of consent of study, whichever comes first.  
If the participant is seen in the clinic during the time window that a scheduled telephone call 
is to be made to collect survival data, the clinic visit may replace the survival telephone call.
To ensure current and complete survival data is available at the time of final analyses, 
updated survival status may be requested at any time during the course of the study by the 
sponsor.  Upon sponsor notification, all participants who do not/will not have a scheduled 
study visit or study contact during the sponsor defined time period will be contacted for their 
survival status (excluding participants that have a previously recorded death event in the 
collection tool).
8.2. Safety Assessments
Planned time points for all safety assessments are provided in the respective sub-study SoA.  
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety issues.
8.2.1. Physical Examinations
Physical examinations will be assessed as per the respective sub-study SoA.  The body 
systems included in the scope of examination will be decided by the treating physician based 
on the standard of care at the center.  The details of the physical examination will not be 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 53
recorded on a CRF; however, any abnormalities detected during the physical examination 
will be reported on the medical history or adverse event CRF as appropriate. 
Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
Height and weight will also be measured and recorded as per the SoA.
8.2.2. Vital Signs
Temperature, pulse rate, and blood pressure will be assessed as per the SoA.  Temperature 
and pulse rate need not be recorded in the CRF but abnormalities will be recorded on the 
medical history or AE CRF as appropriate.
Blood pressure and pulse measurements will be assessed in a sitting or supine position 
preferably with an automated device and should be preceded by at least 5 minutes of rest for 
the participant in a quiet setting without distractions and prior to administration of any study 
drug or other study procedure.
8.2.3. Electrocardiograms
A standard 12-lead (with a 10-second rhythm strip) tracing will be used for all ECGs as 
outlined in the SoA. At each time point where triplicate ECG is required, 3 serial 12-lead 
ECGs will be conducted within approximately 5-10 minutes total time to determine mean 
QTc (average of triplicates). 
For remaining timepoints, single ECG will be collected prior to administration of study drug.  
If abnormalities are found on a single ECG, then a triplicate should be performed. When the 
timing of these measurements coincides with a blood collection, the ECG should be obtained 
prior to the nominal time of the blood collection.  
Additional ECGs may be performed as clinically indicated. Clinically significant findings 
seen on follow-up ECGs should be recorded as adverse events.
If participant experiences a cardiac or neurologic AE (specifically palpitations, syncope, 
dizziness, seizures, or stroke) triplicate ECGs should be obtained at time of the event. 
To ensure safety, if there is finding of QTc prolongation (≥60 msec from the pre-dose 
baseline, or >500 msec), ECG must be reviewed by qualified personnel at the site as soon as 
the finding is made, overreading the machine reading and ensuring that the Fridericia 
correction formula is applied.  If manual reading verifies the observation, repeat ECGs 
should be immediately performed at least 2 times approximately 2 minutes apart.  In such 
cases, when reporting ECG data in CRF, manual reading should be reported. The Fridericia 
correction formula is:
QTCF = QT / RR interval 1/3
ECG values of potential clinical concern are listed in Section 10.7.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 54
8.2.4. Clinical Safety Laboratory Assessments
See Section 10.2 for the list of clinical safety laboratory tests to be performed and the SOA of 
each sub-study for the timing and frequency.  All protocol-required laboratory assessments, 
as defined in Section 10.2, must be conducted in accordance with the laboratory manual and 
the sub-study SOA. Unscheduled clinical laboratory measurements may be obtained at any 
time during the study to assess any perceived safety issues.  
The investigator must review the laboratory report prior to each dosing, 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 30 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 Section 10.6 for suggested actions and follow-up assessments in the event of potential 
drug-induced liver injury.
Results from the protocol-specified laboratory assessments that should be recorded in the 
CRF will be outlined in the CRF Completion Guidelines.
8.2.5. 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 for 
each sub-study.  Home pregnancy tests may be utilized for visits indicated in the SoA for 
each sub-study, if compliant with local regulatory requirements. The home urine pregnancy 
testing kit must have a sensitivity of at least 25 mIU/mL. The pregnancy test outcome should 
be documented in the participant’s source documents/medical records.
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 end of the study.  Pregnancy tests may also be 
repeated if requested by IRBs/ ECs or if required by local regulations.
8.2.6. ECOG Performance Status
ECOG Performance Status will be evaluated as outlined in the SOA for each sub-study. 
Refer to Table 3 for ECOG Performance Status Criteria.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 55
Table 3.
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, 1982.18
8.2.7. Local Site Injection Tolerability Assessment
Assessments to monitor local tolerability to sasanlimab SC injections will be performed as 
outlined in the respective SoA. 
Any observed abnormality at the injection site will be judged by the investigator to determine 
whether a corresponding AE should be reported; otherwise details of these assessments will 
not be recorded on the CRF. When appropriate, at the discretion of the investigator, a 
participant with an ISR may be referred for a dermatological consultation and skin biopsy 
may be obtained for future examination of the ISR. If injection site reaction is noted, site 
tolerability assessments should continue until the symptoms resolve.
8.2.8. 30/60/90/180 Day Follow-Up Visits
The initial safety follow-up visit will be conducted in the clinic 30 days after last dose of 
study drug.  The 60-, 90-, and 180-day follow-up visits will be performed via remote contact 
(eg, telephone). The investigator may conduct these follow-up visits in clinic if any concerns 
are noted during the remote contact.  Refer to Section 8.1.1 for guidance on tumor 
assessment during the Follow-up periods. Refer to the respective sub-study SoA.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 56
8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 3.
The definitions of device-related safety events (ADEs and SADEs) can be found in 
Appendix 8.  Device deficiencies are covered in Section 8.3.9.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or 
the participant's legally authorized representative). 
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).
Each participant 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 
any study related procedure and/or receiving study intervention), through and including a 
minimum of 90 calendar days after the last administration of the study intervention.
During the long-term follow-up period in this study for survival, only SAEs will be actively 
elicited and collected after completion of the active collection period described above. 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.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
If the participant withdraws from the study treatment and also withdraws consent for the 
collection of future information, the active collection period ends when consent is withdrawn.
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 and Pfizer concurs with that assessment.
If a participant definitively 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.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 57
Investigators are not obligated to actively seek 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.
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 the 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.
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/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).

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 58
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 towards 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.
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational Exposure
Exposure to the study intervention under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.3.5.1. Exposure During Pregnancy
An 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.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 59

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 exposure during pregnancy:  
o
A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by ingestion, inhalation, or skin 
contact.
o
A male family member or healthcare provider who has been exposed to the study 
intervention by 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 
preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported).

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 60
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 liveborn 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 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 
authorized use.  However, if the infant experiences an SAE associated with such a drug, the 
SAE is reported together with the exposure during breastfeeding.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 61
8.3.5.3. Occupational Exposure
An occupational exposure occurs when a person receives unplanned direct contact with the 
study intervention, which may or may not lead to the occurrence of an AE.  Such persons 
may include healthcare providers, family members, and other roles that are involved in the 
trial participant’s care.
The investigator must report occupational exposure to Pfizer Safety within 24 hours of the 
investigator’s awareness, regardless of whether there is an associated SAE.  The information 
must be reported using the CT SAE Report Form.  Since the information does not pertain to a 
participant enrolled in the study, the information is not recorded on a CRF; however, a copy 
of the completed CT SAE Report Form is maintained in the investigator site file.
8.3.6. Cardiovascular and Death Events
See Section 10.7 for ECG findings of concern.
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs
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.  An AE should still be reported for signs or symptoms due to progression of the 
malignancy.
8.3.8. Adverse Events of Special Interest
Any AE that is suspected to be a potential irAE is considered an AE of special interest 
(AESI). Specific guidance for the management of irAEs is provided in Section 10.10.
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.
8.3.8.1. Lack of Efficacy
Lack of efficacy (see Section 10.3.1) is reportable to Pfizer Safety only if associated with an 
SAE.
8.3.9. Medical Device Deficiencies
The medical device being provided for use in some sub-studies is the prefilled syringe for SC 
injection; see the respective sub-study appendices for details on whether the medical device 
will be included in the sub-study. In order to fulfill regulatory reporting obligations 
worldwide, the investigator is responsible for the detection and documentation of events 
meeting the definitions of device deficiency that occur during the study with such devices.
The definition of a Medical Device deficiency can be found in Appendix 8.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 62
NOTE: Deficiencies fulfilling the definition of an AE/SAE will also follow the processes 
outlined in Sections 8.3.1 through 8.3.4 and Appendix 3 of the protocol.
8.3.9.1. Time Period for Detecting Medical Device Deficiencies
Medical device deficiencies or malfunctions of the device will be detected, documented, and 
reported during all periods of the study in which the medical device is used.
If the investigator learns of any device deficiency at any time after a participant has been 
discharged from the study, and such incident is considered reasonably related to a medical 
device provided for the study, the investigator or site staff will promptly notify the sponsor.
The method of documenting medical device deficiencies is provided in Appendix 8.
8.3.9.2. Follow-up of Medical Device Deficiencies
Follow-up applies to all participants, including those who discontinue study intervention.
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency.
New or updated information will be recorded on a follow-up form with all changes signed 
and dated by the investigator.
8.3.9.3. Prompt Reporting of Medical Device Deficiencies to Sponsor
Device deficiencies will be reported to the sponsor within 1 day after the investigator 
determines that the event meets the protocol definition of a medical device deficiency.  
Information will be provided to the sponsor as described in the IP Manual.  
Any device deficiency that is associated with an SAE must be reported to Pfizer Safety 
within 24 hours upon the investigator’s awareness as outlined in Sections 8.3.1.1 and 8.3.1.2.
The sponsor will be the contact for the receipt of device deficiency information.
8.3.9.4. Regulatory Reporting Requirements for Device Deficiencies
The investigator will promptly report all device deficiencies occurring with any medical 
device provided for use in the study in order for the sponsor to fulfill the legal responsibility 
to notify appropriate regulatory authorities and other entities about certain safety information 
relating to medical devices being used in clinical studies.
The investigator, or responsible person according to local requirements (eg, the head of the 
medical institution), will comply with the applicable local regulatory requirements relating to 
the reporting of device deficiencies to the IRB/EC.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 63
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 administration site, or at the wrong 
time, or at the wrong dosage strength, or from inadvertent exposure.
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:

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.

Incorrect study intervention taken by participant.

Overdosing.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF.
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.
8.4. Treatment of Overdose
Administration of any dose of sasanlimab greater than the assigned dose level at any 
scheduled administration visit will be considered an overdose. 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 64
Sponsor does not recommend specific treatment for an overdose for any of the study drugs.
In the event of an overdose, the treating physician should:
1. Provide the appropriate supportive treatment as clinically indicated.
2. Contact the medical monitor within 24 hours.
3. Closely monitor the participant for any signs of toxicity, AEs, and laboratory 
abnormalities for at least 6 months after the overdose.
4. Obtain a plasma 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 (determined on a case-by-case basis).
5. Document the quantity of the excess dose as well as the duration of the overdose in the 
CRF.
6. Overdose is reportable to Safety only when associated with an SAE.
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.
Instructions for treatment of overdose for the drugs to be administered in combination with 
sasanlimab will be specified in the respective sub-study appendices.
8.5. Pharmacokinetics
The PK sampling schedule is specified in the respective appendix for each sub-study and 
may be modified based on emerging PK data.  Additional PK samples may be drawn on 
discussion with sponsor (ie, to investigate a safety event, etc).
All efforts will be made to obtain the PK samples at the scheduled nominal time relative to 
dosing. However, the exact time of the sample collection will always be noted on the source 
document and CRF.  If a scheduled blood sample collection cannot be completed for any 
reason, the missed sample time may be re-scheduled with agreement of clinical investigators, 
participant and sponsor. 
PK samples will be analyzed using a validated analytical method.
Details regarding the collection, processing, storage and shipping of the PK blood samples 
will be provided to the investigator site prior to initiation of the trial. The samples must be 
processed and shipped as indicated to maintain sample integrity. Any deviations from the 
processing steps (eg, sample collection and processing steps, interim storage or shipping 
conditions), including any actions taken, must be documented and reported to the sponsor. 
On a case-by-case basis, the sponsor may make a determination as to whether sample 
integrity has been compromised. Any deviation from the specified sample handling 
procedure resulted in compromised sample integrity, will be considered a protocol deviation.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 65
As part of understanding the PK of the study interventions, samples may be used for
metabolite identification and/or further bioanalytical evaluation, as well as for other internal
exploratory purposes. These data may not be included in the Clinical Study Report (CSR).  
Samples collected for this purpose will be retained in accordance with local regulations and,
if not used within this timeframe, may be destroyed.
8.5.1. Blood for PK Analysis of Sasanlimab
Blood samples (3-mL whole blood at each time point) will be collected for PK analysis of 
sasanlimab, as outlined in the respective sub-study SoAs.  Refer to the Laboratory Manual 
for instructions for specific details on collection tubes, processing, and shipping.
8.5.2. Blood for PK Analysis of Combination Target Agents
Blood samples will be collected for PK analysis as described in the respective sub-study 
SoAs. Refer to the Laboratory Manual for instructions for specific details on collection 
tubes, processing, and shipping.
8.6. Pharmacodynamics
Exploratory analyses may be performed in response to emerging data on possible interactions 
between study treatments.
As part of understanding the pharmacodynamics of the investigational product, samples 
collected in the sub-study may be used for evaluation of the bioanalytical method, as well as 
for other internal exploratory purposes.  These data will not be included in the CSR. 
The pharmacodynamic samples must be processed and shipped as indicated in the 
instructions provided to the investigator site to maintain sample integrity. Any deviations 
from the pharmacodynamic 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 decide 
whether sample integrity has been compromised.
8.7. Genetics
8.7.1. Specified Genetics
Genetic assessments for all sub-studies will be performed utilizing tumor and blood samples 
as collected and described in the respective sub-study SoAs.
Biospecimen to confirm eligibility:  DNA samples may be analyzed for the purpose of 
confirming the presence of DNA alterations (eg, BRAFV600E) if required for enrollment to the 
study arm.  
In the event of DNA extraction failure, a replacement genetic blood sample may be requested 
from the participant, or the participant’s tumor biopsy may be used to confirm the presence 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 66
of the DNA alterations.  See the Genetics section of the individual sub-studies for additional 
details of the eligibility assessments.
Baseline tumor biopsy:  Whole exome sequencing of participant’s tumor biopsy will be 
performed on qualifying specimens to characterize DNA alterations that may be associated 
with response to therapy.  TCR sequence analysis may be performed on qualifying tumor 
biopsies to assess associations between tumor-associated TCRs and clinical outcomes.
Blood for cell-free DNA analysis: samples may be analyzed for epigenetic and/or genetic
associations with clinical outcomes.
Blood for specified genetic research:
Whole genome sequencing of participants’ blood samples collected prior to initiation of 
study therapy may be performed to confirm somatic vs germline nature of DNA alterations 
detected in matched tumor samples.  Whole genome sequencing of samples may also be 
performed to characterize epigenetic modifications of DNA. Genetic variation at specific loci 
(such as FCGR genes) or epigenetic modifications in peripheral blood may also be assessed 
by targeted assays using PCR or NGS-based methods applied to white blood cells or cell-free 
DNA.
Blood for TCR analysis: A separate peripheral blood specimen will be collected to monitor 
the T Cell Receptor repertoire over the first 2 cycles of therapy according to the SoA of each 
sub-study.
The sequencing methods will not have been validated for diagnostic use to assess 
predisposition to genetic disease.  Details on processes for collection and shipment of these 
samples can be found in the laboratory manual.
8.7.2. Banked Biospecimens for Genetics
A 4-mL blood sample optimized for DNA isolation (Prep D1) will be collected as local 
regulations and IRBs/ECs allow. 
Banked Biospecimens may be used for research related to the interventions and NSCLC. 
Genes and other analytes (eg, proteins, RNA, nondrug metabolites) may be studied using the 
banked samples. 
See Section 10.5 for information regarding genetic research.  Details on processes for 
collection and shipment of these samples can be found in the laboratory manual.
8.8. Biomarkers
Biomarker data collected by investigator sites as part of standard clinical practice may be 
recorded in the CRF.  Such data may include but not be limited to PD-L1 status and presence 
or absence of alterations in genes such as BRAF, EGFR, ALK, ROS1, or KRAS.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 67
Collection of samples for biomarker research is also part of this study.  Results from some of 
the biomarker research may be provided to the investigator.
The following samples for biomarker research will be collected from participants as specified 
in the respective sub-study SoA:

If baseline tumor samples are required prior to initiation of study therapy, the tumor 
collection procedure date should be as close to the start of study therapy as clinically 
feasible, and not before start of systemic cancer therapy.  Tumor samples collected 
prior to systemic cancer therapy may be acceptable in select cases upon consultation 
with the sponsor.  If a suitable tissue sample is not otherwise available, then an FFPE 
tissue sample from a de novo biopsy must be obtained during the screening period.  
The tumor samples should be collected by resection or core needle biopsy; if these 
options are contraindicated, fine needle aspirates are allowed.  Core biopsies should 
be performed using a minimum 18-gauge needle whenever feasible to preserve tissue 
integrity for histological and structural assessment.  A minimum of 3 separate cores 
are requested from the same biopsy site for each biopsy procedure.  Tumor tissue 
from FFPE cell pellet material or from bone biopsies is not adequate and should not 
be provided. Tumor biospecimens should be submitted in the form of a FFPE tumor 
tissue block.  If FFPE tissue blocks cannot be provided, the tissue should be 
submitted as FFPE tissue sections that are 4-5 microns thick on unstained, unbaked, 
slides (Superfrost Plus Gold or equivalent) that are freshly cut (ie, cut no more than 
30 days prior to shipment to the central laboratory).  

Blood samples will be collected from the start of screening as indicated in the
respective sub-study SoAs.  The samples will be stored as whole blood, plasma, or 
serum.
Optional samples for biomarker research that should be collected from participants in the 
study as appropriate are the following:

Sections of tumor samples that are collected after initiation of study therapy are 
requested for assessment of treatment-related changes in tumor phenotype or 
mechanisms of resistance.
Samples may be stored at a facility selected by the sponsor for a maximum of 10 years (or 
according to local regulations) following the last participant’s last visit for the study.
8.8.1. Specified Gene Expression (RNA) Research
RNA may be isolated from qualifying tumor and blood specimens.  The isolated RNA may 
be subjected to next-generation sequencing in order to define transcriptome profiles 
associated with effect of study treatment or clinical outcomes.
Details on processes for collection and shipment of these samples can be found in the 
laboratory manual.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 68
8.8.2. Specified Protein Research
Tumor specimens will be analyzed by immunohistochemistry and/or immunofluorescence.  
The results may be used to confirm study eligibility as specified for the combination 
(biospecimen to confirm eligibility). Available tissue may be used to characterize quantity 
and location of cells and proteins that may be associated with effect of study treatment or 
clinical outcomes.
4-mL blood sample for protein analyses will be collected.  The sample(s) will be analyzed for 
proteins and polypeptides that may be associated with effect of study treatment or clinical 
outcomes.
Details on processes for collection and shipment of these sample(s) can be found in the 
laboratory manual.
8.8.3. Specified Metabolomic Research
4-mL blood sample for metabolomic analyses may be collected for analysis of metabolites 
that may be associated with effect of study treatment or clinical outcomes.
Details on processes for collection and shipment of these sample(s) can be found in the 
laboratory manual.
8.9. Immunogenicity Assessments
Immunogenicity blood samples will be assayed for ADA using a validated assay.  The 
sample analysis will follow a tiered approach of screening, confirmation, and titer 
determination.  Samples tested positive for ADA will be further analyzed for NAb using a 
validated assay in compliance with Pfizer standard operating procedures. Additional details 
regarding the collection, processing, storage, and shipping of the blood samples will be 
provided in the Study Manual.  As part of understanding the PK of the study drugs, samples 
may be used for additional characterization of an observed immunogenicity response and/or 
evaluation of the bioanalytical methods.  These data will be used for internal exploratory 
purposes and will not be included in the clinical report.  Samples collected for this purpose 
will be retained in accordance to local regulations and if not used within this timeframe, will 
be destroyed.
8.9.1. Immunogenicity Assessment of Sasanlimab
Blood samples (6 mL whole blood at each time point) for evaluation of immunogenicity 
(ADA) of sasanlimab will be collected from all participants at the time points as outlined in 
the respective sub-study SoAs.
8.10. Health Economics
Health economics/medical resource utilization and health economics parameters evaluated in 
this study will be specified in the respective sub-study SoAs (Section 12.8.5 for 
Sub-Study A).

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 69
8.11. End of Treatment (EOT) Visit
Participants who discontinue study treatment will undergo the EOT visit and obtain 
assessments per the respective sub-study SoA. The EOT assessments will be conducted at 
the visit that the participant is discontinued from study treatment or no longer than 1 week 
after the decision to discontinue the participant from study drug. The tumor assessments 
must be completed if not completed in the last 8 weeks and prior response is other than PD.  
Laboratory assessments must be completed if not completed in the prior 7 days.
If the EOT visit falls within 7 days of the 30-day follow-up visit, the EOT visit can be used to 
satisfy the requirements for both visits.
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. Estimands and Statistical Hypotheses
9.1.1. Estimands
For estimands refer to the respective appendix for each sub-study.  For Sub-Study A, refer to 
Section 12.3; for Sub-Study B, refer to Section 13.3.
9.2. Sample Size Determination
Approximately 375 participants are expected to be assigned to study intervention based on 
eligibility, assuming that 5 combinations will be initially explored in the umbrella study; 
refer to the respective sub-study appendix for the sample size determination for each sub-
study.
9.2.1. Phase 1b Dose Finding
The total number of participants will depend on the number of dose levels and escalation and 
de-escalations needed to determine the MTD/RP2D of each combination and the number of 
participants evaluable for DLT at each dose level.
For details of each sub-study’s Phase 1b dose finding refer to the respective appendix.  
9.2.2. Phase 2 Dose
After the RP2D of a combination is determined, the study will proceed to Phase 2 to assess 
efficacy.  Details of each sub-study’s respective Phase 2 design and sample size is in an 
appendix.  

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 70
9.3. Analysis Set
For purposes of analysis, the following analysis sets are defined:
Participant Analysis Set
Description
Full analysis set 
The full analysis set includes all participants who receive at 
least 1 dose of study drug.  Participants will be classified 
according to the treatment actually received.  
Safety analysis set
The safety analysis set includes all participants who receive at 
least 1 dose of study drug.  Participants will be classified 
according to the study treatment actually received.  In a 
non-randomized study the full analysis set and safety analysis 
set are identical.
Per-protocol analysis set
The per-protocol analysis set is a subset of the full analysis set 
and will not include participants who do not meet criteria that 
could impact the key objectives of the study. These criteria 
will be pre-specified in the statistical analysis plan. The per 
protocol analysis set will be used for sensitivity analyses of the 
primary efficacy endpoint.
DLT-Evaluable analysis 
set
The DLT-evaluable analysis set includes all participants who 
receive at least 1 dose of study treatment in the Phase 1b and 
either experience DLT during the DLT-observation period or 
complete the DLT-observation period without 
DLT. Participants without DLTs receive less than 75% of the 
planned dose of each study drug in during the DLT 
observation period for reasons other than treatment-related 
toxicity are not evaluable for DLT. All participants deemed 
non-evaluable for DLT may be replaced.
Biomarker analysis set
The biomarker analysis set for each biomarker is a subset of 
the safety analysis set and includes all participants with at least 
1 biomarker evaluated pre-dose.
Pharmacodynamic 
analysis set
The pharmacodynamic analysis set is a subset of the safety 
analysis set and includes participants with at least 1 biomarker 
evaluated pre- and post-dose.
Immunogenicity analysis 
set
The immunogenicity analysis set is a subset of the safety 
analysis set and includes participants who have at least 
1 analyzed sasanlimab ADA/NAb sample.
PK analysis set
The PK concentration analysis set is a subset of the safety 
analysis set and will include participants who have at least 
1 concentration measurement for the measured analytes related 
to the study drug (ie, sasanlimab, etc).

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 71
Participant Analysis Set
Description
The PK parameter analysis set is a subset of the safety analysis 
set and will include participants who have at least 1 of the PK 
parameters of interest for the measured analytes related to the 
study drug (ie, sasanlimab, etc).
9.4. Statistical Analyses
The SAP will be developed and finalized for each sub-study 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.
9.4.1. General Considerations
Each sub-study will be reported separately and by Phase 1b and Phase 2.
9.4.2. Primary Endpoint(s)
Phase 1b
DLT during the DLT-observation period is the primary safety endpoint of the Phase 1b for 
the combination evaluated.  Analyses of DLT are based on the DLT-evaluable analysis set.
Phase 2
Refer to sub-study appendices for primary efficacy endpoints.
9.4.3. Secondary Endpoints
9.4.3.1. Efficacy Analysis
Refer to sub-study appendices for secondary efficacy analyses.
9.4.3.2. Safety Analyses
All safety analyses will be performed on the safety population.
Simple summary statistics (descriptive) will be presented for participants with SAEs, AEs of 
special interest, laboratory abnormalities, and other secondary safety endpoints during the 
on-treatment period (defined as the time from the first dose of study treatment through 
minimum of 30 days after last dose of study treatment or the start day of new anti-cancer 
drug – 1 day) unless otherwise specified in the SAP.
9.4.3.2.1. Adverse Events
AEs will be graded by the investigator according to the CTCAE version 5.0 and coded using 
the MedDRA.  AE data will be reported in tables and listings.  Summaries of AEs by mapped 
terms, appropriate thesaurus level, toxicity grade, and seriousness and relationship to study 
treatment will be presented, as well as summaries of AEs leading to death and premature 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 72
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.  Listings of DLTs and deaths will be provided.
9.4.3.2.2. 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 
using shift tables.   For laboratory tests without CTCAE grade definitions, results will be 
categorized as normal, abnormal, or not done.
9.4.3.3. PK Analyses of Sasanlimab
Concentrations for sasanlimab will be summarized descriptively (n, mean, SD, coefficient of 
variation (CV), median, minimum, maximum, geometric mean, its associated CV, and 95% 
confidence interval) by arm, cycle, and day.  
PK parameters including Ctrough, Cmax, Tmax, and AUC for sasanlimab will be determined 
from the respective concentration-time data using standard non-compartmental methods as 
data permit.  Additionally, if data permit or if considered appropriate, PK parameters such as 
t½, CL, and Vd will also be estimated.  Actual sample collection times will be used for the 
parameter calculations.  Non-compartmental PK parameters, when calculated, will be 
summarized descriptively by sub-study and cycle.
The trough concentrations for sasanlimab will be plotted for each combination arm using a 
box whisker plot by cycle and day to assess the attainment of steady state.
Summary data may be compared with the historical data of sasanlimab and combination 
study drugs as single agents to assess any potential drug interaction effects.
9.4.3.4. Analysis of Immunogenicity Data of Sasanlimab
For the immunogenicity data, the percentage of participants with positive ADA and NAb (if 
analyzed) each will be summarized by dose level or by treatment. For participants with 
positive ADA or NAb, the magnitude (titer), time of onset, and duration of ADA or NAb 
response will also be described, if data permit.
9.4.4. Exploratory Endpoints
9.4.4.1. Analyses of Biomarker Endpoints
Summary statistics (eg, the mean and standard deviation, median, and minimum/maximum 
levels of continuous, and frequencies and percentages of categorical biomarker measures) 
will be determined for baseline and on-treatment biomarkers. Those biomarkers showing 
significant association (at significance level of 0.05) with objective response rate will be used 
to define participant subgroups for time-to-event analyses.  Further details will be specified 
in the SAP.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 73
9.4.5. Other Safety Analyses
All safety analyses will be performed on the safety population.
9.4.5.1. Electrocardiogram Analyses
ECG measurements (either single measurement or an average of the triplicate measurements 
when available) 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 heart rate (QTc) using standard correction factors [ie, 
Fridericia’s (default correction), and possibly a study specific factor, as appropriate].  Data 
will be summarized and listed for QT, RR interval, PR interval, QRS complex, and QTc.
Categorical analysis will be conducted for the maximum change from baseline in corrected 
QT and the maximum post baseline corrected QT interval.
9.4.6. Other Analyses
Pharmacogenomic or biomarker data from Banked Biospecimens may be collected during or 
after the trial and retained for future analyses; the results of such analyses are not planned to 
be included in the CSR.
PK, efficacy, biomarker, and safety data from both Part 1 and Part 2 of a sub-study may be 
pooled for PK/PD analyses using appropriate modeling to explore any association between 
study drug exposure, biomarkers, safety, and/or efficacy endpoints. The results of these 
analyses, if performed, may be reported separately.
Potential impact of immunogenicity on PK, clinical responses, and safety/tolerability may be 
explored, if data warrant, and may be reported separately.
9.5. Interim Analyses
Interim analyses will be determined by sub-study and details provided in each corresponding 
Appendix as necessary.
9.6. Data Monitoring Committee or Other Independent Oversight Committee
An external Data Safety Monitoring Committee will not be established for the study.  For the 
purpose of this protocol, Pfizer procedures for periodic safety review will be applied by an 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 74
internal safety review team with medical and statistical capabilities to review individual and 
summary data collected in the safety and clinical databases.  Procedures include:
Surveillance for SAEs according to regulatory guidelines.
Discussions between the investigators and the sponsor of AEs and laboratory tests alterations 
seen at each dose level performed in an ongoing manner at regular teleconferences and/or 
meetings to determine the safety profile and risk/benefit ratio and decide if further enrollment 
is appropriate.
As this is an open-label study, the sponsor will conduct unblinded reviews of the data during 
the course of the study for the purpose of safety assessment, facilitating dose de-escalation 
decisions, facilitating PK/PD modeling, and/or supporting clinical development.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 75
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 and 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.
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 guidelines, the IRB/EC, European regulation 536/2014 
for clinical studies (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.
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 ICH GCP that the investigator becomes aware 
of.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 76
10.1.2. Financial Disclosure
Investigators and sub-investigators 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 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 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 guidelines, HIPAA 
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 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.
The participant 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.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained.  
The authorized person obtaining the informed consent must also sign the ICD.
Participants 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.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 77
A participant who is rescreened is not required to sign another ICD if the rescreening occurs 
within 30 days from the previous ICD signature date.
Unless prohibited by local requirements or IRB/EC decision, the ICD will contain a separate 
section that addresses the use of samples for optional additional research.  The optional 
additional research does not require the collection of any further samples. The investigator or 
authorized designee will explain to each participant the objectives of the additional research.  
Participants will be told that they are free to refuse to participate and may withdraw their 
consent at any time and for any reason during the storage period.  A separate signature will 
be required to document a participant's agreement to allow any specimens to be used for 
additional research.  Participants who decline to participate in this optional additional 
research will not provide this separate signature.
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 identification.  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. 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 
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.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 78
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.
Exploratory Analyses Results Reporting
Results from exploratory analyses will be reported in the CSR where possible. However, 
given the exploratory nature of the objectives and endpoints, the analyses may not be 
completed 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 scientific 
conferences and/or in peer-reviewed scientific journals.
Data Sharing
Pfizer provides researchers secure access to participant-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 available data from these trials 
24 months after study completion.  Participant-level data will be anonymized in accordance 
with applicable privacy laws and regulations.  CSRs will have personally identifiable 
information redacted.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 79
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.
10.1.6. 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.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
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.
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 (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, remote, or on-site monitoring), are provided in the 
monitoring plan.
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
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, ICH GCP, and all applicable regulatory requirements.
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.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 80
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.
10.1.7. 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 can be found in the clinical monitoring plan.
10.1.8. 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.
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 
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 GCP guidelines;

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 81

Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.
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.
10.1.9. 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 
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.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 82
10.1.10. 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 study portal and study team on 
demand (SToD) system.
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card at the time of informed 
consent.  The contact card contains, at a minimum, protocol and study intervention 
identifiers, participant numbers, contact information for the investigator site, and contact 
details for a contact center in the event that the investigator site staff cannot be reached to 
provide advice on a medical question or problem originating from another healthcare 
professional not involved in the participant’s participation in the study.  The contact number 
can also be used by investigator staff if they are seeking advice on medical questions or 
problems; however, it should be used only in the event that the established communication 
pathways between the investigator site and the study team are not available.  It is therefore 
intended to augment, but not replace, the established communication pathways between the 
investigator site and the study team for advice on medical questions or problems that may 
arise during the study.  The contact number is not intended for use by the participant directly, 
and if a participant calls that number, he or she will be directed back to the investigator site.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 83
10.2. Appendix 2: Clinical Laboratory Tests
The following safety laboratory tests will be performed at times defined in the SoA of each 
sub-study.  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.  Local laboratories may be used for all protocol-
specified laboratory assessments.  Local laboratories to be used must be confirmed 
acceptable by the investigator and submit reference range documents for each test utilized.
Samples for all laboratory assessments in Table 4 will be drawn at the time points indicated 
in the respective sub-study Schedule of Activities.  Laboratory tests may be performed up to 
3 days prior to the scheduled clinic visit. Additional laboratory assessments may be required 
for the sub-studies and will be listed in the respective appendices.
Table 4.
Master Protocol-Required Safety Laboratory Assessments
Hematology
Chemistrya
Hemoglobin
Platelet count
WBC count
Absolute neutrophils
Absolute Lymphocytes
Absolute Monocytes
Absolute Eosinophils
Absolute Basophils
ALT
AST
Bicarbonate or CO2
CRP
Alkaline phosphatase
Sodium
Potassium
Magnesium
Chloride
Total calcium
Total bilirubin
Total protein
BUN or urea
Creatinine
Creatinine clearanceb
Uric acid
Glucose (random)
LDH
Albumin
Phosphorus or Phosphate
Amylase
Lipase
Serology
Hepatitis B surface 
(HBV)
Hepatitis C antibody 
(HCV)
Coagulation
INR
aPTT or PTT
Urinalysis
Protein (qual)
Blood (qual)
Microscopic analysis 
(Reflex Testing)c
Other
FSH (if applicable)
Endocrinology
ACTH
TSH
Free T4
Pregnancy Test
For female 
participants of 
childbearing 
potential, serum or 
urine.
a.
For potential Hy's Law cases, in addition to repeating AST and ALT, laboratory tests should include 
albumin, creatine kinase, total bilirubin, direct and indirect bilirubin, gamma-glutamyl transferase, 
prothrombin time (PT)/INR, alkaline phosphatase, total bile acids and acetaminophen drug and/or protein 
adduct levels.
b.
Estimated creatinine clearance according to Cockcroft-Gault formula, or by 24-hour urine collection, or 
according to local institutional method.
c.
Only required if urine dipstick is positive for blood or protein. If ≥2+ protein on urine dipstick, collect 
spot urine sample to calculate UPCR or collect 24 hr urine.
Investigators must document their review of each laboratory safety report.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 84
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 conditions 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/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses should be reported regardless of sequelae.

The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will 
be reported as an AE or SAE if they fulfill the definition of an AE or SAE as per 
Section 8.3.8.1.  Also, “lack of efficacy” or “failure of expected pharmacological 
action” does not constitute an AE or SAE.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 85
Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which 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 SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
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, which 
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 
serious.  When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 86
An SAE is defined as any untoward medical occurrence that, at any dose:
Hospitalization for elective treatment of a preexisting condition that did not worsen from 
baseline is not considered an AE.
d.
Results in persistent 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 (e.g., sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization 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 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 Intensity section).

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 patient 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.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 87
10.3.3. Recording/Reporting and Follow up of AEs and/or SAEs
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording adverse events on the CRF 
and for reporting serious adverse events on the CT SAE Report Form to Pfizer Safety.  
These requirements are delineated for 3 types of events: (1) SAEs; (2) nonserious adverse 
events (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 
investigation under study 
during pregnancy or
breastfeeding, and 
occupational exposure
All AEs/SAEs associated 
with exposure during 
pregnancy or breastfeeding
Occupational exposure is not 
recorded.
All (and EDP supplemental 
form for EDP)
Note: Include all SAEs 
associated with exposure 
during pregnancy or 
breastfeeding. Include all 
AEs/SAEs associated with 
occupational exposure.  

When an AE/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/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/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 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 88
AE and SAE Recording/Reporting
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/SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories: 
GRADE
Clinical Description of Severity
1
MILD adverse event
2
MODERATE adverse event
3
SEVERE adverse event
4
LIFE-THREATENING consequences; urgent intervention indicated
5
DEATH RELATED TO adverse event
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.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE.

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.

The investigator will use clinical judgment to determine the relationship.

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.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 89
Assessment of Causality

For each AE/SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE/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.

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.

If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings including histopathology.  

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to the sponsor within 24 hours 
of receipt of the information.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 90
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.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 91
10.4. Appendix 4: Contraceptive Guidance and Collection of Pregnancy Information
Contraceptive guidance and collection of pregnancy information is included in the respective 
sub-study appendices (Section 12.10.2 for Sub-Study A; Section 13.10.2 for Sub-Study B).

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 92
10.5. Appendix 5: Genetics
Use/Analysis of DNA

Genetic variation may impact a participant’s response to study intervention, 
susceptibility to, and severity and progression of disease.  Therefore, where local 
regulations and IRBs/ECs allow, a blood sample will be collected for DNA analysis.

The scope of the genetic research may be narrow (eg, 1 or more candidate genes) or 
broad (eg, the entire genome), as appropriate to the scientific question under 
investigation.

The samples may be analyzed as part of a multi-study assessment of genetic factors 
involved in the response to study intervention or study interventions of this class to 
understand treatments for the disease(s) under study or the disease(s) themselves.

The results of genetic analyses may be reported in the CSR or in a separate study 
summary, or may be used for internal decision making without being included in a 
study report.

The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality. 

The samples will be retained as indicated:

Samples for specified genetic analysis (see Section 8.7.1) will be stored for up to 
15 years or other period as per local requirements.

Samples for banking will be stored indefinitely or for another period as per local 
requirements (Section 8.7.2).

Participants may withdraw their consent for the storage and/or use of their Banked 
Biospecimens at any time by making a request to the investigator; in this case, any 
remaining material will be destroyed.  Data already generated from the samples will 
be retained to protect the integrity of existing analyses.

Banked Biospecimens will be labeled with a code.  The key between the code and the 
participant’s personally identifying information (eg, name, address) will be held at the 
study site and will not be provided to the sample bank.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 93
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments
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 an “adaptor” or are “susceptible.”
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:
o
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).
o
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.  

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 94
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.  The possibility of hepatic 
neoplasia (primary or secondary) should be considered.
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s law, 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, 
supplement (herbal) use and consumption, family history, sexual history, travel history, 
history of contact with a jaundiced person, surgery, blood transfusion, history of liver or 
allergic disease, and potential occupational exposure to chemicals, should be collected.  
Further testing for acute hepatitis A, B, C, D, and E infection and liver imaging (eg, biliary 
tract) 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.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 95
10.7. Appendix 7: ECG Findings of Potential Clinical Concern
ECG Findings That May Qualify as AEs

Marked sinus bradycardia (rate <40 bpm) lasting minutes.

New PR interval prolongation >280 msec.

New prolongation of 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 SAEs

QTcF prolongation >500 msec.

New ST-T changes suggestive of myocardial ischemia.

New-onset left bundle branch block (QRS >120 msec).

New-onset right bundle branch block (QRS >120 msec).

Symptomatic bradycardia. 

Asystole:

In awake, symptom-free patients 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 patients 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).

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 96

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 SAEs

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.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 97
10.8. Appendix 8: Medical Device Adverse Events, Adverse Device Effects, Serious 
Adverse Events, and Device Deficiencies: Definition and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
Definitions of a Medical Device Deficiency
The definitions and procedures detailed in this appendix are in accordance with ISO 14155. 
Both the investigator and the sponsor will comply with all local medical device reporting 
requirements.
The detection and documentation procedures described in this protocol apply to all sponsor 
medical devices provided for use in the study (see Section 6.1.2 for the list of sponsor 
medical devices).
10.8.1. Definition of AE and ADE
AE and ADE Definition 

An AE is defined as any untoward medical occurrence, unintended disease or 
injury, or untoward clinical signs (including abnormal laboratory finding) in study 
participants, users, or other persons, whether or not related to the investigational 
medical device.  This definition includes events related to the investigational 
medical device or comparator for study participants, users, and other persons.  This 
definition also includes events related to procedures for study participants only.

An ADE is defined as an adverse event related to the use of an investigational 
medical device.  This definition includes any adverse events resulting from 
insufficient or inadequate instructions for use, deployment, implantation, 
installation, or operation, or any malfunction of the investigational medical device 
as well as any event resulting from use error or from intentional misuse of the 
investigational medical device.
10.8.2. Definition of SAE, SADE, and Unanticipated Serious Adverse Device Effect
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is an AE that:
a. Led to death.
b. Led to serious deterioration in the health of the participant, that either resulted in:
A life-threatening illness or injury. 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

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 98
An SAE is an AE that:
A permanent impairment of a body structure or a body function.
Inpatient or prolonged hospitalization, Planned hospitalization for a preexisting condition, 
or a procedure required by the protocol, without serious deterioration in health, is not 
considered an SAE.
Medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment to a body structure or a body function.
c.
Led to fetal distress, fetal death or a congenital abnormality or birth defect.
SADE Definition

A SADE is defined as an adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event.
USADE Definition

A USADE is a serious adverse device effect which by its nature, incidence, 
severity or outcome has not been identified in the current version of the risk 
analysis management file.
10.8.3. Definition of Device Deficiency
Device Deficiency Definition

A device deficiency is an inadequacy of a medical device with respect to its 
identity, quality, durability, reliability, safety, or performance. Device deficiencies 
include malfunctions, use errors, and inadequate labeling.
10.8.4. Recording/Reporting and Follow-up of AEs and/or SAEs and Device 
Deficiencies
AE, SAE and Device Deficiency Recording

When an AE/SAE/device deficiency 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/SAE/device deficiency 
information in the participant’s medical records, in accordance with the 
investigator’s normal clinical practice and on the appropriate form of the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of following the reporting process described 
in the IP Manual.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 99
AE, SAE and Device Deficiency Recording

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/SAE.

For device deficiencies, it is very important that the investigator describes any 
corrective or remedial actions taken to prevent recurrence of the incident.
o
A remedial action is any action other than routine maintenance or servicing 
of a medical device where such action is necessary to prevent recurrence of 
a device deficiency.  This includes any amendment to the device design to 
prevent recurrence.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE/device deficiency.

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.

The investigator will use clinical judgment to determine the relationship.

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 in his/her assessment.

For each AE/SAE/device deficiency, the investigator must document in the 
medical notes that he/she has reviewed the AE/SAE/device deficiency 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.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 100
Assessment of Causality

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements
Follow-up of AE/SAE/Device Deficiency

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/SAE/device deficiency as 
fully as possible.  This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare providers.

If a participant dies during participation in the study or during a recognized follow-
up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings including histopathology.  

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to the sponsor within 24 hours 
of receipt of the information.
10.8.5. 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.
10.8.6. Reporting of SADEs
SADE Reporting to Pfizer Safety
NOTE: There are additional reporting obligations for medical device incidents that are 
potentially related to SAEs that must fulfill the legal responsibility to notify appropriate 
regulatory authorities and other entities about certain safety information relating to medical 
devices being used in clinical studies. 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 101
SADE Reporting to Pfizer Safety

Any device deficiency that is associated with an SAE must be reported to the 
sponsor within 24 hours after the investigator determines that the event meets the 
definition of a device deficiency.

The sponsor shall review all device deficiencies and determine and document in 
writing whether they could have led to an SAE.  These shall be reported to the 
regulatory authorities and IRBs/ECs as required by national regulations.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 102
10.9. Appendix 9: RECIST (Response Evaluation Criteria In Solid Tumors) version 1.1 
Guidelines
Adapted from E.A. Eisenhauer, et al (2009).19
Categorizing Lesions at Baseline
Measurable Lesions 
Lesions that can be accurately measured in at least 1 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). 
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 <15 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.

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.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 103
RECORDING TUMOR ASSESSMENTS 
All sites of disease must be assessed at baseline (Screening visit).  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 inevaluable. 
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 post-baseline. 
If 2 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 the 
lesion is considered to have disappeared, 0 mm should be recorded; otherwise if a lesion is 
determined to be present but too small to measure, the lesion status will indicate too small to 
measure and judged to be less than 10 mm and 5 mm will be used as a default measurement 
in the calculation of the sum of the diameters.
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, INEVALUABLE, PRESENT WITHOUT 
UNEQUIVOCAL PROGRESSION, UNEQUIVOCAL PROGRESSION.  Multiple 
non-target lesions in one organ may be recorded as a single item on the case report form 
(eg, ‘multiple enlarged pelvic lymph nodes’ or ‘multiple liver metastases’).
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 
should be discussed with the radiologist and the sponsor to determine if substitution is 
possible.  If not, subsequent objective statuses are not evaluable. 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 104
Target Disease
Complete Response (CR): Complete disappearance of all target lesions with the exception of 
nodal disease.  All target nodes must decrease to normal size (short axis <10 mm).  All target 
lesions must be assessed.
Partial Response (PR): Greater than or equal to 30% decrease under baseline of the sum of 
diameters of all target measurable lesions.  All target lesions must be assessed. 
Stable Disease : Does not qualify for CR, PR or Progression.  All target lesions must be 
assessed.  Stable Disease can follow PR only in the rare case that the sum increases by less 
than 20% from the nadir (smallest sum of diameters consider baseline and all assessments 
prior to the time point under evaluation), but enough that a previously documented 30% 
decrease no longer holds. 
Progressive Disease (PD): 20% increase in the sum of diameters of target measurable lesions 
above the smallest sum observed (over baseline if no decrease in the sum is observed during 
therapy), with a minimum absolute increase of 5 mm. 
Not evaluable (NE): Progression has not been documented, and 

1 or more target lesions have not been assessed; or

Assessment methods used were inconsistent with those used at baseline; or

1 or more target lesions cannot be measured accurately (eg, poorly visible unless due 
to being too small to measure); or

1 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 (if 
being followed).  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 (if being 
followed) 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 stable 
disease or PR in target disease, progression due to unequivocal increase in non-target disease 
should be rare. 
Not evaluable (NE): Progression has not been determined and 1 or more non-target lesion 
sites have not been assessed or assessment methods used were inconsistent with those used at 
baseline or 1 or more non-target lesions cannot be assessed (eg, poorly visible or unclear 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 105
images) or 1 or more non-target lesions were excised or irradiated and have not reappeared or 
increased. 
New Lesions 
The appearance of any new unequivocal malignant lesion indicates PD.  If a new lesion is 
equivocal, for example due to its small size, continued assessment will clarify the etiology.  
If repeat assessments confirm the lesion, then progression should be recorded on the date of 
the initial assessment.  A lesion identified in an area not previously scanned will be 
considered a new lesion.
Supplemental Investigations
If CR determination depends on a residual lesion that decreased in size but did not disappear 
completely, it is recommended the residual lesion be investigated with biopsy or fine needle 
aspirate.  If no disease is identified, objective status is CR.
If progression determination depends on a lesion with an increase possibly due to necrosis, 
the lesion may be investigated with biopsy or fine needle aspirate to clarify status. 
Subjective Progression
Participants requiring discontinuation of treatment without objective evidence of disease 
progression should not be reported as PD on tumor assessment CRFs.  This should be 
indicated on the end of treatment CRF as off treatment due to Global Deterioration of Health 
Status.  Every effort should be made to document PD even after discontinuation of study 
treatment. 
Determination of Tumor Response by RECIST
When both target and non-target lesions are present, individual assessments will be recorded 
separately.  New lesions will also be recorded separately.  Determination of tumor response 
at each assessment based on target, non-target and new lesions is summarized in the 
following table.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 106
Objective Response Status at Each Assessment for Participants with Measurable 
Disease at Baseline
Target Lesions
Non-target Lesions
New Lesions
Objective status
CR
CR
No
CR
CR
Non-CR/Non-PD or not 
all evaluated
No
PR
PR
Non-PD* or not all 
evaluated
No
PR
Stable Disease
Non-PD* or not all 
evaluated
No
Stable Disease
Not Evaluable
Non-PD
No
Not Evaluable
PD
Any
Yes or No
PD
Any
PD
Yes or No
PD
Any
Any
Yes**
PD
*Non PD includes CR and Non CR/Non PD
** New lesions must be unequivocal
Determination of Best Overall Response
The best overall response is the best response recorded from the start of the treatment until 
disease progression/recurrence (taking as reference for progressive disease the smallest sum 
on study).  For CR and PR, the participant’s best response assignment will depend on the 
achievement of both measurement and confirmation criteria.  CR and PR must be confirmed 
by 2 measurements at least 4 weeks apart.  In the case of Stable Disease, follow up 
measurements must have met the Stable Disease criteria at least once after start of the 
treatment at a minimum interval of 6 weeks.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 107
10.10. Appendix 10: Management of Immune-Related Adverse Events (irAEs) for 
Sasanlimab
Gastrointestinal irAEs
Severity of Diarrhea/Colitis
(NCI-CTCAE v5.0)
Initial Management
Follow-up Management
Grade 1
Diarrhea: <4 stools/day over
Baseline
Colitis: asymptomatic
-Continue study treatment
-Symptomatic treatment (eg
loperamide)
-Close monitoring for worsening 
symptoms.
-Educate participant to
report worsening
immediately.
-If worsens:
Treat as Grade 2, 3 or 4.
Grade 2
Diarrhea: 4 to 6 stools per day over
Baseline; IV fluids indicated 
<24 hours; not interfering with ADL
Colitis: abdominal pain; blood in
stool
-Withhold study treatment
-Symptomatic treatment
-If improves to Grade ≤1:
Resume study treatment.
-If persists >5-7 days or recurs:
Treat as Grade 3 or 4.
Grade 3 to 4
Diarrhea (Grade 3): ≥7 stools per day
over Baseline; incontinence; IV
fluids ≥24 hours; interfering with 
ADL
Colitis (Grade 3): severe abdominal
pain, medical intervention indicated,
peritoneal signs
Grade 4: life-threatening, perforation
-Withhold for Grade 3
-Permanently discontinue study 
treatment for Grade 4 or 
recurrent Grade 3
-1.0 to 2.0 mg/kg/day 
prednisone IV or equivalent
-Add prophylactic antibiotics 
for opportunistic infections
-Consider lower endoscopy
-If improves:
-Continue steroids until Grade
≤1, then taper over at least 
1 month; resume study treatment
following steroids taper (for 
initial Grade 3).
-If worsens, persists >3 to
5 days, or recurs after
improvement.
-Add infliximab 5 mg/kg (if no 
contraindication).
-Note: infliximab should not be
used in cases of perforation or 
sepsis.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 108
Dermatological irAEs
Grade of Rash 
(NCI-CTCAE v5.0)
Initial Management
Follow-up Management
Grade 1 to 2
Covering ≤30% body surface area
-Continue study treatment  
-Symptomatic therapy (for 
example, antihistamines, 
topical steroids)
-If persists >1 to 2 weeks or recurs: 
-Withhold study treatment
-Consider skin biopsy
-Consider 0.5-1.0 mg/kg/day 
prednisone or equivalent. Once
improving, taper steroids over at 
least 1 month, consider prophylactic 
antibiotics for opportunistic
infections, and resume study 
treatment following steroids taper.
-If worsens: Treat as Grade 3 to 4.
Grade 3 to 4
Grade 3: Covering >30% 
body surface area;
Grade 4: Life
threatening 
consequences
-Withhold study 
treatment for Grade 3
-Permanently discontinue for
Grade 4 or recurrent Grade 3
-Consider skin biopsy
-Dermatology consult
-1.0 to 2.0 mg/kg/day 
prednisone or equivalent
-Add prophylactic antibiotics 
for opportunistic infections
-If improves to Grade ≤1:
-Taper steroids over at least 1 month; 
resume study treatment following
steroids taper (for initial Grade 3).

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 109
Pulmonary irAEs
Grade of Pneumonitis
(NCI-CTCAE v5.0)
Initial Management
Follow-up Management
Grade 1
Radiographic changes only
-Consider withholding study 
treatment
-Monitor for symptoms
every 2 to 3 days
-Consider Pulmonary and
Infectious Disease consults
-Re-assess at least
every 3 weeks.
-If worsens: Treat as Grade 2
or Grade 3 to 4.
Grade 2
Mild to moderate new symptoms
-Withhold study treatment
-Pulmonary and Infectious 
Disease consults
-Monitor symptoms 
daily; consider 
hospitalization
-1.0 to 2.0 mg/kg/day 
prednisone or equivalent
-Add prophylactic 
antibiotics for opportunistic 
infections
-Consider bronchoscopy, 
lung biopsy
-Re-assess every 
1 to 3 days If
improves:
-When symptoms return to Grade
≤1, taper steroids over at least
1 month, and then resume study 
treatment following steroids 
taper.
-If not improving after 2 weeks 
or worsening: Treat as Grade 3
to 4.
Grade 3 to 4
Grade 3: Severe new symptoms;
New/worsening hypoxia;
Grade 4: Life-threatening
-Permanently
discontinue study 
treatment.
-Hospitalize
-Pulmonary and 
Infectious Disease 
consults
-1.0 to 2.0 mg/kg/day 
prednisone or equivalent
-Add prophylactic antibiotics 
for opportunistic infections
-Consider bronchoscopy, lung
biopsy
-If improves to Grade ≤1:
-Taper steroids over at least 1 
month.
-If not improving after 48 hours
or worsening: Add additional
immunosuppression (for
example, infliximab, 
cyclophosphamide, IV
immunoglobulin, or 
mycophenolate mofetil).

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 110
Hepatic irAEs
Grade of Liver Test Elevation
(NCI-CTCAE v5.0)
Initial Management
Follow-up Management
Grade 1
Grade 1 AST or ALT >ULN to
3.0 x ULN and/or Total
bilirubin > ULN to
1.5 x ULN
-Continue study treatment
-Continue liver function monitoring
-If worsens: Treat as Grade 2 or 3 - 4.
Grade 2
AST or ALT >3.0 to ≤5 x
ULN and/or total bilirubin 
>1.5 to ≤3 x ULN
-Withhold study treatment
-Increase frequency of
monitoring to every 3 days
-If returns to Grade ≤1:
-Resume routine monitoring; 
resume study treatment.
-If elevation persists >5 to 7 days or 
worsens: 
-Treat as Grade 3 to 4.
Grade 3 to 4
AST or ALT >5 x ULN and/or 
total bilirubin >3 x ULN
-Permanently discontinue 
study treatment
-Increase frequency of
monitoring to every 1 to
2 days
-1.0 to 2.0 mg/kg/day 
prednisone or equivalent
-Add prophylactic antibiotics 
for opportunistic infections
-Consult gastroenterologist/ 
hepatologist
-Consider obtaining MRI/CT
scan of liver and liver biopsy if 
clinically warranted
-If returns to Grade ≤1:
-Taper steroids over at least 1 month.
-If does not improve in >3 to 5 days,
worsens or rebounds:
-Add mycophenolate mofetil 1 gram 
(g) twice daily.
-If no response within an additional
3 to 5 days, consider other 
immunosuppressants per local
guidelines.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 111
Renal irAEs
Grade of Creatinine Increased
(NCI-CTCAE v5.0)
Initial Management
Follow-up
Management
Grade 1
Creatinine increased >ULN to 1.5 x
ULN
-Continue study treatment
-Continue renal function
monitoring.
-If worsens: Treat as
Grade 2 to 3 or 4.
Grade 2 to 3
Creatinine increased >1.5 and ≤6 x
ULN
-Withhold study treatment  
-Increase frequency of monitoring to
every 3 days
-1.0 to 2.0 mg/kg/day prednisone or 
equivalent.
-Add prophylactic antibiotics for
opportunistic infections
-Consider renal biopsy
-If returns to Grade ≤1:
-Taper steroids over at
least 1 month, and resume
study treatment following
steroids taper.
-If worsens:
-Treat as Grade 4.
Grade 4
Creatinine increased >6 x ULN
-Permanently discontinue study 
treatment 
-Monitor creatinine daily
-1.0 to 2.0 mg/kg/day prednisone or 
equivalent.
-Add prophylactic antibiotics for
opportunistic infections Consider 
renal biopsy
-Nephrology consult
-If returns to Grade ≤1:
Taper steroids over at least 
1 month.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 112
Cardiac irAEs
Myocarditis
Initial Management
Follow-up
Management
New onset of cardiac signs or 
symptoms and / or new laboratory
cardiac biomarker elevations (eg, 
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
(eg, azathioprine,
cyclosporine A, 
abatacept).
*Suggested guidelines include: Local guidelines, ESC, or AHA guidelines
ESC guidelines website:  https://www.escardio.org/Guidelines/Clinical-Practice-
Guidelines AHA guidelines website:
http://professional.heart.org/professional/GuidelinesStatements/searchresults.jsp?q=&y=&t=1001

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 113
Endocrine irAEs
Endocrine Disorder
Initial Management
Follow-up
Management
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 
-Rule-out secondary endocrinopathies (ie,
hypopituitarism / hypophysitis)
-Continue hormone 
replacement/suppression
and monitoring of 
endocrine function as 
appropriate.
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
-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.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 114
Endocrine irAEs
Endocrine Disorder
Initial Management
Follow-up
Management

-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

-Add prophylactic antibiotics for
opportunistic infections

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 115
Other irAEs* (not described above)
Grade of other irAEs 
(NCI-CTCAE v5.0)
Initial Management
Follow-up Management
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
-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
* Refer to Section 6.6.1 for irAE management principles based on AE severity.
For sasanlimab as the backbone therapy for combinations with different molecular-targeted agents, potential 
overlapping toxicities can be expected. 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/professionals/physician_gls/pdf/immunotherapy.pdf.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 116
10.11. Appendix 11: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
1L
first-line
ACTH
adrenocorticotropic hormone
ADA
antidrug antibodies
ADE
adverse device effect
ADL
activities of daily living
AE
adverse event
AESI
adverse event of special interest
AHA
American Heart Association
AJCC
American Joint Committee on Cancer
ALK
anaplastic lymphoma kinase
ALT
alanine aminotransferase
ANC
absolute neutrophil count
aPTT
activated partial thromboplastin time
aRCC
advanced renal cell carcinoma
ASCO
American Society of Clinical Oncology
AST
aspartate aminotransferase
ASTCT
American Society for Transplantation and Cellular Therapy
ATP
adenosine triphosphate
AUC
area under the concentration-time curve
AV
atrioventricular
BCG
Bacille Calmette Guérin
BCRP
breast cancer resistance protein
BID
twice a day
Bini
binimetinib
BLRM
Bayesian Logistic Regression Model
BNP
brain natriuretic peptide
bp
blood pressure
bpm
beats per minute
BRAF
B-Raf proto-oncogene serine/threonine protein kinase
BUN
blood urea nitrogen
BVN
bivariate normal
cfDNA
cell-free DNA
CDx
companion diagnostic
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CK-MB
creatine kinase-muscle type, myocardial band
CL
total clearance of drug from serum
Cmax
maximum concentration

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 117
Abbreviation
Term
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
coronavirus disease 2019
CR
complete response
CRF
case report form
CRO
contract research organization
CRP
C-reactive protein
CRS
cytokine release syndrome
CSR
Clinical Study Report
CT
computed tomography 
clinical trial
CTCAE
Common Terminology Criteria for Adverse Events
ctDNA
circulating tumor DNA
CTFG
Clinical Trial Facilitation Group
CTLA-4
cytotoxic T-lymphocyte-associated protein 4
Ctrough
trough concentrations
Ctrough-DN
dose-normalized trough concentration
CV
coefficient of variation
CXDX
Cycle X Day X
CYP
Cytochrome P450
DBP
diastolic blood pressure
DCR
disease control rate
DHP
dihydropyridine
DILI
drug-induced liver injury
DLT
dose limiting toxicity
DNA
deoxyribonucleic acid
DR
duration of response
DU
dispensable unit
EC
ethics committee
ECG
electrocardiogram
ECHO
echocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
EDP
exposure during pregnancy
EGFR
epidermal growth factor receptor
EMA
European Medicines Agency
Enco
encorafenib
EOI
end of infusion
EOT
end of treatment
ERK
extracellular receptor kinase
ESC
European Society of Cardiology
EU
European Union
EudraCT
European Union Drug Regulating Authorities Clinical Trials 
(European Clinical Trials Database)

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 118
Abbreviation
Term
EWOC
escalation with overdose control
FDA
Food and Drug Administration
FDG-PET
fluorodeoxyglucose positron emission tomography
FFPE
formalin-fixed paraffin-embedded
FSH
follicle-stimulating hormone
FT4
free thyroxine
GCP
Good Clinical Practice
G-CSF
granulocyte colony-stimulating factor
GGT
gamma-glutamyl transferase
GH
growth hormone
GI
gastrointestinal
GLP
Good Laboratory Practice
HBV
hepatitis B virus
HCV
hepatitis C virus
HFSR
hand-foot skin reaction
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
HR
heart rate
HRT
hormone replacement therapy
IB
Investigator’s Brochure
ICD
informed consent document
ICH
International Council for Harmonisation
ICI
immune checkpoint inhibitor
ID
identification
IFN
interferon
Ig
immunoglobulin
IGF-1
insulin-like growth factor 1
IL
interleukin
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 event
IRB
Institutional Review Board
IRR
Infusion-related reaction
IRT
Interactive Response Technology
ISO
International Organization for Standardization
ISR
injection site reaction
IV
intravenous(ly)
IWR
interactive Web-based response
JM
juxta-membrane
KRAS
Kirsten rat sarcoma

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 119
Abbreviation
Term
LDH
lactate dehydrogenase
LFT
liver function test
LH
luteinizing hormone
LVEF
left ventricular ejection fraction
mAb
monoclonal antibody
MAD
maximum administered dose
MAP
meta-analytic-predictive
MedDRA
Medical Dictionary for Regulatory Activities
MEK
mitogen-activated protein kinase 
MHC
major histocompatibility complex
mOS
median overall survival
mPFS
median progression-free survival
MRI
magnetic resonance imaging
msec
Millisecond(s)
MTD
maximum tolerated dose
mTPI
modified toxicity probability interval
MUGA
multigated acquisition
N/A
not applicable
NAb
neutralizing antibodies
NCI-CTCAE
National Cancer Institute Common Terminology Criteria for 
Adverse Events
NCCN
National Comprehensive Cancer Network
ND
next dose
NE
not evaluable
NGS
next generation sequencing
NIMP
noninvestigational medicinal product
NOAEL
no observed adverse effect level
NSCLC
non-small cell lung cancer
OAT
organic anion transporter
OCT
organic cation transporter
OD
overdose
OR
objective response
ORR
objective response rate
OS
overall survival
PBMC
peripheral blood mononuclear cell
PCR
polymerase chain reaction
PD
progressive disease or disease progression
pharmacodynamic
PD-1
programmed death - 1
PDGFR
platelet-derived growth factor receptor
PD-L1/PD-L2
programmed death ligand-1 / programmed death ligand-2
PDx
programmed death - 1, - L1, or - L2
PE
physical examination

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 120
Abbreviation
Term
PET
positron emission tomography
PFS
progression-free survival
P-gp
p-glycoprotein
PK
pharmacokinetic(s)
PR
partial response
PRL
prolactin
PRO
Patient Reported Outcomes
Pr(OD)
probability of overdosing
Pr(TT)
probability of target toxicity
pT
probability of toxicity
PT
prothrombin time
PTT
partial thromboplastin time
PTEN
phosphatase and tensin homolog
PVC
premature ventricular contraction/complex
QD
once daily
Q3W
every 3 weeks
Q4W
every 4 weeks
QRS
Q wave, R wave and S wave
QT
time from the beginning of the QRS complex to the end of the T 
wave
QTc
corrected QT interval
QTcF
QTc corrected using Fridericia's formula
qual
qualitative
RBC
red blood cell
RCC
renal cell carcinoma
RECIST v1.1
Response Evaluation Criteria in Solid Tumors version 1.1
RNA
ribonucleic acid
ROS1
c-ros oncogene 1
RP2D
recommended Phase 2 dose
RPED
retinal pigment epithelial detachment
RVO
retinal vein occlusion
SADE
serious adverse device effect
SAE
serious adverse event
SAP
Statistical Analysis Plan
SARS-CoV2
severe acute respiratory syndrome coronavirus 2
SBP
systolic blood pressure
SC
Subcutaneous(ly)
SD
standard deviation
SoA
schedule of activities
SOP
standard operating procedure
SRSD
single reference safety document
SToD
study team on demand
ST-T
ST-segment and T-wave

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 121
Abbreviation
Term
SUSAR
Suspected Unexpected Serious Adverse Reaction
t½
terminal phase half-life
T4
thyroxine
TBili
total bilirubin
TCR
T-cell receptor
TdP
Torsades de Pointes
TGF
transforming growth factor
TIGIT
T cell immunoreceptor with Ig and ITIM domains
Tmax
time to reach maximum concentration
TNF
tumor necrosis factor
TNM
Tumor Node Metastasis
TPS
Tumor Proportion Score
TSH
thyroid-stimulating hormone
TT
target toxicity
TTR
time to tumor response
UC
urothelial carcinoma
UD
under dose
UGT
uridine 5’-diphospho-glucuronosyltransferase
ULN
upper limit of normal
UPCR
urinary protein creatinine ratio
UPM
unit probability mass
US
United States
USADE
unanticipated serious adverse device effect
Vd
volume of distribution
VEGFR
vascular endothelial growth factor receptor
WBC
white blood cell
WOCBP
woman of childbearing potential

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 122
10.12. Appendix 12: 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).
10.12.1. Eligibility
While SARS-CoV2 testing is not mandated for this study, local clinical practice standards for 
testing should be followed. A patient 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. Patients with active infections are excluded from study participation as 
per Exclusion criterion #4, Active infections requiring systemic therapy, or Exclusion 
criterion #13 Participants with active, uncontrolled viral infection. When the infection 
resolves, the patient may be considered for re-screening. 
10.12.2. 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 (e.g., 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 any AEs and SAEs since the last contact. Refer to 
Section 8.3.  

Review and record any new concomitant treatments or changes in concomitant 
treatments since the last contact. 

Review and record contraceptive method and results of pregnancy testing if 
applicable for the participant. Confirm that the participant is adhering to the 
contraception method(s) required in the protocol. Refer to Section 10.12.3.1 of 
this appendix regarding pregnancy tests.

Assess ECOG performance status.
Study participants must be reminded to promptly notify site staff about any change in their 
health status. 
10.12.3. Alternative Facilities for Safety Assessments
Alternative facilities to the study site may be used as described in this section.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 123
10.12.3.1. 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. 
Participants may have safety labs completed at a local laboratory even in the absence of a 
public emergency; however, this section is included to highlight the option to use local labs if 
needed to facilitate collection of safety laboratory assessments during a public 
emergency. The local laboratory may be a standalone institution or within a hospital. The 
following safety laboratory evaluations may be performed at a local laboratory:

Hematology panel

Chemistry panel 

Endocrinology

Coagulation panel

Pregnancy test (if applicable)
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. Decisions about dose modifications (if applicable) based on results of the 
local laboratory tests remains the responsibility of the investigator or medically qualified 
staff.   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 eCRF.  
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 IU/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 eCRF. Confirm that the 
participant is adhering to the contraception method(s) required in the protocol.
10.12.3.2. Electrocardiograms, MUGA/Echocardiograms, Visual Acuity Exams (when 
required per the SOA)
If the participant is unable to visit the study site for ECGs, MUGA/Echo, or the eye exams, 
the participant may visit an alternative facility to have these assessments performed. 
Qualified study site personnel must order, receive, and review results. Participants may have 
these procedures completed at an alternative facility to the site even in the absence of a 
public emergency; however, this section is included to highlight the option to use an 
alternative facility if needed to allow completion of procedures during a public emergency.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 124
10.12.4. Study Intervention 
Investigational product that can be orally administered at home may be shipped by courier to 
study participants if permitted by local regulations and in accordance with storage and 
transportation requirements for the study intervention. Pfizer does not permit the shipment 
of study intervention by mail. The tracking record of shipments and the chain of custody 
of the study interventions must be kept in the participant’s source documents/medical 
records. 
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.
The guidance below is intended to support decision making, but it is not meant to supersede 
clinical assessment of any individual study participant case.
Regarding the continued administration of study drug treatment to ongoing participants who 
have active confirmed (positive by regulatory authority-approved test) or presumed (test 
pending/clinical suspicion) SARS-CoV2 infection, the following is recommend:

For symptomatic participants with active SARS-CoV2 infection, study drug 
treatment 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. It is requested that the site inform the study team when 
study drug treatment is restarted.

Continue to consider potential drug-drug interactions for any concomitant 
medication administered for treatment of SARS-CoV2 infection.
10.12.5. Home Health Visits 
A home health care service may be utilized to facilitate scheduled visits per the Schedule of 
Activities if feasible and locally permitted. 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. All assessments must be performed by someone meeting local 
requirements for performing the assessments. The following may be performed during a 
home health visit (when required per the SOA): 

Physical Examination

Weight

Vital Signs

ECG

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 125

Dermatologic Exam

Visual Acuity Exam

ECOG performance status

Laboratory sample collection of tests listed in Section 10.12.3.1 of this appendix.

PROs

Review and record any AEs and SAEs since the last contact. Refer to 
Section 8.3.  

Review and record any new concomitant treatments or changes in concomitant 
treatments since the last contact. 

Review and record contraceptive method if applicable for the participant. Confirm 
that the participant is adhering to the contraception method(s) required in the 
protocol.
10.12.6. 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.
It is recommended that the investigator discuss temporary or permanent discontinuation of 
study intervention with the study sponsor.
10.12.7. Efficacy Assessments
If the participant is unable to visit the study site for CT/MRI, the participant may visit an 
alternative facility to have the CT/MRI performed. Qualified study site personnel must order, 
receive, and review results. Participants may have imaging completed at an alternative 
facility to the site even in the absence of a public emergency; however, this section is 
included to highlight the option to use an alternative facility if needed to allow completion of 
imaging during a public emergency.
10.13. Appendix 13: Potential Drug-Drug Interactions
This section presents examples of drugs that are referenced in the sub-studies as either 
prohibited or to be taken with caution; it does not contain a complete list of potential drug-
drug interactions. Please refer to the Concomitant Therapy section of the master protocol 
(Section 6.5) and the respective sub-study appendices (Sub-Study A: Section 12.6.5) for 
comprehensive concomitant therapy requirements and restrictions for sasanlimab and the 
combination therapies.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 126
Examples of Strong and Moderate CYP3A4 Inhibitors
Strong CYP3A4 inhibitors
Moderate CYP3A4 inhibitors
elvitegravir/ritonavir (RIT)
indinavir or indinavir/RIT
lopinavir/RIT
nelfinavir
ritonavir
saquinavir or saquinavir/RIT
tipranavir/RIT
danoprevir/RIT
telaprevir
itraconazole
ketoconazole
clarithromycin
mibefradil
conivaptan
mifepristone
voriconazole
nefazodone
cobicistat
boceprevir
posaconazole
telithromycin
troleandomycin
grapefruit juice
paritaprevir and ritonavir and (ombitasvir and/or 
dasabuvir) 
posaconazole
ritonavir
telaprevir
telithromycin
troleandomycin
Pomegranates, star fruits, Seville oranges, and 
juice of any of these products
aprepitant 
ciprofloxacin
conivaptan
cyclosporine
diltiazem
dronedarone
erythromycin
fluconazole
fluvoxamine
tofisopam
verapamil
Examples of CYP3A4 inhibitors from fda.gov and University of Washington Drug Interaction Database, not 
considered exhaustive.  Potent CYP3A4 inhibitors are defined as those drugs that increase the AUC of oral 
midazolam or other CYP3A4 substrates ≥5-fold.  Moderate inhibitors are defined as those drugs that increase 
the AUC of oral midazolam or other CYP3A4 substrates CYP3A4 ≥2 to <5-fold.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 127
Examples of Strong and Moderate CYP3A Inducers
Strong CYP3A Inducers
Moderate CYP3A Inducers
St. John’s Wort
avasimibe
carbamazepine 
mitotane
phenobarbital
phenytoin 
rifampin
rifapentine
apalutamide
enzalutamide 
ivosidenib
lumacaftor
bosantan
efavirenz
etavirine
primidone
Examples of CYP3A inducers from fda.gov and University of Washington Drug Interaction Database, not 
considered exhaustive.  
Strong CYP3A inducers are defined as those drugs that decrease the AUC of CYP3A substrates ≥80%.  
Moderate CYP3A inducers are drugs that decrease the AUC of CYP3A substrates by ≥50% to 80%.
Examples of P-gp Inhibitors
P-gp Inhibitors 
elvitegravir/ritonavir (RIT)
indinavir or indinavir/RIT
lopinavir/RIT
nelfinavir
ritonavir
saquinavir or saquinavir/RIT
tipranavir/RIT
danoprevir/RIT
telaprevir
itraconazole
ketoconazole
clarithromycin
mibefradil
conivaptan
mifepristone

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 128
As the list of medications with potential drug-drug interactions is a dynamic list continually 
changing when new information becomes available, the following websites should be used 
when a concomitant medication is considered to be either prohibited or to be taken with 
caution as referenced in the sub-study appendices (eg, a moderate or strong CYP3A, P-gp, or 
UGT1A1 inhibitor and/or inducer): 

FDA list of examples of clinical substrates, inhibitors, and inducers of CYP and/or
UGT enzymes: 
o
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-
drug-interactions-table-substrates-inhibitors-and-inducers#table3-1
o
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-
drug-interactions-table-substrates-inhibitors-and-inducers#table3-2
o
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-
drug-interactions-table-substrates-inhibitors-and-inducers#table3-3

FDA list of examples of clinical substrates and inhibitors of transporters:
o
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-
drug-interactions-table-substrates-inhibitors-and-inducers#table5-1
o
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-
drug-interactions-table-substrates-inhibitors-and-inducers#table5-2

University of Washington Drug-Drug Interaction database 
(https://www.druginteractioninfo.org/)

Literature including lists of potential UGT1A1 perpetrators:
o
Xia Lv, Yangliu Xia, Moshe Finel, Jingjing Wu, Guangbo Ge, Ling Yang.
Recent progress and challenges in screening and characterization of UGT1A1 
inhibitors. Acta Pharmaceutica Sinica B. 2019; 9(2): 258-278. 
https://doi.org/10.1016/j.apsb.2018.09.005

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 129
10.14. Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the table of contents (TOC).  The protocol amendment summary of changes 
tables for past amendment(s) can be found below:
Document History
Document
Version Date
Summary and Rationale for Changes
Original protocol
18 June 2020
N/A
Protocol 
Amendment 1
04 August 2020

A visit was added for Cycle 5, Day 
8 to collect a sasanlimab PK 
sample and perform an ECG 
assessment at the sasanlimab Tmax 
at steady-state.

Blood sample collection for 
sasanlimab PK and 
immunogenicity assessments was 
extended to occur every 6 months 
after Cycle 13 until End of 
Treatment.

Modified DLT criterion #8 to 
differentiate thresholds between 
Grade 3 and 4 non-hematologic 
laboratory abnormalities, and 
modified DLT criterion #9 to add 
liver function laboratory 
abnormality thresholds in addition 
to Hy’s Law.

Modified Inclusion criterion #6 to 
clarify that patients with locally 
advanced disease must not be 
amenable for definitive therapy.

For Sub-Study A, added 
clarification of known and potential 
overlapping toxicities between 
sasanlimab and encorafenib plus 
binimetinib in Section 12.2.3.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 130
Document History
Document
Version Date
Summary and Rationale for Changes
Original protocol
18 June 2020
N/A
Protocol 
Amendment 2
07 December 2020 
•
Details from Sub-Study A were 
removed from the Synopsis 
(Section 1.1) to focus the Protocol 
Summary on the high-level aspects 
of this umbrella study and direct 
readers to the sub-study appendices 
for additional details. 
•
The Clinical Overview of 
sasanlimab was updated to reflect 
data from the recently revised IB 
and publication (Section 2.2.2).
•
The sasanlimab fixed dose was 
updated in the master protocol to 
reflect that either 300 mg Q4W or 
 will be administered 
in the sub-studies, and a 
justification for the 
 
dose was provided (Sections 4.1, 
4.3.1, 6.1). The starting dose for 
Sub-Study A was moved from the 
master protocol to Sub-Study A 
section (Section 12.4.4.1). 
•
DLT criterion #4 was modified to 
not overlap with criterion #5 
(Section 4.3.3).
•
Master Inclusion criterion #10 was 
deleted from the master protocol 
(Section 5.1) because the 
requirements for tumor specimens 
will vary depending on the patient 
population and molecular testing 
specific to each sub-study, and 
therefore will be included in each 
sub-study appendix.
CCI
CCI

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 131
Document History
Document
Version Date
Summary and Rationale for Changes
Original protocol
18 June 2020
N/A

Master Inclusion criterion #11 was 
edited to clarify the minimum life 
expectancy for previously treated 
participants (Section 5.1).

Master Exclusion criterion #8 was 
edited to remove the requirement 
that patients with asymptomatic 
brain metastasis need to be off anti-
epileptic therapy, as per 
Investigator feedback and 
consistency with study ARRAY-
818-202 (Section 5.1).

Instructions for Allocation to Study 
Intervention, including IRT 
wording, was moved from 
Sub-Study A (Section 12.6.1.1) to 
the master protocol (Section 6.3.1) 
because it will apply to all 
sub-studies.

It was clarified in the master 
protocol that therapeutic use of 
steroids may be allowed according 
to the toxicity management 
guidelines in each sub-study; 
instructions were also added to 
clarify that sasanlimab should not 
be resumed during such use of 
steroids, as indicated in the IB 
(Section 6.5.6).

The timeframe for long-term 
follow-up visits/survival visits was 
updated from 90 days or 3 months 
to 12 weeks for consistency with 
the sasanlimab program 
(Sections 8.1.3, 12.1).

It was clarified in Section 8.3.7 that 
progression of the malignancy 
under study is not to be captured as 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 132
Document History
Document
Version Date
Summary and Rationale for Changes
Original protocol
18 June 2020
N/A
an SAE unless it results in fatal 
outcome, to align with 
Section 10.3.2.

Instructions for tumor tissue 
samples were updated to allow for 
fine needle aspiration to ease site 
and subject burden, and to remove 
the number of required slides 
because this may differ for each 
sub-study and phase (Sections 8.8
and 12.8.4).

Number of participants in the 
master protocol was edited to 
remove specifics and instead refer 
to the respective sub-studies, due to 
variations in numbers and design 
among sub-studies (Sections 1.1, 
9.2). 

CO2 is now allowed in lieu of 
bicarbonate clinical laboratory 
testing (Section 10.2).

Instructions for measurable lesions 
by X-ray were removed because 
X-ray is not allowed for tumor 
assessments in this study 
(Section 10.9).

Guidance for Alternative Measures 
During Public Emergencies was 
added per Pfizer new standard 
(Section 10.12).

List of CYP3A inhibitors and 
inducers was moved from Sub-
Study A Section 12.10.3 to master 
protocol Section 10.13, as it will 
apply to multiple sub-studies. 
Drugs were also added to these 
lists.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 133
Document History
Document
Version Date
Summary and Rationale for Changes
Original protocol
18 June 2020
N/A

List of P-gp inhibitors was added to 
master protocol Section 10.13.

Sentence that was applicable only 
to Sub-Study A was moved from 
the CYP3A appendix (12.10.3) to 
Sub-Study A Section 12.6.5.1.1.

In Sub-Study A SoA, the rows for 
Echocardiogram/MUGA and 
dermatologic exam were 
re-formatted to clarify that 
Echocardiogram/MUGA is 
required at EOT visit and the 
dermatologic exam is required at 
EOT and Day 30 visit 
(Section 12.1).

Patient Reported Outcomes of 
EORTC QLQ-C30/LC13 were 
added as required procedures and 
secondary outcomes in Sub-Study 
A on Day 1 of each Cycle in 
Phase 2 (Sections 12.1, 12.3, 
12.8.5, 12.9.1.5.2.6).

Post-baseline ECOG assessments 
were removed from Sub-Study A 
as they will not be used for data 
analysis (Section 12.1).

Blood volumes for PK and 
immunogenicity sampling were 
added to Sub-Study A SoA
footnotes and predose restrictions 
were modified because they do not 
affect the PK analysis 
(Section 12.1).

Sub-Study A SoA footnote for 
tumor history (footnote g) was 
clarified to include molecular 
profiling data, if available, in 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 134
Document History
Document
Version Date
Summary and Rationale for Changes
Original protocol
18 June 2020
N/A
accordance with Master protocol 
Section 8.8 (Section 12.1). 

Sub-Study A SoA footnotes for 
biospecimen eligibility 
confirmation (footnote dd) and 
tumor biopsies (footnote ee) were 
modified to reflect that tumor tissue 
is only required for Phase 2 
because it may not be feasible to 
provide sufficient archived tumor 
specimens or perform new biopsies 
for NSCLC patients after multiple 
lines of therapy (Section 12.1).

PD-L1 expression in baseline 
tumor samples was removed as a 
secondary objective/endpoint from 
Sub-Study A Phase 1b because it 
may not be feasible to provide 
sufficient archived tumor 
specimens or perform new biopsies 
for NSCLC patients after multiple 
lines of therapy (Section 12.3).

Examples of PK parameters were 
removed from the PK Endpoint in 
Sub-Study A to allow flexibility in 
PK analysis, and the description of 
PK analyses was updated 
(Section 12.3, 12.9.1.5.2.3).

Wording for the PD-L1 expression 
objective and endpoint in Phase 2 
of Sub-Study A was adjusted for 
clarity (Section 12.3).

Sub-study Inclusion criterion #16 
regarding tumor specimens in 
Sub-Study A was edited to apply 
only to Phase 2 and to clarify what 
constitutes sufficient tumor sample, 
in accordance with the removal of 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 135
Document History
Document
Version Date
Summary and Rationale for Changes
Original protocol
18 June 2020
N/A
the PD-L1 expression secondary 
endpoint in Phase 1b 
(Section 12.5.1).   
•
Radiologic images will not need to 
be sent to a central vendor for 
Phase 1b subjects in Sub-Study A 
because efficacy is not a primary 
endpoint or focus for Phase 1b of 
Sub-Study A (Section 12.8.1.1).
•
Specifications for tumor samples in 
Sub-Study A were modified to 
reflect the modified Sub-Study A 
SoA and modified Sub-Study A 
Inclusion criteria (Section 12.8.4).
•
Administrative changes were made 
to improve readability and 
consistency of structure and 
wording across the sub-studies and 
master protocol.
Protocol 
Amendment 3
28 April 2021 
•
Exclusion criterion for QTcF was 
moved from the Master Protocol 
(Section 5.2) and will be added to 
the Sub-Study-specific exclusion 
criteria as appropriate because QT 
prolongation/cardiac events are not 
currently a risk specific to 
sasanlimab, but may be risks for 
the combination drugs.
•
Information was added regarding 
the administration of sasanlimab 
 dose from vials 
(Section 6.1.1).
•
Edited language for study 
discontinuation per the updated 
sponsor protocol template 
(Section 7.2).
•
Added a 180-day post-last-dose 
follow-up visit, and added home 
CCI

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 136
Document History
Document
Version Date
Summary and Rationale for Changes
Original protocol
18 June 2020
N/A
pregnancy tests for the follow-up 
visits, in accordance with the 
Clinical Trial Facilitation Group 
(CTFG) Recommendations related 
to contraception and pregnancy 
testing in clinical trials
(Sections 8.2.5, 8.2.8, 12.1).

Timeframe of 5-10 minutes was 
added to the triplicate ECGs in the 
ECG assessment instructions 
(Section 8.2.3) and the SoA
footnotes (Section 12.1).

Added Sub-Study B (sasanlimab + 
axitinib + SEA-TGT) to Section 13.

Figure 2 was updated to better 
reflect Sub-Study A design.

Administrative changes were made 
to improve readability and 
consistency of structure and 
wording across the sub-studies and 
master protocol.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 137
11. REFERENCES
1.
Johnson ML, Braiteh F, Grilley-Olson JE, et al. Assessment of Subcutaneous vs 
Intravenous Administration of Anti-PD-1 Antibody PF-06801591 in Patients With 
Advanced Solid Tumors: A Phase 1 Dose-Escalation Trial. JAMA Oncol. 
2019;5(7):999-1007.
2.
Gandhi L, Rodriguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus Chemotherapy 
in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378(22):2078-92.
3.
Mok TSK, Wu YL, Kudaba I, et al. Pembrolizumab versus chemotherapy for 
previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-
cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 
trial. Lancet. 2019;393(10183):1819-30.
4.
Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus 
Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 
2016;375(19):1823-33.
5.
Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously 
treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a 
randomised controlled trial. Lancet. 2016;387(10027):1540-50.
6.
NCCN. National Comprehensive Cancer Network.  NCCN Guidelines Version 
3.3030.  Non-small cell cancer: NCCN evidence blocks. 2020. Available from: 
https://www.nccn.org/professionals/physician_gls/default.aspx#nscl. Accessed on: 31 
Mar 2020.
7.
TAXOTERE (docetaxel). US Prescription Information (USPI); May 2010 2018, 
Bridgewater, NJ: Sanofi-Aventis U.S. LLC. Available from: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210498lbl.pdf.
8.
Cretella D, Digiacomo G, Giovannetti E, et al. PTEN Alterations as a Potential 
Mechanism for Tumor Cell Escape from PD-1/PD-L1 Inhibition. Cancers (Basel). 
2019;11(9).
9.
Mariathasan S, Turley SJ, Nickles D, et al. TGFbeta attenuates tumour response to 
PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018;554(7693):544-
48.
10.
Perea F, Sanchez-Palencia A, Gomez-Morales M, et al. HLA class I loss and PD-L1 
expression in lung cancer: impact on T-cell infiltration and immune escape. 
Oncotarget. 2018;9(3):4120-33.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 138
11.
Ascierto PA, Ferrucci PF, Fisher R, et al. Dabrafenib, trametinib and pembrolizumab 
or placebo in BRAF-mutant melanoma. Nat Med. 2019;25(6):941-46.
12.
Taylor MH, Lee C-H, Makker V, et al. Phase IB/II Trial of lenvatinib plus 
pembrolizumab in patients with advanced renal cell carcinoma, endometrial cancer, 
and other selected advanced solid tumors. J Clin Oncol. 2020;38:1154-63.
13.
McCoach CE, Blumenthal GM, Zhang L, et al. Exploratory analysis of the 
association of depth of response and survival in patients with metastatic non-small-
cell lung cancer treated with a targeted therapy or immunotherapy. Ann Oncol. 
2017;28(11):2707-14.
14.
Pfizer. PF-06801591 Investigator's Brochure Document on file. 2020.
15.
Choi BC, Penkov K, Bondarenko I, et al., editors. 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. 
European Society for Medical Oncology; September 18-20, 2020.
16.
Edge SB, Byrd DR, Carducci MA, et al. AJCC cancer staging manual.  6497th ed. 
Springer New York; 2010.
17.
Smith TJ, Khatcheressian J, Lyman GH, et al. 2006 update of recommendations for 
the use of white blood cell growth factors: an evidence-based clinical practice 
guideline. J Clin Oncol. 2006;24(19):3187-205.
18.
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the 
Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649-55.
19.
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.
20.
Planchard D, Smit EF, Groen HJM, et al. Dabrafenib plus trametinib in patients with 
previously untreated BRAF(V600E)-mutant metastatic non-small-cell lung cancer: an 
open-label, phase 2 trial. Lancet Oncol. 2017;18(10):1307-16.
21.
Ascierto PA, Dummer R. Immunological effects of BRAF+ MEK inhibition. 
Oncoimmunology. 2018;7(9):e1468955.
22.
Dummer R, Ascierto PA, Gogas HJ, et al. Overall survival in patients with BRAF-
mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 139
encorafenib (COLUMBUS): a multicentre, open-label, randomised, phase 3 trial. 
Lancet Oncol. 2018;19(10):1315-27.
23.
Dummer R, Ascierto PA, Gogas HJ, et al. Encorafenib plus binimetinib versus 
vemurafenib or encorafenib in patients with BRAF-mutant melanoma 
(COLUMBUS): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 
2018;19(5):603-15.
24.
BRAFTOVI (encorafenib). US Prescription Information (USPI); June 2018 2018, 
Boulder, CO: Array BioPharma Inc. Available from: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210496lbl.pdf.
25.
MEKTOVI (binimetinib). US Prescription Information (USPI); June 2018 2018, 
Boulder, CO: Array BioPharma Inc. Available from: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210498lbl.pdf.
26.
Ascierto PA, McArthur GA, Dreno B, et al. Cobimetinib combined with vemurafenib 
in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results 
from a randomised, double-blind, phase 3 trial. Lancet Oncol. 2016;17(9):1248-60.
27.
Flaherty KT, Infante JR, Daud A, et al. Combined BRAF and MEK inhibition in 
melanoma with BRAF V600 mutations. N Engl J Med. 2012;367(18):1694-703.
28.
Larkin J, Ascierto PA, Dreno B, et al. Combined vemurafenib and cobimetinib in 
BRAF-mutated melanoma. N Engl J Med. 2014;371(20):1867-76.
29.
Long GV, Stroyakovskiy D, Gogas H, et al. Combined BRAF and MEK inhibition 
versus BRAF inhibition alone in melanoma. N Engl J Med. 2014;371(20):1877-88.
30.
Robert C, Karaszewska B, Schachter J, et al. Improved overall survival in melanoma 
with combined dabrafenib and trametinib. N Engl J Med. 2015;372(1):30-9.
31.
Urner-Bloch U, Urner M, Jaberg-Bentele N, et al. MEK inhibitor-associated 
retinopathy (MEKAR) in metastatic melanoma: Long-term ophthalmic effects. Eur J 
Cancer. 2016;65:130-8.
32.
Array BioPharma. Binimetinib Investigator's Brochure. Document on file. 2019.
33.
Array BioPharma. Encorafenib Investigator's Brochure. Document on file. 2019.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 140
34.
Kefford R, Arkenau H, Brown M, et al. Phase I/II study of GSK2118436, a selective 
inhibitor of oncogenic mutant BRAF kinase, in patients with metastatic melanoma 
and other solid tumors. Journal of Clinical Oncology. 2010;28(15_suppl):8503-03.
35.
Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for 
Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in 
international clinical trials in oncology. J Natl Cancer Inst. 1993;85(5):365-76.
36.
Bergman B, Aaronson NK, Ahmedzai S, et al. The EORTC QLQ-LC13: a modular 
supplement to the EORTC Core Quality of Life Questionnaire (QLQ-C30) for use in 
lung cancer clinical trials. EORTC Study Group on Quality of Life. Eur J Cancer. 
1994;30A(5):635-42.
37.
Neuenschwander B, Matano A, Tang Z, et al. A Bayesian industry approach to phase 
I combination trials in oncology. In Statistical Methods in Drug Combination Studies.  
Chapman & Hall/CRC Biostatistics Series.  Edited by: Zhao W, Yang H. 2015. p. 95-
135.
38.
Neuenschwander B, Capkun-Niggli G, Branson M, et al. Summarizing historical 
information on controls in clinical trials. Clin Trials. 2010;7(1):5-18.
39.
Spiegelhalter DJ, Abrams KR, Myles JP. Bayesian approaches to clinical trials and 
health-care evaluation.  13. John Wiley & Sons; 2004.
40.
Fayers P, Aaronson N, Bjordal K, et al. EORTC QLQ-C30 Scoring Manual (ed 3). 
Brussels, Belgium. EORTC publications; 2001.
41.
Pfizer. Axitinib Investigator's Brochure Document on file. 2020.
42.
Schiller JH, Larson L, Ignatius Ou SH, et al. Efficacy and safety of axitinib in 
patients with advanced non–small-cell lung cancer: results from a phase II study. J 
Clin Oncol. 2009;27(23):3836-41.
43.
INLYTA (axitinib). US Prescription Information (USPI); June 2020 2020: Pfizer, Inc. 
Available from: http://labeling.pfizer.com/ShowLabeling.aspx?id=759.
44.
Gálffy G, Lugowska I, Poddubskaya E, et al., editors. JAVELIN Medley VEGF: a 
phase 2 study of avelumab + axitinib in patients with previously treated nonsmall cell 
lung cancer (NSCLC) or treatment-naive, cisplatin-ineligible urothelial cancer (UC). 
Society for Immunotherapy of Cancer (SITC) 35th Anniversary Annual Meeting; 
2020.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 141
45.
Seattle Genetics. SGN-TGT Investigator's Brochure Document on file. 2019.
46.
Bendell JC, Bedard P, Bang Y.-J., et al., editors. Phase Ia/Ib dose-escalation study of 
the anti-TIGIT antibody tiragolumab as a single agent and in combination with 
atezolizumab in patients with advanced solid tumors. AACR; 2020.
47.
Rodriguez-Abreu D, Johnson ML, Hussein MA, et al. Primary analysis of a 
randomized, double-blind, phase II study of the anti-TIGIT antibody tiragolumab 
(tira) plus atezolizumab (atezo) versus placebo plus atezo as first-line (1L) treatment 
in patients with PD-L1-selected NSCLC (CITYSCAPE). J Clin Oncol. 2020;38:9503.
48.
Ahn M, Niu J, Kim D, et al. Vibostolimab, an anti-TIGIT antibody, as monotherapy 
and in combination with pembrolizumab in anti-PD-1/PD-L1-refractory NSCLC. Ann 
Oncol. 2020;31:S754-S840.
49.
Niu J, Nagria A, Voskoboynik M, et al. Safety and efficacy of vibostolimab, an anti-
TIGIT antibody, plus pembrolizumab in patients with anti-PD-1/PD-L1-naive 
NSCLC. Ann Oncol. 2020;31:S754-S840.
50.
Patil N, Cho BC, Johnson ML, et al., editors. Efficacy of tiragolumab + atezolizumab 
in PD L1 IHC and TIGIT subgroups in the phase II CITYSCAPE study in first-line 
NSCLC. World Conference on Lung Cancer; 2020; Singapore.
51.
Kudo M. Scientific rationale for combined immunotherapy with PD-1/PD-L1 
antibodies and VEGF inhibitors in advanced hepatocellular carcinoma. 
Cancers.12(5):1089.
52.
Powles TB, Loriot Y, Bellmunt J, et al. Avelumab first-line (1L) maintenance + best 
supportive care (BSC) vs BSC alone for advanced urothelial carcinoma (UC): 
association between clinical outcomes and exploratory biomarkers. Ann Oncol. 
2020;31:S552-3.
53.
Neal JW, Lim FL, Felip E, et al. Cabozantinib in combination with atezolizumab in 
NSCLC patients previously treated with an immune checkpoint inhibitor: results from 
cohort 7 of the COSMIC-021 study. J Clin Oncol. 2020;38:9610.
54.
Ji Y, Wang S-J. Modified toxicity probability interval design: a safer and more 
reliable method than the 3 + 3 design for practical phase I trials. J Clin Oncol. 
2013;31(14):1785-91.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 142
12. APPENDIX A: SUB-STUDY A: SASANLIMAB + ENCORAFENIB + BINIMETINIB
12.1. Schedule of Activities (SoA): Sub-Study A
The SoA table provides an overview of the sub-study visits and procedures.  Refer to 
Section 8 of the master protocol and Section 12.8 of this sub-study appendix for detailed 
information on each procedure and assessment required for compliance with the protocol. 
The investigator may schedule unplanned visits in addition to those listed in the SoA table, in 
order to conduct evaluations or assessments required to protect the well-being of the 
participant, or if otherwise clinically indicated.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 143
Table 5.
Schedule of Activities Sub-Study A Phase 1b and Phase 2
Visit Identifiera
Abbreviations used in this 
table may be found in 
Appendix 11, Section 10.11
Screeningb
(≤28 days 
prior to 
first dose)
Treatment Period
Follow-Upe
Cycle 1c
(Days 1 to 28)
Cycle 2c
(Days 1 to 28)
Cycle 3 
& 4 
(Days 1 
to 28) 
Cycle 5 (Days 1 
to 28)
Cycle ≥6 
(Days 1 
to 28)
Day 1 Day 8 
(Phase 
1b 
Only)
Day 15 Day 1 Day 15
Day 1
Day 1
Day 8 
(Phase 
1b 
Only)
Day 1
EOTd Day 30e
Day 60,  
Day 90, 
Day 180 e
Survivale
Visit Window
±1
±2
±2
±2
±2
±2
±1
±2
±7
±7
±7
Informed consentf
X
Tumor and medical historyg
X
Substance and tobacco use
X
X
Physical examinationh
X
X
X
X
X
X
X
X
X
Height
X
Weight
X
X
X
X
X
X
X
Vital signs (BP/pulse rate/ 
temp)i
X
X
X
X
X
X
X
X
X
X
ECOG performance statusj
X
X
Triplicate 12-lead ECGk
X
X
Single 12-lead ECGk
X
X
X
X
X
X
X
X
X
Echocardiogram/MUGAl
X
X (C3 
only)
C6D1, 
C9D1, 
C12D1, 
and 
every 
6 months 
thereafter
X
Ophthalmic examinationm
X
Visual acuity examm
X
X
X
X
X
X
Dermatologic exam
X
X
X (C3 
only)
X
C7D1 
and then 
every 
X
X

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 144
Table 5.
Schedule of Activities Sub-Study A Phase 1b and Phase 2
Visit Identifiera
Abbreviations used in this 
table may be found in 
Appendix 11, Section 10.11
Screeningb
(≤28 days 
prior to 
first dose)
Treatment Period
Follow-Upe
Cycle 1c
(Days 1 to 28)
Cycle 2c
(Days 1 to 28)
Cycle 3 
& 4 
(Days 1 
to 28) 
Cycle 5 (Days 1 
to 28)
Cycle ≥6 
(Days 1 
to 28)
Day 1 Day 8 
(Phase 
1b 
Only)
Day 15 Day 1 Day 15
Day 1
Day 1
Day 8 
(Phase 
1b 
Only)
Day 1
EOTd Day 30e
Day 60,  
Day 90, 
Day 180 e
Survivale
8 weeks 
thereafter
Laboratory Assessments of 
Hematology and Blood 
Chemistryn
X
X
X
X
X
X
X
X
X
X
X
Coagulationn
X
X
X
X
X
X
X
X
Urinalysiso
X
X
X
X
Pregnancy testp
X
X
X
X
X
X
X
X
X
Hepatitis B, C testsq
X
Endocrinology testsn
X
Every 4 cycles starting at C4D1
Allocation to study 
interventionr
X
Administration of study 
treatment (sasanlimab)s
X
X
X
X
X
Administration of study 
treatment (encorafenib)t
Continuous QD
Administration of Study 
treatment (binimetinib)u
Continuous BID
Dispensing of encorafenib and 
binimetinib
X
X
X
X
X
Local site injection 
tolerability assessmentv
X
X
X
X
X
Tumor assessmentw
X
Every 8 wks (±7 days) from C1D1 for the first 18 months, then every 12 wks (±7 days) thereafter according to calendar, regardless of 
treatment delays and until progressive disease assessed by investigator using RECIST v1.1 or start of new anti-cancer therapy
Patient Reported Outcomes: 
EORTC QLQ-C30/LC13x
X

X

X
X

X
X




Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 145
Table 5.
Schedule of Activities Sub-Study A Phase 1b and Phase 2
Visit Identifiera
Abbreviations used in this 
table may be found in 
Appendix 11, Section 10.11
Screeningb
(≤28 days 
prior to 
first dose)
Treatment Period
Follow-Upe
Cycle 1c
(Days 1 to 28)
Cycle 2c
(Days 1 to 28)
Cycle 3 
& 4 
(Days 1 
to 28) 
Cycle 5 (Days 1 
to 28)
Cycle ≥6 
(Days 1 
to 28)
Day 1 Day 8 
(Phase 
1b 
Only)
Day 15 Day 1 Day 15
Day 1
Day 1
Day 8 
(Phase 
1b 
Only)
Day 1
EOTd Day 30e
Day 60,  
Day 90, 
Day 180 e
Survivale
Nonserious and serious 
adverse eventsy
X













Prior and Concomitant 
medication/surgery/ 
radiation & non-drug 
supportive interventionsz
X
X
X
X
X
X
X
X
X
X
X
X
Survival & subsequent anti-
cancer therapy
X
X
X
X
Contraception checkaa
X
X
X
X
X
X
X
X
X
Remote visit
X
X
X
PK, Pharmacodynamic, Pharmacogenomic, and Immunogenicity
Sasanlimab PKbb
X
X
X
X
X (C3 
only)
X
X
X (C7, 
C10, 
C13, then 
every 6 
cycles 
until 
EOT)
Encorafenib PKcc
X
X
X
X
Binimetinib PKcc
X
X
X
X
Blood biospecimen to 
confirm eligibilitydd
X
Baseline tumor biopsyee
X
Biobanked biospecimen for 
geneticsff
X

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 146
Table 5.
Schedule of Activities Sub-Study A Phase 1b and Phase 2
Visit Identifiera
Abbreviations used in this 
table may be found in 
Appendix 11, Section 10.11
Screeningb
(≤28 days 
prior to 
first dose)
Treatment Period
Follow-Upe
Cycle 1c
(Days 1 to 28)
Cycle 2c
(Days 1 to 28)
Cycle 3 
& 4 
(Days 1 
to 28) 
Cycle 5 (Days 1 
to 28)
Cycle ≥6 
(Days 1 
to 28)
Day 1 Day 8 
(Phase 
1b 
Only)
Day 15 Day 1 Day 15
Day 1
Day 1
Day 8 
(Phase 
1b 
Only)
Day 1
EOTd Day 30e
Day 60,  
Day 90, 
Day 180 e
Survivale
Blood for cell-free (cf) 
DNA analysisgg
X
X
X (C3
only)
X
Blood for specified genetic 
researchhh
X
X
X
X
X (C3 
only)
Blood for T-Cell Receptor 
(TCR) analysiskk
X
X
X
X
X (C3 
only)
Immunogenicity for 
sasanlimabll
X
X
X (C3 
only)
X
X (C7, 
C10, 
C13, and 
then 
every 
6 cycles 
until 
EOT)
X
a.
Day relative to start of study intervention (Day 1).
b.
Screening: To be performed within 28 days prior to first dose.  Visit may be conducted over multiple days.
c.
For Phase 1b, during Cycle 1, the D1, D8, and D15 visits occur in clinic. For Phase 1b, during Cycle 2, only D1 visit occurs in clinic and for D15 only 
clinical laboratory assessments will be performed.  For Phase 2, during Cycle 1, Day 1 visit occurs in clinic, no Day 8 visit occurs, and Day 15 will be 
on-site full visit.  For Phase 2 Cycle 2, Day 1 in clinic and Day 15 labs occur locally.
d.
End of Treatment (EOT) Visit: See Section 8.11. Conducted at the visit that the participant is discontinued from study treatment or no longer than 1 week 
after the decision to discontinue the participant from study drug.
e.
Follow-up:  See Section 8.2.8.  The initial safety follow-up visit will be conducted at the study clinic 30 days after the last dose of study drug.  The 60, 90, 
and 180-day follow-up may be conducted by remote contact (eg. telephone).  Survival Follow-up: See Section 8.1.3. Only to be performed for participants 
enrolled in Phase 2. Participants will be contacted every 12 weeks (±7 days) after the last clinic visit until death, lost-to-follow-up, study discontinued by 
sponsor, end of study, or participant withdrawal of consent of study, whichever comes first.
f.
Informed Consent: Must be obtained prior to undergoing any study specific procedures.  May be obtained more than 28 days prior to first dose.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 147
Table 5.
Schedule of Activities Sub-Study A Phase 1b and Phase 2
Visit Identifiera
Abbreviations used in this 
table may be found in 
Appendix 11, Section 10.11
Screeningb
(≤28 days 
prior to 
first dose)
Treatment Period
Follow-Upe
Cycle 1c
(Days 1 to 28)
Cycle 2c
(Days 1 to 28)
Cycle 3 
& 4 
(Days 1 
to 28) 
Cycle 5 (Days 1 
to 28)
Cycle ≥6 
(Days 1 
to 28)
Day 1 Day 8 
(Phase 
1b 
Only)
Day 15 Day 1 Day 15
Day 1
Day 1
Day 8 
(Phase 
1b 
Only)
Day 1
EOTd Day 30e
Day 60,  
Day 90, 
Day 180 e
Survivale
g.
Tumor History: Includes history of disease under study including details of primary diagnosis, treatment history, staging, and molecular profiling data (if 
available).  Medical History: Includes history other than the cancer under study.  Abnormalities observed during screening are to be considered as medical 
history.
h.
Physical examination (PE): See Section 8.2.1.
i.
Vital Signs: See Section 8.2.2. Includes temperature, blood pressure (BP), pulse rate.  On Day 1 of each cycle, vital signs are to be measured prior to 
administration of any study drug (pre-dose).
j.
Eastern Cooperative Oncology Group (ECOG) Performance Status: See Section 8.2.6.
k.
Triplicate/Single 12 Lead electrocardiogram (ECG): See Section 8.2.3.  When triplicate ECG is requested, 3 serial 12-lead ECGs will be conducted 
within approximately 5-10 minutes total time.  Triplicate ECGs on C1D1 will be collected prior to administration of any study drug.  For remaining 
timepoints, single ECG will be collected prior to administration of study drug.  When coinciding with blood sample draws for PK, ECG assessment is to be 
performed prior to blood sample collection, such that the blood sample is collected at the nominal time.
l.
Echocardiogram or multigated acquisition (MUGA) Scan: Section 12.8.2.1. The same modality used during screening is to be used for all subsequent 
timepoints.  Assessment will also be performed if a participant experiences an AE which may be related to cardiac dysfunction in the opinion of the 
investigator.
m. Ophthalmic Examination: See Section 12.8.2.3.
n.
Hematology, Blood Chemistry, Endocrinology, and Coagulation assays: See Appendix 2 (Section 10.2) and Section 12.10.1 for Laboratory Tests list.  
Not necessary to repeat on C1D1 if performed within 7 days prior to C1D1 as part of Screening.  Subsequent assessments must be performed within 
72 hours prior to the scheduled visit. Hematology and chemistry assessments on Cycle 2 Day 15 may be drawn at a lab local to the participant and do not 
require on-site visit.
o.
Urinalysis: Dipstick is acceptable.  No need to repeat on C1D1 if baseline assessment is performed within 72 hours prior to that date. See Section 10.2 and 
Section 12.10.1 for urinalysis details.
p.
Pregnancy Test (Serum/Urine): For female participants of childbearing potential, a serum or urine pregnancy test, with sensitivity of at least 25 mIU/mL, 
will be performed on 2 occasions prior to starting study therapy, once at screening and once at the C1D1 visit before dosing.  Participants with a confirmed 
positive pregnancy test(s) must not be dosed. Pregnancy tests will also be routinely performed throughout the study as per SoA and additionally whenever 
1 menstrual cycle is missed or when potential pregnancy is otherwise suspected.  Additional pregnancy tests may also be performed if requested by IRB/EC 
or if required by local regulations. At the 60, 90, and 180-day remote follow-up visits, pregnancy tests may be conducted via home kits.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 148
Table 5.
Schedule of Activities Sub-Study A Phase 1b and Phase 2
Visit Identifiera
Abbreviations used in this 
table may be found in 
Appendix 11, Section 10.11
Screeningb
(≤28 days 
prior to 
first dose)
Treatment Period
Follow-Upe
Cycle 1c
(Days 1 to 28)
Cycle 2c
(Days 1 to 28)
Cycle 3 
& 4 
(Days 1 
to 28) 
Cycle 5 (Days 1 
to 28)
Cycle ≥6 
(Days 1 
to 28)
Day 1 Day 8 
(Phase 
1b 
Only)
Day 15 Day 1 Day 15
Day 1
Day 1
Day 8 
(Phase 
1b 
Only)
Day 1
EOTd Day 30e
Day 60,  
Day 90, 
Day 180 e
Survivale
q.
Hepatitis B, C: In the case of apparent ongoing HBV or HCV infection, reflex serum viral load testing will be performed.
r.
Allocation: The participant allocation number will be assigned using an IRT system. Participants can be allocated in IRT no more than 3 days prior to 
dosing.
s.
Study Treatment (sasanlimab): Will be administered once every 28 days as 1 SC injection totaling 300 mg.  
t.
Study Treatment (encorafenib): Once daily oral administration.  See Section 12.6 for details. 
u.
Study Treatment (binimetinib): Twice daily oral administration.  See Section 12.6 for details.  
v.
Local Site Injection Tolerability Assessment for sasanlimab: See Section 8.2.7.
w.
Tumor Assessments: See Section 8.1.1 and Section 12.8.1.1.  Tumor response assessments will be determined in accordance with RECIST v1.1.
x.
Patient Reported Outcome: Required in Phase 2 only. The questionnaires should be administered prior to any other scheduled assessments or drug 
administrations. See Section 12.8.5.
y.
Nonserious and Serious AE Assessments: See Section 8.3.  AEs and SAEs are documented and recorded at each visit using NCI CTCAE version 5.0.
z.
Concomitant Medications and Non-Drug Supportive Interventions: Includes supportive care drugs (eg, anti-emetic treatment and prophylaxis), drugs 
used to treat AEs or chronic diseases, and non-drug supportive interventions (eg, transfusions).  Reporting period for concomitant medications for AEs and 
SAEs are to follow respective AE and SAE reporting period.
aa. Contraceptive Check: See Section 12.10.2.  Male participants who are able to father children and female participants who are of childbearing potential will 
need to affirm that they meet the criteria for correct use of the selected methods of contraception throughout the study and continue for 6 months after the 
last dose.  The investigator or his or her designee will discuss with the participant the need to use the appropriate contraception methods consistently and 
correctly and document such conversation in the participant’s chart.  The investigator or his or her designee will instruct the participant to call immediately if 
the selected contraception methods are discontinued, or if pregnancy is known or suspected in the participant or participant’s partner.
bb. Blood for sasanlimab PK: One 3-mL sample will be drawn for sasanlimab on each day indicated on the SOA. All samples taken on Day 1 of a cycle will be 
collected within 6 hours prior to dosing of sasanlimab.
cc. Blood for encorafenib and binimetinib PK: One 5-mL sample will be drawn for both encorafenib and binimetinib PK on each day indicated on the SOA. 
All samples will be collected within 2 hours prior to dosing of either encorafenib or binimetinib. 
dd. Biospecimen to confirm eligibility: See Section 8.7.1.  A 20-mL blood sample will be collected to confirm eligibility via ctDNA assay. In Phase 2, if 
ctDNA assay results cannot be interpreted, reflex testing of tumor tissue will be initiated. This blood sample may also be used for possible future 
development of a medical device/diagnostic test (See Section 12.8.4).

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 149
Table 5.
Schedule of Activities Sub-Study A Phase 1b and Phase 2
Visit Identifiera
Abbreviations used in this 
table may be found in 
Appendix 11, Section 10.11
Screeningb
(≤28 days 
prior to 
first dose)
Treatment Period
Follow-Upe
Cycle 1c
(Days 1 to 28)
Cycle 2c
(Days 1 to 28)
Cycle 3 
& 4 
(Days 1 
to 28) 
Cycle 5 (Days 1 
to 28)
Cycle ≥6 
(Days 1 
to 28)
Day 1 Day 8 
(Phase 
1b 
Only)
Day 15 Day 1 Day 15
Day 1
Day 1
Day 8 
(Phase 
1b 
Only)
Day 1
EOTd Day 30e
Day 60,  
Day 90, 
Day 180 e
Survivale
ee. Baseline Tumor Biopsy: For Phase 2 only, participants will submit a tumor biospecimen obtained by a procedure performed prior to Cycle 1 Day 1.  The 
tumor specimen may be used for specified analyses (Sections 8.7.1 and 8.8.2) or exploratory biomarker analysis (Section 8.8).
ff.
Banked biospecimen for genetics: A 4-mL blood sample will be collected on Cycle 1 Day 1 prior to dosing with any study drug and retained in a biobank 
for possible assessments of genes and other analytes (eg, proteins, RNA, nondrug metabolites), unless prohibited by local regulations or by decision of the 
institutional review board or ethics committee (Section 8.7.2).
gg. Blood for cell-free (cf) DNA Analysis: A 20-mL blood sample for preparation of plasma will be collected prior to dosing with any study drug, and on Day 
1 of Cycles 2 and 3 for exploratory analyses as described in Section 8.7.1.
hh. Blood for specified genetic research: A 4-mL whole blood sample will be collected prior to dosing with any study drug for exploratory genetic and 
epigenetic analyses as described in Section 8.7.1. 
ii.
NA.
jj.
NA.
kk. Blood for T-Cell Receptor (TCR) Analysis: A 6-mL whole blood sample will be collected into a tube optimized for DNA preservation prior to dosing with 
any study drug on specified visits (Section 8.7.1).
ll.
Blood for sasanlimab Immunogenicity (anti-drug antibody [ADA] and neutralizing antibodies [NAb]) Testing: One 6-mL sample will be drawn on 
each day indicated in the SoA. All samples taken on Day 1 of a cycle will be taken within 6 hours prior to sasanlimab dosing.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 150
12.2. Introduction for Sub-Study A
12.2.1. Study Rationale
There are several common treatment options for advanced/metastatic BRAFV600 NSCLC (per 
current NCCN guidelines).  These include treatment with single-agent pembrolizumab 
(anti-PD-1) for PD-L1high tumors and anti-PD-1/chemotherapy.  However, the highest 
response rate reported for these tumors is with the combination of dabrafenib, targeting  
BRAFV600 and a MEK inhibitor, trametinib, where the reported response rate was 64%.20  
Dabrafenib/trametinib has become a standard of care for the treatment of BRAFV600
advanced/metastatic NSCLC. However, tumor responses observed with 
dabrafenib/trametinib are not durable, as the percentage of treated patients who maintained 
responses for 10.4 months is only 32%.20  There is evidence that BRAF + MEK inhibitor 
combinations can stimulate anti-tumor immunity.21  However, in doing so, there is likely to 
be induction of immune checkpoints, such as PD-L1, that can limit anti-tumor activity.20  
Clinical studies in patients of BRAFV600-mutant melanoma treated with triplet therapies 
containing a PD-1 or PD-L1 inhibitor plus a BRAF + MEK inhibitor doublet provide 
evidence that combining the PD-1/PD-L1 inhibitors with targeted therapy yields an 
improvement in the durability of responses and trends toward improvement in PFS and OS. 
ORR was comparable between the targeted agents alone and the triplets.11,12  Therefore, in 
Sub-Study A, a triplet combination of sasanlimab, encorafenib, and binimetinib will be 
evaluated to assess safety and clinical activity in patients with advanced/metastatic 
BRAFV600-mutant NSCLC.
12.2.2. Background
Encorafenib is a potent and selective ATP-competitive inhibitor of BRAFV600-mutant kinase.  
Mutations in the BRAF gene, such as BRAFV600E, can result in constitutively activated 
BRAF kinase that may stimulate tumor cell growth.  Encorafenib inhibited in vitro growth of 
tumor cell lines expressing BRAFV600 E, D, and K mutations.
Binimetinib is a potent and selective allosteric, ATP-uncompetitive inhibitor of MEK1/2. 
MEK proteins are upstream regulators of the ERK pathway.  In vitro, binimetinib inhibited 
ERK phosphorylation in cell-free assays as well as viability and MEK-dependent
phosphorylation of BRAF-mutant human melanoma cell lines.  Binimetinib also inhibited in 
vivo ERK phosphorylation and tumor growth in BRAF-mutant murine xenograft models.22,23
Encorafenib and binimetinib target 2 different kinases in the RAS/RAF/MEK/ERK pathway. 
Compared with either drug alone, co-administration of encorafenib and binimetinib resulted 
in greater anti-proliferative activity in vitro in BRAF mutation-positive cell lines and greater 
anti-tumor activity with respect to tumor growth inhibition in BRAFV600E-mutant human 
melanoma xenograft studies in mice. Additionally, the combination of encorafenib and 
binimetinib delayed the emergence of resistance in BRAFV600E-mutant human melanoma 
xenografts in mice compared to either drug alone.21
Encorafenib 450 mg orally QD in combination with binimetinib 45 mg orally BID have 
received marketing approval for the treatment of patients with unresectable or metastatic 
melanoma with a BRAFV600E or BRAFV600K mutation in several jurisdictions, including the 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 151
US and EU (BRAFTOVI® [encorafenib] prescribing information; MEKTOVI® [binimetinib] 
prescribing information).  Regulatory approval of encorafenib and binimetinib in 
combination was based on the Phase 3 COLUMBUS study (Study CMEK162B2301 
[NCT01909453]; randomized, 2-part, open-label, multicenter, international clinical 
study).24,25
See the master protocol Introduction (Section 2) for background on sasanlimab.
12.2.2.1. Clinical Overview: Clinical Safety of Encorafenib in Combination with 
Binimetinib
COLUMBUS results demonstrated improved tolerability in the encorafenib 450 mg QD + 
binimetinib 45 mg BID arm compared with single-agent encorafenib 300 mg QD.22,23  This is 
consistent with a body of literature that suggests the combination of a BRAF inhibitor and a 
MEK inhibitor results in improved tolerability compared with either agent alone.26-30
Among participants receiving encorafenib plus binimetinib combination therapy in the 
COLUMBUS study, the most frequent adverse events (≥20% of participants, all grades) were 
fatigue (43%), nausea (41%), diarrhea (36%), vomiting (30%), abdominal pain (28%), 
arthralgia (26%), myopathy (23%), hyperkeratosis (23%), rash (22%), headache (22%), 
constipation (22%), visual impairment (20%) and serous retinopathy (20%).  Most of these 
toxicities were generally reversible and manageable by supportive medical care, dose 
modifications or discontinuation.  Other clinically important adverse events occurring in 
<10% of participants were facial paresis, pancreatitis, panniculitis, drug hypersensitivity and 
colitis.  The most frequent laboratory abnormalities (≥2%, Grade 3 or 4) were increased GGT 
(11%), increased ALT (6%), increased creatine phosphokinase (5%), increased fasting 
glucose (5%), increased creatinine (4%), anemia (4%), hyponatremia (4%), increased AST 
(3%), neutropenia (3%) and lymphopenia (2%). 
Important potential adverse events associated with the administration of the combination of 
encorafenib and binimetinib established primarily from safety data from the COLUMBUS 
study and, where indicated, from other studies of the combination, include:
New primary malignancies: Based on its mechanism of action, encorafenib may promote 
malignancies associated with activation of RAS through mutation or other mechanisms.  
Cutaneous and non-cutaneous malignancies occurred in participants, including cutaneous 
squamous carcinoma/keratoacanthoma (2.6%; median time to first occurrence of 5.8 months) 
and basal cell carcinoma (1.6%).
Left ventricular dysfunction: Symptomatic or asymptomatic decreases in ejection fraction 
occurred in 7% of patients, with Grade 3 left ventricular dysfunction occurring in 1.6% of 
participants.
Hemorrhage: Hemorrhage occurred in 19% of participants, with events ≥Grade 3 occurring 
in 3.2% of participants.  Fatal intracranial hemorrhage in the setting of new or progressive 
brain metastases occurred in 1.6% of participants.  The most frequent hemorrhagic events 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 152
were gastrointestinal, including rectal hemorrhage (4.2%), hematochezia (3.1%), and 
hemorrhoidal hemorrhage (1%).
Venous thromboembolism: Occurred in 6% of participants, including 3.1% of participants 
who developed pulmonary embolism.
Ocular toxicities: Serous retinopathy is a class effect of MEK inhibitors. It is generally 
asymptomatic or mildly symptomatic and reversible.31  Serous retinopathy occurred in 20% 
of participants.  Symptomatic serous retinopathy occurred in 8% of participants with no cases 
of blindness.  The median time to onset of the first event of serous retinopathy (all grades) 
was 1.2 months.  RVO is a known class-related adverse reaction of MEK inhibitors and may 
occur in participants treated with binimetinib in combination with encorafenib.  In 
participants with BRAF mutation-positive melanoma across multiple clinical trials, 0.1% of 
participants experienced RVO.
Pneumonitis/Interstitial Lung Disease: Pneumonitis occurred in 0.3% of participants with 
BRAF mutation-positive melanoma across multiple clinical trials.
Hepatotoxicity: The incidence of Grade 3 or 4 increases in liver function laboratory tests 
was 6% for ALT, 2.6% for AST and 0.5% for alkaline phosphatase.  No participant 
experienced Grade 3 or 4 serum bilirubin elevation. 
CK Elevation/Rhabdomyolysis: Asymptomatic elevations of laboratory values of serum 
CK occurred in 58% of participants.  Rhabdomyolysis was reported in 0.1% of participants 
with BRAF mutation-positive melanoma across multiple clinical trials.
QTc Prolongation: QT prolongation has been observed in participants treated with BRAF 
inhibitors.  Encorafenib is associated with dose-dependent QTc interval prolongation in some 
participants.  In the COLUMBUS study, an increase in QTcF to 500 msec was measured in 
0.5% of participants.
Embryo-Fetal Toxicity: Encorafenib or binimetinib can cause fetal harm when administered 
to pregnant women.
Detailed information regarding clinical safety is presented in the respective IBs for 
encorafenib and binimetinib.32,33
12.2.3. Benefit/Risk Assessment
The primary risks of the combination of encorafenib plus binimetinib treatment are included 
in the respective product labels and include known class effects of BRAF and MEK 
inhibitors in the treatment of patients with melanoma.  The combination of encorafenib plus 
binimetinib has a lower frequency and severity of pyrexia compared with dabrafenib plus 
trametinib.  For the encorafenib/binimetinib doublet, almost all cases of pyrexia presenting as 
an SAE were associated with secondary causes of infection of progressive melanoma.  The 
safety of encorafenib/binimetinib in the first- or second-line treatment of advanced/metastatic 
BRAFV600 NSCLC is under active clinical investigation in a separate study (NCT03915951).

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 153
While no detailed safety analyses are available for this study, the doses listed in the 
respective product labels of 450 mg encorafenib QD and 45 mg binimetinib BID have been 
tolerated. Detailed information regarding nonclinical studies and clinical PK are presented in 
the respective IBs for encorafenib and binimetinib, which are the SRSDs for this study.
For the triplet combination of sasanlimab with encorafenib/binimetinib there is a low 
likelihood of combinatorial toxicities based on the frequency of events observed in the clinic 
for these agents.  In Study B8011001 of single-agent sasanlimab, there was 1 case of 
pneumonitis out of 106 participants evaluated in the SC expansion cohorts.  In the 
COLUMBUS study of encorafenib in combination with binimetinib, the incidence of 
pneumonitis was 0.3%.  It is expected that pneumonitis will be remain uncommon in the 
triplet combination and measures are included in this protocol to guide dosing and use of 
concomitant therapy for treatment emergent pneumonitis.  The other class of AE where there 
is the potential for combinatorial toxicity is hepatotoxicity.  Liver function test abnormalities 
(ALT elevations) of at least Grade 3 were observed in 6% of participants treated with 
encorafenib/binimetinib in the COLUMBUS study and 1 out of 106 participants treated with 
sasanlimab.  Lower level elevations were also observed in these studies and there is the 
potential for additive effects.  Adding the observed frequencies of AEs for these 3 agents, the 
frequency of Grade 3 or higher AEs with the potential for overlapping toxicity is expected to 
be less than 10%.  In addition, based on the clinical experience as detailed in the SRSDs for 
encorafenib and binimetinib and the potential class effect of PD-1 inhibitors overall, other 
rarely overlapping toxicities may include (but are not limited to) ocular toxicities, skin-
related toxicities, nausea/vomiting, diarrhea, cardiac toxicities, and pyrexia. For this reason, 
the recommended dose modification guidelines for the potential overlapping toxicities are 
provided in Sections 12.10.4 and 12.10.5.   
There is specific guidance to the investigator for dosing and concomitant therapy for 
participants experiencing both of these classes of AEs, which are considered to be immune-
related, in Section 12.6.6.2.  Therefore, the guidance in this protocol is expected to mitigate 
the risk these 2 classes of toxicities which might be increased in frequency and/or severity in 
this study.  Given the expected clinical activity of all 3 agents in previously untreated 
participants with advanced/metastatic BRAFV600-mutant NSCLC the benefit/risk assessment 
is positive for the initiation of clinical investigation of sasanlimab in combination with 
encorafenib and binimetinib.
12.3. Objectives, Endpoints, and Estimands for Sub-Study A
The following objectives and endpoints are specific to the Sub-Study A combination of 
sasanlimab + encorafenib + binimetinib in participants with NSCLC with BRAFV600
mutations (Table 6):
Table 6.
Sub-Study A Objectives and Endpoints
Objectives
Endpoints
Primary: 
Primary: 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 154
Table 6.
Sub-Study A Objectives and Endpoints
Objectives
Endpoints
Phase 1b
Phase 1b

To assess the DLT rate and estimate the 
MTD of sasanlimab in combination with 
encorafenib and binimetinib to determine 
the RP2D for the combination.

DLTs during the DLT-observation 
period.
Phase 2
Phase 2

To assess the durable ORR of sasanlimab
in combination with encorafenib and 
binimetinib. 

Durable OR, defined as confirmed CR 
or PR lasting for at least 10 months 
from the date of first CR or PR, as 
assessed by the investigator using 
RECIST v1.1.
Secondary: 
Secondary: 
Phase 1b
Phase 1b

To assess the overall safety and tolerability 
of sasanlimab in combination with 
encorafenib and binimetinib.

AEs graded according to the NCI-
CTCAE v5.0 and changes in clinical 
laboratory parameters.

To assess the anti-tumor activity of 
sasanlimab in combination with 
encorafenib and binimetinib.

Durable OR and OR as assessed by the 
investigator using RECIST v1.1.

To characterize the PK of sasanlimab, 
encorafenib, and binimetinib when 
administered in combination.

PK parameters of sasanlimab, 
encorafenib, binimetinib and 
applicable metabolites (ie, Ctrough) 
when administered in combination, as 
data permit.

To evaluate the immunogenicity of 
sasanlimab when given in combination 
with encorafenib and binimetinib.

ADA and NAb (ie, incidence) against 
sasanlimab, as data permit.
Phase 2
Phase 2

To assess other measures of anti-tumor 
activity of sasanlimab in combination with 
encorafenib and binimetinib.

OR, DR, TTR, PFS by investigator 
assessment using RECIST v1.1, and 
OS.

To assess the overall safety and tolerability 
of sasanlimab in combination with 
encorafenib and binimetinib.

AEs graded according to the NCI-
CTCAE v5.0 and changes in clinical 
laboratory parameters.

To characterize the PK of sasanlimab, 
encorafenib, and binimetinib when 
administered in combination

PK parameters of sasanlimab, 
encorafenib, binimetinib, and 
applicable metabolites (ie, Ctrough) 
when administered in combination, as 
data permit.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 155
Table 6.
Sub-Study A Objectives and Endpoints
Objectives
Endpoints

To evaluate the immunogenicity of 
sasanlimab when given in combination 
with encorafenib and binimetinib.

ADA and NAb (ie, incidence) against 
sasanlimab, as data permit.

To assess the association between anti-
tumor activity and PD-L1 expression in 
baseline tumor biopsies.

OR by PD-L1 expression in baseline 
tumor samples.

To assess the effects of sasanlimab, 
encorafenib, and binimetinib on patient-
reported health-related quality of life. 

Health-related quality of life as 
measured by EORTC QLQ-C30/LC13 
Exploratory:
Exploratory:
Phase 1b and Phase 2
Phase 1b and Phase 2

To understand the relationship between the 
therapeutic intervention(s) being studied 
and the biology of the participant’s 
disease.

Biomarkers, consisting of DNA, RNA, 
protein, metabolites or defined cell 
types, resulting from analyses of 
peripheral blood and/or tumor tissue 
biospecimen obtained at baseline, on 
treatment or at end-of-study.
Phase 2
Phase 2

To assess additional measure of anti-tumor 
activity of sasanlimab in combination with 
encorafenib and binimetinib. 

Depth of response by investigator 
assessment using RECIST v1.1. 
Estimands
This section defines the estimands associated with the primary endpoints of the sub-study.
The primary endpoint definitions and the observations that will be considered in the 
derivation of the endpoints are described or referenced below.
Phase 1:
Primary Estimand (DLT): DLT rate estimated based on data from DLT-evaluable 
participants during the DLT-evaluation period (Cycle 1 – first 28 days of study treatment) in 
Phase 1b.

Variable: Occurrence of DLTs.

Analysis population: DLT-evaluable participants defined as participants who receive 
at least 1 dose of the combination study treatment in Phase 1b and either experience 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 156
DLT during the DLT-evaluation period or complete the DLT-evaluation period 
without DLT.  Participants without DLTs who receive less than 75% of the planned 
dose of each study drug in Cycle 1 for reasons other than treatment-related toxicity 
are not evaluable for DLT.  All participants deemed non-evaluable for DLT may be 
replaced.

Population-level summary measure: DLT rate defined as the number of 
DLT-evaluable participants with DLTs in the DLT-evaluation period divided by the 
number of DLT-evaluable participants in the DLT-evaluation period.
Phase 2:
Primary Estimand (Durable OR): the treatment effect of 
sasanlimab + encorafenib + binimetinib assessed by the Durable ORR, based on Investigator 
assessment per RECIST v1.1, in the analysis population. 

Variable: Durable objective response defined as confirmed CR or PR according to 
RECIST v1.1 based on investigator assessment, lasting for at least 10 months from 
the date of first CR or PR until the date of the first documentation of PD, death, or 
start of new anticancer therapy.  Both CR and PR must be confirmed by repeat 
assessments performed no less than 4 weeks after the criteria for response are first 
met.

Analysis population: all participants who received at least 1 dose of study drug 
without regard to tolerability or duration of treatment.

Population-level summary measure: Durable ORR defined as the proportion of 
participants in the analysis population with durable OR and 2-sided 95% CI for 
durable ORR using the Clopper-Pearson method. Participants who do not have a post-
baseline tumor assessment due to early progression of disease, who receive anti-
cancer therapies other than the study treatments prior to reaching a CR or PR for 10 
months, or who die, have PD, or stop tumor assessments for any reason prior to 
reaching a CR or PR for 10 months will be counted as non-responders in the 
assessment of durable OR.  Each participant will have a durable objective response 
status (0: no durable OR; 1: durable OR).
12.4. Study Design for Sub-Study A
See Section 4.1 for the overall study design in the master protocol.
Sub-Study A will start with a Phase 1b safety part with 3 available dose levels (see Table 7).  
The enrollment criteria for Phase 1b includes participants with BRAFV600-mutated NSCLC in 
any line of therapy.  Approximately 9-18 participants will be enrolled in Phase 1b, starting 
with dose level 0 (Table 7 and Figure 2).
Guidance for Phase 1b dosing (dose level to be evaluated in the next cohort) and enrollment 
(number of participants to be enrolled in the next cohort) decisions will be based on a 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 157
Bayesian Logistic Regression Model (BLRM).  The BLRM incorporates single-agent and 
available combination DLT data (historical and prospectively across dose cohorts) to 
estimate the posterior probability of under-dosing, target dosing and overdosing, thereby 
reducing participant risk and increasing efficiency and precision during dose finding with 
combination treatments.
Phase 2 will begin once the combination RP2D from the Phase 1b is selected.  
Approximately 62 participants will be enrolled into the Phase 2 part to assess durable OR and 
participant safety.
Figure 2.
Sub-Study A Design
12.4.1. Phase 1b Design
The sasanlimab dose will remain fixed for all dosing cohorts in the Phase 1b part of 
Sub-Study A.
Beginning with the starting dose level, cohorts of 3-6 participants will be enrolled, treated, 
and monitored during the 28-day DLT evaluation period (Cycle 1).  Participants without 
DLTs who receive less than 75% of the planned dose of the study intervention in Cycle 1 for 
reasons other than treatment-related toxicity are not evaluable for DLT.  A minimum of 
3 DLT-evaluable participants will be required; additional participants will be enrolled in the 
specific enrollment cohort to replace participants who are not considered DLT-evaluable, 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 158
where required.  When all DLT-evaluable participants treated in a given enrollment cohort 
have completed the DLT observation period or experienced a DLT, whichever occurs first, 
the posterior distribution for the risk of DLT for new participants at different dose levels for 
the combination of interest will be evaluated.  The posterior distributions will be summarized 
to provide the posterior probability that the risk of DLT lies within the intervals shown 
below:

Underdosing: [0, 0.16);

Target toxicity: [0.16, 0.33);

Excessive toxicity: [0.33, 1].
In addition to accumulating safety data and observed DLTs, decisions on further participant 
enrollment and dose level selection will be guided by the escalation with overdose control 
(EWOC) criterion.  A combination dose may only be used for newly enrolled participants if 
the risk of excessive toxicity at that combination dose is less than 25% (0.25).  Refer to 
Section 12.10.6 for further details of the BLRM.
An RP2D below the MTD, or highest safe dose tested, may be determined based on other 
safety, clinical activity, PK, and pharmacodynamic data. Before expanding into Phase 2, 
safety will be confirmed in at least 9 DLT-evaluable participants treated at the RP2D for each 
combination.
Table 7.
Sub-Study A Combination:  Sasanlimab + Encorafenib + Binimetinib –
Available Dose Levels
Dose Level
Sasanlimab
Encorafenib
Binimetinib
1
300 mg SC Q4W
450 mg QD
45 mg BID
0 (starting dose)
300 mg SC Q4W
300 mg QD
45 mg BID
-1
300 mg SC Q4W
300 mg QD
30 mg BID
DLT period = 1 cycle. The treatment cycle is 28 days.
BLRM dose escalation schema will be used for the dose-finding phase of the study.
12.4.2. Phase 2 Design
Phase 2 will enroll approximately 62 participants with BRAFV600-mutated NSCLC and will 
evaluate the activity and safety of sasanlimab + encorafenib + binimetinib.
12.4.3. Rationale for the Sub-Study A Combination
See Section 2.1 for the overall study rationale in the master protocol.
Combinations of a BRAF inhibitor with a MEK inhibitor have become a standard in the 
treatment of participants with BRAFV600-mutant melanoma and NSCLC.  Clinical and 
preclinical data suggests that the combination of a BRAF inhibitor such as encorafenib with a 
MEK inhibitor, such as binimetinib, will promote an anti-tumor immune response in 
BRAFV600-mutant tumors.  Clinical and preclinical evidence also suggest that combining 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 159
encorafenib and binimetinib with a PD-1 blocking monoclonal antibody, will lead to deeper 
and more sustained anti-tumor control.  Therefore, in this sub-study, a triplet combination of 
sasanlimab, encorafenib, and binimetinib will be evaluated to assess safety and clinical 
activity in participants with advanced/metastatic NSCLC.
12.4.4. Justification for Dose in Sub-Study A
12.4.4.1. Starting Dose for Phase 1b
The starting dose of sasanlimab in Sub-Study A is 300 mg Q4W and will remain constant 
throughout the study. Refer to master protocol Section 4.3 for the justification for this 
starting dose.
The starting dose level for encorafenib is 300 mg QD and binimetinib is 45 mg BID in 
combination with sasanlimab. This corresponds to 1 dose level below the labeled doublet 
dose of 450 mg QD encorafenib and 45 mg BID binimetinib for metastatic melanoma.  A 
subanalysis of the COLUMBUS trial indicated that this dose level was associated with 
improved tolerability over the 450 mg QD encorafenib and 45 mg BID binimetinib dose level 
along with comparable clinical activity.24,25  
12.4.4.2. Criteria for Dose Escalation/De-Escalation
Refer to Section 12.10.6 for criteria for dose escalation/de-escalation via BLRM for 
Sub-Study A.
12.4.5. Dose Limiting Toxicity
Refer to master protocol Section 4.3.3 for the definition of DLT.
The DLT observation period is the first 28 days starting with the first dose of any study drug 
in the combination.
12.4.6. Maximum Tolerated Dose
A dose level combination is a potential candidate for being the MTD level when all the 
following criteria are met:

≥6 participants have been treated at that dose;

Probability of target dosing >50%; and

Probability of overdosing <25%.
12.4.7. Recommended Phase 2 Dose (RP2D) Definition
Refer to master protocol Section 4.3.5.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 160
12.5. Study Population for Sub-Study A
Participants must meet all of the general inclusion and exclusion criteria as specified in 
the master protocol (Section 5) plus the following Sub-study A specific inclusion and 
exclusion criteria.
12.5.1. Inclusion Criteria for Sub-Study A
Phase 1b and Phase 2:
14. BRAFV600E mutation in tumor tissue or plasma as determined by a local laboratory assay 
and documented in a local pathology report.  Other Class 1 BRAFV600 mutations (eg, 
V600K, V600D, and V600R) will be permitted by prior discussion with the sponsor.  
Only PCR or NGS-based local assay results will be acceptable. 
15. Able to swallow, retain, and absorb oral medications.
Phase 1b only:
16. Any line of therapy for locally advanced/metastatic NSCLC.  For Stage IIIB, disease 
relapse during treatment or within 6 months of chemoradiation with durvalumab 
consolidation will be considered metastatic disease.
Phase 2 only:
17. Previously untreated for locally advanced/metastatic NSCLC.
18. Able to provide a sufficient amount of plasma and tumor (primary or metastatic, archival 
or newly obtained); approximately 15 slides (minimum of 10 slides) or block are 
required.
12.5.2. Exclusion Criteria for Sub-Study A
Phase 1b only:
17. Receipt of anticancer medications or investigational drugs within the following intervals 
before the first dose of study intervention:
a.
≤14 days for chemotherapy, targeted small-molecule therapy, radiation therapy, or 
antineoplastic biologic therapy.
b. ≤14 days or 5 half-lives (minimum of 14 days) for investigational agents or devices. 
For monoclonal antibodies, <28 days from the last dose.
Phase 2 only:
18. Prior therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 161
Phase 1b and Phase 2:
19. Participants who have documentation of any of the following: activating EGFR mutation
(mutations located in exons 18-21), ALK fusion oncogene, or ROS1 rearrangement.
Testing for EGFR mutation is required if status is unknown.
20. Prior treatment with any BRAF inhibitor (eg, dabrafenib, vemurafenib, 
XL281/BMS908662, etc) or MEK inhibitor (eg, trametinib, cobimetinib, selumetinib, 
RDEA119, etc). 
21. History or current evidence of RVO or current risk factors for RVO (eg, uncontrolled 
glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability 
syndromes).
22. Concurrent or anticipated use of a non-topical medication known to be a strong/moderate 
CYP3A4 inhibitor or CYP3A inducer within 7 days prior to first dose of study 
intervention and throughout study duration.
23. LVEF <50% as determined by MUGA or echocardiogram.
24. Triplicate average baseline QTcF >450 msec for male participants or QTcF >470 msec
for female participants or QTcF >480 msec in participants with right bundle branch block 
or a history of prolonged QT syndrome.
12.6. Study Intervention for Sub-Study A
Study Treatments:
For purposes of this sub-study, study intervention refers to sasanlimab, encorafenib, and 
binimetinib.  The prefilled syringe of sasanlimab is a medical device. Refer to Section 6.1.1
for details about the administration of sasanlimab. 
Participants will receive the following study treatments in each 28-day cycle:
Phase 1b Dose Levels:
Sasanlimab SC, 300 mg (150 mg/mL, 2 mL) prefilled syringe on Day 1 of each cycle
Encorafenib: 300 mg (4 × 75 mg oral capsules) QD (Dose levels 0 and -1), Encorafenib 450 
mg (6 × 75 mg oral capsules) QD (Dose level 1).
Binimetinib: 30 mg (2 × 15 mg oral tablets) BID (Dose level -1), 45 mg (3 × 15 mg oral 
tablets) BID (Dose levels 0 and 1).

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 162
Phase 2 Dose Levels: 
RP2D/MTD of sasanlimab 300 mg + encorafenib + binimetinib
Table 8.
Study Interventions: Sub Study A (Sasanlimab + Encorafenib + 
Binimetinib)
Intervention Name
Sasanlimab
Encorafenib
Binimetinib
Type
Biologic Product
small molecule product
small molecule product
Dose Formulation
Solution for injection
Capsule
Tablet
Unit Dose Strength
150 mg/mL, 2 mL 
(300 mg total) pre-filled 
syringe
75 mg
15 mg
Dosage Level(s)
300 mg Q4W
300 mg QD, 450 mg QD
45 mg BID, 30 mg BID
Route of Administration
Subcutaneous
Oral
Oral
Use
Experimental
Experimental
Experimental
IMP or NIMP 
IMP
IMP
IMP
Sourcing
Provided centrally by the 
sponsor 
Provided centrally by the 
sponsor
Provided centrally by 
the sponsor
Packaging and Labeling
Study intervention will 
be provided in a 2-mL 
Prefilled syringe for 
300 mg dose.  Each 
prefilled syringe will be 
labeled as required per 
country requirement.
Study intervention will 
be provided in high-
density polyethylene 
bottles. Each bottle will 
be labeled as required per 
country requirement.
Study intervention will 
be provided in high-
density polyethylene 
bottles. Each bottle will 
be labeled as required 
per country 
requirement.
Former Names or 
Aliases
PF-06801591
RN888
BRAFTOVI®
LGX818
ONO-7702
W0090
MEKTOVI®
ARRAY-438162
MEK162
ONO-7703
W0074
12.6.1. Administration of Encorafenib and Binimetinib
Encorafenib will be self-administered orally without regard to food. Encorafenib should be 
taken daily in the morning at approximately the same time (± 2 hours) every day. Participants 
should be directed to take encorafenib and binimetinib together as applicable. If a participant 
vomits at any time after dosing, the dose should not be re-administered. Doses of encorafenib 
that are omitted for AEs or any other reason should not be made up during the day, or at the 
end of the dosing period. Additional information regarding encorafenib administration is 
provided in the IP Manual.
Binimetinib will be self-administered orally without regard to food. Binimetinib should be 
taken 12 ± 2 hours apart in the morning and in the evening at approximately the same times 
every day. Participants should be directed to take binimetinib and encorafenib together as 
applicable. If a participant vomits at any time after dosing, the dose should not be re-
administered, and the participant should take the next scheduled dose. Doses of binimetinib 
that are omitted for AEs or any other reason should not be made up during the day, or at the 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 163
end of the dosing period.  Additional information regarding binimetinib administration is 
provided in the IP Manual.  
Encorafenib and binimetinib will begin on Cycle 1 Day 1 and will be self-administered 
continuously, except on study visit days, when encorafenib and binimetinib will be 
administered at the study site.  
12.6.2. Preparation, Handling, Storage, Accountability, and Dispensing 
The participant/caregiver should be instructed to maintain the encorafenib and binimetinib 
products in the bottles provided throughout the course of dosing and return the bottles to the 
site at the next study visit. For further details, refer to master protocol Section 6.2.
12.6.3. Measures to Minimize Bias: Randomization and Blinding
This is an open-label sub-study that will not be randomized.
12.6.3.1. Allocation to Study Intervention
Refer to master protocol Section 6.3.1.
12.6.4. Study Intervention Compliance
Refer to master protocol Section 6.4.
12.6.5. Concomitant Therapy for Sub-Study A
In addition to concomitant therapy instructions and restrictions in the master protocol 
Section 6.5, the following concomitant therapy instructions and restrictions apply to 
Sub-Study A.
12.6.5.1. Permitted Concomitant Therapy Requiring Caution and/or Action
12.6.5.1.1. CYP and UGT Substrates and Inhibitors
Encorafenib is a reversible inhibitor of CYP2B6, CYP2C9, CYP3A4 and UGT1A1. It is also 
a time-dependent inhibitor of CYP3A4, and induced CYP2B6, CYP2C9 and CYP3A4 in 
human primary hepatocytes. Permitted medications to be used with caution in this study 
include those that are sensitive substrates of CYP2B6, CYP2C9, CYP3A4 and UGT1A1 or 
those substrates that have a narrow therapeutic index.
There is a potential for encorafenib to induce CYP3A4, which may reduce the 
effectiveness of hormonal contraception methods. Therefore, the use of at least 1 form 
of non-hormonal contraception is required for females of childbearing potential during 
participation in this study. 
Caution should be used in participants receiving concomitant treatment with other drugs that 
are substrates of CYP3A4 as the efficacy of these drugs could be reduced when administered 
with encorafenib.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 164
Encorafenib has been identified to be metabolized by CYP3A4 and to a lesser extent by 
CYP2C19 in vitro.  Concomitant use of moderate and/or strong CYP3A4 inhibitors 
should be avoided throughout the study.  If concomitant use of a strong or moderate 
CYP3A4 inhibitor is unavoidable, consultation with the sponsor is needed prior to concurrent 
use of moderate or strong CYP3A4 inhibitors as the dose of encorafenib will be adjusted 
accordingly during coadministration with moderate or strong CYP3A inhibitor concomitant 
medications. Selection of an alternate concomitant medication with no or minimal enzyme 
inhibition and/or induction potential is recommended in Sub-Study A when co-administered 
with encorafenib.   Participants must avoid consumption of grapefruit, pomegranates, star 
fruits, Seville oranges or products containing the juice of each during the entire study and 
preferably 7 days before the first dose of study drugs, due to potential CYP3A4 interaction 
with encorafenib.
In vitro, binimetinib has been identified to be primarily metabolized by glucuronidation (via 
UGT1A1, with UGT1A3, UGT1A9 and UGT2B7 also contributing). In clinical study sub-
analysis, however, there was no apparent relationship observed between binimetinib 
exposure and UGT1A1 mutation status. In addition, simulations to investigate the effect of 
atazanavir 400 mg (UGT1A1 inhibitor) on the exposure of binimetinib 45 mg predicted 
similar binimetinib Cmax in the presence or absence of atazanavir.32 The possible extent of 
drug interactions mediated by UGT1A1 is expected to be minimal, and likely not clinically 
relevant; however, as this has not been evaluated in a formal clinical study, UGT1A1 
inducers or inhibitors should be administered with caution.
For examples of drugs of CYP3A inhibitors to be used with caution or avoided or where to 
find additional evolving information regarding UGT1A1 perpetrators, please see 
Section 10.13.
12.6.5.1.2. Transporter Substrates and Inhibitors
In vitro data showed that encorafenib is a substrate of the transporter P-gp.  Thus, drugs that 
are known to inhibit or induce P-gp should be used with caution.  Encorafenib is also an
inhibitor of P-gp , BCRP, OAT1, OAT3,  OCT2,  OATP1B1 and OATP1B3, and the co-
administration of drugs that are substrates of these transporters should be used with caution.
Binimetinib has also been shown to be a substrate of P-gp and BCRP.  It is advised that 
inhibitors and inducers of P-gp and BCRP transporters should be taken with caution when 
coadministered with binimetinib. 
For examples of drugs of P-gp inhibitors to be used with caution, please see Section 10.13.
12.6.5.1.3. Drugs with a Conditional or Possible Risk to Prolong QT Interval and/or 
Induce Torsade de Pointes
Investigators should use caution when administering encorafenib with concomitant 
medications with a known, conditional or possible risk to prolong the QT interval and/or 
induce torsade de pointes. Participants receiving such medications must be carefully 
monitored for potentiating of toxicity due to any individual concomitant medication and may 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 165
require dose titration of the concomitant medication. See the CredibleMeds® website: 
Combined List of Drugs That Prolong QT and/or cause Torsades de Pointes (TdP).
12.6.5.2. CYP3A Inducers
Concomitant moderate and/or strong systemic CYP3A inducers, which could significantly 
decrease the exposure of encorafenib, are prohibited throughout the study (Phase 1 and 
Phase 2). For examples of moderate and/or strong CYP3A4 inducers, see Section 10.13.
12.6.6. Dose Interruptions and Modifications for Sub-Study A
12.6.6.1. Dose Interruptions
Following initiation of therapy, treatment with encorafenib and binimetinib may be delayed 
to allow resolution of toxicity.  Participants may resume treatment if no medical condition or 
other circumstance exists that, in the opinion of the Investigator, would make the participant 
unsuitable for further participation in the study.
Individual decisions regarding dose interruptions and modifications should be made using 
appropriate clinical judgment, considering relatedness of the AE to the study treatment and 
the participant’s underlying condition. AEs that have a clear alternative explanation, or 
transient (≤72 hours) abnormal laboratory values without associated clinically significant 
signs or symptoms may be exempt from dose-reduction rules. The treating physician should 
refer to and follow the labeled guidance and/or institutional guidelines for the management of 
toxicities relating to encorafenib and binimetinib.
Some potential immune-related AEs described with anti-PD-1 mAbs, such as sasanlimab, 
may overlap with encorafenib or binimetinib toxicities (eg, ophthalmologic, cardiovascular, 
hepatic, pulmonary AEs, etc).  The treating physician should make assessment and determine 
the related component in the combination regimen to manage the AE and make dose 
interruptions, if needed, accordingly.  Consultation with an appropriate specialist is 
recommended as indicated.  Any AE suspected to be immune-related should be managed 
according to the management guidance of immune-related adverse events in Sections 6.6 and 
10.10. 
Dose interruptions are permitted in the case of medical/surgical events or logistical reasons 
not related to study treatment (e.g., elective surgery, unrelated medical events, vacation, 
holidays). Participants should be placed back on study treatment within 2 weeks (14 days) of 
the scheduled interruption, unless otherwise discussed with the sponsor. The reason for 
interruption will be documented in the participant’s study record. 
If a participant misses >6 weeks (ie, 42 consecutive days) of dosing with encorafenib, 
study treatment with encorafenib will be permanently discontinued.  Due to the
potential for limited efficacy of binimetinib alone in the study population, if a 
participant permanently discontinues treatment with encorafenib, he or she must also 
permanently discontinue treatment with binimetinib.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 166
If a participant misses >6 weeks (ie, 42 consecutive days) of dosing with binimetinib, 
study treatment with binimetinib will be permanently discontinued. If a participant 
discontinues treatment with binimetinib, the participant may continue treatment with 
encorafenib.  Due to the potential for increased toxicity when binimetinib is 
discontinued, the dose of single-agent encorafenib may need to be decreased in 
consultation with the sponsor.
12.6.6.2. Dose Modifications
Doses of encorafenib and binimetinib may be independently reduced for toxicity 
management as outlined in Table 9 and Table 10, respectively.  All dose modifications are 
based on the worst preceding toxicity.  The treating investigator should refer to and follow 
the labeled guidance and/or institutional guidelines for the management of toxicities relating 
to encorafenib and binimetinib.  Detailed guidelines can also be found in Sections 12.10.4
and 12.10.5. 
When the AE that resulted in a dose reduction improves to and remains stable to the 
participant’s baseline for a minimum of 14 days, the dose can be re-escalated to the next 
higher dose level at the discretion of the investigator, provided there are no other 
concomitant toxicities that would prevent drug re-escalation.  There is no limit to the number 
of times the participant can have their dose reduced or re-escalated; however:
No dose re-escalation of encorafenib is allowed after a dose reduction due to prolonged 
QTcF ≥501 msec.
No dose re-escalation of binimetinib is allowed after a dose reduction due to LVEF 
dysfunction. 
No dose re-escalation of binimetinib or encorafenib is allowed after a dose reduction due to 
ocular toxicity ≥Grade 2.
Table 9.
Dose Reductions for Encorafenib for Toxicity Management
Encorafenib Starting Dose
Encorafenib First Dose 
Reduction
Encorafenib Second Dose 
Reduction
450 mg QD
300 mg QD
225 mg QD
300 mg QD
225 mg QD
150 mg QD
Dose reduction below 75 mg QD of encorafenib is not allowed.  Management of participants requiring more 
than 2 dose reductions of encorafenib (1 dose level decrease at a time) should be discussed with the sponsor.
NOTE: Dose reduction should be based on the highest AE grade.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 167
Table 10.
Dose Reductions for Binimetinib for Toxicity Management
Binimetinib Starting Dose
Binimetinib First Dose 
Reduction
Binimetinib Second Dose 
Reduction
45 mg BID
30 mg BID
15 mg BIDa
30 mg BID
15 mg BIDa
N/A
a.
Dose reduction below 15 mg BID of binimetinib is not allowed.
NOTE: Dose reduction should be based on the highest AE grade.
The dose of encorafenib will also be adjusted for participants with concomitant CYP3A4 
inhibitors as specified in Section 12.6.5.1.1.
12.7. Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal
See Section 7 of the master protocol for discontinuation of study intervention and participant 
discontinuation/withdrawal.
12.8. Study Assessments and Procedures for Sub-Study A
See Section 8 for master protocol study assessments and procedures, in addition to the 
following procedures specific to Sub-Study A. 
12.8.1. Efficacy Assessments
12.8.1.1. Tumor Response Assessments
Radiologic images of Phase 2 participants must be made available to a central vendor for 
potential central imaging reading of tumor assessments.
Refer to Section 8.1.1 for tumor response assessments.
12.8.2. Safety Assessments
12.8.2.1. Echocardiogram/ Multigated Acquisition Scan (MUGA)
LVEF should be assessed by transthoracic echocardiogram or MUGA and performed as 
outlined in the SoA.
The same modality used during screening should be used for all subsequent timepoints.  
Additional assessment should also be performed if a participant experiences an AE which 
may be related to cardiac dysfunction in the opinion of the investigator.
The details of the echocardiogram/MUGA will not be recorded on a CRF; however, any 
abnormalities detected on the echocardiogram/MUGA will be reported on the medical 
history or AE CRF as appropriate.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 168
12.8.2.2. Dermatologic Examination
Dermatologic evaluations will be performed at the site by the investigator to monitor for the 
possible development of keratoacanthoma and/or squamous cell carcinoma, as these have 
been reported to occur with selective BRAF inhibitor treatment.27,30,34  This assessment may 
be performed predose or postdose at the time points specified in the SoA.
In case of occurrence of keratoacanthoma or squamous cell carcinoma, participants will 
undergo complete surgical excision of the skin lesion following institutional standards. 
Dermatologic evaluations will be performed by a dermatologist as clinically indicated.
The details of the dermatologic assessment will not be recorded on a CRF; however, any 
abnormalities detected during the examination will be reported on the medical history or 
adverse event CRF as appropriate.
12.8.2.3. Ophthalmic and Visual Acuity Examinations
Full ophthalmic examination will be performed by an ophthalmologist and will include best 
corrected visual acuity, slit lamp examination, intraocular pressure, dilated fundoscopy, and 
optical coherence tomography.  Examination of the retina is required (especially to identify 
findings associated with RPED, serous detachment of the retina and RVO).  Visual acuity 
tests may be performed by qualified site staff.  
Ophthalmic examinations and visual acuity testing will be performed at visits according to 
the SoA.  Further ophthalmic examinations should be guided by specific ocular signs and 
symptoms should they occur during treatment and follow-up as clinically indicated.  
The details of the ophthalmic and visual acuity examinations will not be recorded in the 
CRF; however, any abnormalities detected are to be reported on the AE or medical history 
CRF as appropriate.
Additional Ophthalmic Testing
Patients with clinical suspicion of retinal abnormalities of any grade (eg, RPED, serous 
detachment of the retina, RVO, photopsia, metamorphopsia, impairment of visual acuity) 
must complete at least 1 of the following additional assessments:

For non-vascular abnormalities: optical coherence tomography (spectral domain 
optical coherence tomography recommended)

For vascular abnormalities: fluorescein angiography of the central 30 degrees. 
Images/results of the ophthalmic examinations (at a minimum, optical coherence tomography 
and/or fluorescein angiography) must be sent to the investigational site and be maintained in 
the patient’s source document file.  These images/results must be made available upon 
sponsor request.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 169
12.8.3. Treatment of Overdose
There is no antidote known to over-dosage for either encorafenib or binimetinib.  Supportive 
measures should be instituted.  Please refer to the respective IBs for more information.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the sponsor based on the clinical evaluation of the participant.
12.8.4. Genetics
Results of the local laboratory BRAFV600-mutation status in tumor tissue or plasma will be 
entered in the CRF.
In Phase 2, blood samples or tumor tissue will also be tested to confirm eligibility. 
Assessment of mutation status will first be performed using plasma ctDNA.  In the event that 
a plasma ctDNA result cannot be interpreted, reflex testing of the tumor tissue described in 
Section 8.8 will be performed.  In addition, tumor tissue collected after the participant was 
diagnosed with metastatic disease is preferred.  The tumor tissue sample must not be from 
locations that were previously irradiated.
The blood sample collected to confirm eligibility may also be used for future development of 
a medical device (companion diagnostic [CDx]) that would be used to select future patients 
for treatment with encorafenib, binimetinib, and sasanlimab based on their BRAFV600
mutation status.
12.8.5. Patient Reported Outcomes
PROs will be assessed using the European Organization for Research and Treatment of 
Cancer Quality of Life Questionnaire (EORTC QLQ-C30)35 and its corresponding module 
for lung cancer (EORTC QLQ-LC13).36 The questionnaires will be administered at the time 
points described in the SoA. The questionnaires should be completed prior to any other study 
or medical procedure.
The EORTC QLQ-C30 is a well-known, validated and self-administered PRO questionnaire 
(Aaronson 1993). The EORTC QLQ-C30 consists of 30 questions, which can be grouped 
into 5 functional scales (physical, role, cognitive, emotional, and social); a global health 
status/global quality of life scale; 3 symptom scales (fatigue, pain, nausea and vomiting); and 
6 single items that assess additional symptoms (dyspnea, appetite loss, sleep disturbance, 
constipation, and diarrhea), and financial impact.  All scales and single item measures range 
in score from 0 to 100.  Higher scores on the global health status/quality of life scale 
represent higher health status/quality of life.  Higher scores on the functional scales represent 
higher levels of functioning. Higher scores on the symptom scales/items represent a greater 
presence of symptoms. 
The EORTC QLQ-LC13 is the lung cancer-specific module of the EORTC Quality of Life 
Questionnaire.36  The EORTC QLQ-LC13 consists of 13 questions and includes 1 multi-item 
scale and 9 single items assessing symptoms (dyspnea, cough, haemoptysis, and site-specific 
pain), side effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 170
medication use.  Similar to the EORTC QLQ-C30, higher scores are reflective of a greater 
presence of symptoms.
12.9. Statistical Considerations for Sub-Study A
See Section 9 for master protocol statistical considerations and sub-study specifics below.
12.9.1. Estimands and Statistical Hypotheses
12.9.1.1. Estimands
Refer to Section 12.3 for details of estimands.
12.9.1.2. Statistical Consideration for Phase 1b
The Phase 1B will utilize a Bayesian logistic regression model (BLRM) for dose finding as 
follows:
Identification of a recommended dose
The dosing decision and estimation of the MTD of the triplet combination will be guided by 
the estimation of the probability of DLT in Cycle 1.  However, other evidence such as safety 
data beyond DLT, clinical activity, PK, and PD data will play an important role in the final 
decision.  A RP2D below the MTD may be determined based on these considerations.
Bayesian adaptive approach
The dose finding in the Phase 1b of the study will be guided by a Bayesian analysis of 
Cycle 1 DLTs in DLT-evaluable participants.37    
Triplet combination model
For the triplet combination of encorafenib, binimetinib, and sasanlimab, the Bayesian 
model37 consists of 7 parts, representing:
1. Single-agent encorafenib toxicity;
2. Single-agent binimetinib toxicity;
3. Single-agent sasanlimab toxicity;
4. Interaction between encorafenib and binimetinib;
5. Interaction between binimetinib and sasanlimab;
6. Interaction between encorafenib and sasanlimab;
7. Triple interaction among encorafenib, binimetinib, and sasanlimab.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 171
Single-agent toxicities are modelled using logistic regression for the probability of a 
participant experiencing a DLT against log-dose.  The odds of a DLT are then calculated 
under no interaction for the 2/3 single-agent toxicities, and interaction is accounted for by 
adjusting these odds with an additional model parameter (odds multiplier).  Details of the 
model are given in Section 12.10.6.
Assessment of participant risk
After each dosing cohort of participants completes the DLT evaluation period, the posterior 
distribution for the risk of DLT for different dose combination doses of interest will be 
evaluated. The posterior distributions will be summarized to provide the posterior probability 
that the risk of DLT lies within the following intervals:

Underdosing: [0, 0.16);

Target toxicity: [0.16, 0.33);

Excessive toxicity: [0.33, 1].
The EWOC principle
Dosing decisions are guided by the EWOC principle.  A combination dose may only be used 
for the next dosing cohort of participants if the risk of excessive toxicity ([0.33, 1]) at that 
combination dose is less than 0.25. 
Prior distributions
A meta-analytic-predictive (MAP) approach was used to derive the prior distribution for the 
single-agent model parameters.  The MAP prior for the logistic model parameters for this 
study is the conditional distribution of the parameters given the historical data.37-39  
MAP priors are derived using Bayesian hierarchical models, which take into account possible 
differences between the studies.
A full description of the application of the MAP approach to derive the prior distributions of 
the single-agent model parameters is given in Section 12.10.6.
The prior distribution for the interaction parameters (doublet and triplet combinations) were 
based on the prior understanding of possible drug safety interactions. This prior allows for 
the possibility of either synergistic or antagonistic interaction, and is fully described in    
Section 12.10.6).
It is estimated that up to 18 participants will be enrolled and assigned to treatment with the 
triplet combination which will include at least 6 participants treated at the MTD level and at 
least 9 participants at the RP2D.  The actual number of participants will depend on the 
number of DLT events and dose levels tested.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 172
12.9.1.3. Sample Size Determination
The total sample size is estimated to be approximately 80 participants for the Sub-Study A 
Phase 1b/2.
12.9.1.3.1. Phase 1b Dose Finding
Approximately 9-18 participants will be enrolled in the Phase 1b part.  However, the total 
number of participants will depend on the number of dose levels needed to determine the 
MTD/RP2D of each combination and the number of participants evaluable for DLT at each 
dose level.
Beginning with the first dose level, participants will be enrolled, treated, and monitored in 
cohorts of 3-6 participants during the 28-day DLT evaluation period (Cycle 1).  A minimum 
of 9 participants and up to approximately 18 participants will be enrolled to evaluate DLTs 
during the first cycle of treatment.
12.9.1.3.2. Phase 2 Dose Expansion
Approximately 62 participants will be enrolled in the Phase 2 part of Sub-Study A.
Phase 2 will test the null hypothesis that the durable ORR does not exceed 35% (H0: durable 
ORR ≤35%).  The null hypothesis will be tested against the alternative (H1: durable ORR
>35%) at one-sided level of significance α = 0.025 using the binomial distribution.
Sixty-two (62) participants will provide at least 90% power to reject the null hypothesis if the 
true durable ORR is at least 55% (durable ORR ≥55%).
At the end of Phase 2: 

If there are ≤29 objective durable responders of 62 participants in the Phase 2 part, 
then it will be declared that the null hypothesis cannot be rejected.  

If there are ≥30 objective durable responders of 62 participants in the Phase 2 part, 
then the null hypothesis will be rejected.
12.9.1.4. Analysis Set
Refer to Section 9.3 for analysis sets.
12.9.1.5. General Considerations
12.9.1.5.1. Primary Endpoints
Phase 1b
The primary safety endpoint in Phase 1b is DLTs.  Refer to Section 9.4.2. 
The occurrence of DLTs and AEs constituting DLTs will be summarized for participants in 
the Phase 1b part as described in Section 12.3.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 173
Phase 2
The primary efficacy endpoint in the Phase 2 part is Durable OR.  Refer to Section 12.3.
Durable ORR will be calculated along with the 2-sided 95% CI for durable ORR using the 
Clopper-Pearson method. Participants who do not have a post-baseline tumor assessment due 
to early progression of disease, who receive anti-cancer therapies other than the study 
treatments prior to reaching a CR or PR for 10 months, or who die, have PD, or stop tumor 
assessments for any reason prior to reaching a CR or PR for 10 months will be counted as 
non-responders in the assessment of durable OR.
12.9.1.5.2. Secondary Endpoints
12.9.1.5.2.1. Efficacy Analyses
Additional efficacy endpoints, durable OR (Phase 1b; refer to Section 12.9.1.5.1), OR (Phase 
1b and Phase 2), TTR (Phase 2), DR (Phase 2), and PFS (Phase 2) will be summarized based 
on investigator assessment using RECIST v1.1.  OS will be summarized for Phase 2.

OR is defined as a CR or PR according to RECIST v1.1 based on investigator 
assessment.  Both CR and PR must be confirmed by repeat assessments performed no 
less than 4 weeks after the criteria for response are first met.  Only tumor assessments 
performed on or before the start date of any further anti-cancer therapies will be 
considered in the assessment.

TTR is defined for participants with confirmed objective response (CR or PR) as the 
time from the date of first dose to the date of first documentation of objective tumor 
response which is subsequently confirmed.

DR is defined for participants with confirmed objective response (CR or PR) as the 
time from the first documentation of OR to the first documentation of objective tumor 
progression or to death due to any cause, whichever occurs first.  The censoring rules 
for DR are as described below for PFS but participants will not be censored in the 
analysis of DR due to no adequate baseline assessment as only participants with OR 
are included in the analysis of DR.

PFS is defined as the time from the date of first dose of study treatment to the date of 
first documentation of PD or death due to any cause, whichever occurs first.  PFS 
data will be censored on the date of the last adequate tumor assessment for 
participants who do not have an event (PD or death), for participants who start new 
anti-cancer treatment prior to an event, or for participants with an event after 2 or 
more missing tumor assessments.  Participants who do not have an adequate baseline 
tumor assessment or who do not have any adequate post-baseline tumor assessments 
per RECIST v1.1 will be censored on the date of first dose unless death occurred on 
or before the time of the second planned tumor assessment in which case the death 
will be considered an event.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 174

OS is defined as the time from the date of first dose of study treatment to the date of 
death due to any cause. Participants last known to be alive will be censored at the 
date of last contact.
TTR will be summarized using simple descriptive statistics (eg, median and range).  OR will
be summarized as the proportion of participants in the analysis population with OR and 
corresponding 2-sided 95% CI using the Clopper-Pearson method.  DR, PFS, and OS will be 
analyzed using Kaplan-Meier methods.  Point estimates will be presented with 95% CIs.
12.9.1.5.2.2. Safety Analyses
For Phase 1b primary safety analysis, refer to Section 12.3 for DLT.
For Phase 1b and Phase 2 secondary safety analyses, refer to Sections 9.4.3.2 and 9.4.5.
12.9.1.5.2.3. PK Analyses
Refer to master protocol Section 9.4.3.3 for the analysis of PK endpoints for sasanlimab.
Trough concentrations for encorafenib, binimetinib and any analyzed metabolites will be 
summarized descriptively (n, mean, SD, coefficient of variation [CV], median, minimum, 
maximum, geometric mean, its associated CV, and 95% confidence interval) by cohort/dose 
and cycle/ day.  Exclusions or separate summaries for dose modifications and concomitant 
medications may be considered in data summaries. 
Dose-normalized PK parameters (Ctrough-DN) may be reported as appropriate. 
12.9.1.5.2.4. Immunogenicity Analyses
Refer to master protocol Section 9.4.3.4 for the analysis of immunogenicity endpoint.
12.9.1.5.2.5. Biomarker Analyses
Refer to master protocol Section 9.4.4.1 for the analysis of biomarker endpoints.
12.9.1.5.2.6. Patient Reported Outcomes Analyses
The EORTC QLQ-C30 and EORTC QLQ LC13 will be scored according to its user 
guide/scoring manual.40
At each time point, the number and percentage of participants who complete the EORTC 
QLQ-C30 and EORTC QLQ-LC13 will be summarized, as will the reasons for 
non-completion of these measures. An instrument is considered complete if at least one item 
was answered by the participant.
Summary statistics (mean and standard deviation [SD], median, range, and 95% CI) of 
absolute scores will be reported for each of the total and subscales of the EORTC QLQ-C30 
and the EORTC QLQ-LC13.  The mean change from baseline with 95% CI will also be 
reported by time point. 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 175
12.9.1.5.3. Exploratory Endpoints
Refer to Section 9.4.4 for biomarker exploratory endpoints.
Depth of response is defined as a reduction in tumor burden in target lesions.  Summary 
statistics for depth of response (n, %) will be determined and further described in the SAP.
12.9.1.5.4. Interim Analysis
A futility analysis based on ORR will be performed to allow early termination for futility 
after 30 participants are treated and followed for 2 on-treatment assessments (~4 months), 
without holding participant enrollment.  If based on the observed ORR the probability of a 
true ORR ≥48% is ≤0.10, then the study will be stopped for futility.  For example, the study 
will be stopped for futility if ≤10 confirmed ORs are observed in the first 30 participants 
treated.
The probability of stopping the sub-study (if ≤10 confirmed ORs are observed in the first 
30 participants treated) under the alternative hypothesis is 0.014. 
12.10. Supporting Documentation and Operational Considerations for Sub-Study A
12.10.1. Clinical Laboratory Tests for Sub-Study A
In addition to the clinical laboratory tests required in Master Protocol Section 10.2, the tests 
in Table 11 will be required for participants in Sub-Study A:
Table 11.
Clinical Laboratory Tests Added for Sub-Study A
Hematology
Chemistry
Urinalysis

Hematocrit

RBC

CK (If total CK ≥3 × ULN, then measure 
isoenzymes, serum creatinine and 
myoglobin in blood weekly)

Direct bilirubin if total bilirubin values 
are above ULN

Appearance

Color

Specific gravity

pH

Glucose

Ketones

Nitrite

Leukocytes

Microscopic analysis (Reflex 
Testing)a
a.
Only if urine dipstick is positive for nitrites or leukocytes.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 176
12.10.2. Contraceptive Guidance for Sub-Study A
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; studies to evaluate the development toxicity of sasanlimab have not been 
conducted.  Therefore, the use of a highly effective method of contraception is required
12.10.2.1. 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 6 months 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 a male condom when engaging in any activity that allows for 
passage of ejaculate to another person.

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 12.10.2.4).
12.10.2.2. 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 12.10.2.3).
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 6 months after the last dose 
of study intervention, and agrees not to donate eggs (ova, oocytes) for the purpose 
of reproduction during this period, which corresponds to the time needed to 
eliminate any reproductive safety risk of the study intervention(s).  If the chosen 
highly effective method is a hormonal method, then the use of at least 1 form of 
non-hormonal contraception is required (see Section 12.10.2.4).

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 177
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. 
12.10.2.3. Woman of Childbearing Potential (WOCBP)
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.
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. 

Female on HRT and whose menopausal status is in doubt will be required to 
use one of the non-estrogen 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.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 178
12.10.2.4. 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.
5. Vasectomized partner.

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 
1. Combined (estrogen and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation*:

Oral;

Intravaginal;

Transdermal.
2. Progestogen-only hormone contraception associated with inhibition of ovulation*:

Oral;

Injectable.
3. 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.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 179
*There is a potential for encorafenib to induce CYP3A4, which may reduce the effectiveness 
of hormonal contraception methods. Therefore, the use of at least 1 form of non-hormonal 
contraception is required for females of childbearing potential. One of the following 
acceptable barrier methods must be used in addition to any of the hormonal highly effective 
methods listed above:

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).
12.10.3. Examples of Strong and Moderate CYP3A4 Inhibitors
Refer to Section 10.13.
12.10.4. Recommended Dose Modifications for Encorafenib-related* Adverse Events 
and Overlapping Toxicities with Sasanlimab**
Severity of Adverse Event
Dose Modifications
New Primary Malignancies
RAS mutation-positive malignancies
Permanently discontinue encorafenib and binimetinib.
Uveitis
Grade 1-3
Consult ophthalmologist. Treat with topical steroids 
such as 1% prednisolone acetate suspension and 
iridocyclitics as appropriate.
If considered to be immune-related AE, 

Grade 1: continue sasanlimab 

Grade 2: hold sasanlimab with treatment 
guided by ophthalmologist with or without 
systemic corticosteroids

Grade 3: permanently discontinue 
sasanlimab with treatment guided by 
ophthalmologist on systemic corticosteroids.
If Grade 1 or 2 uveitis considered to be encorafenib 
related and does not respond to specific ocular 
therapy, or for Grade 3 uveitis, withhold encorafenib 
and binimetinib for up to 6 weeks.

If improved, resume at same or reduced 
dose.

If not improved, permanently discontinue.
Grade 4 
Permanently discontinue sasanlimab, encorafenib, 
and binimetinib.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 180
Severity of Adverse Event
Dose Modifications
Other Eye Disorders (i.e., non-Uveitis Events)
Grade 1–2
Maintain dose level of encorafenib and binimetinib 
and increase frequency of ophthalmic monitoring to 
at least every 14 days until stabilization or resolution.
If considered irAE, refer to Uveitis management 
above.
Grade 3
Interrupt dosing of encorafenib and binimetinib and 
refer participant to ophthalmologist within 7 days.

If resolved to Grade ≤1 in ≤21 days, resume 
treatment at 1 reduced dose level of 
encorafenib and binimetinib.

If not resolved to Grade ≤1 in ≤21 days, 
permanently discontinue encorafenib and 
binimetinib and close follow-up with 
ophthalmic monitoring until stabilization or 
resolution.

If considered irAE, refer to Uveitis 
management above.
Grade 4
Permanently discontinue sasanlimab, encorafenib, 
and binimetinib and immediate follow-up with 
ophthalmic monitoring until stabilization or 
resolution.
QTc Prolongation
QTcF >500 msec and ≤60 msec increase from 
baseline
1st occurrence: 

Temporarily interrupt dosing of encorafenib 
until QTcF <500 msec. Then resume 
treatment at 1 reduced dose level of 
encorafenib.
2nd occurrence:

Temporarily interrupt dosing of encorafenib 
treatment until QTcF <500 msec. Then 
resume treatment at 1 reduced dose level of 
encorafenib. 
3rd occurrence: 

Permanently discontinue encorafenib and 
binimetinib.
QTcF >500 msec and >60 msec increase from 
baseline
Permanently discontinue encorafenib and binimetinib.
Hepatotoxicity
Grade 2 AST or ALT increased
Maintain encorafenib dose.

If no improvement within 4 weeks, withhold 
encorafenib until improved to Grade 0-1 or 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 181
Severity of Adverse Event
Dose Modifications
to pretreatment/baseline levels and then 
resume at the same dose.
Refer to Sections 6.6 and 10.10 if considered irAE.
Grade 3 or 4 AST or ALT increased
See Other Adverse Reactions in this table for 
guidance on encorafenib and binimetinib.  
Permanently discontinue sasanlimab.
See Sections 6.6 and 10.10 for irAE.
Dermatologic (Except Palmar-plantar Erythrodysesthesia Syndrome)
Grade 2
If no improvement within 2 weeks, withhold until 
Grade 0-1. Resume at same dose if first occurrence or 
reduce dose if recurrent.
Refer to Sections 6.6 and 10.10 if considered irAE.
Grade 3
Withhold until Grade 0-1. Resume at same dose if 
first occurrence or reduce dose if recurrent.
Refer to Sections 6.6 and 10.10 if considered irAE.
Grade 4
Permanently discontinue sasanlimab, encorafenib, 
and binimetinib.  Refer to Sections 6.6 and 10.10 if
considered irAE.
Hand-foot Skin Reaction (HFSR)/Palmar-plantar Erythrodysesthesia Syndrome
(Dose Adjustment for Encorafenib ONLY)
Grade 1
Maintain dose of encorafenib. Promptly institute 
supportive measures, such as topical therapy, for 
symptomatic relief. Give instruction on life-style 
modifications.
Grade 2
1st occurrence: 

Maintain dose of encorafenib and HFSR 
should be closely monitored. Promptly 
institute supportive measures, such as topical 
therapy, for symptomatic relief. Give 
instruction on life-style modifications.

If no improvement ≤14 days, interrupt 
dosing of encorafenib until resolved to 
Grade ≤1. Resume treatment with 
encorafenib at current dose level. Continue 
supportive measures, such as topical therapy, 
for symptomatic relief.  Give instruction on 
life-style modifications.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 182
Severity of Adverse Event
Dose Modifications
Additional occurrence: 

Treatment with encorafenib may be 
maintained or interrupted based upon the 
investigator’s discretion. Continue 
supportive measures, such as topical therapy, 
for symptomatic relief. Give instruction on 
life-style modifications.
If interrupted dosing of encorafenib per 
investigator’s judgment, interrupt until 
resolved to Grade ≤1. Resume treatment 
with encorafenib at the same dose level or 
1 reduced dose level based upon the 
investigator’s discretion.
Grade 3
1st or 2nd occurrence:

Interrupt dosing of encorafenib until 
resolved to Grade ≤1.  Promptly initiate 
supportive measures, such as topical therapy, 
for symptomatic relief. Give instruction on 
life-style modifications.  Reassess the 
participant weekly.  Then resume treatment 
at 1 reduced dose level of encorafenib.

Consider referral to dermatologist and 
manage HFSR per dermatologist’s 
recommendation.
>3rd occurrence:

Interrupt dosing of encorafenib until 
resolved to Grade ≤1, decision to resume 
treatment with encorafenib at 1 reduced dose 
level or permanently discontinue encorafenib 
should be based upon the investigator’s 
discretion.
Nausea/Vomiting
Grade 1-2
Maintain dose level of encorafenib and binimetinib. 
Promptly institute antiemetic measure.
Grade 3
Interrupt dosing of encorafenib and binimetinib until 
resolved to Grade ≤1. Resume treatment at 1 reduced 
dose level of encorafenib. Resume treatment with 
binimetinib at the current dose if, in the judgment of 
the investigator, the toxicity is considered to be 
unrelated to binimetinib, or at 1 reduced dose level.
Note: Interrupt dosing of encorafenib and binimetinib 
for ≥Grade 3 vomiting or Grade 3 nausea only if the 
vomiting or nausea cannot be controlled with optimal 
antiemetics (as per local practice).

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 183
Severity of Adverse Event
Dose Modifications
Grade 4
Permanently discontinue encorafenib and binimetinib.
Other Adverse Reactions (including renal, hemorrhage)
Recurrent Grade 2 or
First occurrence of any Grade 3
Withhold for up to 4 weeks.

If improves to Grade 0-1 or to 
pretreatment/baseline levels, resume at 
reduced dose.

If no improvement, permanently discontinue
encorafenib and binimetinib.
First occurrence of any Grade 4
Permanently discontinue or withhold for up to 4 
weeks.

If improves to Grade 0-1 or to 
pretreatment/baseline levels, then resume at 
a reduced dose. 

If no improvement, permanently discontinue
encorafenib and binimetinib.
Recurrent Grade 3
Consider permanently discontinuing encorafenib and 
binimetinib.
Recurrent Grade 4
Permanently discontinue encorafenib and binimetinib. 
*For adverse events that may be related to both encorafenib and binimetinib, guidance is provided for the other agent 
also.
** Refer to Section 12.6.6 for management of potential overlapping toxicities. Any adverse event suspected to be 
immune-related should be managed accordingly as in Sections 6.6 and 10.10. Consult appropriate specialist as indicated.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 184
12.10.5. Recommended Dose Modifications for Binimetinib-related* Adverse Events 
and Overlapping Toxicities with Sasanlimab**
Severity of Adverse Event
Dose Modifications
Cardiomyopathy
Asymptomatic, absolute decrease in LVEF of >10% 
from baseline that is also below the LLN
Withhold binimetinib for up to 4 weeks, evaluate 
LVEF every 2 weeks.
Resume binimetinib at a reduced dose if the 
following are present:

LVEF is at or above the LLN and

Absolute decrease from baseline is 10% or 
less and

Participant is asymptomatic.
If LVEF does not recover within 4 weeks 
permanently discontinue binimetinib.
Consult cardiologist to rule out immune-related 
myocarditis, see Section 10.10.
Grade 3-4 (Symptomatic congestive heart failure or 
absolute decrease in LVEF of >20% from baseline 
that is also below LLN)
Permanently discontinue binimetinib. Closely 
monitor LVEF until resolution or up to 16 weeks.
Consult cardiologist to rule out immune-related 
myocarditis, see Section 10.10.
Venous Thromboembolism
Uncomplicated DVT or PE
Withhold binimetinib.

If improves to Grade 0-1, resume at a 
reduced dose.

If no improvement, permanently discontinue 
binimetinib.
Life threatening PE
Permanently discontinue binimetinib.
Serous Retinopathy
Symptomatic serous retinopathy/
Retinal pigment epithelial detachments
Withhold binimetinib for up to 10 days.

If improves and becomes asymptomatic, 
resume at the same dose.

If not improved, resume at a lower dose 
level or permanently discontinue 
binimetinib.
Retinal Vein Occlusion (RVO)
Any Grade
Permanently discontinue binimetinib.
Uveitis
Grade 1-3
Consult ophthalmologist. Treat with topical steroids 
such as 1% prednisolone acetate suspension and 
iridocyclitics as appropriate.
If considered to be immune-related AE, 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 185
Severity of Adverse Event
Dose Modifications
Grade 1: continue sasanlimab.
Grade 2: hold sasanlimab with treatment guided by 
ophthalmologist with or without systemic 
corticosteroids.
Grade 3: permanently discontinue sasanlimab with 
treatment guided by ophthalmologist on systemic 
corticosteroids.
If Grade 1 or 2 considered to be binimetinib related 
and does not respond to specific ocular therapy, or for 
Grade 3 uveitis, withhold binimetinib and encorafenib 
for up to 6 weeks.

If improved, resume at same or reduced 
dose.

If not improved, permanently discontinue 
binimetinib.
Grade 4 
Permanently discontinue binimetinib and sasanlimab.
Other Eye Disorders (ie, Non-retinal Events, non-Uveitis Events
Grade 1-2
Maintain dose level of encorafenib and binimetinib 
and increase frequency of ophthalmic monitoring to 
at least every 14 days until stabilization or resolution.
If considered irAE, refer to Uveitis management 
above.
Grade 3
Interrupt dosing of encorafenib and binimetinib and 
refer participant to ophthalmologist within 7 days.

If resolved to Grade ≤1 in ≤21 days, resume 
treatment at 1 reduced dose level of 
encorafenib and binimetinib.

If not resolved to Grade ≤1 in ≤21 days, 
permanently discontinue encorafenib and 
binimetinib and close follow-up with 
ophthalmic monitoring until stabilization or 
resolution.
If considered irAE, refer to Uveitis management 
above.
Grade 4
Permanently discontinue sasanlimab, encorafenib, 
and binimetinib and immediate follow-up with 
ophthalmic monitoring until stabilization or 
resolution.
Interstitial Lung Disease
Grade 1
Consider withholding sasanlimab if considered irAE, 
see Section 10.10.
Grade 2
Withhold binimetinib for up to 4 weeks.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 186
Severity of Adverse Event
Dose Modifications

If improved to Grade 0-1, resume at a 
reduced dose.

If not resolved within 4 weeks, permanently 
discontinue.
Withhold Sasanlimab if considered irAE, see 
Section 10.10.
Grade 3 or Grade 4
Permanently discontinue binimetinib and sasanlimab.  
See Section 10.10 if considered irAE.
Hepatotoxicity
Grade 2 AST or ALT increased
Maintain binimetinib dose.

If no improvement within 2 weeks, withhold 
binimetinib until improved to Grade 0-1 or 
to pretreatment/baseline levels and then 
resume at the same dose.
Refer to Sections 6.6 and 10.10 if considered irAE.
Grade 3 or 4 AST or ALT increased
See Other Adverse Reactions in this table for 
guidance on encorafenib and binimetinib.  
Permanently discontinue sasanlimab. 
See Sections 6.6 and 10.10 for irAE.
Rhabdomyolysis or Creatine Phosphokinase (CPK) elevations
Grade 4 asymptomatic CPK elevation or
Any Grade CPK elevation with symptoms or with 
renal impairment
Withhold binimetinib dose for up to 4 weeks.

If improved to Grade 0-1 resume at a 
reduced dose.

If not resolved within 4 weeks, permanently 
discontinue binimetinib.
Dermatologic 
Grade 2
If no improvement within 2 weeks, withhold until 
Grade 0-1. Resume at same dose if first occurrence or 
reduce dose if recurrent.
Grade 3
Withhold until Grade 0-1. Resume at same dose if 
first occurrence or reduce dose if recurrent.
Grade 4
Permanently discontinue binimetinib and encorafenib.
Nausea/Vomiting
Grade 1-2
Maintain dose level of encorafenib and binimetinib. 
Promptly institute antiemetic measure.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 187
Severity of Adverse Event
Dose Modifications
Grade 3
Interrupt dosing of encorafenib and binimetinib until 
resolved to Grade ≤1. Then resume treatment at 
1 reduced dose level of encorafenib. Resume 
treatment with binimetinib at the current dose if, in 
the judgment of the investigator, the toxicity is 
considered to be unrelated to binimetinib, or at 1 
reduced dose level.
Note: Interrupt dosing of encorafenib and binimetinib 
for ≥Grade 3 vomiting or Grade 3 nausea only if the 
vomiting or nausea cannot be controlled with optimal 
antiemetics (as per local practice).
If unresolved permanently discontinue binimetinib 
and encorafenib.
Grade 4
Permanently discontinue binimetinib and encorafenib.
Other Adverse Reactions.  Refer to Sections 6.6
and 10.10 if considered irAE
Recurrent Grade 2 or 
First occurrence of any Grade 3
Withhold for up to 4 weeks.

If improves to Grade 0-1 or to 
pretreatment/baseline levels, resume at 
reduced dose.

If no improvement, permanently discontinue 
binimetinib and encorafenib.
First occurrence of any Grade 4
Permanently discontinue or withhold for up to 4 
weeks.

If improves to Grade 0-1 or to 
pretreatment/baseline levels, then resume at 
a reduced dose. 

If no improvement, permanently discontinue 
binimetinib and encorafenib.
Recurrent Grade 3
Consider permanently discontinuing binimetinib and 
encorafenib.
Recurrent Grade 4
Permanently discontinue binimetinib and encorafenib.
*For adverse events that may be related to both binimetinib and encorafenib, guidance is provided for the 
other agent also.
** Refer to Section 12.6.6 for management of potential overlapping toxicities. Any adverse event suspected 
to be immune-related should be managed accordingly as in Sections 6.6 and 10.10.  Consult appropriate 
specialist as indicated.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 188
12.10.6. Detailed Dose Escalation /De-escalation Scheme for BLRM Design for 
Sasanlimab + Encorafenib + Binimetinib
This section provides the details of the statistical model, the derivation of prior distributions 
from historical data, 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 for the encorafenib, binimetinib, and sasanlimab triplet combination.
Statistical Model
The statistical model for combination dose-DLT data comprises single-agent toxicity parts, 
and interaction parts. The single-agent toxicity parts allow the incorporation of single-agent 
toxicity data
Single-Agent Parts 
Let ߨଵሺ݀ଵሻbe the risk of DLT for encorafenib given as a single agent at dose ݀ଵ; ߨଶሺ݀ଶሻbe 
the risk of DLT for binimetinib given as a single agent at dose ݀ଶ; and ߨଷሺ݀ଷሻbe the risk of 
DLT for sasanlimab given as a single agent at dose ݀ଷ.  These single agent dose-DLT models 
are 2 parameter logistic regression models:
encorafenib:
logit൫ߨଵሺ݀ଵሻ൯ൌlogሺߙଵሻ൅ߚଵlogሺ݀ଵ݀ଵ
∗
⁄
ሻ
binimetinib:
logit൫ߨଶሺ݀ଶሻ൯ൌlogሺߙଶሻ൅ߚଶlogሺ݀ଶ݀ଶ
∗
⁄
ሻ
sasanlimab:
logit൫ߨଷሺ݀ଷሻ൯ൌlogሺߙଷሻ൅ߚଷlogሺ݀ଷ݀ଷ
∗
⁄
ሻ
where ݀ଵ
∗=450 mg, ݀ଶ
∗=45 mg, and ݀ଷ
∗ൌ300 mg are used to scale the doses of encorafenib, 
binimetinib, and sasanlimab, respectively.  Hence, ߙଵ, ߙଶ, and ߙଷ(all >0) are the single-
agent odds of a DLT at ݀ଵ
∗mg, ݀ଶ
∗mg, and ݀ଷ
∗mg, respectively; and  ߚଵ, ߚଶ, and ߚଷ(all >0) 
are the increase in the log-odds of a DLT by a unit increase in log-dose.
Interaction Parts
Under an assumption that there is no interaction, the risk of a DLT at dose ݀ଵof encorafenib, 
dose ݀ଶof binimetinib, and dose ݀ଷof sasanlimab is:
ߨଵଶଷ
଴ሺ݀ଵ, ݀ଶ, ݀ଷሻൌ1 െ൫1 െߨଵሺ݀ଵሻ൯൫1 െߨଶሺ݀ଶሻ൯൫1 െߨଷሺ݀ଷሻ൯
To model the interaction between encorafenib, binimetinib, and sasanlimab, the following 
4 odds multipliers are introduced.
ߟଵଶ: 2-way interaction between encorafenib and binimetinib 
ߟଵଷ: 2-way interaction between encorafenib and sasanlimab
ߟଶଷ: 2-way interaction between binimetinib and sasanlimab

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 189
ߟଵଶଷ: 3-way interaction between encorafenib, binimetinib, and sasanlimab
The risk of DLT for combination dose ሺ݀ଵ, ݀ଶ, ݀ଷሻis then given by:
odds൫ߨଵଶଷሺ݀ଵ, ݀ଶ, ݀ଷሻ൯ൌ݃ሺߟଵଶ, ߟଵଷ, ߟଶଷ, ߟଵଶଷሻൈodds൫ߨଵଶଷ
଴ሺ݀ଵ, ݀ଶ, ݀ଷሻ൯
݃ሺߟଵଶ, ߟଵଷ, ߟଶଷ, ߟଵଶଷሻൌexpሺߟଵଶൈ݀ଵ݀ଵ
∗
⁄
ൈ݀ଶ݀ଶ
∗
⁄
ሻ
                                                                ൈexpሺߟଵଷൈ݀ଵ݀ଵ
∗
⁄
ൈ݀ଷ݀ଷ
∗ሻ
⁄
                                                                ൈexpሺߟଶଷൈ݀ଶ݀ଶ
∗
⁄
ൈ݀ଷ݀ଷ
∗ሻ
⁄
                                                              ൈexpሺߟଵଶଷൈ݀ଵ݀ଵ
∗
⁄
ൈ݀ଶ݀ଶ
∗
⁄
ൈ݀ଷ݀ଷ
∗
⁄
ሻ
where oddsሺߨሻൌߨሺ1 െߨሻ
⁄
; ߟ௜௝is the log-odds ratio between the interaction and no 
interaction model at the reference doses of drug i and j and a zero dose of the third drug.  For 
example, ߟଶଷis the log-odds ratio between the interaction and no interaction model at 
encorafenib = 0 mg, binimetinib = 45 mg and sasanlimab = 300 mg.  Therefore, ߟଵଶ൅ߟଵଷ൅
ߟଶଷ൅ߟଵଶଷis the log-odds ratio between the interaction and no interaction model at the 
reference doses for all 3 drugs.  Here ߟൌ0 corresponds to no interaction, with ߟ൐0 and 
ߟ൏0 representing synergistic and antagonistic toxicity, respectively.
Inclusion of the Doublet Data
Based on the preliminary data from the Phase 1b part of study CMEK162X2110, a total 
47 participants were enrolled at the starting dose level of 45 mg for binimetinib in 
combination with escalating doses of encorafenib (ranging from 50 mg to 800 mg).  Forty-
four (44) participants were DLT-evaluable.  This information from study CMEK162X2110 
was incorporated in the assessment of prior distribution of DLT, starting dose, data scenarios, 
and simulations of triplet via a direct down-weighting approach. The weight was calculated 
using the formula below assuming moderate heterogeneity between the populations included 
in the binimetinib + encorafenib doublet and triplet in terms of DLT; 
ݓൌ
1
1 ൅2߬ଶ
ߪଶܰ
where, N= Total number of participants enrolled in the CMEK162X2110 (N=44) 
            σ = population standard deviation (σ =2)
            τ = heterogeneity between populations in the CMEK162X2110 and current trial (τ
                  =0.25)
Prior Specifications
The Bayesian approach requires the specification of prior distributions for all model 
parameters, which include the single agent parameters logሺߙଵሻ, logሺߚଵሻfor ecorafenib, 
logሺߙଶሻ, logሺߚଶሻfor binimetinib, logሺߙଷሻ, logሺߚଷሻfor sasanlimab, and the interaction 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 190
parameters ߟൌሺߟଵଶ, ߟଵଷ, ߟଶଷ, ߟଵଶଷሻ.  A meta-analytic-predictive (MAP) approach was used 
to derive the prior distribution for the single-agent model parameters. 
Prior Distribution for the Logistic Parameters for Single Agent
This section illustrates the derivation of prior distributions for single agent model parameters 
(logሺߙ௦ሻ, logሺߚ௦ሻ)’s using the available single agent dose-DLT information via a MAP 
approach.
Description of the Meta-Analytic-Predictive Approach
The aim of the MAP approach is to derive a prior distribution for the logistic parameters 
൫logሺߙ∗ሻ, logሺߚ∗ሻ൯of the new trial using DLT data from historical studies.  Let ݎௗ௦and ݊ௗ௦
be the number of participants with a DLT, and the total number of participants at dose ݀in 
historical trial ݏ(ݏൌ1, … , 〈ܵ〉).  The corresponding probability of a DLT is ߨௗ௦.  The model 
specifications are as follows:
ݎௗ௦| ߨௗ௦~ Binomialሺߨௗ௦, ݊ௗ௦ሻ
logitሺߨௗ௦ሻൌlogሺߙ௦ሻ൅ߚ௦logሺ݀/݀∗ሻ
൫݈݋݃ሺߙ௦ሻ, ݈݋݃ሺߚ௦ሻ൯หߤ, ߰௚ሺ௦ሻ~ Bivariate Normal ሺBVNሻ൫ߤ, ߰௚ሺ௦ሻ൯,
s ൌ1, … , 〈ܵ〉
൫݈݋݃ሺߙ∗ሻ, ݈݋݃ሺߚ∗ሻ൯หߤ, ߰௚ሺ∗ሻ~ BVN൫ߤ, ߰௚ሺ∗ሻ൯
The historical trials are partitioned into 〈ܩ〉exchangeability groups, with the exchangeability 
group membership of historical trial ݏbeing represented by ݃ሺݏሻ.  The new trial is assigned 
to exchangeability group ݃ሺ∗ሻ.  The parameter ߤൌሺߤଵ, ߤଶሻ  is the mean for the logistic 
parameters, and ߰௚is the between-trial covariance matrix for exchangeability group ݃ൌ
1, … , 〈ܩ〉.  Covariance matrix ߰௚is defined by the standard deviations ሺݐ௚ଵ, ݐ௚ଶሻ, and 
correlation ݎ(a common value for ݎis used across all groups).  The parameters ݐ௚ଵand ݐ௚ଶ
quantify the degree of between trial heterogeneity for exchangeability group ݃.  With 
different prior distributions for the parameter sets ൫ݐ௚ଵ, ݐ௚ଶ൯it is possible to allow for 
differential discounting for the historical strata.  In this way the quality and relevance of 
historical data can be accounted for in the meta-analysis.  The following priors will be used 
for these parameters:  
normal priors for ߤଵand ߤଶ, 
log-normal priors for ݐ௚ଵand ݐ௚ଶ, and 
uniform prior for ݎ.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 191
The MAP prior for single-agent model parameters in the new trial, ൫݈݋݃ሺߙ∗ሻ, ݈݋݃ሺߚ∗ሻ൯, is the 
predictive distribution 
൫݈݋݃ሺߙ∗ሻ, ݈݋݃ሺߚ∗ሻ൯หሺݎௗ௦, ݊ௗ௦∶ݏൌ1, … , 〈ܵ〉ሻ
Since the predictive distribution is not available analytically, the Markov chain Monte Carlo 
(MCMC) method is used to simulate values from this distribution.  This is implemented 
using Just Another Gibbs Sampler (JAGS) version 4.8.
Single-Agent Encorafenib
Dose-DLT data from the encorafenib IB (Edition 10) from Study CLGX818X2101 as 
presented in Table 12 are used to derive the prior of the single agent logistic parameters for 
encorafenib.
Table 12.
Historical Dose Limiting Toxicity data from study CLGX818X2101
Encorafenib Dose (mg; QD)
Number of Participants
Number of Participants with 
DLTs
50
4
0
100
9
1
150
6
0
200
3
0
300
5 (escalation); 14 (expansion)
1(escalation); 2 (expansion)
450
6 (escalation); 27 (expansion)
0 (escalation); 9(expansion)
550
4
1
700
2
2
Weakly informative normal priors are assumed for ߤଵ௘and ߤଶ௘, with means corresponding to 
a 50% chance of DLT at encorafenib = 450 mg and a doubling in dose leading to a doubling 
in the odds of the risk of a DLT, respectively.  Priors for ݐଵ௘and ݐଶ௧௘are assigned such that 
(1) their medians correspond to moderate to large between trial heterogeneity, and (2) their 
uncertainty (95% prior interval) cover plausible between-trial standard deviations 
(Table 13).37
Table 13.
Prior Distributions for the Parameters of the MAP Model Used to Derive 
the Prior for the Single-Agent Encorafenib Model Parameters
Parameter
Prior Distribution
ߤଵ௘
N (mean = 0, sd = 2)
ߤଶ௘
N (mean = 0, sd = 1)
ݐଵ௘
log-normal (mean = log (0.50), sd = log (2)/1.96)
ݐଶ௘
log-normal (mean = log (0.25), sd = log (2)/1.96)
ݎ௘
Uniform (-1,1)

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 192
Single-Agent Binimetinib
Dose-DLT data in the binimetinib IB (Edition 16) from studies ARRAY-162-111 and 
CMEK162X1101 as presented in Table 14 are used to derive the prior of the single agent 
logistic parameters for binimetinib.
Table 14.
Historical Dose Limiting Toxicity Data from Study Array-162-111 and 
Study CMEK162X1101
Study Array-162-111
Study CMEK162X1101
Binimetinib dose 
(mg BID)
Number of 
Participants
Number of 
Participants with 
DLTs
Number of 
Participants
Number of 
Participants with 
DLTs
30
3
0
6
0
45
43
2
15
2
60
40
2
80
3
2
Weakly informative normal priors are assumed for ߤଵ௕and ߤଶ௕, with means corresponding to 
a 50% chance of DLT at binimetinib = 45 mg, and a doubling in dose leading to a doubling 
in the odds of the risk of a DLT, respectively.  The priors for between-trial heterogeneity 
parameters are set in the following way:
•
Priors for ݐଵଵ௕and ݐଵଶ௕(ARRAY-162-111) are assigned such that (1) their medians 
correspond to moderate between-trial heterogeneity, and (2) their uncertainty (95% 
prior interval) cover plausible between-trial standard deviations.
•
Priors for ݐଶଵ௕and ݐଶଶ௕(CMEK162X1101) are assigned such that (1) their medians 
correspond to large between-trial heterogeneity, and (2) their uncertainty (95% prior 
interval) cover plausible between-trial standard deviations.
Study ARRAY-162-111 is a Phase 1 study conducted in advanced or metastatic cancer 
participants the US.  Study CMEK162X1101 is a study in Japanese participants with 
advanced solid tumors whose disease has progressed despite standard therapy or for whom 
no standard therapy exists.  The participant population in Study CMEK162X1101 is less 
similar to Study B8011011 and hence large between trial heterogeneity is assumed.
Table 15.
Prior Distributions for the Parameters of the MAP Model Used to Derive 
the Prior for the Single-Agent Binimetinib Model Parameters
Parameter
Prior Distribution
ߤଵ௕
N (mean = 0, sd = 2)
ߤଶ௕
N (mean = 0, sd=1)
ݐଵଵ௕
log-normal (mean = log (0.25), sd = log (2)/1.96)
ݐଵଶ௕
log-normal (mean = log (0.125), sd = log (2)/1.96)
ݐଶଵ௕
log-normal (mean = log (1), sd = log (2)/1.96)
ݐଶଶ௕
log-normal (mean = log (0.5), sd = log (2)/1.96)
ݎ௕
Uniform (-1,1)

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 193
Table 15.
Prior Distributions for the Parameters of the MAP Model Used to Derive 
the Prior for the Single-Agent Binimetinib Model Parameters
Parameter
Prior Distribution
(ݐଵଵ௕,ݐଵଶ௕) = the degree of between trial heterogeneity for Study ARRAY-162-111; (ݐଶଵ௕
,ݐଶଶ௕) = the degree of between-trial heterogeneity for Study CMEK162X1101.
Single Agent PF-06801591
Dose-DLT data from study B8011001 presented in Table 16 are used to derive the prior of 
the single agent logistic parameters for sasanlimab.
Table 16.
Historical Dose Limiting Toxicity data from Study B8011001
Sasanlimab Dose (mg/once per 
cycle)
Number of Participants
Number of Participants with 
DLTs
300
15
0
Weakly informative normal priors are assumed for ߤଵ௣and ߤଶ௣, with means corresponding to 
a 50% chance of DLT at sasanlimab = 300mg, and a doubling in dose leading to a doubling 
in the odds of the risk of a DLT, respectively. Priors for ݐଵ௣and ݐଶ௣are assigned such that (1) 
their medians correspond to moderate between trial heterogeneity, and (2) their uncertainty 
(95% prior interval) cover plausible between-trial standard deviations (Table 17).37
Table 17.
Prior Distributions for the Parameters of the MAP Model Used to Derive 
the Prior for the Single-Agent Sasanlimab Model Parameters
Parameter
Prior Distribution
ߤଵ௣
N (mean = 0, sd = 2)
ߤଶ௣
N (mean = 0, sd=1)
ݐଵ௣
log-normal (mean = log (0.25), sd = log (2)/1.96)
ݐଶ௣
log-normal (mean = log (0.125), sd = log (2)/1.96)
ݎ௣
Uniform (-1,1)
N=normally distributed; sd=standard deviation.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 194
Prior Distribution for the Interaction Parameters
Normal priors for the log-odds multipliers ߟଵଶ, ߟଵଷ, ߟଶଷ, ߟଵଶଷ  are used.  The prior for 
ߟଵଶ, ߟଵଷ, ߟଶଷ, ߟଵଶଷare specified as percentiles of increase in the odds of DLT due to possible 
interaction in combination therapy at reference doses;
ߟଵଶis normally distributed, with mean -0.198 and standard deviation 0.101 (corresponds to 
20% decrease in DLT odds at median and no increase in DLTs at 97.5th percentile)
ߟଵଷis normally distributed, with mean 0 and standard deviation 0.467 (corresponds to no 
increase in DLT odds at median and 2.5-fold increase in DLTs at 97.5th percentile)
ߟଶଷis normally distributed, with mean 0 and standard deviation 0.467 (corresponds to no 
increase in DLT odds at median and 2.5-fold increase in DLTs at 97.5th percentile)
ߟଵଶଷis normally distributed, with mean 0 and standard deviation 0.354 (corresponds to no 
increase in DLT odds at median and 2-fold increase in DLTs at 97.5th percentile).
ߟଵଶ:  2-way interaction between encorafenib and binimetinib;
ߟଵଷ:   2-way interaction between encorafenib and sasanlimab;
ߟଶଷ:   2-way interaction between binimetinib and sasanlimab;
ߟଵଶଷ: 3-way interaction among encorafenib, binimetinib, and sasanlimab.
Summary of Prior Distributions 
The prior distributions of the model parameters are provided in Table 18. 
Table 18.
Prior Distribution for the Model Parameters
Parameter
Mean
Standard Deviations
Correlation
Encorafenib single agent parameters: BVN MAP Prior
൫logሺߙଵሻ, logሺߚଵሻ൯
-0.904, 0.268 
0.822, 0.630
0.117
Binimetinib single agent parameters: BVN MAP Prior
൫logሺߙଶሻ, logሺߚଶሻ൯
-2.785, 0.376
0.596, 0.860
-0.330
Sasanlimab single agent parameters: BVN MAP Prior
൫logሺߙଷሻ, logሺߚଷሻ൯
-3.247, -0.0135 
1.165, 1.009
0.00001
Interaction parameters: Normal prior
ߟଵଶ
-0.198
0.101
ߟଵଷ
0
0.467
ߟଶଷ
0
0.467
ߟଵଶଷ
0
0.354
ߟଵଶ: 2-way interaction between encorafenib and binimetinib;
ߟଵଷ: 2-way interaction between encorafenib and sasanlimab;
ߟଶଷ: 2-way interaction between binimetinib and sasanlimab;
ߟଵଶଷ: 3-way interaction between encorafenib and binimetinib and sasanlimab.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 195
From Table 19, encorafenib = 300 mg (QD), binimetinib = 45 mg (BID), and 
sasanlimab = 300 mg once per cycle is an acceptable starting dose for this triple combination.  
Table 19.
Summary of Prior Distribution of DLT Rates for the Triplet Combination 
of Encorafenib in Combination with Binimetinib and Sasanlimab
Encorafenib 
(mg QD)
Binimetinib 
(mg BID)
Prior probabilities that DLT 
rate is in the interval:
Mean
SD
Quantiles
[0, 
0.16)
[0.16, 
0.33)
[0.33,1]
2.5%
50%
97.5%
300
30
0.5815
0.3482
0.0704
0.1645
0.101
0.039
0.141
0.424
300
45
0.5176
0.3723
0.1101
0.1829
0.116
0.039
0.155
0.479
450
30
0.4429
0.4072
0.1499
0.2037
0.124
0.043
0.176
0.515
450
45
0.4246
0.3840
0.1915
0.2172
0.141
0.038
0.184
0.570
Sasanlimab dose fixed at 300 mg per cycle.
Hypothetical On-Study Data Scenarios
To illustrate the performance of the Bayesian model used to guide dose finding, hypothetical 
dose finding scenarios following the provisional dose levels specified in the protocol are 
displayed.  In each case, the possible recommended dose that can be used in the next cohort 
of participants is shown.  These recommended doses are determined using the model-based 
assessment of the risk of DLT in future participants, EWOC criteria and maximum amount of 
escalation allows (100% of current dose).  In practice, the dose recommended by the 
proposed model may be regarded as guidance.  The final recommendation will be based on 
overall safety profile and PK data.
Table 20 shows data scenarios for the triplet combination and the corresponding 
recommendations for the next dose.
Table 20.
Next Dose Recommendation and the Interval probability of Target 
Toxicity and Overdosing at Next Dose
Dose Tested 
(first 2 dose cohorts)
D/N*
Next Dose options
Pr(TT) 
at ND
Pr(OD) 
at ND
Scenario
Enco 
(mg 
QD)
Bini 
(mg 
BID)
Sasanlimab
(mg once 
per cycle)
Enco 
(mg
QD)
Bini 
(mg 
BID)
Sasanlimab 
(mg once 
per cycle)
1
300
450
45
45
300
300
0/3
1/3
450
300
45
45
300
300
0.462
0.409
0.124
0.047
2
300
300
45
45
300
300
1/3
0/3
450
300
45
45
300
300
0.449
0.420
0.137
0.056
3
300
300
45
30
300
300
2/3
0/3
300
300
45
30
300
300
0.544
0.541
0.199
0.110
4
300
300
45
45
300
300
1/3
1/3
300
300
45
30
300
300
0.538
0.542
0.177
0.105
5
300
300
45
30
300
300
2/3
1/4
300
30
300
0.597
0.211

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 196
Table 20.
Next Dose Recommendation and the Interval probability of Target 
Toxicity and Overdosing at Next Dose
Dose Tested 
(first 2 dose cohorts)
D/N*
Next Dose options
Pr(TT) 
at ND
Pr(OD) 
at ND
Scenario
Enco 
(mg 
QD)
Bini 
(mg 
BID)
Sasanlimab
(mg once 
per cycle)
Enco 
(mg
QD)
Bini 
(mg 
BID)
Sasanlimab 
(mg once 
per cycle)
Operating Characteristics 
A simulation study is used to illustrate the properties of the dose finding model guided by 
BLRM.  Several example scenarios were investigated and each scenario 1000 trials were 
simulated, with results summarized below.
Simulation Scenarios 
Several scenarios are considered for the triplet (Table 21).  Scenario 1 represents the case 
when the distribution of DLT coincides with prior, ie, the true DLT probability equals to 
mean of prior DLT.  Scenario 2 represents an over and under dosing. Scenario 3 represents 
under dosing and target dosing.
Table 21.
Combination A: Dose Limiting Toxicity Rate Scenarios (Fixed Sasanlimab 
Dose 300 mg Once Per Cycle)
Encorafenib 
(mg; QD)
Binimetinib (mg; BID)
30
45
30
45
Scenario 1. Prior Means
Scenario 2. Under-Dose and Over-Dose
300
0.164
0.183
0.100
0.183
450
0.204
0.217
0.297
0.484
Scenario 2. Under-Dose and Target 
Dose
300
0.10
0.12
450
0.201
0.297
Simulation Details 
Simulations were performed using R version 3.6.1 (The R-project for Statistical Computing.  
https://www.r-project.org/), and JAGS 4.0 to perform the Markov Chain Monte Carlo 
(MCMC) analyses. 
For each scenario, data for 1000 trials were generated, with a cohort size of 3.  At any time 
during the course of dose finding, escalation to doses where the risk of overdose exceeds 
25% is not permitted.  The ‘next dose recommendation’ is the dose with maximum 
probability of overdose among all dose levels that meet the EWOC criteria.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 197
A simulation of dose-escalation is performed using the starting dose of sasanlimab 300 mg, 
binimetinib 45 mg, and encorafenib 300 mg.  CMEK162X2110 doublet data is considered in 
this exercise.  The maximum number of participants per trial was set to 30.  Each trial was 
stopped when the following criteria were met:
•
At least 6 participants have been treated at the recommended MTD ݀ሚ. 
•
The dose ݀ሚsatisfies 1 of the following conditions:
•
The probability of target toxicity at dose ݀ሚexceeds 50%, ie, Pr (0.16 ≤ߨௗ෨<0.33) ≥50%;
•
A minimum of 12 participants have been treated in the trial.
The following metrics were assessed in the simulations:
•
Percentage of participants receiving dose combination(s) in the target toxicity 
interval; 
•
Percentage of participants receiving an overdose;
•
Percentage of participants receiving an under dose;
•
Probability that recommended MTD at the end of the trial is in the target toxicity 
interval;
•
Probability that recommended MTD is an overdose;
•
Probability that recommended MTD is an under dose;
•
Percentage of trials stopped without MTD declaration;
•
Average sample size.
Simulation Results 
Operating characteristics for triplet dose escalation are presented in Table 22.  The 
percentage of trials with a correctly identified MTD ranges from 92.1% to 96.1%.  The 
average sample size was approximately 9 participants for all scenarios.
Table 22.
Combination A: Operating Characteristics
Scenarios
Participant allocation 
(%)
Pr (declare MTD)
(%)
% stop 
(no 
MTD)
Average 
sample 
size
TT
OD
UD
TT
OD
UD
Prior means
100
0
0
92.1
0
0
8.0
8.5
With under dose 
and overdose
81.1
18.9
0
92.1
0
0
8.0
8.5

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 198
Table 22.
Combination A: Operating Characteristics
Scenarios
Participant allocation 
(%)
Pr (declare MTD)
(%)
% stop 
(no 
MTD)
Average 
sample 
size
TT
OD
UD
TT
OD
UD
With under dose 
and target dose
64.0
0
35.9
96.1
0
0
3.9
8.8

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 199
13. APPENDIX B: SUB-STUDY B: SASANLIMAB + AXITINIB + SEA-TGT
13.1. Schedule of Activities (SoA): Sub-Study B
The SoA table provides an overview of the sub-study visits and procedures.  Refer to 
Section 8 of the master protocol and Section 13.8 of this sub-study appendix for detailed 
information on each procedure and assessment required for compliance with the protocol. 
The investigator may schedule unplanned visits in addition to those listed in the SoA table, in 
order to conduct evaluations or assessments required to protect the well-being of the 
participant, or if otherwise clinically indicated.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 200
Table 23.
Schedule of Activities Sub-Study B Phase 1b & Phase 2
Visit Identifiera
Pre-
Scree
ningb
Scree
ningb
(≤28
days 
prior 
to 
first 
dose)
Treatment Period
Follow-Upd
Cycle 1 
(Days 1 to 21)
Cycle 2 
(Days 1 to 21)
Cycles 3 & 4 
(Days 1 to 
21) 
Cycle 5 (Days 1 
to 21)
Cycles ≥ 6 
(Days 1 to 
21)
Day 1
Day 8
Day 1 Day 8
Day 1
Day 1
Day 8
Day 1
EOTc Day 30d
Days 
60, 90, & 
180d
Survivald
Visit Window
±1
±2
±2
±2
±2
±2
±2
±7
±7
±7
Informed consente
X
X
Eligibility review
X
X
X
Tumor and medical historyf
X
Substance and tobacco use
X
X
Physical examinationg
X
X
X
X
X
X
X
X
X
Height
X
Weight
X
X
X
X
X
X
X
In-clinic Vital signsh
X
X
X
X
X
X
X
X
X
X
Home Blood Pressure Monitoringi
(continuous starting C1D1)
ECHO/MUGAj
X
X
ECOG performance statusk
X
X
Triplicate 12-lead ECGl
X
Single 12-lead ECGl
X
X
X
X
X
X
X
X
Laboratory Assessments of 
Hematology and Blood 
Chemistrym
X
X
X
X
X
X
X
X
X
X
X
Coagulationm
X
X
X
X
X
X
X
X
Urinalysisn
X
X
X
X
X
X
X
X
X
X
X
Pregnancy testo
X
X
X
X
X
X
X
X
X
Hepatitis B, C testsp
X
Endocrinology testsm
X
Every 4 cycles starting at C4D1
Allocation to study interventionq
X
Dispensing of axitinib
X
X
X
X
X

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 201
Table 23.
Schedule of Activities Sub-Study B Phase 1b & Phase 2
Visit Identifiera
Pre-
Scree
ningb
Scree
ningb
(≤28
days 
prior 
to 
first 
dose)
Treatment Period
Follow-Upd
Cycle 1 
(Days 1 to 21)
Cycle 2 
(Days 1 to 21)
Cycles 3 & 4 
(Days 1 to 
21) 
Cycle 5 (Days 1 
to 21)
Cycles ≥ 6 
(Days 1 to 
21)
Day 1
Day 8
Day 1 Day 8
Day 1
Day 1
Day 8
Day 1
EOTc Day 30d
Days 
60, 90, & 
180d
Survivald
Administration of study treatment 
sasanlimabr
X
X
X
X
X
Administration of study treatment 
SEA-TGTs
X
X
X
X
X
Administration of study treatment 
axitinibt
Continuous BID starting C1D1
Local site injection tolerability 
assessmentu
X
X
X
X
X
Tumor assessmentv
X
Every 6 wks (±7 days) from C1D1 for the first 12 months, then every 12 wks (±7 days) thereafter according to calendar, 
regardless of treatment delays and until progressive disease assessed by investigator using RECIST v1.1 or start of new anti-
cancer therapy
Nonserious and serious adverse 
eventsw
X












Prior and Concomitant 
medication/surgery/ radiation & 
non-drug supportive 
interventionsx
X
X
X
X
X
X
X
X
X
X
Survival & subsequent anti-cancer 
therapy
X
X
X
X
Contraception checky
X
X
X
X
X
X
X
X
X
Remote visit
X
X
X
PK for sasanlimabz
X
X
X 
X
X
X
X (C7, 
C10, C13, 
C16, then 
every 6
cycles)

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 202
Table 23.
Schedule of Activities Sub-Study B Phase 1b & Phase 2
Visit Identifiera
Pre-
Scree
ningb
Scree
ningb
(≤28
days 
prior 
to 
first 
dose)
Treatment Period
Follow-Upd
Cycle 1 
(Days 1 to 21)
Cycle 2 
(Days 1 to 21)
Cycles 3 & 4 
(Days 1 to 
21) 
Cycle 5 (Days 1 
to 21)
Cycles ≥ 6 
(Days 1 to 
21)
Day 1
Day 8
Day 1 Day 8
Day 1
Day 1
Day 8
Day 1
EOTc Day 30d
Days 
60, 90, & 
180d
Survivald
PK for SEA-TGTaa
X
X
X
X
X
X
X
(C7, C10, 
C13, C16, 
then every 
6 cycles)
PK for axitinibbb
X
X
X 
X
X
X
Baseline tumor biospecimencc
X
Biobanked biospecimen for 
geneticsdd
X
Blood for cell-free (cf) DNA 
analysisee
X
X 
X (C4 only)
X
Blood for specified genetic 
researchff
X
X
X
X 
Blood for T-Cell Receptor (TCR) 
analysisii
X
X
X
X 
Immunogenicity for sasanlimabjj
X
X 
X
X
X (C7, 
C10, C13, 
C16 and 
then every 
6 cycles)
X
Immunogenicity for SEA-TGTkk
X
X 
X
X
X (C7, 
C10, C13, 
C16 and 
then every 
6 cycles)
X
a.
Day relative to start of study intervention (Day 1).

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 203
Table 23.
Schedule of Activities Sub-Study B Phase 1b & Phase 2
Visit Identifiera
Pre-
Scree
ningb
Scree
ningb
(≤28
days 
prior 
to 
first 
dose)
Treatment Period
Follow-Upd
Cycle 1 
(Days 1 to 21)
Cycle 2 
(Days 1 to 21)
Cycles 3 & 4 
(Days 1 to 
21) 
Cycle 5 (Days 1 
to 21)
Cycles ≥ 6 
(Days 1 to 
21)
Day 1
Day 8
Day 1 Day 8
Day 1
Day 1
Day 8
Day 1
EOTc Day 30d
Days 
60, 90, & 
180d
Survivald
b.
The Pre-Screening period is optional and allows local PD-L1 and genetic testing to start after completion of the pre-screening consent, and before the 
Screening period.  Screening: To be performed within 28 days prior to first dose.  Visit may be conducted over multiple days.
c.
End of Treatment (EOT) Visit: Conducted at the visit that the participant is discontinued from study treatment or no longer than 1 week after the decision to 
discontinue the participant from study treatment. See Section 8.11.
d.
Follow-up:  The initial safety follow-up visit will be conducted at the study clinic 30 days after the last dose of study intervention.  The 60, 90, and 180-day 
follow-up may be conducted by remote contact (eg. telephone). See Section 8.2.8. Survival Follow-Up: Only for Phase 2. Participants will be contacted 
every 12 weeks (±7 days) after the last clinic visit until death, lost-to-follow-up, study termination, end of study, or withdrawal of consent. See Section 8.1.3. 
e.
Informed Consent: Must be obtained prior to undergoing any study specific procedures.  May be obtained more than 28 days prior to first dose.
f.
Tumor History: Includes history of disease under study including details of primary diagnosis, treatment history and staging.  Medical History: Includes 
history other than the cancer under study.  Abnormalities observed during screening are to be considered as medical history.
g.
Physical examination (PE): See Section 8.2.1.
h.
Vital Signs: Includes temperature, blood pressure, and pulse rate.  On Day 1 of each cycle, vital signs are to be measured within 60 minutes prior to 
administration of any study intervention (pre-dose), at the completion of the SEA-TGT infusion, and at the completion of the 2-hour-post-dose observation 
period (on Cycles 1, 2, 3 only).    
i.
Home BP monitoring: Participants will monitor their BP at least twice daily (before taking each dose of axitinib) and record the results in the diary. See 
Section 13.8.2.1. 
j.
ECHO/MUGA: The same modality used during screening is to be used for any subsequent assessments. Assessment will also be performed if a participant 
experiences an AE which may be related to cardiac dysfunction in the opinion of the investigator, or as otherwise clinically indicated. See Section 13.8.2.2.
k.
Eastern Cooperative Oncology Group (ECOG) Performance Status: See Section 8.2.6.
l.
Triplicate and Single 12 Lead electrocardiogram (ECG): When triplicate ECG is requested, 3 serial 12-lead ECGs will be conducted within approximately 
5-10 minutes total time.  Triplicate ECGs on C1D1 will be collected prior to administration of any study intervention.  For remaining timepoints, single ECG 
will be collected prior to administration of study intervention.  When coinciding with blood sample draws for PK, ECG assessment is to be performed prior to 
blood sample collection, such that the blood sample is collected at the nominal time. 
m. Hematology, Blood Chemistry, Endocrinology, and Coagulation tests: See Sections 10.2 and 13.10.1 for lists of Laboratory Tests.  Not necessary to 
repeat on C1D1 if performed within 7 days prior to C1D1 as part of Screening.  Subsequent assessments must be performed within 72 hours prior to the 
scheduled visit. Hematology and chemistry assessments on C2D8 may be drawn at a lab local to the participant and do not require on-site visit. See 
Section 10.2 for more details about clinical lab assessments.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 204
Table 23.
Schedule of Activities Sub-Study B Phase 1b & Phase 2
Visit Identifiera
Pre-
Scree
ningb
Scree
ningb
(≤28
days 
prior 
to 
first 
dose)
Treatment Period
Follow-Upd
Cycle 1 
(Days 1 to 21)
Cycle 2 
(Days 1 to 21)
Cycles 3 & 4 
(Days 1 to 
21) 
Cycle 5 (Days 1 
to 21)
Cycles ≥ 6 
(Days 1 to 
21)
Day 1
Day 8
Day 1 Day 8
Day 1
Day 1
Day 8
Day 1
EOTc Day 30d
Days 
60, 90, & 
180d
Survivald
n.
Urinalysis: Dipstick is acceptable.  No need to repeat on C1D1 if baseline assessment is performed within 72 hours prior to that date. Urinalysis assessments 
on C2D8 may be drawn at a lab local to the participant and do not require an on-site visit. See Section 10.2 for urinalysis details.
o.
Pregnancy Test (Serum/Urine): For female participants of childbearing potential, a serum or urine pregnancy test, with sensitivity of at least 25 mIU/mL, 
will be performed on 2 occasions prior to starting study therapy, once at screening and once at the C1D1 visit before dosing.  Participants with a confirmed 
positive pregnancy test(s) must not be dosed. Pregnancy tests will also be routinely performed throughout the study as per the SOA and additionally whenever 
1 menstrual cycle is missed or when potential pregnancy is otherwise suspected.  Additional pregnancy tests may also be performed if requested by IRB/EC or 
if required by local regulations. At the 60, 90, and 180-day remote follow-up visits, pregnancy tests may be conducted via home kits.
p.
Hepatitis B, C: In the case of apparent ongoing HBV or HCV infection, reflex serum viral load testing will be performed.
q.
Allocation: The participant allocation number will be assigned using an IRT system.  Participants can be allocated in IRT no more than 3 days prior to 
dosing. See Section 6.3.1 for more details.
r.
Study Treatment sasanlimab: Will be administered 
 
(maximum volume per injection is 2 mL). 
Sasanlimab should be administered first, followed by axitinib, and then SEA-TGT. See Section 6.1.1. 
s.
Study Treatment SEA-TGT: Will be administered once every 21 days as an IV infusion in a stepwise manner. See Section 13.6.1.2. 
t.
Study Treatment axitinib: Twice daily oral administration. See Section 13.6.1.1.
u.
Local Site Injection Tolerability Assessment: See Section 8.2.7.
v.
Tumor Assessments: Tumor response assessments will be determined in accordance with RECIST v1.1. See Section 8.1.1.
w.
Nonserious and Serious AE Assessments:  AEs and SAEs are documented and recorded at each visit using NCI CTCAE version 5.0. See Section 8.3.
x.
Concomitant Medications and Non-Drug Supportive Interventions: Includes supportive care drugs (eg, anti-emetic treatment and prophylaxis), drugs 
used to treat AEs or chronic diseases, and non-drug supportive interventions (eg, transfusions).  Reporting period for concomitant medications for AEs and 
SAEs are to follow respective AE and SAE reporting period. See Sections 6.5 and 13.6.5.
y.
Contraceptive Check:  Male participants who are able to father children and female participants who are of childbearing potential will need to affirm that 
they meet the criteria for correct use of the selected methods of contraception throughout the study and continue for 6 months after the last dose.  The 
investigator or his or her designee will discuss with the participant the need to use the appropriate contraception methods consistently and correctly and 
document such conversation in the participant’s chart.  The investigator or his or her designee will instruct the participant to call immediately if the selected 
contraception methods are discontinued, or if pregnancy is known or suspected in the participant or participant’s partner. See Section 13.10.2.
z.
PK for sasanlimab: One 3-mL blood sample will be collected for sasanlimab PK on each day indicated in the SoA. All samples taken on Day 1 of a cycle 
will be collected within 6 hours prior to dosing of sasanlimab. The PK sample may be collected anytime during the visit on sampling days that are not Day 1 
of a cycle.
CCI

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 205
Table 23.
Schedule of Activities Sub-Study B Phase 1b & Phase 2
Visit Identifiera
Pre-
Scree
ningb
Scree
ningb
(≤28
days 
prior 
to 
first 
dose)
Treatment Period
Follow-Upd
Cycle 1 
(Days 1 to 21)
Cycle 2 
(Days 1 to 21)
Cycles 3 & 4 
(Days 1 to 
21) 
Cycle 5 (Days 1 
to 21)
Cycles ≥ 6 
(Days 1 to 
21)
Day 1
Day 8
Day 1 Day 8
Day 1
Day 1
Day 8
Day 1
EOTc Day 30d
Days 
60, 90, & 
180d
Survivald
aa. PK for SEA-TGT: One 3-mL blood sample will be collected for SEA-TGT PK on each day indicated in the SoA. All samples taken on Day 1 of a Cycle will 
be collected at predose (within 6 hours prior to dosing of SEA-TGT) and End of Infusion (EOI), within 15 minutes following infusion stop. The PK sample 
may be collected anytime during the visit on sampling days that are not Day 1 of a cycle.
bb. PK for axitinib: One 3-mL blood sample will be collected for axitinib PK on each day indicated in the SoA. Samples on Day 1 of Cycle 1 and Cycle 5 will 
be collected at predose (within 2 hours prior to axitinib dose) and 3 hours post-axitinib dose. The PK sample will be collected predose (within 2 hours prior to 
axitinib dose) on all other sampling days.
cc. Baseline tumor biospecimen: Phase 2 only. A tumor tissue sample (primary or metastatic, archival or new) will be obtained by a procedure performed prior 
to Cycle 1 Day 1, except as approved by the Sponsor. The sample will be used to confirm PD-L1 status at a central lab (Section 8.8.2), and may also be used 
for specified analyses (Sections 8.7.1 and 8.8.2) or exploratory biomarker analysis (Section 8.8).
dd. Banked biospecimen for genetics: A 4-mL blood sample will be collected on Cycle 1 Day 1 prior to dosing with any study intervention and retained in a 
biobank for possible assessments of genes and other analytes (eg, proteins, RNA, nondrug metabolites), unless prohibited by local regulations or by decision 
of the institutional review board or ethics committee (Section 8.7.2).
ee. Blood for cell-free (cf) DNA Analysis: A 20-mL blood sample for preparation of plasma will be collected prior to dosing with any study intervention and at 
Day 1 of Cycles 2 and 4 for exploratory analyses as described in Section 8.7.1.
ff.
Blood for specified genetic research: A 4-mL whole blood sample will be collected prior to dosing with any study intervention and at Cycle 1 Day 1 (pre-
dose), Cycle 1 Day 8, and at Cycle 2 Day 1 (pre-dose) for exploratory genetic and epigenetic analyses as described in Section 8.7.1. 
gg.
NA.
hh.
NA.
ii.
Blood for T-Cell Receptor (TCR) Analysis: A 6-mL whole blood sample will be collected into a tube optimized for DNA preservation prior to dosing with 
any study intervention and at Cycle 1 Day 1 (pre-dose), Cycle 1 Day 8, and at Cycle 2 Day 1 (pre-dose) (Section 8.7.1).
jj.
Blood for sasanlimab Immunogenicity (anti-drug antibody [ADA] and possibly neutralizing antibodies [NAb]) Testing: All samples (6 mL each) taken 
on Day 1 of a cycle will be taken prior to dosing with any study intervention and within 6 hours prior to sasanlimab dosing. See Section 8.9.
kk. Blood for SEA-TGT Immunogenicity (anti-drug antibody [ADA] and possibly neutralizing antibodies [NAb]) Testing: All samples (5- mL each) taken 
on Day 1 of a cycle will be taken prior to dosing with any study intervention and within 6 hours prior to SEA-TGT dosing. See Section 8.9.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 206
13.2. Introduction for Sub-Study B
13.2.1. Study Rationale
See master protocol Section 2.1 for the Umbrella Study rationale and Section 13.4.3 for the 
Sub-Study B rationale.
13.2.2. Background
See the master protocol Introduction (Section 2) for background on sasanlimab.
13.2.2.1. Background for Axitinib
Axitinib (INLYTA®) is an oral, small molecule, TKI selective for VEGFRs 1, 2 and 3 and is 
approved multinationally for the treatment of advanced RCC after failure of one prior 
systemic therapy (actual indication varies according to region/country) and in combination 
with avelumab or pembrolizumab for the 1L treatment of patients with advanced RCC.
Axitinib is an ATP-competitive inhibitor that binds to the
unphosphorylated (non-activated) “DFG-out” conformation of the catalytic domain of a
receptor tyrosine kinase. In enzymatic assays, axitinib was found to be highly potent
(Ki = 28 picomolar) against the kinase activity of juxta-membrane (JM) domain containing
human VEGFR 2 recombinant protein.41 In additional kinase assays, axitinib showed potent
and ATP-competitive inhibition of the VEGFRs 1, 2, and 3 and PDGFR-β, but not other
closely-related family kinases. Receptor binding studies and cell-based assays, confirmed
that axitinib is a potent and selective inhibitor of VEGFRs 1, 2, and 3. Axitinib was shown
to have antiangiogenic activity in a number of models including spontaneous pancreatic
islet-cell tumors of RIP-TAG-2 transgenic mice model and demonstrated antitumor efficacy
including marked cytoreductive antitumor activity, in multiple tumor models implanted in
athymic mice.
13.2.2.2. Background for SEA-TGT
TIGIT is an adaptive checkpoint receptor expressed on several subsets of T-cells. TIGIT engages 
its ligands in the tumor microenvironment and decreases T-cell activity. SEA-TGT blocks this 
interaction and relieves TIGIT-mediated suppression of antitumor CD8+ T-cells, unleashing 
these cells against the tumor. Furthermore, because SEA-TGT is non-fucosylated, it binds 
FcyRIII with high affinity, resulting in depletion of cells expressing TIGIT, such as T regulatory 
cells (Tregs). Enhanced FcyRIII binding also augments activation of memory T-cells and 
generation of new antigen-specific T-cell responses. These activities increase the antitumor 
activity of SEA-TGT.
SEA-TGT may be unique in its ability to elicit effector T-cell responses; SEA-TGT treatment of 
PBMC cultures resulted in activation of innate immune cells and cytokine production. This 
suggests that SEA-TGT may activate both adaptive and innate arms of the immune system. These 
in vitro results translated to in vivo antitumor activity in the CT26 colon cancer model, where 
SEA-TGT treatment decreased intratumoral Tregs, increased total intratumoral CD8+ effector 
memory T-cells, and resulted in curative antitumor responses. These pharmacodynamic changes 
and antitumor responses were associated with the generation of antigen-specific immunity and 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 207
long-term memory T-cell responses, resulting in complete tumor rejection upon re-challenge. 
Furthermore, SEA-TGT treatment in the MC38 (colon carcinoma) and A20 (lymphoma) 
syngeneic tumor models resulted in tumor growth delay and complete responses (CRs) in both 
models.
Collectively, these data demonstrate the antitumor therapeutic potential of SEA-TGT and suggest 
activity comes both from reduction of Tregs and amplification of naïve and memory T-cell 
responses.
13.2.2.3. Clinical Overview of Sub-Study B Investigational Products 
See the master protocol Introduction (Section 2.2.2) for clinical overview of sasanlimab.
13.2.2.3.1. Clinical Overview of Axitinib 

The efficacy and safety of single-agent axitinib were evaluated in a Phase II open-
label study (NCT00094094; study A4061011) in 32 patients with advanced NSCLC, 
with (n=23) and without (n=9) prior therapy.42
o
The most common (≥20%) treatment-related AEs were fatigue, anorexia, 
diarrhea, nausea, hoarseness, hypertension, and arthralgia; most were Grade 
≤2 in severity. Grade ≥3 treatment related AEs included fatigue (n=7), 
hypertension (n=3), and hyponatremia (n=3); other grade ≥3 treatment related 
AEs occurred in 1 participant each.
o
Three patients had confirmed PR (ORR =9%); disease control rate (PR + 
stable disease) was 41%. Median duration of response was 8.3 months (95% 
CI, 5.9,10.6). Median PFS was 4.9 months overall (95% CI, 3.6,7.0). Median 
OS was 14.8 months (95% CI, 10.7,not estimable). 

The efficacy and safety of axitinib in combination with avelumab were demonstrated 
in the Javelin Renal 101 study (NCT02684006; B9991003) in which 886 patients 
with untreated advanced RCC were randomly assigned to receive either avelumab 
plus axitinib (N = 442) or sunitinib (N = 444).43
o
The most common (≥20%) adverse reactions in patients receiving axitinib in 
combination with avelumab were diarrhea, fatigue, hypertension, 
musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, 
dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, 
dyspnea, abdominal pain, and headache. Serious adverse reactions occurred in 
35% of patients receiving axitinib in combination with avelumab and those 
that occurred in ≥1% of patients included diarrhea (2.5%), dyspnea (1.8%), 
hepatotoxicity (1.8%), venous thromboembolic disease (1.6%), acute kidney 
injury (1.4%), and pneumonia (1.2%). Fatal adverse reactions occurred in 
1.8% of patients receiving axitinib in combination with avelumab and 
included sudden cardiac death (1.2%), stroke (0.2%), myocarditis (0.2%), and 
necrotizing pancreatitis (0.2%).43

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 208
o
There was a statistically significant improvement in PFS (HR=0.69; 95% CI, 
0.56, 0.84) with median PFS of 13.8 months (95% CI; 11.1, not estimable) in 
the axitinib + avelumab group and 8.4 months (95% CI; 6.9,11.1) in the 
sunitinib group. The confirmed ORR was 51% (95% CI, 46.6,56.1) in the 
axitinib + avelumab group versus 26% (95% CI, 21.7, 30) in the sunitinib 
group.43

The efficacy and safety of axitinib in combination with avelumab was also evaluated 
in the Javelin Medley VEGF study (B9991027, NCT03472560) that included 41 
patients with advanced/metastatic NSCLC who had received at least 1 prior platinum-
containing therapy and 20 patients with advanced/metastatic UC who were treatment 
naïve.44
o
The most common (>10%) treatment related AEs in the NSCLC cohort were 
hypertension (39%), hypothyroidism (29%), decreased appetite (27%), 
diarrhea (22%), fatigue (22%), and hand-foot syndrome (15%); and in the UC 
cohort were asthenia (20%), decreased appetite (15%), fatigue (15%), and 
hypertension (15%).44  
o
Avelumab + axitinib showed antitumor activity in both cohorts, and tumor 
reduction was observed regardless of PD-L1 expression status. The confirmed 
ORR was 31.7% (95% CI: 18.1,48.1) in the NSCLC cohort and 10% (95% CI: 
1.2,31.7) in the UC cohort (all partial responses). Median PFS was 5.5 months 
(95% CI: 2.5,7.0) in the NSCLC cohort and 2.3 months (95% CI: 1.8,5.6) in 
the UC cohort. 

The efficacy of axitinib in combination with pembrolizumab was investigated in the 
Keynote-426 study (NCT02853331) in 861 patients with untreated advanced RCC.43
o
The most common adverse reactions (≥20%) in patients receiving axitinib and 
pembrolizumab were diarrhea, fatigue/asthenia, hypertension, 
hypothyroidism, decreased appetite, hepatotoxicity, palmar-plantar 
erythrodysesthesia, nausea, stomatitis/mucosal inflammation, dysphonia, rash, 
cough, and constipation. Serious adverse reactions occurred in 40% of patients 
receiving axitinib in combination with pembrolizumab and those that occurred 
in ≥1% of patients receiving axitinib in combination with pembrolizumab 
included hepatotoxicity (7%), diarrhea (4.2%), acute kidney injury (2.3%), 
dehydration (1%), and pneumonitis (1%). Fatal adverse reactions occurred in 
3.3% of patients receiving axitinib in combination with pembrolizumab and 
included 3 cases of cardiac arrest, 2 cases of pulmonary embolism and 1 case 
each of cardiac failure, death due to unknown cause, myasthenia gravis, 
myocarditis, Fournier's gangrene, plasma cell myeloma, pleural effusion, 
pneumonitis, and respiratory failure.43
o
There were statistically significant improvements in OS, PFS, and ORR in the 
axitinib + pembrolizumab group vs. the sunitinib group. OS at 1 year was 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 209
90% (95% CI; 86,92) in the axitinib + pembrolizumab group vs 78% (95%
CI; 74,82) in the sunitinib group. Median PFS (HR=0.69; 95% CI; 0.56,0.84) 
was 15 months (95% CI; 12.6,17.7) vs 11 months (95% CI; 8.7,12.5), and the 
confirmed ORR was 59% (95% CI; 54,64) vs 36 % (95% CI; 31,40) in the 
axitinib + pembrolizumab group vs. the sunitinib group, respectively.43
See Section 13.4.3 for the rationale of combining a PD-1/PD-L1 inhibitor with a VEGR 
inhibitor in this study. Additional information regarding clinical safety and efficacy is 
presented in the IB for axitinib.41
13.2.2.3.2. Clinical Overview of SEA-TGT 
The first-in-human study currently ongoing is a Phase 1, dose-escalation study to evaluate the 
safety and tolerability of SEA-TGT IV Q3W as a monotherapy and in combination with 
sasanlimab in participants with advanced malignancies (SGNTGT-001, NCT04254107). The 
monotherapy study will evaluate alternate dosing schedules, identify the maximum tolerated 
dose (MTD), maximum administered dose (MAD), or an alternative recommended active 
dose (not exceeding MTD).  The SEA-TGT IV doses explored in this study are 0.01, 0.1, 0.3, 
1, 3, and 6 mg/kg. Based on the multiple potential mechanisms of action, SEA-TGT may be 
an active therapy in a variety of malignancies. Therefore, that initial clinical study began with 
dose escalation in participants with selected advanced malignancies including NSCLC, 
gastric/gastroesophageal cancer, melanoma, classical Hodgkin lymphoma, diffuse large B-
cell lymphoma, and peripheral T-cell lymphoma-NOS.  Once dose escalation is completed, 
safety run-in cohorts will be initiated with sasanlimab. The first cohort will evaluate 
sasanlimab
+ SEA-TGT at 1 dose level below the RP2D. If no DLTs are 
observed in the first 6 participants, 6 additional participants will receive sasanlimab + SEA-
TGT at the RP2D. If no DLTs are observed in this regimen, it will be recommended for 
Phase 2 trials.   Additional information regarding SEA-TGT is presented in the IB.45
As of August 04, 2021, 26 participants have been dosed. No efficacy data is available at this 
time. SEA-TGT monotherapy demonstrated acceptable safety and tolerability at all dose 
levels evaluated. The incidence of non-serious adverse events was low. The most common 
treatment emergent adverse events (>15% of participants) were fatigue, fever, chills, pruritus, 
headache, alkaline phosphatase elevation, and nausea. Among all participants enrolled across 
dose escalation cohorts, a single DLT of Grade 3 pruritic rash was observed in the 6 mg/kg 
cohort (total of 6 participants in this cohort). 
No dose modifications or discontinuations due to AEs or deaths have been reported. 
Overall, safety evaluation of the SEA-TGT dose escalation demonstrates a favorable benefit-
risk profile in this population of patients with advanced malignancies and unmet need 
(preliminary data on file).
CCI

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 210
Recent safety data are available for 2 other anti-TIGIT drugs: tiragolumab and vibostolimab.

Tiragolumab
o
In a Phase 1 study, tiragolumab was evaluated as a monotherapy (n=24) and in 
combination with atezolizumab (n=49) in patients with advanced solid 
tumors. No dose limiting toxicities were seen in the monotherapy or 
combination phases. The most common treatment-related AE in the 
monotherapy phase included fatigue (38%) and anemia (31%) in the 
combination group.46
o
In the randomized, double-blind Phase 2 CITYSCAPE study (NCT03563716), 
135 patients with PD-L1-positive advanced/metastatic NSCLC were randomly 
assigned to receive tiragolumab + atezolizumab (n=67) or placebo + 
atezolizumab (n=68) in the first-line setting. Non-serious AEs that occurred in 
≥20% in either group included asthenia (25% in each group), fatigue (22% in 
tiragolumab + atezolizumab group, 13% in placebo+ atezolizumab group), 
and IRRs (27% in the tiragolumab + atezolizumab group and 10% in placebo
+ atezolizumab group).  Serious AEs that occurred in ≥2 patients in either 
group were influenza (2 tiragolumab + atezolizumab group and 0 in placebo + 
atezolizumab  group), pneumonia (5 tiragolumab + atezolizumab  group and 4 
in placebo+ atezolizumab group), pleural effusion (4 tiragolumab + 
atezolizumab  group and 0 in placebo + atezolizumab  group), and pulmonary 
embolism (0 tiragolumab + atezolizumab  group and 2 in placebo + 
atezolizumab  group).47

Vibostolimab
o
In a Phase 1 study, vibostolimab was evaluated as a monotherapy and in 
combination with pembrolizumab in various advanced solid tumors and 
demonstrated a manageable profile. In Part 2 of the Phase 1 study, 
vibostolimab was evaluated as a monotherapy (n=41) and in combination with 
pembrolizumab (n=38) in patients with NSCLC whose disease progressed on 
prior PDx therapy.48 The most common treatment-related AEs (≥10% in either 
arm) were pruritus, fatigue, rash, arthralgia, and decreased appetite. Ten 
patients reported Grade 3-4 treatment-related AEs; the most common were 
lipase increase and hypertension. One patient in the vibostolimab + 
pembrolizumab arm died due to treatment-related pneumonitis. 
o
In this same study, 41 patients with PDx-naïve NSCLC received vibostolimab 
+ pembrolizumab. The most common (≥20%) treatment-related AEs were 
pruritus (34%), hypoalbuminemia (29%), and pyrexia (20%). Grade 3-4 
treatment-related AEs occurred in 6 patients (15%); no deaths due to 
treatment-related AEs were reported.49

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 211
See Section 13.4.3 for the rationale of combining a PD-1/PD-L1 inhibitor with an anti-TIGIT 
in this study.
13.2.3. Benefit/Risk Assessment
Single-agent axitinib has demonstrated anti-tumor activity and a manageable safety profile in 
patients with advanced NSCLC, as described in Section 13.2.2.3.1.
Axitinib is approved in combination with either pembrolizumab or avelumab for aRCC as 
described in Section 13.2.2.1, and has a well-characterized safety profile, as described in 
Section 13.2.2.3.1.  Sasanlimab is similar in mechanism of action to pembrolizumab; 
therefore, it is expected that sasanlimab combined with axitinib will follow a similar toxicity 
profile as the approved axitinib plus pembrolizumab combination. AEs with potential 
combinational toxicities are hepatotoxicity, hypothyroidism, diarrhea, nausea, 
asthenia/fatigue and decreased appetite. There is specific guidance to the investigator for 
dosing and concomitant therapy for participants experiencing these AEs, which are 
considered to be immune-related, in Section 10.10.  
Other anti-TIGIT drugs, tiragolumab and vibostolimab, have been well-tolerated and 
efficacious as monotherapies and in combination with PD-1/PD-L1 inhibitors in first-line 
treatment of advanced NSCLC and PDx-refractory advanced NSCLC. The safety profile of 
tiragolumab in combination with atezolizumab was deemed similar to that of single-agent 
PD-1/PD-L1 inhibitors, while the efficacy of the combination demonstrated significant 
improvement in PFS and ORR over atezolizumab alone in PD-L1-positive, advanced 
NSCLC. The combination of vibostolimab and pembrolizumab was well-tolerated and 
demonstrated modest antitumor activity in PDx-refractory NSCLC, and promising antitumor 
activity in PDx-naïve NSCLC. See Section 13.2.2.3.2 and Section 13.4.3 for more details and 
references for the safety and efficacy, respectively, of these combinations. It is expected that 
sasanlimab combined with SEA-TGT will follow a similar toxicity profile as that of 
tiragolumab + atezolizumab and vibostolimab + pembrolizumab. 
For the triplet combination of sasanlimab + axitinib + SEA-TGT, the safety profile has not 
been characterized.  Study participants may experience adverse reactions that are not 
currently observed in the single-agent or combination profiles for each of the drugs.  Such 
risks exist with current standard of care treatments.  Despite advances in the treatment 
landscape for patients with advanced NSCLC without driver mutations, progression-free 
survival remains modest. While the introduction of immune checkpoint inhibition improved 
clinical outcomes compared to chemotherapy, not all patients benefit from single-agent PD-
1/PD-L1 inhibitors. The combination of sasanlimab with SEA-TGT, another ICI, would 
theoretically introduce overlapping toxicities of some immune related AEs (irAEs) in 
general. The recommended irAE management guidelines are provided in Section 10.10. The 
recommended dose modification guidelines for toxicities due to SEA-TGT and axitinib are 
provided in Sections 13.10.4 and 13.10.5, respectively.     
The dose modification and toxicity management guidance in this protocol is expected to 
mitigate the risk of these classes of toxicities, which might be increased in frequency and/or 
severity in this study. Further, the inclusion and exclusion criteria are intended to ensure 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 212
participants with related risk factors are not enrolled in this study, and ongoing safety 
monitoring will be conducted according to the SoA.
Taking into account the measures to minimize risk to study participants, the potential risks 
identified in association with the combination of sasanlimab, axitinib, and SEA-TGT are 
justified by the anticipated benefits that may be afforded to participants with advanced 
NSCLC.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of sasanlimab, axitinib, and SEA-TGT may be found in the IBs, which are the 
SRSDs for this sub-study.
13.3. Objectives, Endpoints, and Estimands for Sub-Study B
The following objectives and endpoints are specific to the Sub-Study B:
Table 24.
Sub-Study B Objectives and Endpoints
Objectives
Endpoints
Primary:
Primary:
Phase 1b
Phase 1b

To assess the DLT rate and estimate 
the MTD of sasanlimab in 
combination with axitinib and SEA-
TGT to determine the RP2D for the 
combination.

DLTs during the DLT-observation 
period.
Phase 2
Phase 2

To assess the ORR of sasanlimab in 
combination with axitinib and SEA-
TGT.

OR, defined as confirmed CR or PR, 
as assessed by the investigator using 
RECIST v1.1.
Secondary:
Secondary:
Phase 1b
Phase 1b

To assess the overall safety and 
tolerability of the combined 
investigational products.

AEs graded according to the NCI-
CTCAE v5.0 and changes in clinical 
laboratory test parameters.

To assess the anti-tumor activity of
the combined investigational 
products.

OR, DR, TTR, PFS by investigator 
assessment using RECIST v1.1.

To characterize the PK of the 
investigational products.

PK parameters (Cmax, Ctrough) of 
sasanlimab, axitinib, and SEA-TGT, 
as data permit.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 213
Table 24.
Sub-Study B Objectives and Endpoints
Objectives
Endpoints

To evaluate the immunogenicity of 
sasanlimab.

ADA (ie, incidence) against 
sasanlimab, as data permit.

To evaluate the immunogenicity of 
SEA-TGT.

ADA (ie, incidence) against SEA-
TGT, as data permit.
Phase 2
Phase 2

To assess other measures of 
anti-tumor activity of the combined 
investigational products.

DR, TTR, PFS by investigator 
assessment using RECIST v1.1, and 
OS.

To assess the overall safety and 
tolerability of the combined
investigational products.

AEs graded according to the NCI-
CTCAE v5.0 and changes in clinical 
laboratory test parameters.

To characterize the PK of the 
investigational products.

PK parameters (Cmax, Ctrough) of 
sasanlimab, axitinib, and SEA-TGT, 
as data permit.

To evaluate the immunogenicity of 
sasanlimab.

ADA against sasanlimab, as data 
permit.

To evaluate the immunogenicity of 
SEA-TGT.

ADA against SEA-TGT, as data 
permit.

To assess the association between 
anti-tumor activity and PD-L1 
expression.

OR by PD-L1 expression in 
available tumor tissue (archival or 
de novo, primary or metastatic).
Exploratory
Exploratory
Phase 1b 
Phase 1b 

To understand the relationship
between the therapeutic 
interventions being studied and the 
biology of the participant’s NSCLC.

Biomarkers, consisting of DNA, 
RNA, protein, metabolites or 
defined cell types, resulting from 
analyses of peripheral blood and/or 
tumor tissue biospecimen obtained 
at baseline, on treatment or at end-
of-study.
Phase 2
Phase 2

To understand the relationship 
between the therapeutic 
interventions being studied and the 
biology of the participant’s NSCLC.

Biomarkers, consisting of DNA, 
RNA, protein, metabolites or 
defined cell types, resulting from 
analyses of peripheral blood and/or 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 214
Table 24.
Sub-Study B Objectives and Endpoints
Objectives
Endpoints
tumor tissue biospecimen obtained 
at baseline, on treatment or at end-
of-study.
Estimands
This section defines the estimands associated with the primary endpoints of the sub-study.
The primary endpoint definitions and the observations that will be considered in the 
derivation of the endpoints are described or referenced below.
Phase 1b:
Primary Estimand (DLT): DLT rate estimated based on data from DLT-evaluable 
participants during the DLT-evaluation period (Cycle 1 – first 21 days of study treatment) in 
Phase 1b.
Variable: Occurrence of DLTs.
Analysis population: DLT-evaluable participants defined as participants who receive at least 
1 dose of the combination study treatment in Phase 1b and either experience DLT during the 
DLT-evaluation period or complete the DLT-evaluation period without DLT.  Participants 
without DLTs who receive less than 75% of the planned dose of each study intervention in 
Cycle 1 for reasons other than treatment-related toxicity are not evaluable for DLT.  All 
participants deemed non-evaluable for DLT may be replaced.
Population-level summary measure: DLT rate defined as the number of DLT-evaluable 
participants with DLTs in the DLT-evaluation period divided by the number of DLT-
evaluable participants in the DLT-evaluation period.
Phase 2:
Primary Estimand (OR): the treatment effect of sasanlimab + axitinib + SEA-TGT assessed 
by the ORR, based on Investigator assessment per RECIST v1.1, in the analysis population. 

Variable: Objective response defined as confirmed CR or PR according to RECIST 
v1.1 based on investigator assessment.  Both CR and PR must be confirmed by repeat 
assessments performed no less than 4 weeks after the criteria for response are first 
met.

Analysis population: all participants who received at least 1 dose of study 
intervention without regard to tolerability or duration of treatment.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 215
•
Population-level summary measure: ORR is defined as the proportion of participants 
in the analysis population with an OR and 2-sided 95% CI for ORR using the 
Clopper-Pearson method. Participants who do not have a post-baseline tumor 
assessment due to early progression of disease, who receive anti-cancer therapies 
other than the study treatments prior to reaching a CR or PR, or who die, or have PD, 
or stop tumor assessments for any reason prior to reaching a CR or PR will be 
counted as non-responders in the assessment of OR.  Each participant will have an 
objective response status (0: no OR; 1: OR).
13.4. Study Design for Sub-Study B
See Section 4.1 for the overall study design in the master protocol.
Figure 3 illustrates the design of Sub-Study B. Sub-Study B will start with a Phase 1b dose-
finding safety part to identify the RP2D for the triplet combination of sasanlimab +axitinib + 
SEA-TGT. Approximately 20 participants with any line of previous therapy will be enrolled 
in Phase 1b. Phase 2 will evaluate the anti-tumor activity and additional safety of the triplet 
combination in approximately 60 participants in the 1L or 2L/3L who have progressed on or 
after prior PDx treatment. The sasanlimab dose of 
 will remain fixed for all 
cohorts in Phase 1b and Phase 2 of Sub-Study B. Doses of axitinib and SEA-TGT will be 
identified via the mTPI dose-finding design. See Sections 13.4.1 and 13.4.2 for more details 
on the study design of Phase 1b and Phase 2, respectively.
Figure 3.
Sub-Study B Design
CCI

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 216
13.4.1. Phase 1b Design
Phase 1b will enroll participants in any line therapy for advanced NSCLC with no restrictions 
on the types of previous therapies, and who have any PD-L1 expression status. First, the 
safety of the sasanlimab and axitinib combination will be confirmed. Up to 2 dose levels of 
axitinib given in combination with sasanlimab 
 will be investigated (Table 25). The 
decision to de-escalate (from 5 mg BID to 3 mg BID) will be based on mTPI decision criteria 
based on the number of DLT evaluable patients and number of DLTs in those participants.
Initially 3-4 participants will be treated with sasanlimab 
 axitinib 5 mg BID 
and monitored during the 21-day DLT evaluation period (Cycle 1). If the mTPI decision 
criteria allows escalation, then the triplet cohort may be opened. Otherwise, the doublet 
cohort can be expanded with an additional 3 patients enrolled or de-escalated to the lower 
dose (3 mg BID) per the mTPI decision criteria. 
Table 25.
Sub-Study B Phase 1b, Doublet Cohorts Dose Levels
Dose Level
Sasanlimab
Axitinib
0 (Starting Dose)
5 mg BID
-1
3 mg BID
DLT period = 1 cycle of 21 days.
mTPI dose finding schema will be used for dose finding.
After the safety of the doublet is confirmed, the triplet combination may be opened. Up to 
three dose levels of SEA-TGT may be investigated (Table 26) and initially 3-4 participants 
will be treated and monitored at the starting dose level. The enrollment of subsequent 
participants (dose escalation or de-escalation cohorts) will be guided by mTPI design. At 
least 6 patients will be treated at the RP2D of the triplet combination before proceeding to 
Phase 2.
Table 26.
Sub-Study B, Phase 1b, Triplet Cohorts Dose Levels
Dose Level
Sasanlimab
Axitinib*
SEA-TGT
1
3 or 5 mg BID
3 mg/kg IV Q3W
0 (Starting 
Dose)
3 or 5 mg BID
1 mg/kg IV Q3W
-1
3 or 5 mg BID
0.3 mg/kg IV Q3W
DLT period = 1 cycle of 21 days.
mTPI dose finding schema will be used for dose finding.
*Axitinib dose will be determined by the doublet cohorts and will be fixed in the triplet cohorts.
A minimum of 3 DLT-evaluable participants will be required in each cohort; additional 
participants will be enrolled in the specific enrollment cohort to replace participants who are 
not considered DLT-evaluable, where required.  When all DLT-evaluable participants treated 
in a given enrollment cohort have completed the DLT observation period or experienced a 
DLT, whichever occurs first, the posterior probabilities for the risk of DLT for new 
CCI
CCI
PPD
CCI
CCI
CCI
CCI
CCI

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 217
participants at different dose levels for the combination of interest will be evaluated. If the 
toxicity rate of the currently used dose level is far smaller than the target probability of 
toxicity (pT) of 0.30, the mTPI will recommend escalating the dose level; if it is close to pT, 
the mTPI will recommend continuing at the current dose; if it is far greater than pT, the mTPI 
will recommend de-escalating the dose level. The mTPI dose de-escalation/escalation 
recommendation will be based on the estimated toxicity rate and 3 intervals (underdosing, 
target toxicity, and excessive toxicity) as shown below:

If current dose is in the underdosing [0, 0.25) toxicity interval: escalate to next higher 
dose;

If current dose is in the target toxicity [0.25, 0.35) toxicity interval: stay at current 
dose;

If current dose is in the excessive toxicity or overdosing [0.35, 1] toxicity interval:
de-escalate to a lower dose
Refer to Section 13.9 and Section 13.10.6 for more details on the mTPI design and decision 
rules.
The number of participants to be enrolled in Phase 1b will depend upon the observed safety 
profile, which will determine the number of participants at each dose level and the number of 
dose levels explored. 
It is anticipated that up to approximately 20 total participants will be enrolled in Phase 1b 
starting with Dose Level 0 of the doublet cohorts, and including the triplet cohorts. 
An RP2D below the MTD, or highest safe dose tested, may be determined based on other 
safety, clinical activity, PK, and pharmacodynamic data.
Cumulative DLT data will continue to be evaluated using the mTPI design in the Phase 2 
part. Should emerging data indicate that the dose level tested in the Phase 2 expansion cohort 
is more toxic than previously estimated (≥35% DLT rate), the next lower dose level may be 
explored, and may be declared as the RP2D for the triplet combination.
13.4.2. Phase 2 Design
Once the RP2D of the triplet is defined, the Phase 2 part of the study may be initiated. 
Patients will be allocated to 1 of 3 treatment arms based on lines of prior therapy and PD-L1 
TPS. For participants with previously untreated NSCLC, competitor data for PDx/TIGIT 
doublet combinations suggest that clinical activity may be enriched in the subgroup of 
patients with PD-L1 TPS ≥50% as compared to those with PD-L1 TPS 1-49%.50  Therefore, 
participants will be enrolled into 2 separate treatment arms based on PD-L1 expression to 
allow for estimation of clinical activity in each subgroup:

Treatment Arm B1 (n=20):  treatment-naïve participants with low PD-L1 (levels 
1-49%);  

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 218

Treatment Arm B2 (n=20):  treatment-naïve participants with high PD-L1 (levels 
≥50%). 
Given the existing data and high unmet need, a 3rd group of patients who have received prior 
checkpoint treatment is planned:

Treatment Arm B3 (n=20):  patients whose disease has progressed on prior PD-1/PD-
L1 therapy and who have PD-L1 TPS ≥ 1%.
Phase 2 will enroll a total of approximately 60 participants and will evaluate the anti-tumor 
activity and further evaluate the safety of the triplet combination of sasanlimab + axitinib + 
SEA-TGT.
13.4.3. Rationale for the Sub-Study B Combination
See Section 2.1 for the overall study rationale in the master protocol.
Despite advances in the treatment landscape for patients with advanced NSCLC, progression-
free survival (PFS) remains modest. While the introduction of PD-1/PD-L1 inhibitors
improved clinical outcomes compared to chemotherapy,49 not all patients benefit from single-
agent PD-1/PD-L1 inhibitors.  
Recent data for PD-1/PD-L1 inhibitors combined with anti-TIGIT have demonstrated
improvement in clinical outcomes over single-agent PD-1/PD-L1 inhibitors in patients with
advanced NSCLC, regardless of PD-L1 status:

CITYSCAPE (NCT03563716), a randomized double-blind, Phase 2 study in 
advanced NSCLC (N=67; TPS ≥1%) indicated that the addition of anti-TIGIT 
tiragolumab to atezolizumab resulted in superior ORR & PFS versus atezolizumab + 
placebo:50
o
ORR was 31% vs 16% in the tiragolumab + atezolizumab arm vs placebo + 
atezolizumab arm. Odds Ratio=2.57 (1.07, 6.14). 
o
Median PFS was 5.4 months in the tiragolumab + atezolizumab arm vs 
3.6 months in the placebo + atezolizumab arm. HR= 0.57 (0.37, 0.90).
o
A greater magnitude of improvement was seen in the TPS ≥50% group.50

Vibostolimab combined with pembrolizumab in patients with NSCLC whose disease
progressed on prior PDx therapy (n=38): ORR was 5% (95% CI: <1, 18) and median
duration of response was 13 months (95% CI: 4, 13).48

Vibostolimab combined with pembrolizumab in patients with PDx-naïve NSCLC, 
(n=41; both TPS ≥1% and <1%): ORR was 29% (95% CI: 16, 46) and median PFS 
was 5.4 months (95% CI: 2.1, 8.2); median duration of response was not reached.49
In addition to inhibition of PD-1/PD-L1 and TIGIT, VEGF pathway inhibition may make the 
tumor microenvironment more responsive. Successfully targeting these non-overlapping 
mechanisms may lead to additive or synergistic activity. Single-agent axitinib has 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 219
demonstrated antitumor activity in patients with advanced NSCLC who have either received 
prior therapy or not (see Section 13.2.2.3.1).
The VEGF pathway has been linked with tumor immunosuppression.51 Elevated expression 
of genes characteristic of angiogenesis has been associated with reduced OS benefit from 
avelumab in patients who otherwise show elevated immune activity in tumor.52 These 
findings are consistent with the hypothesis that inhibition of the VEGF pathway in 
conjunction with PD-1/PD-L1 inhibitors will improve patient benefit. This hypothesis has 
been supported by the clinical studies reported below. Clinical benefit from the combination 
of avelumab + axitinib in renal cancer and from maintenance avelumab following 
chemotherapy in advanced urothelial carcinoma is associated with elevated TIGIT 
expression. TIGIT may therefore limit clinical benefit in the context of anti-tumor immunity 
enabled by VEGF pathway and PD(L)1 inhibition. The addition of a TIGIT antagonist in 
such a setting is expected to further improve clinical benefit.
Combinations of PD-1/PD-L1 inhibitors + VEGFR inhibitors (without anti-TIGIT) have 
demonstrated clinical proof of concept with acceptable safety profiles in several 
malignancies, including advanced NSCLC:
•
Avelumab +axitinib (n=41; PDx naïve advanced NSCLC): ORR=32% (95% CI: 18.1,
48.1). Clinical activity in this population was not associated with PD-L1 expression. 
Avelumab + axitinib combination responders were associated with an activated 
immune profile, including the TIGIT pathway.44
•
Cabozantinib + atezolizumab (n=30; advanced NSCLC patients previously treated 
with an ICI, 2L setting):  ORR of 27% (80% CI: 16, 40).53
•
Lenvatinib + pembrolizumab: (n=21; 11[52%] received prior ICI, advanced NSCLC): 
ORR=33% (95% CI: 14.6, 57.0). This combination demonstrated a manageable 
safety profile and promising antitumor activity in patients with selected solid 
tumors.12
13.4.4. Justification for Dose in Sub-Study B
13.4.4.1. Starting Dose for Phase 1b
The starting dose of sasanlimab in Sub-Study B is 
and will remain constant 
throughout the study. Refer to master protocol Section 4.3 for the justification for this 
starting dose.
The axitinib dose of 5 mg orally twice daily, with or without food, was selected for the 
starting dose to test dose limiting toxicity in combination with sasanlimab and SEA-TGT.  
The 5 mg BID dose has proven to be safe and efficacious as a single agent and in 
combination with checkpoint inhibitors for the treatment of patients with aRCC. It is the dose 
approved by regulatory authorities worldwide.43
The SEA-TGT starting dose was chosen based on PK and PD data in the ongoing first-in-
human study SGNTGT-001, in the absence of an MTD. Single-agent doses explored in that 
study were 0.01, 0.1, 0.3, 1, 3, and 6 mg/kg; SEA-TGT monotherapy demonstrated 
acceptable safety and tolerability at all dose levels evaluated (Section 13.2.2.3.2). The data
CCI

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 220
showed strong biologic activity at the lowest dose tested (0.01 mg/kg), sustained target 
engagement and linear PK were observed starting at 0.3 mg/kg, and minimal PD differences 
were observed between 1 and 3 mg/kg. Based on these data and the DLT event at 6 mg/kg
(Grade 3 pruritic rash), no further dose escalation will occur. Therefore the 1 and 3 mg/kg
doses were recommended for further development.
13.4.4.2. Criteria for Dose Escalation/De-Escalation
Refer to Section 13.10.6 for criteria for dose escalation/de-escalation via mTPI for 
Sub-Study B.
13.4.5. Dose Limiting Toxicity
Refer to master protocol Section 4.3.3 for the definition of DLT.
The DLT observation period is the first 21 days starting with the first dose of any study 
intervention in the combination.
13.4.6. Maximum Tolerated Dose
The MTD is the highest studied dose level associated with a DLT rate of <35% among the 
participants treated at that dose level following the mTPI method.
13.4.7. Recommended Phase 2 Dose (RP2D) Definition
Refer to master protocol Section 4.3.5.
13.5. Study Population for Sub-Study B
Participants must meet all of the general inclusion and exclusion criteria as specified in 
the master protocol (Section 5) plus the following Sub-Study B specific inclusion and 
exclusion criteria:
13.5.1. Inclusion Criteria for Sub-Study B
Phase 1b and Phase 2:
14. Urinary protein <2+ by urine dipstick. If dipstick is ≥2+, then a 24-hour urinary protein 
<2g per 24 hours. 
15. Baseline blood pressure readings of ≤150 mm Hg (systolic) and ≤90 mm Hg (diastolic), 
as documented by 2 blood pressure readings taken at least 1 hour apart.
16. Left ventricular ejection fraction (LVEF) ≥ lower limit of normal as assessed by either 
MUGA scan or ECHO.
Phase 1b only:
17. Any line of therapy for locally advanced/metastatic NSCLC.  

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 221
Phase 2 only:
18. Able to provide a sufficient amount of plasma and tumor (primary or metastatic, archival 
or newly obtained); approximately 15 slides (minimum of 10 slides) or block are required 
for central lab determination of PD-L1 tumor expression and exploratory analyses. If 
archived tissue is not available and a fresh tumor biopsy is not considered appropriate in 
the opinion of the investigator, discussion with the sponsor is required.
Phase 2 Arms B1 and B2 (1st Line) only:
19. Previously untreated for advanced/metastatic NSCLC.
20. PD-L1 TPS 1%-49% (Arm B1) or ≥50% (Arm B2), as determined by local lab assay.
Phase 2 Arm B3 (2nd/3rd Line) only:
21. One or 2 prior lines of therapy for advanced/metastatic NSCLC.

Must have received prior immune checkpoint inhibitor treatment (at least anti-
PD-1/PD-L1 directed therapy) and platinum-based doublet chemotherapy, 
sequentially or concomitantly, and have documented disease progression 
while or after receiving the therapy.  
22. PD-L1 TPS ≥1% as determined by local laboratory assay.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 222
13.5.2. Exclusion Criteria for Sub-Study B
Phase 1b and Phase 2:
17. Documentation of any tumor-driving molecular alteration including but not limited to: 
BRAF, activating EGFR (mutations located in exons 18-21), ALK, ROS1, MET, RET.
Testing for EGFR mutation is required if status is unknown.
18. Central lung lesion involving major blood vessels.
19. History of Grade ≥ 2 hemoptysis.
20. Gastrointestinal abnormalities including:

Inability to take oral medication.

Requirement for IV alimentation.

Prior surgical procedures affecting absorption, including total gastric resection.

Treatment for active peptic ulcer disease in the past 6 months.

Active GI bleeding as evidenced by clinically significant hematemesis, hematochezia 
or melena in the past 3 months without evidence of resolution by endoscopy or 
colonoscopy.

Malabsorption syndromes.
21. Requirement of anticoagulant therapy with oral vitamin K antagonists (see 
Section 13.6.5.3 for allowed anticoagulant therapies). 
22. Active bleeding disorder or other history of significant bleeding episodes within 30 days 
before first dose of study treatment.
23. History of aneurysm.
24. Evidence of inadequate wound healing.
25. Triplicate average baseline QTcF > 480 msec.
Phase 1b only:
26. Concurrent or anticipated use of strong CYP3A4/5 inducers or strong CYP3A4 inhibitors 
within 14 days or 5 half-lives (whichever is longer) prior to Cycle 1 Day 1 and 
throughout the study. The topical use of these drugs is permitted (eg, 2% ketoconazole 
cream).

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 223
Phase 2 only:
27. Prior use of any anti-TIGIT mAb or anti-VEGF pathway therapy.
28. Concurrent or anticipated use of strong CYP3A4/5 inducers within 14 days or 5 half-lives 
(whichever is longer) prior to Cycle 1 Day 1 and throughout the study.
Phase 2 Arms B1 and B2 (1st- Line) only:
29. Prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents. 
Phase 2 Arm B3 (2nd/3rd - Line) only:
30. Confirmed progressive disease on the first or second imaging tumor assessment after 
initiation of therapy for advanced/metastatic NSCLC.
13.6. Study Intervention for Sub-Study B
Study Treatments:
For purposes of this sub-study, study intervention refers to sasanlimab, axitinib, and SEA-
TGT.  
Phase 1b Dose Levels:
See Table 25 and Table 26 for dose scheme in the Doublet Cohorts and Triplet Cohorts, 
respectively. Participants will receive the following study treatments in each 21-day cycle:
•
Sasanlimab SC, 
 (50 mg/mL, 2 mL per vial) on Day 1 of each cycle
•
Axitinib: 
o
5 mg BID (1 × 5 mg oral tablet) (Doublet Cohorts Dose Level 0) or
o
3 mg BID (3 × 1 mg oral tablet) (Doublet Cohorts Dose Level -1) 
o
Triplet Cohorts Dose Level will be 1 of the 2 doses above based on dose 
finding.
o
Intra-patient dose increases up to 10 mg BID will be permitted according to 
guidelines in Section 13.6.1.1.
CCI

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 224
•
SEA-TGT IV (15 mg/mL, 150 mg/ vial) on Day 1 of each cycle: 
o
1 mg/kg (Triplet Cohorts Dose Level 0) or 
o
3 mg/kg (Triplet Cohorts Dose Level 1) or
o
0.3 mg/kg (Triplet Cohorts Dose level -1) 
Phase 2 Dose Levels: 
RP2D of sasanlimab SC 
+ axitinib BID + SEA-TGT IV Q3W
Table 27.
Study Interventions: Sub-Study B (Sasanlimab + Axitinib + SEA-TGT)
Intervention Name
Sasanlimab
Axitinib
SEA-TGT
Type
Biologic Product
Small Molecule Product
Biologic Product
Dose Formulation
Solution for injection
Tablet
Solution for IV 
infusion
Unit Dose Strength
50 mg/mL, 2 mL (100 
mg total) vial
1 mg and 5 mg tablets
15 mg/mL (150 
mg/vial)
Dosage Level(s)
3 mg and 5 mg BID
0.3, 1, or 3 mg/kg Q3W
Route of Administration
Subcutaneous
Oral
Intravenous
Use
Experimental
Experimental
Experimental
IMP or NIMP 
IMP
IMP
IMP
Sourcing
Provided centrally by the 
sponsor 
Provided centrally by the 
sponsor
Provided centrally by 
the sponsor
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 high-
density polyethylene 
bottles. Each bottle will 
be labeled as required 
per country requirement.
Study intervention will 
be provided in vials. 
Each vial will be 
labeled as required per 
country requirement.
Former Names or 
Aliases
PF-06801591
RN888
Inlyta®
AG-013736
SGN-TGT
13.6.1. Administration of Sub-Study B Investigational Products
Sasanlimab should be administered first, followed by axitinib, and then SEA-TGT, when 
possible and in accordance with axitinib BID schedule.
Refer to Section 6.1.1 for details about the administration of sasanlimab, and below for 
details about administration of the other Sub-Study B products. 
13.6.1.1. Administration of Axitinib
Axitinib will be swallowed whole with a glass of water and with or without food. Axitinib 
should be taken 12 ± 2 hours apart in the morning and in the evening at approximately the 
CCI
CCI

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 225
same times every day. If a participant vomits at any time after dosing, the dose should not be 
re-administered, and the participant should take the next scheduled dose. Any missed dose 
may be taken up to 3 hours before the next scheduled dose, otherwise it should be skipped. 
Doses that are omitted for AEs should not be made up during the day, or at the end of the 
dosing period.  Additional information regarding axitinib administration is provided in the IP 
Manual.  
Axitinib will begin on Cycle 1 Day 1 and will be self-administered at home twice per day 
continuously, except on study visit days, when it should be administered at the study site.   
Axitinib intra-patient dose increase is permitted in Phase 1b and Phase 2 after completing 16 
weeks of axitinib treatment for participants who tolerate the current axitinib dose with no 
Grade ≥2 drug-related adverse events for 2 consecutive weeks, and have blood pressure 
≤150/90 mm Hg, and are not receiving antihypertensive medication. These participants will 
have the option to have their axitinib dose increased by one dose level in subsequent cycles, 
up to a maximum dose of 10 mg BID; the available doses are 3 mg BID, 5 mg BID, 7 mg 
BID, and 10 mg BID. Particular attention should be provided to a patient’s overall safety 
profile prior to implementing intra-patient dose increase for axitinib.
13.6.1.2. Administration of SEA-TGT
SEA-TGT will be administered on Day 1 of every 21-day cycle by IV infusion. SEA-TGT 
must not be administered as an IV push or bolus. 
Weight-based dosing is based on the participant’s actual body weight and weight must be 
measured at each visit per the SoA. Doses must be adjusted for participants who experience a 
≥10% change in weight compared to the body weight used to calculate the initial dose. Other 
dose adjustments for changes in body weight are permitted per institutional standard. 
Rounding is permissible within 5% of the nominal dose.
Infusion duration will vary depending on the method of infusion administration and the dose. 
Refer to the IP Manual for further details. SEA-TGT will be administered via stepwise 
infusion. In a stepwise infusion, the infusion rate is increased at set time intervals until a 
defined maximum rate of infusion is reached. As clinical experience with stepwise infusion 
of SEA-TGT evolves, the maximum rate and/or the infusion rate may change (ie, increase or 
decrease); the method of administration may also change. The IP Manual will specify any 
such changes.
Participants will be observed for at least 2 hours post-dose on Cycles 1, 2, and 3.
If a participant does not tolerate the infusion, the infusion duration for that participant may be 
increased; the infusion duration in subsequent infusions may also be increased per 
investigator discretion with medical monitor/sponsor approval. Conversely, if a participant 
tolerates consecutive infusions without IRR Grade >1, the infusion duration may be 
shortened (ie, administered at a faster rate) at the discretion of the investigator following 
consultation with the medical monitor/sponsor, the implementation of which may be dose-

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 226
cohort specific. For additional information regarding management of IRRs, see 
Section 13.6.6.1.1.
Pre-medication is not required. However, subjects who experience IRRs may receive 
subsequent treatment with premedication as indicated in Section 13.10.4. In such cases, 
premedication should be administered at least 30 minutes prior to the infusion and includes 
antihistamines (eg, diphenhydramine 50 mg IV or equivalent); famotidine 40 mg IV or 
equivalent, corticosteroids (e.g., hydrocortisone 100 mg IV or equivalent), or antipyretics, 
such as acetaminophen/paracetamol (eg, 500 to 1,000 mg oral dose).
Please refer to the IP manual for further instructions on the administration of SEA-TGT.
13.6.2. Preparation, Handling, Storage, Accountability, and Dispensing 
Refer to master protocol Section 6.2.
For axitinib, the participant/caregiver should be instructed to maintain the tablets in the 
bottles provided throughout the course of dosing and return the bottles to the site at the next 
study visit. 
Please refer to the IP manual for further instructions on the preparation and handling of 
axitinib and SEA-TGT.
13.6.3. Measures to Minimize Bias: Randomization and Blinding
This is an open-label sub-study that will not be randomized.
13.6.3.1. Allocation to Study Intervention
Refer to master protocol Section 6.3.1.
13.6.4. Study Intervention Compliance
Refer to master protocol Section 6.4.
SEA-TGT must be administered by the appropriately designated study staff at the 
investigational site and compliance will be documented.  Deviation(s) from the prescribed 
dosage regimen should be recorded in the eCRF.
13.6.5. Concomitant Therapy for Sub-Study B
In addition to concomitant therapy instructions and restrictions in the master protocol 
Section 6.5, the following concomitant therapy instructions and restrictions apply to 
Sub-Study B.
13.6.5.1. Permitted Concomitant Therapy Requiring Caution and/or Action
13.6.5.1.1. CYP and UGT Substrates and Inhibitors
Axitinib is metabolized primarily in the liver by CYP3A4/5 and to a lesser extent by 
CYP1A2, CYP2C19, and UGT1A1. Concomitant use of strong CYP3A4/5 inhibitors should 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 227
be avoided in Phase 1b of Sub-Study B as adjusting the axitinib dose during the DLT period 
could confound dose selection.  If concomitant use of a strong CYP3A4/5 inhibitor is 
unavoidable in Phase 2, consultation with the sponsor is needed prior to concurrent use of the 
strong CYP3A4/5 inhibitor as the dose of axitinib will need to be adjusted by approximately 
one-half. Selection of an alternate concomitant medication with no or minimal enzyme 
inhibition and/or induction potential is recommended in Sub-Study B when co-administered 
with axitinib.   
Participants must avoid consumption of grapefruit, pomegranates, Carambola (starfruit), 
Seville oranges or products containing the juice of any during the entire study and preferably 
starting 7 days before the first dose of study interventions, due to potential CYP3A4/5 
interaction with axitinib.
For examples of drugs of CYP3A inhibitors to be used with caution or avoided, please see 
Section 10.13.
13.6.5.2. CYP3A Inducers
Coadministration of axitinib with strong systemic CYP3A4/5 inducers (eg, rifampin, 
dexamethasone, phenytoin, carbamazepine, rifabutin, rifapentin, phenobarbital, and St. 
John’s wort) are prohibited throughout the study (Phase 1 and Phase 2). Selection of 
concomitant medication with no or minimal CYP3A4/5 induction potential is recommended. 
Moderate CYP3A4/5 inducers (eg, bosentan, efavirenz, etravirine, modafinil, and nafcillin) 
may also reduce the plasma exposure of axitinib and should be avoided if possible. For 
examples of moderate and/or strong CYP3A4 inducers, see Section 10.13.
13.6.5.3. Supportive Care
Participants who need to be on anticoagulant therapy during axitinib treatment should be 
treated with low molecular weight heparin. If low molecular weight heparin cannot be
administered, coumadin or other coumarin derivatives or other anti-coagulants
(including direct Xa inhibitors and direct thrombin inhibitors) may be allowed; however, 
appropriate monitoring of prothrombin time/international normalized ratio (PT/INR) should 
be performed.
13.6.5.4. Surgery
See Section 6.5.7 for master protocol surgery restrictions. If a major surgery or an 
interventional procedure (eg. endoscopy) is required, treatment with axitinib must be 
interrupted at least 2 days before the procedure and the patient BP should be monitored 
closely for hypotension. Patients may resume axitinib 2 weeks after major surgery assuming 
the wound has completely healed and there are no wound healing complications (eg. delayed 
healing, wound infection or fistula).
13.6.6. Dose Interruptions and Modifications for Sub-Study B
During the study, any adverse event considered to be related to treatment needs to be further 
assessed for the potential causality to which of the 3 investigational products. Dose 
interruption and modification are performed accordingly as explained below.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 228
13.6.6.1. SEA-TGT Dose Modifications
In the event of drug-related toxicity during SEA-TGT therapy, dosing may be delayed and/or 
reduced as described in Section 13.10.4. SEA-TGT dose delays >21 days should be 
discussed with the medical monitor. If clinical benefit is demonstrated, subsequent treatment 
with SEA-TGT may be at a reduced dose level or a prolonged dose interval. The type and 
severity of the AE observed will be taken into consideration to inform the decision. 
Participants who experience AEs that meet the criteria for permanent discontinuation of 
SEA-TGT may not resume SEA-TGT, including at a lower or modified dose. 
13.6.6.1.1. Infusion-Related Reactions 
IRRs usually occur within 24 hours of infusion and may manifest as a combination of signs or 
symptoms including fever, rigors, flushing, itching, various types of rash, urticaria, dyspnea,
nausea, vomiting, back or abdominal pain, and/or hypotension. IRRs may occur during the 
infusion of SEA-TGT. The infusion should be administered at a site properly equipped and
staffed to manage anaphylaxis. Dose modifications and management of IRRs are in 
Section 13.10.4.
All supportive measures consistent with optimal participant care should be given throughout 
the study according to institutional standards. Supportive measures may include, but are not 
limited to, any or all of the following:
●
Slowing, interruption, or other adjustments in the administration of SEA-TGT
●
Potential premedication or postmedication for infusions, for example:
○
Antihistamines, such as diphenhydramine 50 mg IV or equivalent
○
Famotidine 40 mg IV or equivalent
○
Antipyretics, such as acetaminophen 500–1,000 mg PO
○
Antiemetics, such as ondansetron
○
IV fluid support, such as normal saline
○
Anti-rigor medication, such as meperidine
○
Vasopressors
○
Corticosteroids, such as hydrocortisone 100 mg IV or equivalent,
or methylprednisolone 40 mg IV or equivalent (See Master 
Section 6.5.6 regarding steroid use in this study)
13.6.6.1.2. Allergic/ Hypersensitivity Reactions 
Allergic/hypersensitivity reactions to SEA-TGT are differentiated from IRRs to SEA-TGT 
by being defined as occurring >24 hours after infusion of SEA-TGT. 
Allergic/hypersensitivity reactions may manifest in the same manner as IRRs. All 
participants should be closely observed while receiving SEA-TGT, and after administration 
in accordance with Section 13.6.1.2. Guidance on SEA-TGT dose modifications is in 
Section 13.10.4. 
See Section 6.6.1 for further information on hypersensitivity reactions.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 229
13.6.6.1.3. Cytokine Release Syndrome
Cytokine release syndrome (CRS) is an acute inflammatory response characterized by fever
and may be accompanied by multiple organ dysfunction. ASTCT grading will be used for 
CRS events, and grading is dependent on the degree of supportive care needed. Grades 1 and
2 have fever with or without constitutional symptoms that require less intensive care. Grade 3 
and above require more intensive care, such as vasopressors and high percentage oxygen
therapy. Dose modifications and management of CRS are in Section 13.10.4. Monitoring and
additional support should be performed per institutional practice.
13.6.6.2. Axitinib Dose Modifications
In the event of drug-related toxicity during axitinib therapy, dosing may be delayed and/or 
reduced as described in Section 13.10.5. Recommended axitinib dose reductions are provided 
in Table 28. 
The dose of axitinib will also be adjusted for participants with concomitant CYP3A4/5 
inhibitor as specified in Section 13.6.5.1.1.
Table 28.
Dose Reductions for Axitinib for Toxicity Management
Axitinib Starting Dose
Axitinib First Dose Reduction
Axitinib Second Dose Reduction
3 mg BID
2 mg BID
N/A
5 mg BID
3 mg BID
2 mg BID
NOTE: Dose reduction should be based on the highest AE grade.
13.6.6.2.1. Management of Axitinib-Related Hypertension
Patients should contact the site for guidance if their systolic BP rises above 150 mm Hg, 
diastolic BP rises above 100 mm Hg, or if they develop symptoms perceived to be related to 
elevated BP (eg, headache, visual disturbance). To treat an increase in BP, standard 
antihypertensives can be used (eg, thiazide or thiazide-like diuretics, angiotensin II receptor 
blockers, angiotensin converting-enzyme inhibitors, or dihydropyridine [DHP] calcium 
channel blockers). Bradycardic agents (eg, beta adrenergic blockers with or without alpha-
blocking properties, and non-DHP calcium channel blockers, clonidine, digoxin) should be 
avoided to the extent possible (See concomitant restrictions in Section 13.6.5).
13.6.6.2.2. Bleeding Risks
The sponsor should be contacted to consider permanent discontinuation of axitinib if a 
patient develops symptomatic brain metastasis, tumor encasing vasculature, hemoptysis, or 
other risks for pulmonary hemorrhage while on study treatment. If brain metastases are 
successfully treated or if participant no longer needs anticoagulation or bleeding disorders 
resolve, then the treatment could be re-started at the discretion of the investigator and upon
discussion with the sponsor.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 230
13.7. Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal
See Section 7 of the master protocol for discontinuation of study intervention and participant 
discontinuation/withdrawal.
13.8. Study Assessments and Procedures for Sub-Study B
See Section 8 for master protocol study assessments and procedures, in addition to the 
following procedures specific to Sub-Study B. 
13.8.1. Efficacy Assessments
13.8.1.1. Tumor Response Assessments
Refer to Section 8.1.1 for tumor response assessments.
13.8.2. Safety Assessments
13.8.2.1. Home Blood Pressure Monitoring (Vital Signs)
In addition to the vital signs procedures in the master protocol Section 8.2.2, home BP 
monitoring will be required. Participants will receive a BP monitoring device and will 
monitor their BP at home/outside of the clinic at least twice daily (before taking each dose of 
axitinib) and record the results in the diary. Participants should be instructed to contact the 
study site immediately for guidance if SBP >150 mm Hg, or DBP >100 mm Hg, or if they 
develop symptoms perceived to be related to elevated BP (eg, headache, visual disturbance); 
different BP thresholds may be used per Investigator clinical judgement. 
13.8.2.2. Echocardiogram/ Multigated Acquisition Scan (MUGA)
LVEF should be assessed by transthoracic echocardiogram or MUGA and performed as 
outlined in the SoA.
The same modality used during screening should be used for all subsequent assessments.  
Additional assessments should also be performed if a participant experiences an AE which 
may be related to cardiac dysfunction in the opinion of the investigator, or if otherwise 
clinically indicated.
The details of the echocardiogram/MUGA will not be recorded on a CRF; however, any 
abnormalities detected on the echocardiogram/MUGA will be reported on the medical 
history or AE CRF as appropriate.
13.8.3. Treatment of Overdose for Sub-Study B
See master protocol Section 8.4 for sasanlimab overdose information.
13.8.3.1. Treatment of Overdose for Axitinib 
There is no specific treatment for axitinib overdose.  Supportive measures should be 
instituted.  Please refer to the respective IBs for more information.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 231
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the sponsor based on the clinical evaluation of the participant.
13.8.3.2. Treatment of Overdose for SEA-TGT
Weight-based dosing for SEA-TGT is based on the participant’s actual body weight. An 
overdose of SEA-TGT is defined as a ≥10% change above the weight-based dose. In the 
event of an overdose of SEA-TGT, study site personnel should:

Care for and medically stabilize the participant until there is no immediate risk of 
complications or death, if applicable. There is currently no known antidote for an 
overdose of SEA-TGT. 

Notify the medical monitor/sponsor as soon as they become aware of the overdose, 
to discuss details of the overdose (e.g., exact amount of SEA-TGT administered, 
participant weight) and AEs, if any. 
13.8.4. Biomarkers
PD-L1 protein expression in NSCLC is determined by using TPS, which is the percentage of 
viable tumor cells showing partial or complete membrane staining at any intensity, The 
specimen should be considered to have PD-L1 expression if TPS ≥1% and high PD-L1 
expression if TPS ≥50%.
Results of the local laboratory PD-L1 results will be entered in the CRF.
In Phase 2, blood samples or tumor tissue will also be tested centrally to confirm PD-L1 
status and for exploratory biomarker analyses. Tumor tissue testing is described in 
Section 8.8.  Tumor tissue collected after the participant was diagnosed with metastatic 
disease is preferred.  The tumor tissue sample must not be from locations that were 
previously irradiated.
13.9. Statistical Considerations for Sub-Study B
See Section 9 for master protocol statistical considerations and sub-study specifics below.
13.9.1. Estimands and Statistical Hypotheses
13.9.1.1. Estimands
Refer to Section 13.3 for details of estimands.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 232
13.9.1.2. Statistical Consideration for Phase 1b
A safe dose will be determined using the adaptive modified toxicity probability interval 
(mTPI) design. The mTPI design uses a Bayesian statistics framework and a beta/binomial 
hierarchical model to compute the posterior probability of 3 dosing intervals that reflect the 
relative difference between the toxicity rate of each dose level to the target rate (pT=0.30).54
The mTPI dose de-escalation/escalation recommendation will be based on the estimated 
toxicity rate and 3 intervals (underdosing, target toxicity, and excessive toxicity) as shown 
below:

If current dose is in the underdosing [0, 0.25) toxicity interval: escalate to next higher 
dose;

If current dose is in the target toxicity [0.25, 0.35) toxicity interval: stay at current 
dose;

If current dose is in the excessive toxicity or overdosing [0.35, 1] toxicity interval: de-
escalate to a lower dose. 
See Section 13.10.6 for the dose-escalation decisions for the given study that are pre-
calculated under the mTPI design and presented in a two-way table. 
13.9.1.3. Sample Size Determination
The total sample size is estimated to be approximately 80 participants for the Sub-Study B 
Phase 1b and Phase 2. The sample size is estimated to be approximately 20 participants for 
Phase 1b and 60 participants for Phase 2.
13.9.1.3.1. Phase 1b Dose Finding
Approximately 20 participants will be enrolled in the Phase 1b dose finding to evaluate DLTs 
during the first cycle of treatment in order to confirm the safety of the doublet and triplet 
combinations and identify the RP2D.   However, the total number of participants will depend 
on the observed safety profile, which will determine the number of patients at each dose level 
and the number of dose levels explored. Beginning with the first dose level, participants will 
be enrolled, treated, and monitored in cohorts of 3-4 participants during the 21-day DLT 
evaluation period (Cycle 1). At least 6 patients will be treated at the RP2D of the triplet 
combination before proceeding to Phase 2.
Phase 1b will use the mTPI dose finding design with the target toxicity rate of 0.30 with 
target toxicity interval of (0.25, 0.35). 
13.9.1.3.2. Phase 2 
Phase 2 will enroll approximately 60 subjects who will be dosed at the RP2D of the triplet in 
3 treatment arms: 

B1 (n=20):  treatment-naïve patients with low PD-L1 levels: TPS 1-49%;  

B2 (n=20):  treatment-naïve patients with high PD-L1 levels: TPS ≥50%. 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 233

B3 (n=20):  patients whose disease has progressed on prior PD-1/PD-L1 therapy and 
have PD-L1 TPS ≥ 1%.
The primary goal of Phase 2 is to estimate the ORR with standard error ≤0.11. Twenty 
patients per each treatment arm will provide the specified precision of ORR estimates. 
13.9.1.4. Analysis Set
Refer to Section 9.3 for analysis sets.
13.9.1.5. General Considerations
13.9.1.5.1. Primary Endpoints
Phase 1b
The primary endpoint in Phase 1b is DLTs during the DLT-observation period.  Refer to 
Section 9.4.2. 
The occurrence of DLTs and AEs constituting DLTs will be summarized for participants in 
the Phase 1b part as described in Section 13.3.
Phase 2
The primary efficacy endpoint in Phase 2 is OR.  Refer to Section 13.3.
ORR will be calculated along with the 2-sided 95% CI for ORR using the Clopper-Pearson 
method. Participants who do not have a post-baseline tumor assessment due to early 
progression of disease, who receive anti-cancer therapies other than the study treatments 
prior to reaching a CR or PR, or who die, have PD, or stop tumor assessments for any reason 
prior to reaching a CR or PR will be counted as non-responders in the assessment of OR.
13.9.1.5.2. Secondary Endpoints
13.9.1.5.2.1. Efficacy Analyses

TTR is defined for participants with confirmed objective response (CR or PR) as the 
time from the date of first dose to the date of first documentation of objective tumor 
response which is subsequently confirmed.

DR is defined for participants with confirmed objective response (CR or PR) as the 
time from the first documentation of OR to the first documentation of objective tumor 
progression or to death due to any cause, whichever occurs first.  The censoring rules 
for DR are as described below for PFS but participants will not be censored in the 
analysis of DR due to no adequate baseline assessment as only participants with OR 
are included in the analysis of DR.

PFS is defined as the time from the date of first dose of study treatment to the date of 
first documentation of PD or death due to any cause, whichever occurs first.  PFS 
data will be censored on the date of the last adequate tumor assessment for 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 234
participants who do not have an event (PD or death), for participants who start new 
anti-cancer treatment prior to an event, or for participants with an event after 2 or 
more missing tumor assessments.  Participants who do not have an adequate baseline 
tumor assessment or who do not have any adequate post-baseline tumor assessments 
per RECIST v1.1 will be censored on the date of first dose unless death occurred on 
or before the time of the second planned tumor assessment in which case the death 
will be considered an event.

OS is defined as the time from the date of first dose of study treatment to the date of 
death due to any cause. Participants last known to be alive will be censored at the 
date of last contact.
OR will be summarized as the proportion of participants in the analysis population with OR 
and corresponding 2-sided 95% CI using the Clopper-Pearson method.  TTR will be 
summarized using simple descriptive statistics (eg, median and range). DR, PFS, and OS will 
be analyzed using Kaplan-Meier methods.  Point estimates will be presented with 95% CIs.
13.9.1.5.2.2. Safety Analyses
For Phase 1b primary safety analysis, refer to Section 13.3 for DLT.
For Phase 1b and Phase 2 secondary safety analyses, refer to Sections 9.4.3.2 and 9.4.5.
13.9.1.5.2.3. PK Analyses
Refer to master protocol Section 9.4.3.3 for the analysis of PK endpoints for sasanlimab.
Peak (Cmax) and trough (Ctrough) concentrations for axitinib and SEA-TGT will be 
summarized descriptively (n, mean, SD, coefficient of variation [CV], median, minimum, 
maximum, geometric mean, its associated CV, and 95% confidence interval) by cohort/dose 
and cycle/ day.  Exclusions or separate summaries for dose modifications and concomitant 
medications may be considered in data summaries. Additional analytes may be evaluated as 
necessary.
Dose-normalized PK parameters (ie, Ctrough-DN) may be reported as appropriate. 
13.9.1.5.2.4. Immunogenicity Analyses
Refer to master protocol Section 9.4.3.4 for the analysis of immunogenicity endpoint for 
sasanlimab.
For SEA-TGT, the percentage of participants with positive ADA and NAb (if analyzed) will 
be summarized by treatment and pooled. For participants with positive ADA, the magnitude 
(titer), time of onset, and duration of ADA or NAb response will also be described, if data 
permit.
13.9.1.5.2.5. Biomarker Analyses
Refer to master protocol Section 9.4.4.1 for the analysis of biomarker endpoints.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 235
13.9.1.5.3. Exploratory Endpoints
Refer to Section 9.4.4 for biomarker exploratory endpoints.
13.9.1.5.4. Interim Analysis
There will be no interim analysis in Sub-Study B. 
13.10. Supporting Documentation and Operational Considerations for Sub-Study B
13.10.1. Clinical Laboratory Tests for Sub-Study B
In addition to the clinical laboratory tests required in Master Protocol Section 10.2, the tests 
in Table 29 will be required for participants in Sub-Study B:
Table 29.
Clinical Laboratory Tests Added for Sub-Study B
Hematology
Chemistry

Hematocrit

Fasting blood glucose

CK

Troponin*
Note: If urinalysis protein is ≥2+ dose adjustment may be needed; See Section 13.10.5.
*Troponin is required only at Screening or C1D1, and whenever clinically indicated throughout the study.
13.10.2. Contraceptive Guidance for Sub-Study B
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; studies to evaluate the development toxicity of sasanlimab have not been 
conducted.  Therefore, the use of a highly effective method of contraception is required
13.10.2.1. 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 6 months 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. 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 236
OR

Must agree to use contraception/barrier as detailed below:
o
Agree to use a male condom when engaging in any activity that allows for 
passage of ejaculate to another person.
o
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 13.10.2.4).
13.10.2.2. 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 13.10.2.3).
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 6 months after the last dose 
of study intervention, and agrees not to donate eggs (ova, oocytes) for the purpose 
of reproduction during this period, 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.
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. 
13.10.2.3. Woman of Childbearing Potential (WOCBP)
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;

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 237

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.
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. 

Female on HRT and whose menopausal status is in doubt will be required to 
use one of the non-estrogen 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.
13.10.2.4. 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.
5. Vasectomized partner.

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 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 238
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 
1. Combined (estrogen and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation:

Oral;

Intravaginal;

Transdermal.
2. Progestogen-only hormone contraception associated with inhibition of ovulation:

Oral;

Injectable.
3. 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 acceptable barrier methods must be used in addition to the highly 
effective methods that are user dependent listed above:

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).
13.10.3. Examples of Strong and Moderate CYP3A4 Inhibitors
Refer to Section 10.13.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 239
13.10.4. Recommended Dose Modification and Management of SEA-TGT-related 
Adverse Events 
Toxicity
NCI CTCAE 
Severity Grade
SEA-TGT Dose Modification & AE 
Management
Hepatotoxicity
ALT and/or AST 
elevation >3 x ULN and 
total bilirubin >2 x ULN
Discontinue SEA-TGT.
ALT and/or AST 
elevation >3 x ULN with 
the appearance of clinical 
symptoms of hepatic 
injury
Discontinue SEA-TGT.
Other
Grade 3
Withhold SEA-TGT dose until toxicity is Grade 
≤ 2 or returns to baseline, and then resume 
treatment at the same dose level after discussion 
with the medical monitor/Sponsor. 
Grade 4
Withhold SEA-TGT dose until toxicity is Grade 
≤ 2 or returns to baseline. Either resume 
treatment at a lower dose level after discussion 
with medical monitor or discontinue study 
treatment at the discretion of the investigator.
IRR, allergic reaction, or 
anaphylaxis 
or 
CRS*
Grade 1
Monitor vital signs more frequently until 
symptoms have resolved and subject is 
medically stable. Administer symptomatic 
treatment as medically indicated. 
Consider premedication with subsequent SEA-
TGT treatment. 
Grade 2
Hold SEA-TGT treatment. Monitor vital signs 
more frequently until symptoms have resolved 
and subject is medically stable. Administer 
symptomatic treatment as medically indicated. 
If subject responds promptly and is medically 
stable in the opinion of the investigator, SEA-
TGT treatment may be continued at a slower 
rate. 
Consider premedication with subsequent SEA-
TGT treatment. Consider slower infusion rate. If 
recurrent after the above measures, consider 
dose reduction to 1 dose level below current 
dose. 
Grade 3
Stop SEA-TGT treatment. Institute additional 
medical management as indicated. 

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 240
Toxicity
NCI CTCAE 
Severity Grade
SEA-TGT Dose Modification & AE 
Management
Subjects with an IRR that resolves to baseline or 
Grade ≤1 within approximately 2 hours after 
intervention may continue SEA-TGT at a 
reduced dose for subsequent infusions, if 
approved by the sponsor/medical monitor. 
OR
Permanently discontinue SEA-TGT. 
Grade 4
Permanently discontinue SEA-TGT.
* ASTCT grading will be used for CRS (CTCAE will be used for all other adverse events)
Note: For detailed irAE management guidelines, refer to Section 10.10.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 241
13.10.5. Recommended Dose Modifications for Axitinib-related Adverse Events 
Toxicity
NCI CTCAE 
Severity Grade
Axitinib Dose Modification
Hematologic Laboratory 
Abnormalities
Grade 4
Withhold until recovery to Grade ≤ 2.
Then, reduce by 1 dose level and resume 
treatment.
Grade 4 lymphopenia not associated with 
clinical events, eg, opportunistic infection: study 
treatment may continue without interruption.
AST, ALT with total
bilirubin < 2 x ULN and
PT/INR < 1.5 x ULN
Grade 2
Withhold until resolution to < 2 x ULN or 
baseline.
Restart at same dose level or one lower dose 
level.
Grade 3 and 4
Withhold until resolution to < 2 x ULN or 
baseline.
Restart at one lower dose level.
AST/ALT Elevation with
clinically significant
hepatic dysfunction
(ie, total bilirubin
≥ 2 x ULN excluding
biliary obstruction or
PT/INR ≥ 1.5 x ULN)
Permanently discontinue axitinib.
Non-hematologic
Toxicities, Laboratory
Abnormalities and/or
Other Drug Related
Toxicities
Grade 3
Reduce by 1 dose level.
Grade 3 toxicities controlled with symptomatic
medications, or Grade 3 asymptomatic 
biochemistry (other than LFTs) laboratory 
abnormalities may continue at the same dose 
level per Investigator judgment.
Grade 4
Other non-hematologic/laboratory and non-
laboratory abnormalities: hold treatment until 
recovery to Grade ≤2 then reduce by 1 dose 
level and resume treatment.
Grade 4 asymptomatic biochemistry laboratory 
(other than LFTs) abnormality: study treatment 
may continue without interruption per 
Investigator’s judgment.
Proteinuria
dipstick shows ≥2+
Perform 24-hour urine collection. Dosing may 
continue while waiting for test results.
≥ 2 g proteinuria/
24 hours
Withhold until proteinuria is <2 g/24 hours.
Repeat 24-hour urine collection for proteinuria 
and creatinine clearance (interval at Investigator 
discretion) until proteinuria is <2 g/24 hours.
Then resume at the same dose level or reduce by 
1 dose level as per Investigator judgment.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 242
Toxicity
NCI CTCAE 
Severity Grade
Axitinib Dose Modification
Hypertension
2 systolic BP readings
separated by at least
1 hour show systolic
pressure >150 mm Hg
OR
2 diastolic BP readings
separated by at least 1
hour show diastolic
pressure >100 mm Hg
If not on maximal antihypertensive treatment, 
institute new or additional antihypertensive 
medication and continue at the same dose level.
If on maximal antihypertensive treatment, 
reduce by 1 dose level.
See Section 13.6.6.2 for 
monitoring/management of
axitinib-related hypertension.
2 systolic BP readings
separated by at least
1 hour show systolic
pressure >160 mm Hg
OR
2 diastolic BP readings
separated by at least 1
hour show diastolic
pressure >105 mm Hg
Withhold until BP is < 150/100 mm Hg and 
adjust antihypertensive medication. Then reduce 
by 1 dose level and resume treatment.
If axitinib dosing is temporarily discontinued, 
participants receiving antihypertensive 
medications should monitor closely for 
hypotension. 
The plasma half-life of axitinib is 2-4 hours and 
BP usually decreases within 1-2 days
following dose interruption.
See Section 13.6.6.2 for 
monitoring/management of
axitinib-related hypertension.
Recurrent hypertension
following previous dose
reduction (2 systolic BP
readings separated by at
least 1 hour show
systolic pressure
>150 mm Hg)
OR
Recurrent diastolic BP
>100 mm Hg (2 BP
readings separated by at
least 1 hour) following
previous dose reduction
Repeat dose reduction by 1 lower dose level.
See Section 13.6.6.2 for 
monitoring/management of axitinib-related 
hypertension.
Immune-related AEa
Grade 2
Hold axitinib until recovery to grade ≤1 and re-
start axitinib at the same dose level. Refer to 
specialist as needed.
Grade 3-4
Hold axitinib until recovery to grade ≤1 and re-
start axitinib at a reduced dose level. Refer to 
specialist as needed.

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 243
Toxicity
NCI CTCAE 
Severity Grade
Axitinib Dose Modification
a)
Axitinib dose modifications for irAEs in this table are for sasanlimab-related irAEs. For detailed irAE 
management guidelines, refer to Section 10.10.
13.10.6. Detailed Dose Escalation /De-escalation Scheme for mTPI Design for 
Sasanlimab + Axitinib + SEA-TGT
A safe dose will be determined using the adaptive mTPI design.  The mTPI design uses a 
Bayesian statistics framework and a beta/binomial hierarchical model to compute the 
posterior probability of 3 dosing intervals that reflect the relative difference between the 
toxicity rate of each dose level to the target probability (pT) rate (pT=0.30). If the toxicity 
rate of the currently used dose level is far smaller than pT, the mTPI will recommend 
escalating the dose level; if it is close to pT, the mTPI will recommend continuing at the 
current dose; if it is far greater than pT, the mTPI will recommend deescalating the dose 
level. These rules are conceptually similar to those used by the 3+3 design, except the 
decisions of an mTPI design are based on posterior probabilities calculated under a coherent 
probability model. As shown by Ji and Wang54, mTPI design is more efficient and safer than 
the 3+3 design. They considered 42 scenarios to cover a wide range of practical dose-
response shapes, and concluded that the 3 + 3 design was more likely to treat participants at 
toxic doses above the MTD and less likely to identify the true MTD than the mTPI design. 
For example, the 3 + 3 design exhibited a lower overall toxicity percentage than the mTPI 
design in only 1 of 42 scenarios. 
Decision rules are based on calculating unit probability mass (UPM) of 3 dosing intervals 
corresponding to under, proper, and overdosing in terms of toxicity (Table 30). Specifically, 
the underdosing interval is defined as [0, pT-e1), the overdosing interval (pT+e2, 1], and the 
proper-dosing interval [pT- e1, pT+ e2), where e1 and e2 are small fractions. Based on the 
projected safety profile, e1 is selected as 0.05, and e2 is selected as 0.05. Therefore, the target 
interval for the DLT rate is [0.25, 0.35). The 3 dosing intervals are associated with 3 different 
dose-escalation decisions. The underdosing interval corresponds to a dose escalation (E), 
overdosing corresponds to dose de-escalation (D), and proper dosing corresponds to staying 
at the current dose (S). Given a dosing interval and a probability distribution, the UPM of 
that dosing interval is defined as the probability of a participant belonging to that dosing 
interval divided by the length of the dosing interval. The mTPI design calculates the UPMs 
for the 3 dosing intervals, and the one with the largest UPM informs the corresponding dose-
finding decision, which is the dose level to be used for future participants. For example, if the 
underdosing interval has the largest UPM, the decision will be to escalate, and the next 3-4 
participants will be treated at the next higher dose level. Simulations have demonstrated that 
the decision based on UPM is optimal in that it minimizes a posterior expected loss (ie, 
minimizes the chance of making a wrong dosing decision).

Sasanlimab (PF-06801591)
B8011011
Final Protocol Amendment 4, 21October 2021
PFIZER CONFIDENTIAL
Page 244
Table 30.
Dose Finding Rules
Number of Participants Treated at Current Dose
r\n
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
0
E
E
E
E
E
E
E
E
E
E
E
E
E
E
E
E
1
S
S
S
E
E
E
E
E
E
E
E
E
E
E
E
E
2
D
S
S
S
S
S
S
S
E
E
E
E
E
E
E
E
3
DU
DU
D
S
S
S
S
S
S
S
S
S
S
E
E
E
4
DU
DU
DU
D
D
S
S
S
S
S
S
S
S
S
S
5
DU
DU
DU
DU
DU
D
S
S
S
S
S
S
S
S
6
DU
DU
DU
DU
DU
DU
D
S
S
S
S
S
S
7
DU
DU
DU
DU
DU
DU
DU
D
S
S
S
S
8
DU
DU
DU
DU
DU
DU
DU
DU
DU
D
S
9
DU
DU
DU
DU
DU
DU
DU
DU
DU
DU
10
DU
DU
DU
DU
DU
DU
DU
DU
DU
11
DU
DU
DU
DU
DU
DU
DU
DU
12
DU
DU
DU
DU
DU
DU
DU
13
DU
DU
DU
DU
DU
DU
14
DU
DU
DU
DU
DU
15
DU
DU
DU
DU
16
DU
DU
DU
17
DU
DU
18
DU
E = Escalate to the next higher dose level
S = Stay at the current dose level
D = De-escalate to the next lower dose level
DU = The current dose level is unacceptably toxic and should be eliminated from further dose finding
DLTs = Dose Limiting Toxicities; Targeted DLT rate=30%
Select escalation/de-escalation algorithms for total number of participants treated at the 
current dose level (current and previous cohorts):
With 3 participants treated at current dose level

0 DLT: escalate

1 DLT: remain at the same dose

2 DLTs: de-escalate

3 DLTs: de-escalate and consider current dose as intolerable
With 6 participants treated at current dose level

0-1 DLT: escalate

2-3 DLTs: remain at the same dose

4-6 DLTs: de-escalate and consider current dose as intolerable
                                      Number of DLTs