Special Situations ..................................................................................................111 8.4.1. Potential Cases of Drug-Induced Liver Injury..........................................111CCI CCI PF-06936308 C3621001Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 108.4.2. Exposure to the Investigational Product During Pregnancy or Breastfeeding, and Occupational Exposure ...................................................113 8.4.2.1. Exposure During Pregnancy (EDP) ........................................1138.4.2.2. Exposure During Breastfeeding ..............................................1148.4.2.3. Occupational Exposure ...........................................................114 8.4.3. Medication Errors .....................................................................................115 8.4.3.1. Medication Errors....................................................................115 8.5. Medical Device Complaint Reporting Requirements ...........................................115 9. DATA ANALYSIS/STATISTICAL METHODS.............................................................116 9.1. Analysis Sets .........................................................................................................1169.2. Statistical Methods and Properties ........................................................................117 9.2.1. Statistical Methods for Dose Escalation/De-Escalation ...........................1179.2.2. Statistical Method for Estimating the MTD .............................................118 9.3. Sample Size Determination...................................................................................1189.4. Efficacy Analysis ..................................................................................................1199.5. Safety Analysis......................................................................................................120 9.5.1. Analysis of Pr imary Endpoint ..................................................................120 9.5.2. Analysis of Sec ondary Endpoints.............................................................120 9.5.3. ECG ..........................................................................................................120 9.6. Analysis of Pharmacokinetics ........................................121 9.6.1. Analysis of Pharmacokinetics...................................................................121 9.6.1.1. Tremelimumab Pharmacokinetic Analysis .............................1219.6.1.2. Sasanlimab Pharmacokinetic Analysis....................................122 9.6.3. Analysis of Imm unogenicity Data ............................................................122 9.6.4. Population Pharmacokinetic Analysis or Pharmacokinetic (PK/ Modeling ..............................123 9.7. Data Monitoring Committee .................................................................................123 10. QUALITY CONTROL AND QUALITY ASSURANCE...............................................12311. DATA HANDLING AND RECORD KEEPING ...........................................................123 11.1. Case Report Forms/Electronic Data Record .......................................................123CCI CCI CCI CCI PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 1111.2. Record Retention .................................................................................................124 12. ETHI CS............................................................................................................................125 12.1. I nstitutional Review Board/Ethics Committee ....................................................125 12.2. Ethical Conduct of the Study ..............................................................................125 12.3. Participant Information and Consent ...................................................................125 12.4. Reporting of Safet y Issues and Serious Breaches of the Protocol or ICH GCP .........................................................................................................................126 13. DEFINITION OF EN D OF TRIAL .................................................................................127 13.1. End of Trial in All Participating Countries .........................................................127 13.2. End of trial is Defined as Last Subject Last Visit (L SLV)..................................127 14. SPONSOR DI SCONTI NUATION CRITERIA ..............................................................127 15. PUBLICATION OF S TUDY RESUL TS........................................................................127 15.1. Communication of Results by Pfizer ..................................................................127 15.2. Publications by Investigators ..............................................................................128 16. REFERENCES ................................................................................................................130 PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 12LIST OF TABLES Table 1. PD-1 and PD- L1 expression in breast cancers, according to the molecular subt ype79..................................................................................42 Table 2. Expansion Phase Components, Dosage, Dosage Form, Route of Administration, and Dosing Regimen of the Vaccine -Based Immunother apy Regimen for NSCL C (See Section 5 for detailed Study Treatment instructions.) ..................................................................55 Table 3. Decision Rules ..........................................................................................59 Table 4. AdC68 Available Dose Levels (Part 1) ....................................................82 Table 5. AdC68 Available Dose Levels (Part 2) ....................................................82 Table 6. Dose Modifications for AdC68 Related Toxicity .....................................82 Table 7. Tremelimumab Available Dose Levels (Part 1) .......................................83 Table 8. Tremelimumab Available Dose Levels (Part 2) .......................................83 Table 9. Dose Modifications for Tremelimumab Related Toxicity When Given in Combination with AdC68 and pDNA .......................................83 Table 10. Sasanlimab Available Dose Levels (Part 1) .............................................84 Table 11. Sasanlimab Available Dose Levels (Part 2) .............................................84 Table 12. Dose Modifications for Sasanlimab and/or Tremelimumab Related Toxicity ................................ ................................