PF-06936308 C3621001Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 1A PHASE 1 STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF ESCALATING DOSES AND TREATMENT INTENSIFICATION OF A VACCINE-BASED IMMUNOTHERAPY REGIMEN-2 (VBIR-2) (PF-06936308) FOR ADVANCED NON-SMALL CELL LUNG CANCER AND METASTATIC TRIPLE-NEGATIVE BREAST CANCER Investigational Product Number: PF-06936308 Investigational Product Name: Not Applicable (N/A) United States (US) Investigational New Drug (IND) Number: European Clinical Trials Database (EudraCT) Number:N/A Protocol Number: C3621001 Phase: 1 This document and accompanying materials contain confidential information belonging to Pfizer. Except as otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this information in confidence and not copy or disclose it to others (except where required by applicable law) or use it for unauthorized purposes. In the event of any actual or suspected breach of this obligation, Pfizer must be promptly notified . CCI PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 2Document History Document Version Date Summary of Changes and Rationale Amendment 2 22Dec2020 Overarching rationale for the C3621001 Protocol Amendment 2: Part 1 has been completed. Part 2 –Dose Expansion will evaluate the safet y and preliminary anti- tumor activity of VBIR -2 at RP2D in participants with NSCL C. The entire protocol has been updated accordingl y. Rationale: Based on the following strategic reasons, the Sponsor has decided to focus on NSCL C and remove TNBC as a study population in Dose Expansion: a.NSCL C is known to be immuno- responsive (“Hot” tumor) and may remain so in the relapsed s etting; b.More efficient use of resources in a population of significantly larger prevalence, hence greater unmet medical need. PF-06801591 was changed to sasanlimab throughout the document. Rationale: Sasanlimab non- proprietary name was assigned to PF-06801591. Section SOA: Schedule of assessments for the treatment period, maintenance period and PK in Part 2 were added. Rationale: Part 2 (Dose Expansion) was added to the study . Section SOA: PBMC collection during the maintenance period was updated. Rationale: PBMC collection was updated to align with other blood collections. Section 1.2: Background , Section 1.3 VBIR2, Section 1.6 Dose Rationale, and Section 1.6: Clinical overview were updated. PF-06936308 C3621001Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 3Rationale: New information has become available. •Section 2. Part 1 Objectives and Endpoints were updated. Part 2 Objectives and Endpoints were added. Rationale: Part 2 (Dose Expansion) of the study differ from Part 1. •Section 4.1.2 New section: Part 2 Inclusion Criteria were added. Rationale: Population in Part 2 is different from Part 1 •Section 4.2.2 New section: Part 2 Exclusion Criteria were added. Rationale: Population in Part 2 is different from Part 1 •Section 5.4.5 Dose reductions was updated to include guidance for Part 2. Rationale: Information from Part 1 was use to include guidance for dose reductions in Part 2. •Section 9.3 Sample size determination; Part 2 sample size added. Rationale: The Part 2 sample size was determined non-quantitatively, based on typical sample sizes needed for accurate statistical prediction of Early Signals of Efficacy in the Expansion Cohort. •Section 9.4 Efficacy analysis: Clinical Benefit Rate (CBR) endpoint added Rationale: CBR is used in trials using immunotherapy. •Appendix 4 irRECIST was removed. Rationale: irRECIST criteria will no longer be used.C CI PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 4Appendix 7: New section: A lternative Measures During Public Emergencies Rationale: I nstructions to ad dress COVID -19 related study issues. Amendment 1 7 May 2020 Section 1.5 Clinical Overview added. Rationale: New clinical information from the April 2020 PF- 06936308 IB (VBI R-2: Adenovirus, plasmid DNA and anti- CTL A4 tremelimumab). Section 1.6.4.1 Updated PF-06801591 (anti-PD1) clinical information. Rationale: New clinical information from the October 2019 PF- 06801591 (anti - PD1) IB. Section 1.6.4.2 Updated VBIR PrCa PF-06753512 IB (VBIR PrCa: Adenovirus, plasmid DNA and anti- CTL A4 tremelimumab) and B7791001 clinical information, including risk of myocarditis. Rationale: New clinical information from the January 2020 VBIR PF -06753512 IB (VBI R PrCa: Adenovirus, plasmid DNA and anti -CTLA4 tremelimumab) and safet y reports has been incorporated. Cardiac troponi n I testing was added at screening and during treatment (SOA and Section 7.1.9). Rationale: Cardiac monitoring to mitigate the potential risk of my ocarditis. Section 4.2 Exclusion Criteria 1 (brain metastases) and 8 (HIV+ participants) were updated. Ratio nale: I ncorporating language from the 17Sep2018 and 13May 2019 Protocol Administrative Change Letters. Section 4.2 Exclusion criterion for COVID -19/SARS -CoV2 infection added. PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 5Rationale: Guidance regarding COVID -19/SARS -CoV2 infection was required. Section 5.4.3 Added recommendations for dose interruptions/delay s due to Non-related Adverse Events. Rationale: Dose interruptions due to reasons other than treatment -related toxicity include guidance for COVID -19/SARS -CoV2 infection. Section 5.4.3.3 Dose Modifications: Added treatment discontinuation for myocarditis of any grade and Grade ≥3 colitis or diarrhea. Rationale: Based on emerging safet y information, additional discontinuation criteria for potential new adverse events. Original protocol 16-March - 2018 Not applicable (N/A) This amendment incorporates all revisions to date, including amendments made at the request of country health authorities and IRBs/ ECs. PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 6TABLE OF CONTENTS LIST OF TABLES ................................ ................................