Tumor Assessments: Tumor assessments will include all known or suspected disease sites. Imaging may include chest, abdomen and pelvis CT or MRI sc ans, and bone scans. CT or MRI scans, as well as bone scans, when indicated, are to be done every 12 weeks (±5 days) or when if clinically i ndicated until disease progression that requires new treatment modality, permanent discontinuation, or death. Disease progression will be confirmed with 2 consecutive timepoin ts at least 4-8 weeks apart in the absence of rapid clinical deterioration. 18. Serious and Non-serious Adverse Event Monitoring: Adverse events should be documented and recorded at each visit using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTC AE) version 5.0. Participants must be followed for AEs for 6 months after the last study treatment administration or until all drug related toxicities have resolved, whichever is later; or earlier than 6 months should the participant commence another anticancer therapy in the meantime. The time period for actively eliciting and collecting AEs and SAEs (“active collection period”) for each participant begins from the tim e the participant provides informed consent through and including 6 months after the last study treatment administration or until all drug related toxicities have resolved, whichever is later. If the participant begins a new anticancer therapy, the period for recording non-serious AEs on the CRF ends at the time the new treatment is started. How ever, any SAEs occurring during the active collection period must still be reported to Pfizer Safety and recorded on the CRF, irrespective of any intervening treatment. 19. Concomitant Treatments: All concomitant medications and non-drug supportive interventions should be recorded in the CRF.CCI PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 37Schedule of Study Treatment, Pharmacokinetics, Tremelimumab and Sasanlimab Immunogenicity Assessments (Part 2) Protocol Activity Screen (28 days)Treat ment Period Maintenance End of Treatment Post Treat ment Cycle 1 Cycle 2 Every 4 months starting at Month 10End of Treatment Follow -Up (Months after EOT visit) Study Day Day 1Day 29Day 57Day 85Day 113M1 M2 M4 M6 Cycle Day Day 1 Day 29Day 57Day 8528-35 days Visit Window (days)2 2 2 2 2 2 2 4 4 4 Study Treat ment AdC6 81X X pDNA2X X X X X X X2 Tremelimumab3X X X X X X X X X3 Sasanlimab4X X X X X X X X X4 Phar macokinetics Immunogenicity PK for tremelimumab5X X X X X X X X X X X ADA /NAbfor tremelimumab5X X X X X X X X X PK for Sasanlimab6X X X X X X X X X X X ADA /NAbfor Sasanlimab6X X X X X X X X X Abbreviations: ADA = Anti -drug antibody; Adenovirus (AdC68); EOT = End of Treatment; pDNA = Plasmid deoxyribonucleic acid, PK = Pharmacokinetics 1. Adenovirus (AdC68) will be administered intramuscularly on Cycle 1 Day 1 and Cycle 2 Day 1. Tremelimumab and sasanlimab will be administered after the adenovirus for participants assigned to receive these components. 2. Plasmid DNA (pDNA) vaccinations will be administered intramuscularly using an electroporation device on Day 29, Day 57 and Day 85 of each cycle. During the Maintenance period, pDNA vaccinations will be administered every 2 months. All pDNA vaccinations should be administered prio r to admin istering the tremelimumab and sasanlimab . 3. Tremelimumab will be administered subcutaneously in close proximity to the vaccine injected muscle and vaccine draining lymph nodes on Day 1, Day 29, Day 57 and Day 85 of each cycle. During the Maintenance period, tremelimumab will be administered every 2 months. Tremelimumab (both injections) will be administered after the adenovirus or pDNA and before the sasanlimab. PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 38Protocol Activity Screen (28 days)Treat ment Period Maintenance End of Treatment Post Treat ment Cycle 1 Cycle 2 Every 4 months starting at Month 10End of Treatment Follow -Up (Months after EOT visit) Study Day Day 1Day 29Day 57Day 85Day 113M1 M2 M4 M6 Cycle Day Day 1 Day 29Day 57Day 8528-35 days Visit Window (days)2 2 2 2 2 2 2 4 4 4 Study Treat ment 4. Sasanlimab will be administered subcutaneously in close proximity to the vaccine injected musc le and vaccine draining lymph nodes on Day 1, Day 29, Day 57 and Day 85 of each cycle. During the Maintenance period, sasanlimab will be administered each month. Sasanlimab will be administered after the adenovirus or pDNA and after the tremelimumab. 5. Blood samples for determination of tremelimumab drug concentrations and for detection of ADA/NAb against tremelimumab will be co llected as outlined in the schedule of activities . Samples to be collected on dosing days are to be obtained within 6 hours prior to tremelimumab dosing. 6. Blood samples for determination of sasanlimab drug concentrations and for detection of ADA/NAb against sasanlimab will be collected as outlined in t he schedule of activities . Samples to be collected on dosing days are to be obtained within 6 hours prior to sasanlimab dosing. PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 391.INTRODUCTION 1.1.Mechanism of Action/Indication PF-06936308 is a vaccine -based immunotherapy regimen -2 (VBIR -2) that is currentl y being investigated in participants with advanced non -small cell lung cancer (NSCLC) and metastatic triple- negative breast cancer (mTNBC). 1.2.Background and Rationale Lung cancer is the second most common cancer in both men and women, it accounts for approximately 160,000 deaths each y ear in the United States (US). About 80 -85% of lung cancers are histologically classified as Non -Small Cell L ung Cancer (NSCLC), which includes 2 major sub -types:1)Non-squamous carcinoma (including adenocarcinoma, large -cell carcinoma (rare), and other cell t ypes), and 2) Squamous cell (epidermoid) carcinoma.1 The 5 -yearsurvival rate of metastatic NSCL C is 4%.16 Triple -negative breast cancer accounts for 15% to 20% of breast cancers and is histologically defined by a lack of estrogen receptor (ER) and progesterone receptor (PR) expression as well as absence of human epidermal growth factor 2 (HER2) overexpression and/or amplification.4,6 Following neoadjuvant and/or adjuvant chemotherap y,7,8,9,10patients with TNBC have a higher incidence of early visceral recurrence, with a subsequent median survival of appro ximately 1 year.2,3,11 Given these extraordinarily low survival rates, there is a need for new therapies with acceptable side - effect profiles to provide long- term disease control in these patient popula tions. Recent advances in understanding methods to increase immune surveillance and to reduce native immune tolerance have yielded encouraging therapeutic advances in a variet y of tumor types, including NSCL C.12,13,14,15 Unfortunately , these current approaches generall y encompass the use of single -agent immunotherapy , in which onl y a sub -group of patients respond, or show a long -term survival benefit. In contrast, PF -06936308 is a multi -agent, combination approach to the immune treatment of NSCL C. The multi -agent regimen consists of a series of p riming and booster vaccinations containing three antigens, along with 2 immune checkpoint inhibitors, delivered in support of the vaccinations. I t is hoped that this multi- agent approach will more thoroughl y induce, expand, and maintain the pool of T -cells providing the anti -tumor responses at the sites of metastatic NSCL C. As NSCL C is known to express the tumor antigens encoded and expressed by the vaccine, (see below), and as NSCLC is associated with a so -called “inflamed” tumor microenvironment (indicating a an intrinsic level of anti- tumor T -cell infiltration), it is hope this regimen will induce clinically significant responses in participants with metastatic NSCL C that will reduce tumor burden, delay disease progression, and ultimately lead to prolon ged overall survival. PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 40VBIR -2 Regimen The VBI R-2 (PF -06936308) regimen consists of 4 components: (1) PF -06871923 (AdC68), a replication incompetent chimpanzee adenovirus, delivered as a priming vaccination intramuscularl y. AdC68 contains the 3selected non-small cell lung cancer -associated antigens mucin 1 (MUC1), mesothelin (MSL N) and telomerase reverse transcriptase (TERT); (2) PF -06871925, a plasmid DNA (pDNA) construct that encodes the same 3tumor antigens as in the AdC68 viral vector. The pDNA is also delivered intramuscularl y, and is used as a boost vaccination at pre- specified intervals after the viral vector is delivered; (3) PF -06753388 (tremelimumab), an anti -cytotoxic T ly mphocy te-associated antigen -4 (CTLA -4) monoclonal antibody given subcutaneousl y (SC) in conjunction with each vaccination. (4) PF -06801591 (sasanlimab), an anti -programmed death-1 (PD-1) monoclonal antibody also given SC in conjunction with each vaccination. 1.2.1. Non-Small Cell Lung Cancer Treatment Overview Limitations of Treat ing Activating Genetic Mutations Numerous genetic changes have been associated with lung cancer that may serve as activators of the malignant process. Epidermal growth factor receptor (EGFR) is expressed or overexpressed in the majority of NSCL C tumors.17,18,19 Agents targeting EGFR include tyrosine kinase inhibitors (TKIs), such as gefit inib,17erlotinib,18and afatinib.19 In metastatic NSCL C harboring activating EGFR mutations, these treatments may result in some patients obtaining response rates exceeding 60%, accomp anied by median Overall Survival exceeding 2 years. Unfortunatel y, most patients progress in about 9 months, which in 50% of cases is due to a secondary , T790M mutation in exon 20. In addition to EGFR mutations, abnormalities in the anaplastic ly mphoma k inase (ALK) gene have been identified in a subset of NSCL C patients. These gene rearrangements, which appear mutually exclusive with both EGFR and KRAS (Proto -Oncogene) gene mutations, render cancers highl y responsive to ALK inhibitors including crizotini b20and ceritinib.21 For the majorit y of patients diagnosed with advanced -stage NSCL C without targetable driver gene mutations, platinum- based doublet chemotherapy (ChTx) has been the standard of care (SOC) for over 30 years. With the exception of bevacizumab,22,23and despite extensive study of multiple targeted and cy totoxic agents, addition of a third agent to platinum -doublet chemotherap y has not been shown to improve progression -free survival (PFS) or overall survival (OS) over platinum- doublet chemotherapy .24 Targeting driver mutations responsible for tumor progression (EGFR receptor and the echinoderm microtubule - associated protein- like 4 (EML4) -anaplastic ly mphoma kinase (ALK) EML4 -ALK receptor) is modestly effective; however res istance to these therapies inevitabl y ensues.25,26,27 PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 41Advantages of Immunotherapy Regimens with Checkpoint Inhibitors Checkpoint inhibitors, tumor vaccines, and cellular therapies ind uce formation of specific tumor -directed cy totoxic T cells capable of destroy ing cancer cells. This process may involve T- cell memory and longer -term, ongoing anti -tumor effects, which may possibl y provide longer overall survival benefits compared to current therapies, as described below. Checkpoint inhibitors, including anti -PD-1 and anti -CTL A-4, have recently been tested for efficacy in NSCL C, and shown success in the immunotherapy -naïve setting.28,29,30 Initial use of the checkpoint inhibitors ipilimumab (anti- CTLA -4) and nivoluma b (anti -PD-1) for the treatment of NSCLC demonstrated encouraging clinical results, especially in patients with program death -ligand 1 (PD -L1) expression in >50% of their tumor cells.35 In first-line NSCL C, patients with PD -L1+ >50% were treated with nivolumab 3 mg/kg every 2 weeks (Q2W) plus ipilimumab 1 mg/kg every 12weeks (Q12W), or every 6 weeks (Q6W). The ORR was 47% for the ipi/nivo combinat ion versus 23% for nivolumab alone. Median duration of response was not reached with median follow- up times of 12.8 months.37 Participants had a tolerable safet y profile, although Grade 3 or Grade 4 treatment -related adverse events (TRAEs) were observed in 37% of patients, including increased lipase, pneumonitis, adrenal insufficiency and colitis. More recentl y, in 2018, new standards of care have emerged in treatment -naïve, NSCL C without sensitizing EGFR or ALK mutations, using regimens consisting of PD -axis inhibitors combined with a variet y of chemotherap y or other novel agents. In KEYNOTE 189, pemetrexed and platinum -based chemotherap y, along with pembrolizumab, was administered in a Phase 3 trial, and compared to patients receiving the same regimen without pembrolizumab.147 Those patient s receiving pembrolizumab in addition to the pemetrexed and platinum - based chemotherap y achieved a superior 12 -month OS of 69.2 % versus 49.4%, HR = 0.49 and a mPFS of 8.8 months versus 4.9 months. Both groups had the same safet y profile of 65 – 67 % Grad e 3 AEs. Similarly , in IMpower150, patients with non - squamous, treatment -naïve NSCL C without EGFR or ALK driver mutations were treated with bevacizumab plus carboplatin plus paclitaxel (BCP), or atezolizumab plus BCP (ABCP) every 3 weeks for 4 or 6 cy cles, followed b y maintenance therap y with atezolizumab, bevacizumab, or both. Patients treated with ABCP achieved an improved mPFS (8.3 versus 6.8 months, HR = 0.62) and mOS (19.2 versus 14.7 months, HR = 0.78).148 Triple -Negative Breast Cancer Triple -negative breast cancer accounts for 15% to 20% of breast cancers and is histologically defined b y a lack of estrogen receptor and progesterone receptor e xpression and the absence of HER2 overexpression and/or amplification.4,6 Triple -negative breast cancer is a heterogeneous disease, not only on the molecular level, but also on the pathologic and clinical levels. The majority of patients with TNBC respond with high sensitivity to chemotherapi es including anthracy clines and taxanes in the neoadjuvant or adjuvant settings. Responses to chemotherapy occur, but are often short lived and are frequently accompanied by considerable toxicity .39,40,41,42,43 After neoadjuvant and/or adjuvant chemotherap y, patients with TNBC have a higher incidence of early visceral recurrence,7,8,9,10with a PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 42subsequent median survival of approximately 1 year.11 The lack of ER, PR and HER2 expression precludes the use of targeted therapies, and the only approved systemic treatment option is chemotherap y. Various chemotherap y regimens (single agent taxane, capecitabine or combinatio ns paclitaxel + gemcitabine, platinum + gemcitabine) are used in first -line therap y for mTNBC; they are associated with an ORR of 25 -35%, a modest PFS (median PFS of less than 6 months) and a median OS of less than 12 months.46 Given the suboptimal outcomes with chemotherap y, new therapies for mTNBC are urgentl y needed. Classification of Immunoresponsiveness of Tumors Tumors can be broadl y categorized as inflamed or noninflamed.47,48,49 Representative images of tumor CD8 I mmunohistochemistry (IHC) shows three patterns Tcells. Tumors with preexisting immunity are represented b y an abundance of tumor infiltrating l ymphocy tes (TILs), dense functional CD8+T-cell infiltration reflected by interferon gamma (IFN ɤ) signaling, expression of checkpoint markers including PD -L1, and high mutational burden. These characteris tics reflect highl y inflamed tumors. The collective clinical evidence to date suggests that checkpoint inhibitors largel y act b y reinvigorating preexisting antitumor T -cell responses and are most effective in inflamed tumors.50,68,69,70 In a study investigating the relationship between TILs at diagnosis and clinical outcome after anthracy cline -based chemotherap y, the results reported significant prognostic association for TNBC but not for luminal breast cancers. Patients with TNBC with at least 50% TILs (10.5% of patients) had a 5 -year disease -free survival of 89% compared with 62% in luminal breast cancers ( p= 0.018, hazard ratio 0.29, 95% confidence interval 0.11 –0.81).71 PD-1/PD -L1 expression has been studied b y various methods in different cancer subt ypes.72 PD-1 and PD -L1 expression in various breast cancer subtypes are summarized in Table 1 below. Triple -negative breast cancer is frequently (70% –100%) infiltra ted with PD -1+ TILs. Recent clinical trials have demonstrated that blocking of the PD -1/PD -L1 pathway induces an objective and durable remission in patients with advanced solid tumors.12,15,73,74,75 The efficacy of these agents has been primarily linked to the expression of PD -L1 in the tumor cells and PD -1 on activated T ly mphocy tes.76,77,78,79 Table 1 . PD-1 and PD- L1 expression in breast cancers, according to the molecular subtype79 PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 43Immune checkpoint inhibitors in breast cancer: Cy totoxic T -lymphocy te-associated protein 4is an inhibitory receptor found on CD8+and CD4+T cells, and is constitutively expressed on regulatory T cells (Treg cells).80 CTL A - 4 functions to attenuate co -stimulatory signaling by competin g with the stimu latory receptor CD28 expressed by T cells for the ligands CD80 and CD86 presented by antigen -presenting cells.81 The United State s (US) Food and Drug Administration (FDA) approved the use of combination of nivolumab and ipilimumab in treatment for patients with unresectable or metastatic melanoma without a proto -oncogene protein B -raf ( BRAF) mutation. Very promising Phase I and II trials have been reported on increased activity of the combined blockade of CTL A4 and PD -1, nivolumab and ipilimumab,82durvalumab and tremelimumab83and pembrolizumab and ipilimumab84in NSCL C, with an ORR up to 40% across all the studies.85 Hence combination therap y with anti-CTL A -4 and anti -PD-1 therap y may also have application in TNBC patients. Several lines of evidence indicate that a greater number of TILs in the tumor stroma is associated with a higher probabilit y of cure in patients with early stage TNBC.86 In KEYNOTE -012,44a multicenter, nonrandomized Phase 1b trial, the safety and antitumor activity of PD -1 inhibitor pembrolizumab was assessed in patients with heavily pretreated, advanced TNBC. In this trial of 111 TNBC patients whose tumor samples were screened for PD-L1 expression, 58.6% had PD -L1-positive tumors and 32 women were enrolled; single -agent pembrolizumab was given intravenously at 10 mg/kg every 2 weeks to patients with advanced PD -L1–positive t umors. Common toxicities were mild (eg, arthralgia, fatigue, my algia, and nausea). Among the 27 patients who were evaluable for antitumor activity , the overall response rate was 18.5%.44 Part 1 (dose escalation) included participants with advanced NSCL C and mTNBC for whom no standard therap y is available. TNBC will not be included in Part 2 (dose expansion). 1.3.VBIR - 2 1.3.1. Rationale for the Components of VBIR -2 General Background of T -Cell Activity in Cancer Therapy High titers of tumor antigen -specific T cells can be induced by a variet y of methods including checkpoint inhibition, genetic modification (chimeric antigen receptor T cells), and ex-vivo stim ulation or incubation with antigen and anti -gen presenting cells51. Each of these methods has demonstrated the ability to reduce tumor burden in a variet y of cancers. In addition to these approaches, a cancer vaccine will also induce large numbers of pol yclonal, tumor antigen -associated T cells. I t has been shown that using a viral vector carry ing tumor - associated antigens, increases in circulating , vaccine -induced T -cells increase after each vaccination, but require multiple boost vaccinations with additional tumor -specific antigens before high T -cell titers can be reached. Vaccine -induced T cells are expected to be of lower avidity of normal tissues, due to thy mic deletion of high -avidity T cells that are specific for self -antigens. The slower induction of Tcells by vaccines, along with thy mic deletion of high avidit y T cells, might explain the good safet y profile observed to date in patients treated with cancer vaccines. PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 44Hypothesis of Increased Anti -tumor Activity with VBIR -2 To date, anti -tumor activity with current clinical trial vaccines have been encouraging but not yet significantly superior to other clinical immunotherapy trials. We exp ect VBIR -2 to overcome previous vaccine shortcomings (poor target choice, ineffective vaccine technology , immunosuppressive tumor microenvironment) based on the following design improvements: (a) Instead of selecting single antigens and in most cases sing le epitopes as tumor associated antigens (TAAs), VBI R-2 applied a stringent selection and validation process of indication -specific tumor associated antigens (TAAs) (Section 1.3.2). To avert tumor escape and target a broader major histocompatibility complex (MHC) restriction -independent patient population, VBIR -2 encodes three TAA proteins instead of onl y single -antigen protein or peptides; (b)To maximize the TAA -specific immunogenicity , a potent heterologous AdC68 prime/pDNA boost vaccination regimen combined with concomitant tremelimumab administration was selected to boost an enhanced induction and expansion of TAA -specific T cells; (c) To maintain the functio nality of TAA -specific T cells in an immunosuppressive tumor microenvironment, sasanlimab injections are given with every vaccine administration. The combination of all four components (vaccine prime, pDNA boost, anti -CTL A-4 tremelimumab, anti- PD-1sasanl imab) may allow for the induction and maintenance of high titers of durable and functional TAA- specific immune responses. 1.3.2. Selection of Vaccine Antigens (MUC1, MSLN, TERT) A multi -antigen, multi -indication VBIR -2 offers the potential benefit of mitigating t he risk of immune escape b y the tumor while increasing the likelihood of activating tumor -specific immune responses in a broad patient population. The 3TAAs ( MUC1, MSL N, and TERT) were selected based on the following 2criteria: 1) Over expression in NSC LC and TNBC tumors in comparison to surrounding healthy tissues (Pfizer Internal Report VR-VTR -10375: Evaluation of MUC1, MSL N and TERT Antigen Expression in Human Tumor Tissues via I mmunohistochemical Anal ysis), and 2) Evidence that cellular and/or humora l immune responses to the selected antigens correlate with clinical activity with acceptable safet y profile in the clinic .37,88,89 Evidence for selecting the 3 antigens, based on the above criteria, is a follows. Human tumor tissues from different stages of NSCL C (n=100) and TNBC (n=32) and five additional solid tumors spanning different stages including some metastatic tissues were evaluated b y IHC. According to the H -score classification using an antigen- specific semi -quantitative IHC assay , positive anti -MUC1 and anti -TERT staining was detected in the majority of NSCLC and TNBC cancer tissues evaluated (94% and 100% of TNBC and 79% and 91% of NSCL C, respectivel y). Additionally anti-MSLN -staining was detected in 56% of TNBC and 30% of NSCL C tumor tissues analy zed. Consistent with literature, the results confirmed good coverage of the different stages of TNBC and NSCL C by the three antigens.90 Consequently , PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 45MUC1, MSLN, and TERT were selected as vaccine antigens of VBIR -2. High level expression of these antigens were also found in ovarian and pancreatic cancers suggesting these cancer t ypes as additional promising target indications. Antigen Descriptions MUC1 (mucin 1, cell surface associated): MUC1 is a heavily glycosylated transmembrane protein generally expressed on the epithelial surface of a variet y of organs, where it serves a protective function against toxin or pathogen infiltration into internal tissues. MUC1 has been used as a safe vaccine target antigen, and clinical trial results have shown direct correlation between MUC1- specific immunogenicity and clinical activit y.93 In a Phase 2b part of a randomize d, double -blind, placebo -controlled, Phase 2b/3 trial, n = 222 previously untreated patients were enrolled with stage IV NSCL C without a known activating EGFR mutation and with MUC1 expression in at least 50% of tumor cells. Patients were randomized 1:1 t o TG4010 vaccine, which delivers full -length human MUC1 and human IL -2 by a recombinant vaccinia virus (n = 111) or placebo (n= 111) from the beginning of chemotherapy every week for 6 weeks and then every 3weeks up to progression or discontinuation due t o toxicity . The median overall survival (mOS) for non-squamous (non -sq) NSCL C was 14.6 months in the vaccine + chemotherap y arm versus 10.8 months in the placebo + chemotherap y arm. No Grade 3 or 4 or serious adverse events were deemed to be related to T G4010 only . TERT (telomerase reverse transcriptase): Human TERT is the catal ytic subunit of the telomerase enzy me which functions to increase the number of telomere DNA repeats protecting chromosome ends, extending the replicative capacity of the DNA. In health y tissues, TERT activity is minimal, ensuring that cells are able to replicate only for a fixed number of times. A few human cell ty pes with increased replication requirements, such as stem cells or germline cells, or activated l ymphocy tes, show increased TERT expression.95,96 TERT ove rexpression is extremely prevalent in almost all cancer t ypes. In general terms, e levated TERT levels are present in over 85% of tumors where increased cellular life span has been observed .97 In a clinical trial with canine B cell ly mphosarcoma animals, animals that received ChTx plus the canine TERT vaccine demonstrated induction of TERT -specific cellular responses and almost tripled the mOS compared to the ChTx- only control arm.89Moreover, in a phase I/II trial with 22 previously treated stage III-IV NSCL C patients, patients showing a n increased immune response to the Vx- 001 TERT -specific vaccine showed a significantly increased mTTP and mOS.98The correlation of anti -TERT immun e responses and increased survival, manageable safety profile as well as the expression of TERT on almost all cancers, make TERT an attractive cancer vaccine target . More specificall y related to NSCL C, TERT is overexpressed in more than 85% of NSCL C and i s associated with poor prognosis.98 Ina recent Phase I /II trial with 22 previously treated stage III- IV NSCLC patients, subjects showing an immune response to the Vx -001 TERT -specific vaccine showed an increased median time to progression ( mTTP )and median overall survival ( mOS ) relative to those with no evidence of T cell response .37TERT572 specific T -cell responders had a mTTP of 4.2 months (immune responders, n=16) versu s PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 462.1months (non-responders, n=5); p=0.046 and a mOS of 30 months (immune responders, n= 16) v ersus 4.1 months (non- immune responders, n=5); p=0.012 .37 The subcutaneousl y administered TERT572 peptide vaccine + Montanide was well tolerated with th e main toxicity being local skin reactions seen in n=8 (36.4%)of subjects. MSLN (mesothelin): Human MSL N is a gl ycophosphatidylinositol (GPI) -anchored glycoprotein present on the surface of cells lining the pleura, peritoneum and pericardium, and is invol ved in cellular recognition and/or adhesion145. The MSL N gene encodes a 71-kilodalton (kDa) precursor protein that is processed to a 40 -kDa Mesotheli n membrane -bound protein and a 31 -kDa secreted megakary ocyte potentiating factor (MPF) protein.90 MS LN is overexpressed in several human tumors including NSCLC (reference IHC Pfizer internal study report VR- VTR -10375), mesothelioma, ovarian, pancreatic adenocarcinoma, and triple -negative breast cancer.90 In two phase II trials with pancreatic cancer patients, the cancer vaccine (GVAX) pancreatic vaccine induced MSL N -specific cellular responses; the increased response magnitude/or correlated with increased disease -free survival and/or overall survival, making it an attractive cancer vaccine candidate.88 ,89In terms of the amount of MSL N within NSCL C, human tumor tissues from different stages of NSCLC have been evaluated by IHC.90 According to the H- score classification using an antigen -specific semi -quantitative I HC assay , anti -MSL N -staining was detected in 30% of NSCLC tumors. From the standpoint of clinical utility , a live - attenuated Listeria monocytogene (LM) engineered to express MSLN (CRS -207) was us ed in a Phase 1 trial, to vaccinate 17 treatment refractory patients (3 with NSCL C) in a dose escalation of up to 4 intravenous doses at 21 day intervals. CRS -207 was well tolerated with 37% of the patient population surviving for >15 months including 2/3 with NSCL C.146 MSL N specific immune responses recorded and SD reported in 1 NSCLC patient. Summary of Components of VBIR -2 VBIR -2 (PF -06936308) for advanced NSCL C and mTNBC consists of the following components: 1.A priming immunization administered IM with a replication -deficient adenovirus vector derived from chimpanzee that expresses three tumor- associated antigens – MUC1, MSLN, and TERT (AdC68, PF-06871923); 2.Boost vaccinations with plasmid deoxy ribonucleic acid (PF - 06871925, pDNA), encoding the same three antigens administered IM with an electroporation device [intramuscular TriGrid Delivery System Version 2.0 (TDS -IM) V 2.0]; 3.An anti -CTLA4 monoclonal antibody tremelimumab (PF -06753388) given SC in conjunction with each vaccination; and 4.An anti -PD-1 monoclonal antibody sasanlimab (PF-06801591) also given SC in conjunction with each vaccination. PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 47Part 1 of C3621001 evaluated the safet y and tol erability of the vaccine components (AdC68 and pDNA) alone and in combination with increasing doses of tremelimumab and sasanlimab. Part 2 (Expansion) of the study will utilize the following doses: AdC68 6 ×1011 VP, 5 mg of pDNA, 80 mg of tremelimumab and 300 mg of sasanlimab. Tremelimumab will be given locall y by SC injection with the priming and boost vaccinations. This monoclonal antibody has been shown to increase responder frequency and enhance the breadth and magnitude of the T -cell response to the selected cancer vaccine antigens. Sasanlimab , is a humanized, hinge region -stabilized IgG4 monoclonal antibody (mAb) specific for human PD -1that can selectively and reversibl y bind to human PD -1, thereb yblocking the interaction between PD -1and PD -L1/programmed death -ligand 2 (PD-L2). It will be injected subcutaneousl y at an anatomic location close to the injection sites of the vaccine vector and tremelimumab. The objective of using sasanlimab is to help maintain the activity of VBIR -induced T cells du ring the activation, expansion, and the intra - turmoral effector phase of antigen -specific T cell responses. 1.4. Nonclinical Safety 1.4.1. Nonclinical Toxicity Study for VBIR -2 The local and s ystemic toxicity of AdC68/pDNA+tremelimumab was assessed with and without sasanlimab in sexually mature cy nomolgus monkey s. AdC68 (6 x 1011viral particles (VP)/animal) plus tremelimumab (150 mg/animal) with and without sasanlimab (20 mg/kg) were administered on Day 1 (prime), followed b y 2 boost doses of pDNA (5 mg/animal) plus tremelimumab (150 mg/animal) with and without sasanlimab (20mg/kg) administered 28 and 56 day s later. The number of doses is supported by data indicating that the TAA -specific CD8 and CD4 IFN T-cell titers reached a plateau following one AdC68 priming d ose and two pDNA boosts. Necropsy was conducted 8 and 29 day s following the last boost dose administered. The toxicokinetics of sasanlimab and tremelimumab and the immunogenicit y of sasanlimab , tremelimumab, TERT, MUC1, and MSL N were evaluated. The sy stemic exposure of tremelimumab was higher (~2.6x) in females compared to males, at the fixed dose of 150 mg. The male bod y weights were ~2.3x those of females (6.9 to 8.8 kg for males and 3.0 to 3.9 kg for females). Therefore, the observed difference in exposure between males and females was attributed to differences in bod y weight. The systemic exposure of sasanlimab (dose adjusted for body weight; 20 mg/kg) was similar in male and female animals. For tremelimumab, exposure was similar in cy nomolgus monk eys administered AdC68/pDNA+tremelimumab alone or with sasanlimab . In general, exposures for both tremelimumab and sasanlimab were lower on Day s 29 and 57 compared with Day 1, due to anti -drug antibodies (ADA). The incidence of ADA (on Day 57) to tremeli mumab was 60% in cy nomolgus monkey s administered AdC68/pDNA+tremelimumab and 90% PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 48when co-administered with sasanlimab . The incidence of ADA to sasanlimab when co-administered with tremelimumab was 100%. Administration of AdC68/pDNA+tremelimumab alone or with sasanlimab was not associated with an y effects on clinical signs, bod y weights or bod y weight changes, food consumption, ophthalmology , electrocardiology , body temperature, urinal ysis, gross pathology , or organ weights. I njection site reactions were observed on Days 29 and 57 in cynomolgus monkey s administered AdC68/pDNA+tremelimumab alone or with sasanlimab . Following the first dose (Day s 3-8) and at the end of the dosing phase, administration of AdC68/pDNA+tremelimumab alone or with sasanlimab was associated with transient, nonadverse changes in clinical pathology parameters including increased ly mphocy tes, monocy tes, basophils, large unstained cells, fibrinogen, globulins, and C -reactive protein compared to control values that were interpreted to b e in response to immune stimulation following vaccine administration. Administration of AdC68/pDNA+tremelimumab alone or with sasanlimab to cy nomolgus monkey s was not associated with any macroscopic observations or organ weight changes at the end of the dosing or recovery phases of the study (Day s 65 and 86, respectivel y). Microscopicall y, AdC68/pDNA+tremelimumab -and/or AdC68/pDNA+tremelimumab+ sasanlimab -related increases in mononuclear cell infiltrates in the pituitary gland, pancreas, heart, urinary bladder, sciatic nerve, and injection sites were observed. This finding was adverse in the pituitary gland of one female treated with AdC68/pDNA+tremelimumab + sasanlimab at the end of the dosing phase due to increased severity and the widespread infiltra tive nature of the mononuclear cells; however, no mononuclear cell infiltrates were present in an y monkeys treated with AdC68/pDNA+tremelimumab + sasanlimab at the end of the recovery phase (Day 86). Minimal treatment -related nonadverse pituitary gland infiltrates were present in AdC68/pDNA+tremelimumab -treated males at both the end of dosing and end of recovery phase. The female animal noted previously with mononuclear cell infiltrates in the pituitary gland also had nonadverse scattered multifocal perivascular infiltrates of ly mphocy tes and plasma cells in the pancreas. This female also had the highest exposure to tremelimumab on Day s 29 and 57 of the ten animals in the dose group (eg, Area Under the Curve (AUC)= 74,400 µg ·h/mL for this female on Day 57, compared with a mean AUC of 20,700 µg·h/mL for the remaining 4 animals in the group), and did not have detectable ADA to tremelimumab at the completion of the dosing period . Exposure to tremelimumab and other anti -CTL A4 or anti -PD-1 inhibitors has been previously associated with pituitary mononuclear cell infiltrates in monkey s and hy pophy sitis in humans.52,53 In the heart and urinary bladder, treatment -related mononuclear cell infiltrates were interpreted to reflect an exacerbation of background findings and were full y recovered by the end of the recovery phase on Day 86. The chronic active inflammation observed at the injection sites was reversible and a ty pical finding related to IM and SC injections.54,55,56,57,58,59,60,61 Infiltrates in and around the sciatic nerve were minimal and were fully reversed in AdC68/pDNA+tremelimumab - treated monkey s and partially reversed in monkey s treated with AdC68/pDNA+tremelimumab + sasanlimab . PF-06936308 C3621001Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 49A robust increase in IFN- γcellular responses to each of the vaccine antigens (MSLN, MUC1 and TERT) and a robust serum immunoglobulin G (IgG) antibody response to both MUC1 and MSLN were seen in all animals in both the AdC68/pDNA+tremelimumab alone or with sasanlimab dose groups post-vaccination. In summary, administration of a repeat dose (once per 28 days) of AdC68/pDNA+tremelimumab alone or with sasanlimab in sexually mature cynomolgus monkeys was generally well tolerated. 1.5. Clinical Overview Part 1 will enroll up to 40 participants at escalating doses of the VBIR-2 regimen. The clinical experience with PF-06936308 support the safety and design of Protocol C3621001 and the continuation of the clinical development of PF-06936308 in participants with NSCLC. 1.6. Dose Rationale Below are listed the rationales for the doses of the various components: 1.6.1. Clinical AdC68 (PF-06871923) Dosing Anticipated efficacy and safety were considered when selecting the AdC68 dose range for clinical testing. The dose ranges of 1 x 10 9to 5 x 1011VP of a modified adenovirus antigen delivery system have shown a tolerable safety profile in participants with colorectal cancer as well as dose-dependent immune responses to a self-antigen.62 Previously, high doses of different adenovirus vectors were evaluated preclinically. The absence of germ linetransmission was demonstrated in mice and baboons. 63,64 In a separate study in nonhuman primates (NHPs), a dose of 5 x 1012VP/kg was found to be well tolerated.65 Importantly, repeated administration did not appear to alter the toxicity/tolerability profile.66 It is also important to note that these animals were dosed IV per kg body weight, making the total dose substantially higher than the highest dose planned in this study (6 x 10 11VP IM total dose). CCI PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 50Furthermore, since the administration in this study is IM, the s ystemic safet y profile is anticipated to be more favorable.63 Higher doses of adenovirus, up to 2 x 1011VP/kg (total dose in excess of 1 x 1013VP), when admin istered directly into the hepatic artery are tolerated in pa rticipant s with partial ornithine transcarbam ylase deficiency .67 In the VBI R -2 nonclinical toxicity study (AdC68, pDNA, tremelimumab and sasanlimab ) in monkey s, the safet y and VBIR -2 antigen -specific T -cell responses were evaluated following administration of AdC68 at 6 x 1011VP using the same dosing frequency as planned for the VBIR -2 Phase 1 study . As described in Section 1.4, findings were limited t o the injection sites and the draining lymph nodes, as well as mononuclear cell infiltrates in a number of tissues, consistent with those observed with other anti -CTL A4 or anti -PD-1 inhibitors. Administration of AdC68 at 6 x 1011VP with tremelimumab and sasanlimab led to substantial and sustained increases in MUC1 -, MSLN -, and TERT -specific IFN -T-cell responses, which were further boosted b y the pDNA with tremelimumab and sasanlimab treatment. Thus, the AdC68 dose at 6 x 1011VP was generall y safe and efficacious in inducing immune responses in monkey s. Based on the above pre -clinical safet y and VBIR -2 antigen -specific immune response data in NHPs, and the clinical safety data from the ongoing Prostate Cancer VBI R study (PrCa VBIR)99(also using 6 x 1011VP administered I M), a dose of 2 x 1011VP administered I M has been selected as the starting dose for AdC68 in Part 1 of the study . The highest dose of AdC68 planned to be elevated in this study is 6 x 1011VP. 1.6.2. Clinical pDNA (PF- 0681925) Dosing Efficacy and safet y were factors considered to select the pDNA dose for clinical testing. DNA doses of 0.2 to 8mg have been reportedl y delivered in clin ical trials by other sponsors using the Ichor Intramuscular TriGrid Delivery System (TDS -IM) electroporation device. In NHPs, the data collected to date demonstrated that electroporation of a DNA dose of 5 mg can effectively and reproducibly boost AdC68 vector primed IFN- CD8 T -cell responses to a self -antigen in the presence of tremelimumab. A pDNA dose of 10 mg was well tolerated but no significant benefit on the magnitude or responder frequency of the IFN -CD8 T-cell response was observed (the result s are from PrCaVBIR NHP studies; VR- VTR -10228; The Impact of pDNA Dose on Vaccine -Specific Immune Responses at Boost Vaccinations). Thus, a dose of 5 mg is selected for the pDNA for clinical testing. 1.6.3. Clinical Tremelimumab (PF -06753388) Dosing More than 1000 participants with cancer have been treated with tremelimumab as single -agent or in combination with another anti -cancer treatment. Clinical safet y data for tremelimumab, at intravenous (IV) doses ranging from 0.01 to 15 mg/kg, indicate an acceptable sa fety profile in participants with cancer. The established maximum tolerated dose (MTD) for single -agent therap y is 15 mg/kg IV every 12 weeks, a dose level that has been extensively studied in a Phase 3trial in participants with melanoma.101 Diarrhea, pruritus, and rash were the most common treatment -related adverse events (AEs) associated PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 51with tremelimumab. Another important event observed related to tremelimumab was hypopituitarism. Monthly dosing, as planned for this study, was tested in the clinic in participants with melanoma, where administration of up to 10 mg/kg IV monthly ,102was tolerated with no dose-limiting toxicity observed. The most frequent treatment-related AEs being diarrhea, rash, and pruritus. Frequency of Grade 3/4AEs was 27% in the participants dosed with 10mg/kg tremelimumab alone, compared to 16.3 % in participants treated with nivolumab alone, and 27.3 % of participants treated with ipilimumab alone. Treatment- related adverse events leading to therap y discontinuation occurred in 36.4, 7.7, and 14.8 % of participants, respectivel y (most commonly diarrhea, fatigue, and pruritus). 1.6.4. Clinical S asanlimab Dosing Binding of the programmed cell death protein -1ligands, PD -L1and PD- L2, to the programmed cell death protein- 1 (PD -1)receptor found on T cells inhibits T -cell proliferation, cy tokine production, and its cy totoxic functions. Upregulation of PD -1ligands occurs in certain tumor ty pes, and signaling through this pathway can contribute to the inhibition of active T- cell immune surveillance of tumors.103 In syngeneic mouse tumor models, blocking PD - 1activity resulted in decreased tumor growth. Approval of nivolumab/Opdivo (a fully human immunoglobulin G4 [IgG4] anti -PD-1antibody [Ab]), pembrolizumab/Key truda(a humanized IgG4 anti-PD-1Ab), Atezolizumab/Tecentriq (a humanized IgG1 anti-PD-L1Ab), durvalumab/I mfizi®(a humanize IgG1 anti- PD- 1 antibody ), and avelumab/Bavencio (afully human IgG1 anti -PD-L1Ab) for the treatment of multiple tumor indications provide compelling evidence that blockage of the PD- 1pathway is a validated immunotherapeutic approach (Opdivo®United States Package Insert (USPI), 2020; Tecentriq®USPI, 2019; Key truda®USPI , 2020; ImfinziTMUSPI , 2020; Bavencio®USPI , 2019).104,105,106,107,108 1.6.4.1. Sasanlimab Clinical Experience B8011001 (NCT02573259) B8011001 is an ongoing Phase 1, open- label, multi- center , multiple -dose, dose escalation and expansion, safet y, PK, and PD study of sasanlimab. The primary purpose of this study is to evaluate safet y and early signs of efficacy. This clinical study was divided into a dose escalation (Part A) phase and a dose expansion (Part B) phase. One hundred fort y-six participants have been dosed on the study . No dose limiting toxicity was observed and there was no maximum tolerated dose identified. Part A Dose Escalation evaluated 4 pre-specified IV dose levels (0.5, 1, 3, and 10 mg/kg administered every 3 weeks [Q3W]), and 1 subcutaneous (SC) dose level (300 mg administered every 4 weeks [Q4W]) in adult participants with locally advanced or metastatic melanoma, squamous cell cancer of head and neck, ovarian cancer, sarc oma, small cell lung cancer, adenocarcinoma of salivary gland, endometrial adenocarcinoma, malignant peritoneal neoplasm, esophageal adenocarcinoma or renal cell carcinoma. Participant s had progressive disease on ≥1 prior line of therap y for locall y advan ced or metastatic disease or refused standard of care therap y; were not previously treated with an anti -PD-1/PD -L1agent; and PF-06936308 C3621001Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 52had adequate renal, bone marrow, liver, and cardiac function, with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Forty participants were enrolled into Part A with 25 participants total enrolled into the IV dose cohorts and 15 participants enrolled into the SC dose cohort. Part B Dose Expansion evaluated the 300 mg SC dose in a population of 106 participants. This included 68 participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) and 38 participants with locally advanced or metastatic urothelial carcinoma who were anti-PD-1 or anti-PD-L1 treatment-naïve and who had progressive disease on or were intolerant to systemic therapy or for whom standard of care systemic therapy was refused or unavailable. Participants with NSCLC could have received up to 1 line of prior systemic therapy for locally advanced or metastatic disease and if they had known epidermal growth factor receptor (EGFR) activating mutation or an anaplastic lymphoma kinase (ALK) rearrangement were required to have, in addition, at least 1 targeted therapy for their disease. Participants with UC could have received up to 2 lines of prior systemic therapies for locally advanced or metastatic disease. The selected participants had adequate renal, bone marrow, liver, and cardiac function, with ECOG performance status 0 or 1. All participants received 300 mg of sasanlimab SC every 4 weeks. 1.6.4.2. Sasanlimab Clinical Experience in B7791001 (NCT#02616185) B7791001 is a study of a similar vaccine-based immunotherapy regimen in prostate cancer using prostate directed antigens (VBIR PrCA). CCI CCI PF-06936308 C3621001Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 531.6.5. Combination of CTLA-4 and PD-1 Monoclonal Antibodies: Safety Findings Available data suggest that, in both metastatic NSCLC, small-cell lung cancer (SCLC) and melanoma, combined PD-1 and CTLA-4 blockade produce a higher tumor response rate and longer disease control than PD-1 or CTLA-4 blockade alone. Unfortunately, these improved results are associated with an increased rate of toxicity. In the pretreated NSCLC population, pembrolizumab given iv at 2 or 10 mg/kg every 3 weeks combined with ipilimumab iv either at 1 or 3 mg/kg every 3 weeks for four doses was associated with 49% serious treatment-related adverse event rate, compared to 10% with pembrolizumab monotherapy. The most frequent serious adverse events were diarrhea in 6% and pneumonitis in 8% of participants. The recommended dosage for future trials was pembrolizumab 2 mg/kg plus ipilimumab 1 mg/kg both given every 3 weeks intravenously. 116 Similarly a combination of nivolumab (anti-PD-1) plus ipilimumab has been tested.35 Serious treatment-related adverse events were observed in 48% of participants; grade 3–4 adverse events were seen in 55% of participants (most commonly diarrhea, fatigue, and pruritus) compared to 16.3% in participants treated with nivolumab alone, and 27.3 % of participants treated with ipilimumab alone. Combined therapy resulted in 35% of participants discontinuing treatment as compared to 7.7% and 14.8% of participants treated with nivolumab and ipilimumab, respectively. In a Phase 1b study of durvalumab (anti-PD-1) and tremelimumab, there was an increased rate of serious adverse events of 42%, compared to 8% with durvalumab monotherapy. Durvalumab 20 mg/kg given iv every 4 weeks plus tremelimumab 3 mg/kg iv was more toxic, with an increased rate of diarrhea and colitis, without improved efficacy relative to tremelimumab 1 mg/kg. In participants with tremelimumab 1 mg/kg, most adverse events CCI PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 54were manageable and did not require treatment discontinuation. Overall, t reatment-related adverse events and grade 3 or 4 adverse events were more frequent with the regimen of durvalumab 10 mg/kg every 2 weeks plus tremelimumab 1 mg/kg , compared to the regimen with durvalumab 20 mg/kg every 4 weeks plus tremelimumab at 1 mg/kg. Given the above, durvalumab 20 mg/kg every 4 weeks plu s tremelimumab 1 mg/kg regimen has been selected for assessment in phase 3 studies .117,118 In a study of nivolumab alone and nivolumab plus ipilimumab in recurrent small- cell lung cancer (CheckMate 032),119two (2) schedules of administration were compared: nivolumab 1 mg/kg plus ipilimumab 3 mg/kg versus nivolumab 3 mg/kg plus ipilimumab 1 mg/kg. The percentage of grade 3 / 4 toxicities was 30% with 3mg/kg ipilimumab and 19% with 1 mg/kg ipilimumab. Considering the data reported in the literature about the combination anti -PD-1 (or PD -L1) and anti CTL A-4 inhibitor s, the dose and frequency of anti CTLA4 appears to be the major determi nant of toxicity , compared to dose levels of PD -1 or PD -L1. 1.6.6. Clinical Dosing VBIR - 2 The proposed VBIR -2 (PF -06936308) clinical dosage, dosage form, route of administration, and dosing regimen are outlined in Table 2. There are 2 treatment phases in VBIR - 2: (a) Active Treatme nt Phase: Each VBIR -2 cycle will be initiated with an intramuscular AdC68 prim ingvaccination accompanied b ysubcutaneous administrations of tremelimumab and sasanlimab . Three monthly intramuscular pDNA boost vaccinations byelectroporation , along with concomitant administrations of tremelimumab and sasanlimab subcutaneousl y will follow the AdC68 vaccination . The single AdC68 priming vaccination followed by 3pDNA boost vaccinations (each given monthly )conclude s 1treatment cy cleof 4months duration . The second treatment cy cle will be initiated with another priming of intramuscular AdC68 vaccination , with later boost vaccinations of pDNA, along with a subcutaneous administration of tremelimumab and sasanlimab , as noted for C ycle 1 . The second treatme nt cy cle will follow the same injection schedule as outlined for the first cy cle. The activities during the Active Treatment Phase are outlined in the Schedule of A ctivities for Active Treatment. (b) Maintenance Treatment Phase : Following the second treatment cy cle the participants enter a “Maintenance Phase”, consisting of monthly doses of sasanlimab with pDNA and tremelimumab, given at every - other -month intervals. A description of this Maintenance Phase is outlined in the Schedule of Activities for maintenance phase. PF-06936308 C3621001 Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 55Table 2. Expansion Phase Components, Dosage, Dosage Form, Route of Administration, and Dosing Regimen of the Vaccine -Based Imm unotherapy Regimen for NSCLC (See Section 5for detailed Study Treatment instructions.) Component Dosage FormDose Route of AdministrationDosing Regimen AdC68 Liquid 6e11 VP Bilateral IM injectionPriming dose (administered on Cycle 1 Day 1) pDNA* Liquid 5 mg Bilateral IM injection with electroporationEvery 4 weeks after AdC68 dose for a total of 3 doses Tremeli mumab* Liquid 80 mg Bilateral SC injectionEvery 4 weeks for a total of 4 doses per cycle given on the day of AdC68 or pDNA administration Sasanlimab** Liquid 300 mg Bilateral SC injectionEvery 4 weeks for a total of 4 doses given on the day of AdC68 or pDNA administration Abbreviations: AdC68 = Adenovirus C68; IM = Intramuscular; SC = Subcutaneous. *Maintenance Treatment Schedule for pDNA and tremelimumab after Month 8 will be administered every other month starting with Month 10. **M aintenance Treatment Schedule for sasanlimab starting at Month 9 will continue to be administered monthly. Treatment will be continued until disease progression, unacceptable toxicity, death, or participant’s or investigator’s decision. (1) Single Reference Safety Document f or VBIR -2 Additional information for VBI R-2 may be found in the single reference safety document (SRSD), which for this study is the PF -06936308 Investigator Brochure for: AdC68 (PF-06871923), plasmid DNA (PF -06871925), sasanlimab ( PF- 06801591) and tremelimumab (PF- 06753388). (2) Single Reference Safety Document for Intramuscular TriGrid Electroporation Delivery System The SRSD for the Ichor Intramuscular TriGrid Delivery System electroporation device is the Trigrid Delivery System Version 2.0 Investigator Brochure. Additional reference information can be found in the individual tremelimumab IB and the sasanlimab IB. PF-06936308 C3621001Final Protocol Amendment 2, 22 Dec 2020 PFIZER CONFIDENTIAL Page 562. STUDY OBJECTIVES AND ENDPOINTS 2.1. Part 1: Dose Escalation Objectives and Endpoints Primary Objective(s): Part 1 Primary Endpoint(s): Part 1 •To assess safety and tolerability of increasing dose levels of VBIR-2. •To characterize the dose limiting toxicities (DLTs) and overall safety profile of escalated doses of VBIR-2. •To assess safety and tolerability at increasing dose levels of VBIR-2 components in successive cohorts of participants s in order to estimate the Maximum Tolerated Dose (MTD) and select the Recommended Phase 2 Dose (RP2D)/schedule.•Incidence and grade of treatment-emergent adverse events including DLTs (following the 28-day DLT observation period). •Adverse Events as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy.