8.1.2.3. Analysis of other Secondary Endpoints 1.T cell immune response Protocol B7791001 Statistical Analysis Plan PFIZER CONFIDENTIAL Page 17The number of antigen -specific T cell s(expressed as SFC/million PBMC) for each prostate cancer antigen (or antigenic sub region) will be compared between pre-treatment and subsequent post treatment time points in two rounds of analy sis. The first round (Cycle 1 anal ysis)will compare the pretreatment response (Cy cle1 Day 1) to Cy cle 1 Day 15, Cy cle 1 Day 29, C ycle 1 Day 43 and C ycle 1 Day 71; the second round (C ycle 2 analy ses) will compare Cy cle 2 Day 1with remaining timepoints as Cycle 2 Day 29 and C ycle2 Day 99,or End of Treatment , and Cy cle 1 Day 1). Data from the maintenance period may be anal yzed in the same manner if deemed necessary . As appropriate, anal ysis of the immune response endpoints will include fold -change from baseline b y patient a nd fold -change in geometric mean (GM FR) by cohort (by Cycle). The immune response against each peptide pool (5 values: 1 for PSA, 1 for PSCA and 3 for PSMA ) may be anal yzed separately or per antigen (eg 3 PSMA summed) or all pooled to provide the overall T cell response to the selected prostate cancer antigens. In case the re is failure for Cycle 1 Day 1,the S creening sample would be used as the pretreatment sample. Number of t reatment- induced immune responses against the prostate cancer antigens will be defined as the numberof patients with an X -fold (e g,where Xcould defined as 2-fold, 4 -fold) increase in at least Y sampling time points (eg,Y=one time, Y=two timepoints) after treatment as compared to the Cycle1Day 1 (or Screening/Baseline sample if failure for C ycle 1 Day 1) for the same patient . Negative (media only )and positive (anti-CD3) control responses, as we ll as specific T cell responses observed to CMV, EBV, Flu and Tetanus Toxoid (CEFT) will be reported in a similar manner to the prostate cancer antigen data (ie,in two rounds of analy sis). 2.Antibody response specific to the PSMA antigen (Geometric Mean and Seroconversion) The LLOQ for the assay will be provided by the testing labs. Titers below the assay detection limit will be assigned a value of one -half that limit. Geometric Mean Titer :For the anal yses on antibody titer, least squares (ie,estimated) Geometric mean titer (GMT) will be calculated at baseline and post baseline . All statistical analy seswill be performed on the logarithmically (natural base) transformed titer values. See 10.1. Geometric Mean Fold Rise : The least squares ( ie,estimated) GMFR of th e post-vaccination titer value to theprevious titer level (other than at baseline) will be calculated, as well as the associated confidence interval and the median, minimal, and maximal n -fold increase. See 10.1. Protocol B7791001 Statistical Analysis Plan PFIZER CONFIDENTIAL Page 18Seroconversion : Number of patients from negative to positive (eg, k fold above the assay detection ) or with at least an X- foldincrease from baseline (eg ,k=2,3; X=2,4). 8.1.3. Exploratory (Part A) / Secondary (Part B) Efficacy Analyses In this First -In-Patient study anti -tumor activity is an exploratory objective. The main analysis populations will be based on mITT and EP. Tumor response, using RECIST , irRECIST , will be presented in the form of p atient data listings which include, but are not limited to tumor response assessed in comparison to baseline. Traditional response measures in solid tumors, such as ORR and PFS were developed to evaluate chemotherapies and can be unreliable for tracking re sponse to immunotherapies such as cancer vaccines . For example, apparent tumor burden may increase during the first few months of cancer vaccine treatment because of inflammation/T cell infiltration into tumors even in patients who go on to have durable responses. T ime to progression and number of patients with progression could be calculated from first vaccination ( Cycle 1 Day 1), but may also be calculated excluding those progress ions that happened before some specific timepoints ( eg,Day 57, Day 113).Time to response will be calculated from first vaccination ( Cycle 1 Day 1) to time of first response (ie, CR or PR). Additionally, total measurable tumor burden will be evaluated by the irR ECIST criteria that include responses after disease progression that are not captured by RECIST evaluation criteria in solid tumors. For tumor response data, the following anal yses may be performed: 1.Tumor response (CR, PR, SD, PD, etc.) b y cohort a nd visit, separatel y for RECI ST 1.1 and irRECI ST. Investigator provided tumor response will be presented by descriptive statistics (frequency and percentage). 2.Best overall response, b y cohort, across all available tumor assessments from both treatment per iod and maintenance period , separatel y for RECIST 1.1 and irRECI ST. Best overall response will be derived programmaticall y. In the tabular data presentation, a row of CR+PR will be added to show the results of ORR. With RECI ST 1.1, tumor response (CR or PR )confirmation is optional as response rate is not the primary endpoint of the study , hence unconfirmed best overall response will be derived and presented. With irRECI ST, tumor response (irCR or irPR) and disease progression (irPD) are required to be confirmed, however in this study tumor response confirmation is not required, therefore unconfirmed best overall response will be derived and presented. Descriptive statistics (frequency and percentage) will be provided. Selected a d-hoc efficacy anal yses(eg, ORR and radiographic PFS) combining p articipants from Cohorts 7A and 3B may be conducted, as participants in those two cohorts have identical or similar eligibility criteria for study entry and are scheduled to receive the same regimen. Protocol B7791001 Statistical Analysis Plan PFIZER CONFIDENTIAL Page 19Swimmer plots may be used to display duration of treatment and tumor response at each applicable time point. Waterfall plot for individual tumor size percent change from baseline,and spider plot for individual tumor size percent change from baseline over time may bepresented. These plots, if generated, will be presented for RECIST 1.1 and irRECIST separately. For the rPFS analysis in Part B, the Kaplan-Meier analysis may be performed if deemed necessary. If the Kaplan-Meier analysis is performed for radiographic progression-free survival, an event is defined as the first occurrence of “PD” status by investigator, or death, or a PCWG3 defined bone disease progression, whichever comes first, under RECIST. Time zero for all time-to-event analyses will be defined as the first vaccination on Cycle 1 Day 1. This analysis may be performed for the combined cohorts 7A and 3B. For duration of response per RECIST and time to response (from the first vaccination date to the time of the first response, CR or PR) in Part B, descriptive statistics will be provided.Kaplan-Meier analysis may be performed if deemed necessary. These analyses may be performed for the combined cohorts 7A and 3B.