PSA kineticsPSA, PSA velocity, PSA slope and PSA doubling time (PSADT); PSA will be provided from laboratory data. PSA velocity is defined as the slope of the linear regression line of PSA against time in month. PSA slope is the slope of the linear regression line of natural log of PSA against time in month. PSA doubling time is defined as the natural log of 2 divided by the slope of the linear regression line of the natural log of PSA against time in month (see 10.2). These analyses will be conducted both for Central PSA and Local PSA in separate tables. PSA kinetics will be presented at individual level by timepoint (listings and plots). Mean % and absolute change from baseline in PSA kinetics may be presented by cohort. To report PSA-based outcomes, PCWG3 recommends that the percentage of change in PSA from baseline, as well as the maximum decline in PSA, PSA velocity, PSADT and PSA slope that occurs at any point after treatment be reported for each patient using a waterfall plot. Waterfall plots provide a broader and more sensitive display of data, and are more informative until a validated surrogate of clinical benefit is available. A PSA-50 response rate may be calculated by cohort . PSA-50 response rate is defined as the proportion of patients whose on-study PSA declined from baseline by at least 50% at two consecutive measurements at least 3 weeks apart, prior to other systematic anti-cancer therapy. For the subset of PSA-50 responders, a duration of PSA-50 response will be summarized. Duration of PSA-50 response is defined as the period between the first CCI CCI Protocol B7791001 Statistical Analysis Plan PFIZER CONFIDENTIAL Page 20measurement when PSA -50 response was achieved to the measurement when PSA -50 response no longer holds. Swimmer plots may be used to display duration of treatment and PSA values at each applicable time point. CTC The frequency of “traditional” and “all candidate” CTCs in whole blood each expressed as CTC/mL will be assessed in pre treatment (Screening, C ycle 1 Day 1) and post treatment ( eg. Cycle 1 Day 71, C ycle 2 Day 1, Cycle 2 Day 29, Cy cle 2 Day 99,and End of Treatment) samples. Anal ysis of the CTC endpoints may include absolute CTC and fold- change from baseline (pretreatment) by patient a nd % change and mean fold -change b y cohort. MDSC The percentage of MDSCs will be assessed in pretreatment (Screening, Cy cle 1 Day 1) and post treatment samples. MDSC levels will be presented per patient and per cohort b y GMTs and GM FRs. Anal yses of MD SC endpoints may include absolute and fold -change from baseline (pretreatme nt) by patient and % change and mean fold -change b y cohort. Bone scan assessment Given the frequency of bone involvement in patients with progressive, castration -resistant disease, the decreased emphasis of earl y changes in PSA, and the increased availabi lity of cytostatic agents, reliable methods to assess changes in bone are of increasing importance. PCWG 3recognizes that standards for using MRI and PET to assess bone metastases are under active investigation, so only radionuclide bone scans are conside red here. PCWG 3 also recognizes that there are no validated criteria for response on radionuclide bone scan. For control/relieve/eliminate end points, the PCWG 3recommends that post -treatment changes be recorded simply as either “no new lesions” or “new lesions.” However, progression at the first scheduled assessment should be confirmed on a second scan performed 6 or more weeks later, in the absence of clearl y worsening disease or disease -related s ymptoms. In the event of visible lesions disappear ing, this should also be confirmed at the next scheduled assessment. For prevent/delay end points, progressing disease on bone scan is considered when a minimum of two new lesions is observed. PCWG 3does not recommend performing a follow -up bone scan before 12 weeks of treatment unless clinically indicated. At the first 12-week reassessment, defining disease progression requires a confirmatory scan (which shows additional new lesions compared with the first follow- up scan) performed 6 or more weeks later, because lesions visible at the first 12-week assessment may represent disease that was not detected on the pretreatment scan. When further progression is documented on the confirmatory scan, the date of progression recorded for the trial, is the date of th e first scan that shows the change. Protocol B7791001 Statistical Analysis Plan PFIZER CONFIDENTIAL Page 21Correlative analyses Plots may be generated to display PSA kinetics vs. PSA antibodies (serology: Luminex assay). Similar plots may be generated to evaluate individual patient trends on MDSC, CTC and T-cell response.