The censoring date wi ll be determined from the date the subject was last known to be alive. Progression-free Survival (PFS) is defined as the time from cycle 1, day 1 of immunotherapy until first documented local progression or death due to any cause. Disease progression will be assessed usi ng RECIST (version 1.1). RECIST evaluation will be performed by the radiology staff de signated for completing RECIST reads for GI Oncology clinical trials conducted at the SKCCC at Johns Hopkins University. Due to the expectation that some patients may experience delayed clinical responses to therapy, patients with disease progressi on by radiographic imaging or laboratory parameters during a 12 week evaluation period but without rapid clinical deterioration or significant change in performance status that requires additional immediate therapy may continue to receive treatment on study. S ubjects that meet the above criteria and Phase 2 Study of GVAX (with CY) and pembrolizum ab in MMR-p advanced colorectal cancer J16154/Version 5/ January 17, 2018 57continue on study therapy must discontinue treatment upon documentation of disease progression on the second scan. The date of pr ogression will be b ackdated to the time of first RECIST criteria progression. Tumo r assessments will be made using RECIST 1.1 and immune-related respons e criteria (irRC). Local Progression-Free Survival (LPFS) is defined as the duration of time from start of treatment to time of first documented local progression or death due to any cause, whichever occurs first. Individuals will be censored at the date of the last scan for PFS and LPFS if no event occurs. Duration of response (ROR) will be calculate d for subjects who achieve a best overall response of CR or PR with GVAX in combination with pembrolizumab. For such subjects, duration of response is defined as the number of weeks from the start date of PR or CR (whichever response is recorded first) and subsequently confirmed to the first date that recurrent or progressive disease or death is documented. In such cases, recurrent or progressive disease will be assessed relative to the smallest tumor measurements recorded since the start of study treatment. The pr imary analysis of duration of response will be based on the time point responses, best overall response, and PD status that are determined by the review of th e investigator. OR, PFS, LPFS, and DOR will be summarized descriptively using the Kaplan-Meier method. Analysis of PFS, LPFS, and DOR will be restricted to evaluable individuals who complete at least two doses of combination therapy and have at least one follow-up scan, while the analysis of OS will be performed on all evaluable patients as well as all the individuals who complete at least one dos e of pembrolizumab/GVAX. Median event-free survival will be repor ted and the associat ed 95% confidence interval will be estimated using the method of [45]. 12.3.3 Analysis of Safety Endpoints The safety analysis will be performed in all subjects who receiv e any amount of study drug. A baseline measurement and at least 1 laboratory or othe r safety-related measurement obtained after at least 1 dos e of study treatment may be required for inclusion in the analysis of a specific safety parameter (e .g., lab shifts from baseline). A complete list of all AE data will be provided along with an assessment of NCI CTCAE grade and relationship to study drug. The incidence of AEs will be tabulated by subgroups of interest (e.g. grade 3 or high er, organ class, relationship to study drug). For analyses at the indi vidual level, the highest grad e and relationship to study drug will be assumed if multiple events have occurred. Toxicity will be tabulated by type and grade and will be summarized with descriptive statistics . Other safety data will be assessed in terms of physical exam ination, clinical chemistry, hematology, vital signs, and ECGs. Negative binomial regression and Cox proportional hazards models will be used to assess the rate of AE and time to first toxicity, respectively. Phase 2 Study of GVAX (with CY) and pembrolizum ab in MMR-p advanced colorectal cancer J16154/Version 5/ January 17, 2018 5812.3.4 Biomarker Analysis Intratumoral changes in pre- and post-treatm ent core biopsy specimens at week 6 and at the time of progression, if available, will be studied using immunohistochemistry (IHC) and transcriptional analysis. The immune parameters include suppressive pathways (including PD-L2, LAG3, BTLA , TIM3, IDO1, CTLA-4, and Tregs), activation pathways (inclu ding CD137, OX40, CD40, CD40L), cytokines/chemokines or their recepto rs (including CCL12, CXCR4, CCL2, CCL5, CCR2, CCR5). Change standard protein biomarkers such as CEA will be evaluated after each pembrolizumab/GVAX treatment. De scriptive statistic s for both pre and post administration of each immunotherapy and the differences in immune parameters will be computed. Plots will be used to show the changes in immune response over time both for each individual and for each arm. Continuous variables will be summarized with means or medians and standard deviations. Dichotomous and categorical variables will be summarized using proportions with exact 95% confidence intervals and counts. For each im munotherapy, comparisons in the pre and 28 day post-immunotherapy responses will be compared using paired t-tests (or Wilcoxon signed-rank tests if appropriate) for continuous variables and McNemar's tests for dichotomous variables. Associations between immune parameters will be explored graphically (e.g. scatterplots, boxplots) and nu merically (e.g. correlations, χ 2 tests). Regression techniques (linear, logis tic, linear mixed effects models) will be used to explore the differences between the treatment arms cross-sectionally as well as longitudinally. The associations betw een immune parameters and clinical outcomes (OS and DFS) will be evaluated using univariate and multivariate Cox regression models. Analyses will be perfor med using data from all evaluable patients and from the subgroup of patients who receive at least one immunotherapies. Sensitivity analyses will be carried out to ev aluate the extent to which results of data analyses can be affected by early dropouts. The significance level is set at 0.05 for all tests in this phase 2 study. Phase 2 Study of GVAX (with CY) and pembrolizum ab in MMR-p advanced colorectal cancer J16154/Version 5/ January 17, 2018 59REFERENCES 1. The American Cancer Society.