Subject is permanently discontinued from further trial treatment administration.No subsequent dosing Appropriate resuscitation equipment should be available in the room and a physician readily available during the period of drug administration. 4.2.3.2 Immune-Related Adverse Events (IRAEs) Blocking PD-1 function may permit the emergence of auto-reactive T cells and resultant clinical autoimmunity. Rash/pruritis, diarrhea/colitis, pneumonitis, hepatitis, and hypothyroidism were drug-related, presumptive autoimmune events, now termed IRAEs. For the purposes of this study, an IRAE is defined as an AE of unknown etiology, associated with drug exposure and is consistent with an immune phenomenon. Efforts should be made to rule out neopla stic, infectious, metabolic, toxin or other etiologic caus es prior to labeling an AE an IRAE. Serological, immunological, a nd histological (biopsy) da ta should be used to support the diagnosis of an immune-med iated toxicity. Susp ected IRAEs must Phase 2 Study of GVAX (with CY) and pembrolizum ab in MMR-p advanced colorectal cancer J16154/Version 5 / January 17, 2018 24be documented on an AE or SAE CRF. Identification and tr eatment of IRAEs can be found in Appendix B . 4.3 Prohibited and Restricted Therapies Patients may not use any of the following agents during the study:  Any non-study anticancer or immunothera py treatments (inve stigational or non-investigational)  Any other cancer immunotherapy treatments, including but not limited to: IL- 2, interferon, anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-PD-L2 antibodies, anti-CD137 antibodies, anti-OX-40 antibodies, anti-CD40 antibodies, anti-CTLA-4 antibodies, ther apeutic anticancer vaccines, cellular immunotherapies including chimeric antig en receptor–modified T cells, or bi- specific CD3 antibodies.  Systemically active steroids can be used but should be reported to the Principal Investigator and IND Sponsor. Steroid treatment should be titrated down to physiologic dosing prior to resuming study-related treatments (See Section 5.2 for dosing delays for steroids)  Filgrastim (Neupogen® or G-CSF) or sargramostim (Leukine® or GM-CSF)  Prophylactic vaccines (e.g., influenza, pneumococcal, Td/Tdap) within 28 days prior to or after dosi ng combination immunotherapy  Mistletoe 4.4 Dosing Criteria Dosing will be delayed for the following laboratory criteria :  AST, ALT > 3.0 x ULN  Total bilirubin >2.0 (patients with diagnos ed Gilbert’s Syndrome, direct bilirubin should be within normal institutional limits)  Hemoglobin < 8 g/dL  ANC < 1000/uL  Platelets < 75 x 103/uL 4.5 Definition of an Overdose for this Protocol Overdose of pembrolizumab is defined as: The patient has taken (accidentally or in tentionally) a dose of pembrolizumab of ≥1000mg ( ≥5 times the indicated dose). No spec ific information is available on the treatment of overdose of pembrolizumab. In the event of overdose, pembrolizumab should be discontinued and the subject should be obser ved closely for signs of toxicity. Appropriate supportive treatment should be provi ded if clinically indicated. Phase 2 Study of GVAX (with CY) and pembrolizum ab in MMR-p advanced colorectal cancer J16154/Version 5 / January 17, 2018 25 If an adverse experience(s) is associated with (“results from”) the overdose of test drug or vaccine, the adverse experience(s) is reported as a serious adverse experience, even if no other criteria for serious are met. If a dose of test drug or vaccine meeting th e protocol definition of overdose is taken without any associated clinical sympto ms or abnormal laboratory results, the overdose is reported as a non-serious Event of Clinical Interest (ECI), using the terminology “accidental or intentional overdose without adverse effect.” All reports of overdose with and without an adverse experience must be reported within 24 hours to the Sponsor and Merck Gl obal Safety. Merck Global Safety (GS) contact information can be found in Section 6.5.1 . 4.6 Contraception, Use in Pregnancy, Use in Nursing 4.6.1 Contraception The investigational agents may ha ve adverse effects on a fetus in utero . Furthermore, it is not known if the invest igational agents have tran sient adverse effects on the composition of sperm. Non-pregnant, non-br east-feeding women may be enrolled if they are considered highly unlikely to co nceive. Highly unlikel y to conceive is defined as 1) surgically sterilized, or 2) postmenopausal (a woman who is ≥45 years of age and has not had menses for grea ter than 2 years will be considered postmenopausal), or 3) amenorrheaic fo r <2 years without a hysterectomy and oophorectomy and with a documented FSH value in the postmenopausal range, or 4) not heterosexually active for the duration of the study, or 5) heterosexually active and willing to use 2 methods of birth control (which is also required for the female partners of male patients). The 2 birth control methods can be 2 barrier methods or a barrier method plus a hormonal method to prevent pregnancy, used throughout the study starting with Visit 1through 120 days af ter the last dose of study medication. Male patients enrolled in th is study must also agree to use an adequate method of contraception starting with Visit 1 through 120 days after the last dose of study drug. The following are considered adequate barr ier methods of contra ception: diaphragm, condom (by the partner), copper intrau terine device, sponge, or spermicide. Appropriate hormonal contraceptives will include any registered and marketed contraceptive agent that contains an estr ogen and/or a progestational agent (including oral, subcutaneous, intrauterine , or intramuscular agents). Patients should be informed that taki ng the study medication may involve unknown risks to the fetus (unborn baby) if pregnanc y were to occur duri ng the study. In order to participate in the study, they must a dhere to the contraception requirement (described above) for the duration of the st udy. If there is any question that a patient will not reliably comply w ith the requirements for contraception, that patient should not be entered into the study. 4.6.2 Use in Pregnancy Phase 2 Study of GVAX (with CY) and pembrolizum ab in MMR-p advanced colorectal cancer J16154/Version 5 / January 17, 2018 26The investigational agents may have adve rse effects on a fetus; therefore, women with a positive pregnancy test at screening will not be eligible for enrollment. If a patient inadvertently becomes pregnant while on treatment with combination immunotherapy, the patient will immediatel y be removed from the study. The site will contact the patient at least monthly and document the patient’s status until the pregnancy has been completed or terminate d. The outcome of the pregnancy will be reported to the Sponsor and to Merck Globa l Safety without delay. The outcome must be reported to the Sponsor within 24 hours and to Merck Global Safety if the outcome is a serious adverse experi ence (e.g., death, abortion, co ngenital anomaly, or other disabling or life-threatening complication to the mother or newborn). If a male patient’s partner becomes pregnant on study the pregnancy must be reported to the Sponsor and to Merck Global Safety as described in Section 6.5.1 . The study Investigator will make every effort to obt ain permission to follow the outcome of the pregnancy and report the condi tion of the fetus or newborn to the Sponsor and to Merck Global Safety. 4.6.3 Use in Nursing Women It is unknown whether the inve stigational agents are excreted in human milk. Since many drugs are excreted in human milk, a nd because of the potential for serious adverse reactions in the nursing infant, patients who are br east-feeding are not eligible for enrollment. 4.7 Dose Limiting Toxicity Unless otherwise specified below, un acceptable toxicities are defined as:  Treatment-related ≥ grade 4 AEs, or  Treatment-related grade 3 AEs that do not improve to ≤ grade 2 under supportive therapy within 3 weeks.  Death within 30 days of receiving inve stigational agent that is considered related to the agent as a study stopping criterion Hematologic toxicity The only adverse hematologic events that will be considered dose limiting are:  Grade 4 anemia related to study therapy  Grade 4 neutropenia that lasts > th an 7 days or febrile neutropenia  Grade 4 thrombocytopenia th at lasts greater than 7 days or has clinically significant bleeding Electrolyte aberrations  Unexpected Grade 3 or greater labor atory abnormalities should be repeated within 24-72 hours if clinically indi cated and monitored as necessary to determine if event meets toxicity criteria.  Patients may continue therapy without interruption for any electrolyte abnormality that can be corrected with intervention to < grade 2. Diarrhea/Colitis Phase 2 Study of GVAX (with CY) and pembrolizum ab in MMR-p advanced colorectal cancer J16154/Version 5 / January 17, 2018 27Grade 1 Asymptomatic pathologic or radiographic findings only Consider endoscopy to confirm Grade 2 Abdominal pain; mucus or blood in stool Endoscopy is indicated to confirm the etiology of the patient’s symptoms. Hold therapy, start lomotil and budesonide 9mg daily and start systemic steroids.