, tachycardia, enlarged liver) or the abnormal results of an investigation (e.g. , laboratory findings, electrocardiogram). Medical conditions /diseases present before starting the study treatment are only considered adverse events if they worsen after starting the study treatment (any procedures specifi ed in the protocol). Adverse events occurring before starting the study tr eatment but after signing the informed consent form will not be recorded. Abnor mal laboratory values or test results constitute adverse events only if they induce clinical signs or symptoms or require therapy. 6.1.2 Serious Adverse Event (SAE) A serious adverse event is an undesira ble sign, symptom or medical condition which: • Results in death • Is life threatening (defined as an event in which the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe) • Requires inpatient hospitalization or causes prolongation of existing hospitalization (see note belo w for exceptions) > 24 hours • Results in persistent or si gnificant disability/incapacity • Is a congenital anomaly/birth defe ct (note: reports of congenital anomalies/birth defects must also be reported on the Pregnancy Supplemental Form) • Is an important medical event (defined as a medical event(s) that may not be immediately life-threatening or result in death or hospita lization but, based upon appropriate medical and scientific judgment, may jeopardize the subject or may require intervention [eg, medical, surgical] to prevent one of the other serious outcomes listed in the definition above.). Examples of such events include, but are not limited to, intensive treatment in an emergency room or at home for allergic bronchospasm; blood dys crasias or convulsi ons that do not result in hospitalization.) • Is a new cancer (that is no t a condition of the study) • Is associated with an overdose Events not considered to be seriou s adverse events are hosp italizations for the: • Admissions as per protocol for a pla nned medical/surgical procedure or to facilitate a procedure • Routine health assessment requiring ad mission for baseline/trending of health status (eg, routine colonoscopy) Phase 2 Study of GVAX (with CY) and pembrolizum ab in MMR-p advanced colorectal cancer J16154/Version 5 / January 17, 2018 37• Medical/surgical admission for purpose other than remedying ill health state and was planned prior to entry into the study. Appropriate documentation is required in these cases • Admission encountered for another life ci rcumstance that carries no bearing on health status and requir es no medical/surgical inte rvention (eg, lack of housing, economic inadequacy, care-giver respite, family circumstances, administrative). 6.1.3 Adverse Events of Clinical In terest (ECI) for pembrolizumab Selected non-serious and serious adverse events are also known as Events of Clinical Interest (ECI) a nd must be reported within 24 hours to the Sponsor and within 2 working days to Merck Global Safety using the form found in Appendix C . (Attn: Worldwide Product Safety; ). For the time period beginning when the consent form is signed until treatment allocation/randomization, any ECI, or follow up to an ECI, that occurs to any subject must be reported within 24 hours to the Sponsor and within 2 working days to Merck Global Safety if it causes the subject to be excluded from the trial, or is the result of a protocol-s pecified intervention, including but not limited to washout or discontinuation of usual therapy, diet, placebo treatment or a procedure. For the time period beginning at trea tment allocation/ra ndomization through 90 days following cessation of treatment , or 30 days following cessation of treatment if the subject in itiates new anticancer therapy, whichever is earlier, any ECI, or follow up to an ECI, whethe r or not related to Merck product, must be reported within 24 hours to the Sponsor and within 24 hours to Merck Global Safety. Events of clinical interest for this trial include:  An overdose of Merck's product, as defined in Section 4.5 , that is not associated with clinical symptoms or abnormal laboratory results.  An elevated AST or ALT lab value that is greater than or equal to 3X the upper limit of normal and an elevated tota l bilirubin lab value that is greater than or equal to 2X the upper limit of normal and, at the same time, an alkaline phosphatase lab value that is less than 2X the upper limit of normal, as determined by way of protocol -specified laboratory testing or unscheduled laboratory testing.* *Note: These criteria are based upon available regulatory guidance documents. The purpose of the criteria is to specify a th reshold of abnormal hepatic tests that may require an additional eval uation for an underlying etiology. 6.2 Relationship The relationship of an AE to the administ ration of the study drug is to be assessed by the investigator according to the following definitions: Phase 2 Study of GVAX (with CY) and pembrolizum ab in MMR-p advanced colorectal cancer J16154/Version 5 / January 17, 2018 38 No (unrelated, not related, no relation): The time course between the administration of study drug and the occurr ence or worsening of the adverse event rules out a causal relationship and another cause (concomitant drugs, therapies, complications, etc.) is suspected.  Yes (related): The time course between the admi nistration of study drug and the occurrence or worsening of the adverse even t is consistent with a causal relationship and no other cause (concomitant drugs, th erapies, complications, etc.) can be identified. The following factors should also be considered:  The temporal sequence from study drug ad ministration - The event should occur after the study drug is given. The length of time from study drug exposure to event should be evaluated in the clin ical context of the event.  Underlying, concomitant, intercurrent dis eases - Each report should be evaluated in the context of the natural history and c ourse of the disease being treated and any other disease the subject may have.  Concomitant medication - The other medi cations the subject is taking or the treatment the subject receives should be examined to determine whether any of them might be recognized to cause the event in question.  Known response pattern for this class of study drug - Clinical and/or preclinical data may indicate whether a particular res ponse is likely to be a class effect.  Exposure to physical and/or mental stresse s - The exposure to stress might induce adverse changes in the recipi ent and provide a logical a nd better explanation for the event. The pharmacology and pharmacokinetics of the study drug - The known pharmacologic properties (absorption, distri bution, metabolism, and excretion) of the study drug should be considered. Assessment of Grade: The investigator will make an assessment of grade for each AE and SAE reported during the study, which will be recorded in the CRF. The assessment will be based on the National Cancer Institute’s CTCAE (Ver sion 4.03) and graded as shown below: • Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; inte rvention not indicated • Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living • Grade 3: Severe or medically significan t but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self- care activities of daily living • Grade 4: Life-threatening consequen ces; urgent intervention indicated • Grade 5: Death related to AE Any AE that changes in grade during its cour se will be recorded in the CRF at the highest level experi ence by the subject. Phase 2 Study of GVAX (with CY) and pembrolizum ab in MMR-p advanced colorectal cancer J16154/Version 5 / January 17, 2018 39 6.3 Expectedness Unexpected adverse event: An adverse event, which varies in nature, intensity or frequency from information on the invest igational drug/agent provided in the Investigator’s Brochure, package insert or safety reports. Any a dverse event that is not included in the informed consent is considered “unexpected”.