14.6. Tumor Mutation Burden Analysis Tumor Mutation Burden (TMB ) is the number of coding somatic base substitution and indel mutations occurring in a tumor specimen, per megabase (Mb) of coding genome assessed. Approximately 20 mLs of whole blood will be collected using cell free DNA collection tubes at the Week 1 visit prior to dosing. S amples will be shipped to, and analyzed by, Foundation Medicine using their FoundationACT® circulating tumor DNA (ctDNA) assay . Note that Cohort B patients enrolled prior to Amendment 5 that did not have a week 1 TMB sample collected should have this one-time lab drawn at the next feasible visit ( i.e. Week 4, 10, 16 or post -HS110/survival follow -up). Heat Biologics, Inc. Viagenpumatucel -L Protocol HS110 -102 CONFIDENTIAL Amendment 6, 24 May 2019 Page 65 of 95 15. SAFETY MONITORING 15.1. Adverse and S erious Adverse Events All patients will be assessed for pre -existing symptoms during screening (from the date of signature of ICF to immediately prior to first dose of study drug). Symptoms will be documented as AEs from the first dose of study drug until 4 weeks after the last dose of study drug (EOT ) or until death, whichever occurs first. Any AEs occurring after this time period will also be reported, if in the opinion of the Investigator, the event is deemed related to study drug. All AEs will be followed until the event has resolved or, in the case of permanent impairment, until the condi tion stabilizes. The Investigator is responsible for the detection and documentation of events meeting the criteria and definition of an AE or SAE, as provided in this protocol. During the study when there is a safety evaluation, the Investigator or site s taff will be responsible for detecting, documenting, and reporting AEs and SAEs . Adverse Event (AE) An AE is any untoward medical occurrence associated with the use of a medicinal product in humans, whether or not considered related to the medicinal produc t (Code of Federal Regulati ons (CFR) Title 21 part 312.32 [a] ). Note: an AE can, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e. , lack of efficacy), abuse, or misuse. A suspected adverse reaction (SAR) is defined as any AE for which there is reasonable possibility that t he dru g caused the AE (21 CFR 312.32 [a] ). An AE or SAR is considered unexpected if it is not listed in the Investigator’s Brochure or is not listed at the specificity or severity that has been observed or, if an Investigator’s Brochure is not required or available, is not consistent with the risk information described in the general investigational plan or elsewhere in the curre nt application (21 CFR 312.32 [a] ). Serious Adverse Event (SAE) The CFR Title 21 part 312.32 and ICH Guideline for Industry: Clini cal Safety Data Management: Definitions and Standards for Expedited Reporting, ICH -E2a March 1995, as implemented by the US FDA, defines a SAE or serious adverse drug experience as any untoward medical occurrence that at any dose: • Results in death (i.e., t he AE actually causes or leads to death) . • Is life -threatening (with regards to determining if an AE is serious, “life -threatening” is defined as an AE for which the patient 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. If either the investigator or the Sponsor believes that an AE meets the definition of life -threatening, it will be considered life -threatening) . • Requires inpatient hospitalization or prolongation of existing hospitalization . Heat Biologics, Inc. Viagenpumatucel -L Protocol HS110 -102 CONFIDENTIAL Amendment 6, 24 May 2019 Page 66 of 95 • Results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions . • Results in a congenital anomaly/birth defect . • Results in any “other” important medical event. Medical or scientific judgment should be exercised in deciding whether reporting is appropriate in other situations, such as important medical events that may not be immediately life -threatening or result in death or hospit alization but may jeopardize the patient or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition. Examples of such events are intensive treatment in an emergency room or at home for allergic bronc hospasm, blood dyscrasias, or convulsions that do not result in hospitalization, or development of drug dependency or drug abuse. Disease -Related Events or Outcomes not Qualifying as SAEs An event that is part of the natural course of the disease under stu dy (i.e. , disease progression) should not be reported as an SAE. Death due to disease progression is to be recorded on the “Death ” CRF page and not as a SAE; h owever, if the progression of the underlying disease is greater than what would normally be expec ted for the patient, or if the Investigator considers that there was a causal relationship between treatment with study drug or protocol design/procedures and the disease progression, then it must be reported as an SAE. Any new primary cancer must be repor ted as an SAE. Clinical Laboratory Abnormalities and Other Abnormal Assessments as AEs and SAEs Abnormal laboratory findings (e.g., clinical chemistry and hematology) or other abnormal assessments (e.g., vital signs) that are judged by the Investigator as clinically significant (CS) will be recorded as AEs and SAEs if they meet the definition of an AE or SAE. CS abnormal laboratory findings or other abnormal assessments that are detected during the study or are present at baseline and significantly worsen f ollowing the start of the study will be reported as A Es or SAEs; however, abnormal laboratory findings or other abnormal assessments that are associated with the disease being studied, unless judged by the Investigator as more severe than expected for the patient’s condition, or that are present or detected at the start of the study and do not worsen, will not be reported as AEs or SAEs. The Investigator will exercise his or her medical and scientific judgment in deciding whether an abnormal laboratory find ing or other abnormal assessment is CS. 15.2. Relationship to Study Drug The Investigator , or other qualified physician designee, will assess the possible relationship between the AE/SAE and any of the study medications, as well as any concomitant medications according to the following criteria: • Related: AE and administration of one or more study products are related in time, and AE is explained by one or more study products. • Not related: AE is explained by another cause not related to any study product. Heat Biologics, Inc. Viagenpumatucel -L Protocol HS110 -102 CONFIDENTIAL Amendment 6, 24 May 2019 Page 67 of 95 Event ou tcome will be recorded using the following categories: • Recovered/resolved . • Not recovered/not resolved .