Such audits/inspections can occur at any ti me during or after completion of the study. If an audit or inspection occurs, the investigator and institution agree to allow the auditor/inspector direct access to all relevant documents and to allocate his/her time and the time of his/her staff to the a uditor/inspector to discuss findings and any relevant issues. 10.5 Study and Site Closure Upon completion or premature discontinuation of the study, the Site M onitor will conduct site closure activities with the investigator or site staff, as appropriate, in ac cordance with applicable regulations, GCP, and Heat Biologics procedures. In addition, Heat Biologics reserves the right to temporarily suspend or prematurely discontinue this study at any time for reasons , including, but not limited to, safety or ethical issues or severe non -compliance. For this multicenter study, this can occur at 1 or more sites. If Heat Biologics determines such action is needed, Heat Biologics will discuss this with the investigator or the head of the medical institution , where appli cable, including the reasons for taking such action, at that time. When feasible, Heat Biologics will provide advance notification to the investigator or the head of the medical institution, where applicable, of the impending action prior to it s taking ef fect. Heat Biologics will promptly inform all other investigators or the head of the medical institution , where applicable, and/or institutions conducting the study if the study is suspended or prematurely discontinued for safety reasons. Heat Biologics w ill also promptly inform the regulatory authorities of the suspension or premature discontinuation of the study and the reason(s) for the action. If required by applicable regulations, the investigator or the head of the medical institution , where applica ble, must inform the IRB/EC promptly and provide the reason for the suspension or premature discontinuation. 10.6 Records Retention Following closure of the study, the investigator or the head of the medical institution , where applicable , must maintain all site study records, except for those required by local regulations to be maintained by someone else, in a safe and secure location. The records must be maintained to allow easy and timely retrieval, when needed (e.g., audit or inspectio n), and, whenever feasible, to allow any subsequent review of data in conjunction with assessment of the facility, supporting systems, and staff. Where permitted by local laws/regulations or institutional policy, some or all of these records can be mainta ined in a format other than hard copy (e.g., microfiche, scanned, electronic); however, caution needs to be exercised before such action is taken. The investigator must assure that all reproductions are legible and are a true and accurate copy of the orig inal and meet accessibility and retrieval standards, including regenerating a hard copy, if required. Furthermore, the investigator must ensure there is an acceptable back up of these reproductions and that an acceptable quality control process exists for making these reproductions. These records should be retained for not less than 2 years after the last approval of a marketing application in an ICH region and until there are no pending or contemplated marketing applications in an ICH region or at least 2 years have elapsed since the formal discontinuation of clinical development of the Heat Biologics, Inc. Investigational Product: V iagenpumatucel -L Protocol HS110 -201 CONFIDENTIAL Version 4.0; 29 -Oct-2014 Page 67 of 84 investigational produc t. These documents should be retained for a longer period, however, if required by applicable regulatory requirements or by an agreement with the spo nsor. Thereafter, records will not be destroyed without giving the sponsor prior written notice and the opportunity to further store such records. The investigator must notify Heat Biologics of any changes in the archival arrangements, including, but not limited to, the following: archival at an off -site facility, transfer of ownership of the records in the event the investigator leaves the site. 10.7 Provision of Study Results and Information to Investigators When required by applicable regulations, the invest igator signatory for the clinical study report will be determined at the time the report is written. When the clinical study report is completed, Heat Biologics will provide the investigator with a full summary of the study results. The investigator is e ncouraged to share the summary results with the patients, as appropriate. In addition the investigator will be give n reasonable access to review the relevant statistical tables, figures, and reports and will be able to review the results for the entire st udy at the Heat Biologics site or other mutually agreeable location. 10.8 Data Management The data collection tool for this study will be Heat Biologics -defined CRFs. Patient data necessary for analysis and reporting will be entered/transmitted into a validate d database or data system. After the sponsor receives the CRFs, the sponsor’s Medical Monitor (or designee) will review the data for safety information, and the sponsor’s clinical data associates (or designees) will review them for logical consistency and will use automated programs to help identify missing data, selected protocol violations, out-of-range data, and other inconsistencies. Requests for data clarification or correction will be forwarded to the investigative site for timely resolution. Heat Biologics, Inc. Investigational Product: V iagenpumatucel -L Protocol HS110 -201 CONFIDENTIAL Version 4.0; 29 -Oct-2014 Page 68 of 84 Appendix 1 . ECOG Performance Status Scale ECOG PERFORMANCE STATUS73 Grade ECOG 0 Fully active, able to carry on all pre -disease performance without restriction 1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work 2 Ambulatory and capable of all self -care but unable to carry out any work activities. Up and about more than 50% of waking hours 3 Capable of only limited self -care, confined to bed or chai r more than 50% of waking hours 4 Completely disabled. Cannot carry on any self -care. Totally confined to bed or chair 5 Dead Credit: the Eastern Cooperative Oncology Group, Robert Comis M.D., Group Chai r Heat Biologics, Inc. Investigational Product: V iagenpumatucel -L Protocol HS110 -201 CONFIDENTIAL Version 4.0; 29 -Oct-2014 Page 69 of 84 Appendix 2 : Immune -related Response Criteria The overall response according to irRC is derived from time point response assessments based on tumor burden as follows below :67  irCR, co mplete disappearance of all lesions (whether measurable or not, and no new lesions) confirm ed by a repeat, consecutive assessment at least 4 weeks from the date first documented. New non -measurable lesions do not indicate progression, but preclude irCR.  irPR, decrease in tumor burden > 50% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation  irSD, not meeting criteria for irCR or irPR, in absence of irPD  irPD, increase in tumor burden > 25% relative to nad ir (minimum recorded tumor burden) confirm ed by a repeat, consecutive assessment at least 4 weeks from the date first documented . New measurable lesions do not automatically define disease progression but are incorporated into the total tumor burden. Derivation of irRC Overall Responses Measurable Response Nonmeasurable response Overall response Index and new, measurable lesions (tumor burden),* % Non-index lesions New, nonmeasurable lesions Using irRC ↓100 ↓100 ↓100 ↓≥50 ↓≥50 ↓<50 to <25↑ ↓<50 to <25↑ ≥25↑ Absent Stable Unequivocal progression Absent/Stable Unequivocal progression Absent/Stable Unequivocal progression Any Absent Any Any Any Any Any Any Any irCR† irPR† irPR† irPR† irPR† irSD irSD irPD† *Decreases assessed relative to baseline, including measurable lesions only (>5 × 5 mm). †Assuming complete and partial response (irCR and irPR) and progression (irPD) are confirmed by a second, consecutive assessment at least 4 wk apart. Heat Biologics, Inc. Investigational Product: V iagenpumatucel -L Protocol HS110 -201 CONFIDENTIAL Version 4.0; 29 -Oct-2014 Page 70 of 84 Appendix 3 . The Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines The overall response according to RECIST 1.1 is derived from time -point response assessments based on tumor burden as follows below .68 Evaluation of target lesions:  Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non -target) must have reduction in short axis to < 10 mm.  Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.  Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as referenc e the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of 1 or more new lesions is also considered progression).  Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Evaluation of non-target lesions:  Complete Respon se (CR): Disappearance of all non -target lesions and normalization of tumo r marker level. All lymph nodes must be non -pathological in size (<10mm short axis).  Non-CR/Non -PD: Persistence of one or more non -target lesion( s) and/or maintenance of tumo r marker level above the normal limits.  Progressive Disease (PD): Unequivocal progression of existing non -target lesions. (Note: the appearance of 1 or more new lesions is also considered progression). Evaluation of Overall Time Point Response for Patients with Measurable Disease at Baseline Target Lesions Non-target Lesions New Lesions Overall Response CR CR No CR CR Non-CR/Non -PD No PR CR NE No PR PR Non-PD or NE No PR SD Non-PD or NE No SD Not all evaluated Non-PD No NE PD Any Yes or No PD Any PD Yes or No PD Any Any Yes PD CR = Complete Response, PR = Partial Response, SD = Stable Disease, PD = Progressive Disease, NE = Inevaluable *When target lesions show SD/PR and some subset of non -target lesions is inevaluable, a careful decision must be made whet her to call the overall response at this time point SD/PR or N E. This is based on whether the inevaluable lesions, if they showed growth, could cause an overall response of PD in the context of the Heat Biologics, Inc. Investigational Product: V iagenpumatucel -L Protocol HS110 -201 CONFIDENTIAL Version 4.0; 29 -Oct-2014 Page 71 of 84 other lesion responses seen. If the inevaluable non-target lesions comprise a significant proportion of the overall disease burden, the appropriate time point response is NE. Heat Biologics, Inc. Investigational Product: V iagenpumatucel -L Protocol HS110 -201 CONFIDENTIAL Version 4.0; 29 -Oct-2014 Page 72 of 84 Appendix 4. Grading Scale for Injection Site Reactions The grading scale is derived from the FDA Guidance for Industry (http://www.fda.gov/biologicsbloodvaccines/guidancecomplianceregulatoryinformation/guidances/vac cin es/ucm074775.htm#TOXICITYGRADINGSCALETABLES ) Grade 1 Mild Grade 2 Moderate Grade 3 Severe Grade 4 Potentially Life Threatening Pain Does not interfere with activity Repeated use of non-narcotic pain reliever > 24 hours or interferes with activity Any use of narcotic pain reliever or prevents daily activity Emergency room visit or hospitalization Tenderness Mild discomfort to touch Discomfort with movement Significant discomfort at rest Emergency room visit or hospitalization Erythema/Redness 2.5-5 cm 5.1-10 cm > 10 cm Necrosis or exfoliative dermatitis Induration/Swelling* 2.5-5 cm and does not interfere with activity 5.1-10 cm or interferes with activity > 10 cm or prevents daily activity Necrosis * Induration/Swelling should be evaluated and graded using the functional scale as well as the actual measurement. Heat Biologics, Inc. Investigational Product: V iagenpumatucel -L Protocol HS110 -201 CONFIDENTIAL Version 4.0; 29 -Oct-2014 Page 73 of 84 Appendix 5. Amendment Change Log Protocol Change Section Affected Version Where Implemented Added amendment history Title page Version 2.0, Amendment 1 Added pregnancy assessments Protocol synopsis (Eligibility criteria), 5.1 Inclusion Criteria, 6.1.1 SOA Stage A, 6.1.2 SOA Stage B, 6.2 Screening Procedures, 6.3.4 End of Treatment Visit, 6.5.2 Clinical Laboratory Evaluations, 6.5.6 Pregnancy (including 6.5.6.1 - 6.5.6.3), 6.7.3 Discon tinuation Version 2.0, Amendment 1 Added respiratory rate to vital signs 6.2 Screening Procedures, 6.5.1 Physical Examinations, 9.8.3 Vital Signs Version 2.0, Amendment 1 Added docetaxel as a physician's choice regimen Protocol synopsis (Trial design; Dosing regimen, form and route), 4.0 Trial Design, 6.1.1 SOA Stage A, 6.1.2 SOA Stage B, 7.2.1 Physican's Choices, 7.5.2 Prohibited Medications Version 2.0, Amendment 1 Eliminate immune monitoring and blood banking after Week 22 in Stage A and Week 19 in Stage B 6.1.1 SOA Stage A, 6.1.2 SOA Stage B, 6.3.2.13 Week A31 Assessments and every 9 weeks thereafter, 6.3.3.10 Week B28 Assessments and every 9 weeks thereafter, 6.6.2 Immunological Response Version 2.0, Amendment 1 Updated treatment period to 1 year; previously listed as 2 years Protocol synopsis (Trial design; Dosing regimen, form and route; Eligibility criteria), 4.0 Trial Design, 5.1 Inclusion Criteria, 6.3.2.11 Week A25 Assessments and every 9 weeks thereafter, 6.3.3.9 Week B25 Assessments and eve ry 9 weeks thereafter, 6.3.3.10 Week B28 Assessments and every 9 weeks thereafter, 6.7.1 Patient Completion Version 2.0, Amendment 1 Updated eligibility requirement from two lines of conventional therapy to two lines of therapy, including conventional therapy, targeted therapy, immunotherapy, or investigational therapy administered through a clinical trial Protocol synopsis (Trial design), 4.0 Trial Design Version 2.0, Amendment 1 Added abstinence as an acceptable form of contraception Protocol synopsis (Eligibility criteria), 5.1 Inclusion Criteria Version 2.0, Amendment 1 Remove Stage B for patients randomized to the control group Protocol synopsis (Trial design), 4.0 Trial Design, 6.1.2 Schedule of Assessments; 6.3.3 Stage B Assessments; 6.7. 3 Study Discontinuation Version 2.0, Amendment 1 Heat Biologics, Inc. Investigational Product: V iagenpumatucel -L Protocol HS110 -201 CONFIDENTIAL Version 4.0; 29 -Oct-2014 Page 74 of 84 Protocol Change Section Affected Version Where Implemented Remove blood banking for patients randomized to the control group 6.1.1, 6.1.2 Schedule of Assessments; 6.3 On-study Procedures Version 2.0, Amendment 1 Remove Blood for exploratory analysis from Stage B table - duplicate entry to "Immunologic Response" entry 6.1.2 Schedule of Assessments; Version 2.0, Amendment 1 Add Hematology and Chemistry to BL procedures if screening labs done >2 weeks prior to first dose 6.1.1 Schedule of Assessments; 6.3.1 Baselin e Assessments Version 2.0, Amendment 1 Add language that pre -medication with anesthetic cream is allowed 7.5.1 Permitted Medications Version 2.0, Amendment 1 Updated the Schedule of Events descriptions to match the tables 6.3 On Study Procedures Version 2.0, Amendment 1 Remove Weeks B4, B5, B8 and B9 visits to be consistent with text indicating weekly clinic visits for 12 weeks followed by every 3 weeks thereafter 6.1.2 SOA – After First Progression; 6.3 On Study Procedures Version 2.0, Amendment 1 Modi fication of schedule of Vital Signs and targeted Physical Exam in Stage B to align with the ECGs 6.1.2 SOA – After First Progression; 6.3 On Study Procedures; 6.5.1 Physical Examination Version 2.0, Amendment 1 Update title Cover page, Sponsor Protocol Approval page, Investigator Protocol Agreement page, Synopsis Version 3.0, Amendment 2 Expanded on reference to serum collected for immunologic response 6.5.2 Immunologic Response Version 3.0, Amendment 2 Note that cyclophosphamide is administered every other week for 12 weeks 7.1.2 Cyclophosphamide Version 3.0, Amendment 2 Prohibit dose modifications of viagenpumatucel -L but allowed dose reductions of Physician’s Choice drugs as needed for management of toxicity according to the investigator’s standard of care 7.7 Dose Modifications (formerly Dose Delays) Version 3.0, Amendment 2 Remove radiotherapy as a prior regimen for eligibility Synopsis, 5.1 Inclusion Criteria Version 3.0, Amendment 2 Heat Biologics, Inc. Investigational Product: V iagenpumatucel -L Protocol HS110 -201 CONFIDENTIAL Version 4.0; 29 -Oct-2014 Page 75 of 84 Protocol Change Section Affected Version Where Implemented Reduce viagenpumatucel -L dosing in the maintenance period from every 3 week s to every 9 weeks Synopsis; 4.0 Trial Design; 6.1 SOA; 6.3.2.8 -12 Assessments at Weeks 16, 19, 22+9x, 25+9x, and 28+9x Version 3.0, Amendment 2 Do not treat any patients after progression Synopsis, 2.1 Background Rationale, 2.2 Study -Specif ic Rationale, 3.2 Secondary Objectives, 4.0 Trial Design (including Figure 1), 6.1 SOA, 6.3.4 LTFU Visits, 6.4.1 Physical Examination, 6.5.1 Tumor Assessments, 6.6.3 Discontinuation from Study Treatment, 7.2.1 Physician’s Choices, 9.6 Secondary Efficacy Endpoints and Analyses Version 3.0, Amendment 2 Add 6 -month immune -related disease control rate and 6 -month disease control rate as study endpoints Synopsis; 3.2 Secondary Objectives; Figure 1; 9.6.2 -5 irDCR, DCR, 6m - irDCR,and 6mDCR Version 3.0, Amendment 2 Remove known allergy to soy or egg products as an exclusion criteria Synopsis, 5.2 Exclusion Criteria Version 3.0, Amendment 2 Biopsy only collected in patients randomized to viagenpumatucel -L Synopsis, 4.0 Trial Design, 6.1 SOA, 6.3.1 Baseline Assessments Version 3.0, Amendment 2 Move post -treatment biopsy to Week 13 Synopsis, 4.0 Trial Design, 6.1 Schedule of Assessments, 6.3.2.6 -7 Assessments at Weeks 10 and 13 Version 3.0, Amendment 2 Stop immune response testing in patients receiving physi cian’s choice regimens after Week 1 Synopsis; 4.0 Trial Design; 6.1 SOA; 6.3.2.4 -7 Assessments at Weeks 4, 7, 10, and 13; 6.3.2.10 Assessments Week22+9x, 6.3.3 EOT, 6.5.2 Immunologic Response Version 3.0, Amendment 2 Remove dose and route requirements for physician’s choice regimens Synopsis, 6.1 SOA, 7.2.1 Physician’s Choices Version 3.0, Amendment 2 Update Sponsor address Contact Page Version 3.0, Amendment 2 Allow patients on stable low dose steroids after consulting Medical Monitor 7.5.2 Prohibited Medications Version 3.0, Amendment 2 Heat Biologics, Inc. Investigational Product: V iagenpumatucel -L Protocol HS110 -201 CONFIDENTIAL Version 4.0; 29 -Oct-2014 Page 76 of 84 Protocol Change Section Affected Version Where Implemented Add pemetrexed as a physician’s choice Synopsis, 4.0 Trial Design, 7.2.1 Physician’s Choices Version 3.0, Amendment 2 Add interim analysis Synopsis, 4.0 Trial Design, 8.3 Trial Stopping Rules Version 3.0, Amendment 2 Allow patients who have received 3 prior lines of therapy Synopsis, 5.1 Inclusion Criteria Version 3.0, Amendment 2 Allow patients to provide archival biopsy tissue Synopsis, 2.4 Rationale for Performing Tumor Biopsies, 3.3 Exploratory Objectives, 4.0 Tr ial Design, 6.1 SOA, 6.5.2.5 Antigen Screening of Baseline or Archival Tumor Biopsy, 9.7 Exploratory Endpoints and Analysis Version 3.0, Amendment 2 Moved exploratory objectives to a separate section (rather than a subset of secondary endpoints) Synopsis, 3.3 Exploratory Objectives Version 3.0, Amendment 2 Added grading scale for injection site reactions Appendix 4. Grading Scale for Injection Site Reactions Version 3.0, Amendment 2 Added Data Monitoring Committee Synopsis, 8.2 Data Monitoring Committee, 8.3 Trial Stopping Rules Version 3.0, Amendment 2 Allow G -CSF 7.5.1 Permitted Medications Version 3.0, Amendment 2 Indicated where randomization will occur (at baseline) 6.1 Schedule of Assessments, 6.3.1 Baseline Assessments Version 3.0, Amendment 2 Updated and expanded the maintenance visit 6.1 Schedule of Assessments, 6.3.2.10 -15 Assessments at Weeks 22, 28, 31, 40, 49, and 52 Version 3.0, Amendment 2 Added concomitant medication assessment 6.3.1 Baseline Assessments Version 3.0, Amendment 2 Removed volumes of samples collected 6.3.2 Visit Assessments (throughout) Version 3.0, Amendment 2 Specified CT and MRI for tumor assessments 6.3.2 Visit Assessments (throughout) Version 3.0, Amendment 2 Heat Biologics, Inc. Investigational Product: V iagenpumatucel -L Protocol HS110 -201 CONFIDENTIAL Version 4.0; 29 -Oct-2014 Page 77 of 84 Protocol Change Section Affected Version Where Implemented Take immune response samples from all patients Synopsis, 4.0 Trial Design, 6.1 SOA, 6.3.2.4 Week 4 Assessments, 6.3.2.6 Week 10 Assessments, 6.3.2.7 Week 13 Assessments, 6.3.2.10 Week 22 Assessments, 6.3.3 End of Treatment Visit, 6.5.2 Immunologic Response Version 4.0, Amendment 3 Eliminate immune res ponse and blood banking at Weeks 7 and 40 Synopsis, 4.0 Trial Design, 6.1 SOA, 6.3.2.5 Week 7 Assessments, 6.5.2 Immunologic Response Version 4.0, Amendment 3 Combine immune response and blood banking into a single category Former section 6.5.3, Schedule of Assessments, 6.5.2 Immunologic Response, Version 4.0 , Amendment 3 Update immunologic response methodology and endpoints Synopsis, 6.5.2 Immunologic Response , 9.7 Exploratory Endpoints and Analysis Version 4.0 , Amendment 3 Indicate preference for tissue sections rather than FFPE 6.3.1 Baseline Assessments, 6.3.2.7 Week 13 Assessments, 6.5.2.5 Antigen Screening of Baseline or Archival Tumor Biopsy Version 4.0 , Amendment 3 Describe make up doses of vaccine and CY 7.1.1 Viagenpumatucel -L (HS -110), 7. 1.2 Cyclophosphamide Version 4.0 , Amendment 3 Clarify steroid therapy use and define low-dose steroid therapy 7.5.2 Prohibited Medications Version 4.0 , Amendment 3 Indicate that patients in the experimental arm should receive G - CSF only after a Grade 3 neutropenia 7.5.1 Permitted Medications Version 4.0, Amendment 3 Indicate that patients may not receive other investigative therapies 7.5.2 Prohibited Medications Version 4.0, Amendment 3 Not require patients with progressive disease to discontinue study treatment 6.6.3 Discontinuation from Study Treatment Version 4.0, Amendment 3 Indicate that dose should be taken with food and water in the morning 7.1.2 Cyclophosphamide Version 4.0, Amendment 3 Heat Biologics, Inc. Investigational Product: V iagenpumatucel -L Protocol HS110 -201 CONFIDENTIAL Version 4.0; 29 -Oct-2014 Page 78 of 84 Protocol Change Section Affected Version Where Implemented Indicate that only patients in the experimental group should discontinue study treatment for a Grade 4 event definitely or probably related to therapy 6.6.3 Discontinuation from Study Treatment Version 4.0, Amendment 3 Indicate in that Grade 3 or greater adverse events or unexpected Grade 4 toxicities should be assessed as possibly, probably , or definitely related to study drug to stop the trial 8.3 Trial Stopping Rules Version 4.0, Amendment 3 Indicate that patients in the control group can have a reduced volume of blood collected for immune response 6.1 SOA Version 4.0, Amendment 3 Exclude patient with any condition requiring active steroid or other immunosuppressive therapy Synopsis, 5.2 Exclusion Criteria Version 4.0, Amendment 3 Exclude patients with prior treatment with a cancer vaccine Synopsis, 5.2 Exclusion Criteria Version 4.0, Amendment 3 Include patients with no more than 3 lines of prior therapy Synopsis, 5.1 Inclusion Criteria Version 4.0, Amendment 3 Collect information on caffeine consumption and supplemental oxygen use 7.5 Concomitant Medications Version 4.0, Amendment 3 Interim analysis for trial stopping will occur after 41 patients in the experimental group have had blood samples taken at Week 10 Synopsis, 4.0 Trial Design Version 4.0 Amendment 3 Added exploratory analysis after 14 patients in the experimental group have had blood samples taken at Week 10. Synopsis, 4.0 Trial Design Version 4.0, Amendment 3 Specify that cyclophosphamide should be taken by mouth 7.1.2 Cyclophosphamide Version 4.0, Amendment 3 Heat Biologics, Inc. Investigational Product: V iagenpumatucel -L Protocol HS110 -201 CONFIDENTIAL Version 4.0; 29 -Oct-2014 Page 79 of 84 Protocol Change Section Affected Version Where Implemented Long -term follow -up will be until study termination or death, whichever occurs first 6.3.4 Long -term Follow -up Visits Version 4.0, Amendment 3 Stress that follow -up needs to continue even if patients initiate other therapy 6.3.4 Long -term Follow -up Visits Version 4.0, Amendm ent 3 Changed the order of Patient Withdrawal from Study and Discontinuation from Study Treatment 6.6.2 Discontinuation from Study Treatment, 6.6.3 Patient Withdrawal from Study Version 4.0, Amendment 3 Point out that withdrawal of consent for treatment is not the same as withdrawal of consent for follow -up 6.6.3 Patient Withdrawal from Study Version 4.0, Amendment 3 Removed “other than viagenpumatucel -L” from the sentence on concomitant investigational agents 7.5.2 Prohibited Medications Version 4.0, Amendment 3 Noted that during follow -up there are no prohibited medications and patients may enroll in any appropriate investigational study 7.5.2 Prohibited Medications Version 4.0, Amendment 3 Updated safety from number of AE/SAE to proportion of AE/SAE 9.6.1 Safety Version 4.0, Amendment 3 Prior adjuvant or neoadjuvant chemotherapy or definitive chemoradiation with curative intent , or a repeat course of a prior line of systemic therapy does not count as a prior line of therapy if last administration oc curred at least 12 months prior to enrollment Synopsis, 5.1 Inclusion Criteria Version 4.0, Amendment 3 State when the primary analysis will be conducted Synopsis, 4.0 Trial Design, 9.5.1 Overall Survival Version 4.0, Amendment 3 Heat Biologics, Inc. Investigational Product: V iagenpumatucel -L Protocol HS110 -201 CONFIDENTIAL Version 4.0; 29 -Oct-2014 Page 80 of 84 Protocol Change Section Affected Version Where Implemented Added Heat Biologics lo go Cover page Version 4.0, Amendment 3 Defined AEs to be recorded as possibly, probably, or definitely related to study medication 8.1.5 Reporting Adverse Events Version 4.0, Amendment 3 Heat Biologics, Inc. Investigational Product: V iagenpumatucel -L Protocol HS110 -201 CONFIDENTIAL Version 4.0; 29 -Oct-2014 Page 81 of 84 REFERENCES 1 Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013.