All appropriate treatment areas should have access to a copy of the CTCAE version 5.0. A copy of the CTCAE version 5.0 can be downloaded from the CTEP web site (http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm ). 7 NIH REPORTING REQUIREMENTS/DATA SAFETY MONITORING PLAN 7.1 DEFINITIONS Please refer to definitions provided in Policy 801: Reporting Research Events found at: https://irbo.nih.gov/confluence/pages/viewpage.action?pageId=36241835#Policies&Guidance- 800Series-ComplianceandResearchEventReportingRequirements. 7.2 OHSRP OFFICE OF COMPLIANCE AND TRAINING / IRB REPORTING 7.2.1 Expedited Reporting Please refer to the reporting requirements in Policy 801: Reporting Research Events and Policy 802 Non-Compliance Human Subjects Research found at: https://irbo.nih.gov/confluence/pages/viewpage.action?pageId=36241835#Policies&Guidance- 800Series-ComplianceandResearchEventReportingRequirements. Note: Only IND Safety Reports that meet the definition of an unanticipated problem will need to be reported per these policies. 7.2.2 IRB Requirements for PI Reporting at Continuing Review Please refer to the reporting requirements in Policy 801: Reporting Research Events found at: https://irbo.nih.gov/confluence/pages/viewpage.action?pageId=36241835#Policies&Guidance- 800Series-ComplianceandResearchEventReportingRequirements. 7.3 NCI CLINICAL DIRECTOR R EPORTING Problems expeditiously reported to the OHSRP in the NIH eIRB system will also be reported to the NCI Clinical Director/designee; therefore, a separate submission for these reports is not necessary. In addition to those reports, all deaths that occur within 30 days after receiving a research intervention should be reported via email unless they are due to progressive disease. 58 Abbreviated Title: Neoadjuvant IO for HNSCC Version Date: August 31, 2022 To report these deaths, please send an email describing the circumstances of the death to NCICCRQA@mail.nih.gov within one business day of learning of the death. 7.4 INSTITUTIONAL BIOSAFETY C OMMITTEE (IBC) REPORTING CRITERIA 7.4.1 Serious Adverse Event Reports to IBC The Principal Investigator (or delegate) will notify IBC of any unexpected fatal or life- threatening experience associated with the use of BN-Brachyury as soon as possible but in no event later than 7 calendar days of initial receipt of the information. Serious adverse events that are unexpected and associated with the use of the BN-Brachyury, but are not fatal or life- threatening, must be reported to the NIH IBC as soon as possible, but not later than 15 calendar days after the investigator’s initial receipt of the information. Adverse events may be reported by using the FDA Form 3500a. 7.4.2 Annual Reports to IBC Within 60 days after the one-year anniversary of the date on which the IBC approved the initial protocol, and after each subsequent anniversary until the trial is completed, the Principal Investigator (or delegate) shall submit the information described below. Alternatively, the IRB continuing review report can be sent to the IBC in lieu of a separate report. Please include the IBC protocol number on the report. 7.4.3 Clinical Trial Information A brief summary of the status of the trial in progress or completed during the previous year. The summary is required to include the following information: the title and purpose of the trial clinical site the Principal Investigator clinical protocol identifiers; participant population (such as disease indication and general age group, e.g., adult or pediatric); the total number of participants planned for inclusion in the trial; the number entered into the trial to date whose participation in the trial was completed; and the number who dropped out of the trial with a brief description of the reasons the status of the trial, e.g., open to accrual of subjects, closed but data collection ongoing, or fully completed, if the trial has been completed, a brief description of any study results. 7.4.4 Progress Report and Data Analysis Information obtained during the previous year's clinical and non-clinical investigations, including: 59 Abbreviated Title: Neoadjuvant IO for HNSCC Version Date: August 31, 2022 a narrative or tabular summary showing the most frequent and most serious adverse experiences by body system a summary of all serious adverse events submitted during the past year a summary of serious adverse events that were expected or considered to have causes not associated with the use of the gene transfer product such as disease progression or concurrent medications if any deaths have occurred, the number of participants who died during participation in the investigation and causes of death a brief description of any information obtained that is pertinent to an understanding of the gene transfer product’s actions, including, for example, information about dose-response, information from controlled trials, and information about bioavailability. 7.5 NIH REQUIRED DATA AND SAFETY MONITORING PLAN 7.5.1 Principal Investigator/Research Team The clinical research team will meet weekly when patients are being actively treated on the trial to discuss each patient. Decisions about opening study arms to enrollment will be made based on the toxicity data from prior patients. All data will be collected in a timely manner and reviewed by the principal investigator or a lead associate investigator. Events meeting requirements for expedited reporting as described in section 7.2.1 will be submitted within the appropriate timelines. The principal investigator will review adverse event and response data on each patient to ensure safety and data accuracy. The principal investigator will personally conduct or supervise the investigation and provide appropriate delegation of responsibilities to other members of the research staff. 7.5.2 Safety Monitoring Committee (SMC) This protocol will be periodically reviewed by an intramural Safety Monitoring Committee. Initial review will occur as soon as possible after the annual NIH Intramural IRB continuing review date. Subsequently, each protocol will be reviewed as close to annually as the quarterly meeting schedule permits or more frequently as may be required by the SMC based on the risks presented in the study. For initial and subsequent reviews, protocols will not be reviewed if there is no accrual within the review period. The SMC review will focus on unexpected protocol-specific safety issues that are identified during the conduct of the clinical trial. Written outcome letters will be generated in response to the monitoring activities and submitted to the Principal investigator and Clinical Director or Deputy Clinical Director, CCR, NCI. 60 Abbreviated Title: Neoadjuvant IO for HNSCC Version Date: August 31, 2022 7.5.3 Independent Monitoring Committee A committee of two NIH physician investigators who are not affiliated with the Genitourinary Malignancies Branch and are not listed as key study personnel on the study will convene every 3-4 months for adverse event review of new subjects, in addition to the annual Safety Monitoring Committee. Meeting minutes will be generated and submitted to the Principal investigator and Clinical Director or Deputy Clinical Director, CCR, NCI.