AEs occurring during the collection and reporting period will be documented appropriately regardless of relationship. AEs will be followed through resolution. SAEs will be: Assessed for severity and relationship to study product and alternate etiology (if not related to study product) by a licensed study physician listed on the Form FDA 1572 as the site principal investigator or sub-investigator. Recorded on the appropriate SAE report form, the medical record and captured in the clinical database. Followed through resolution by a licensed study physician listed on the Form FDA 1572 as the site principal investigator or sub-investigator. For timeframe of recording adverse events, please refer to section 5.1. All serious adverse events recorded from the time of first investigational product administration must be reported to the sponsor with the exception of any listed in section 7.4. 7.3 REPORTING OF SERIOUS ADVERSE EVENTS Any AE that meets protocol-defined serious criteria or meets the definition of Adverse Event of Special Interest that require expedited reporting must be submitted immediately (within 24 hours of awareness) to OSRO Safety using the CCR SAE report form. Any exceptions to the expedited reporting requirements are found in section 7.4. All SAE reporting must include the elements described in section 7.2. SAE reports will be submitted to the Center for Cancer Research (CCR) at: OSROSafety@mail.nih.gov and to the CCR PI and study coordinator. CCR SAE report form and instructions can be found at: https://ccrod.cancer.gov/confluence/display/CCRCRO/Forms+and+Instructions Following the assessment of the SAE by OSRO, other supporting documentation of the event may be requested by the OSRO Safety and should be provided as soon as possible. 7.4 WAIVER OF EXPEDITED REPORTING TO CCR As death due to disease progression is part of the study objectives, and captured as an endpoint in this study, it will not be reported in expedited manner to the sponsor. However, if there is evidence suggesting a causal relationship between the study drug and the event, report the event in an expedited manner according to section 7.3. 7.5 SAFETY R EPORTING CRITERIA TO THE PHARMACEUTICAL COLLABORATORS 7.5.1 Reporting to Astellas All events listed below must be reported in the defined timelines to CCRsafety@mail.nih.gov. 53 Short Title: Enzalutamide Vaccine in mCRPC Version Date: 03/29/2022 The CCR Office of Regulatory Affairs will send all reports to the manufacturer as described below. The Investigator should complete and submit an SAE Medwatch 3500 Form, containing all information that is required by the Regulatory Authorities, to Astellas by either e-mail or fax within 24 hours of awareness whether or not related to the study drug. If submission of this SAE by email or fax or is not possible within 24 hours, the local drug safety contact (IRB, Investigator, etc.) should be informed by phone. The SAE documentation, including the Medwatch 3500 Form and available source records, should be emailed or faxed to: Astellas Pharma Global Development – United States Email: Safety-us@us.astellas.com Fax number: (847) 317-1241 The following minimum information is required: Study number/IIT regulatory identifier Subject number, sex and age The date of report A description of the SAE (event, seriousness of the event) Causal relationship to the study drug Follow-up information for the event should be sent within 7 days as necessary. 7.5.2 Reporting to Bavarian Nordic, Inc The investigator should also submit all Medwatch 3500 Forms that are submitted to the FDA to: Bavarian Nordic, Inc. Email: pharmacovigilance@bavarian-nordic.com Fax number: 888-465-1219 Attention: Karen Latina 7.6 REPORTING PREGNANCY All required pregnancy reports/follow-up to OSRO will be submitted to: OSROSafety@mail.nih.gov and to the CCR PI and study coordinator. Forms and instructions can be found here: https://ccrod.cancer.gov/confluence/display/CCRCRO/Forms+and+Instructions 7.6.1 Paternal Exposure Male patients should refrain from fathering a child or donating sperm during the study and for three (3) months after the last dose of enzalutamide. Pregnancy of the patient’s partner is not considered to be an AE. However, the outcome of all pregnancies (spontaneous miscarriage, elective termination, ectopic pregnancy, normal birth, or congenital abnormality) occurring from the date of the first dose until three (3) months after the last dose should, if possible, be followed up and documented. 54 Short Title: Enzalutamide Vaccine in mCRPC Version Date: 03/29/2022 7.7 REGULATORY R EPORTING F OR S TUDIES C ONDUCTED UNDER CCR S PONSORED IND Following notification from the investigator, CCR, the IND sponsor, will report any suspected adverse reaction that is both serious and unexpected. CCR will report an AE as a suspected adverse reaction only if there is evidence to suggest a causal relationship between the study product and the adverse event. CCR will notify FDA and all participating investigators (i.e., all investigators to whom the sponsor is providing drug under its INDs or under any investigator’s IND) in an IND safety report of potential serious risks from clinical trials or any other source, as soon as possible, in accordance to 21 CFR Part 312.32. All serious events will be reported to the FDA at least annually in a summary format. 7.8 SPONSOR PROTOCOL DEVIATION REPORTING A Protocol Deviation is defined as any non-compliance with the clinical trial Protocol, Manual of Operational Procedures (MOP) and other Sponsor approved study related documents, GCP, or protocol-specific procedural requirements on the part of the participant, the Investigator, or the study site staff inclusive of site personnel performing procedures or providing services in support of the clinical trial. It is the responsibility of the study Staff to document any protocol deviation identified by the Staff or the site Monitor in the CCR Protocol Deviation Tracking System (PDTS) online application. The entries into the PDTS online application should be timely, complete, and maintained per CCR PDTS user requirements. In addition, any deviation to the protocol should be documented in the participant’s source records and reported to the reviewing IRB per their guidelines. OSRO required protocol deviation reporting is consistent with E6(R2) GCP: Integrated Addendum to ICH E6(R1): 4.5 Compliance with Protocol; 5.18.3 (a), and 5.20 Noncompliance; and ICH E3 16.2.2 Protocol deviations. 8 CLINICAL MONITORING Clinical site monitoring is conducted to ensure: that the rights of the participants are protected; that the study is implemented per the approved protocol, Good Clinical Practice and standard operating procedures; and the quality and integrity of study data and data collection methods are maintained. Monitoring for this study will be performed by NCI CCR Office of Sponsor and Regulatory Oversight (OSRO) and Regulatory Oversight Support (SROS) Services contractor. Clinical site monitoring activities will be based on OSRO standards, FDA Guidance E6(R2) Good Clinical Practice: Integrated Addendum to ICH E6(R1) March 2018, and applicable regulatory requirements. Details of clinical site monitoring will be documented in a Clinical Monitoring Plan (CMP) developed by OSRO. CMPs will be protocol-specific, risk-based and tailored to address human subject protections and integrity of the study data. OSRO will determine the intensity and frequency of monitoring based on several factors, including study type, phase, risk, complexity, expected enrollment rate, and any unique attributes of the study and the site. The Sponsor will conduct a periodic review of the CMP to confirm the plan's continued appropriateness. A change 55 Short Title: Enzalutamide Vaccine in mCRPC Version Date: 03/29/2022 to the protocol, significant or pervasive non-compliance with GCP, or the protocol may trigger CMP updates. OSRO SROS Monitoring visits and related activities will be conducted throughout the life cycle of each protocol. The first activity is before the study starts to conduct a Site Assessment Visit (SAV) (as warranted), followed by a Site Initiation Visit (SIV), Interim Monitoring Visit(s) (IMVs), and a study Close-Out Visit (COV). Some monitoring activities may be performed remotely, while others will occur at the study site(s). Monitoring visit reports will describe visit activities, observations, and associated action items or follow-up required for resolution of any issues, discrepancies, or deviations. Monitoring reports will be distributed to the study PI, NCI CCR QA, CCR Protocol Support Office, coordinating center (if applicable), and the Sponsor regulatory file. The site Monitor will inform the study team of any deviations observed during monitoring visits.