No interrogations regarding clinically actionable findings will be made after the primary analysis. 6 DATA COLLECTION AND EVALUATION 6.1 DATA COLLECTION The PI will be responsible for overseeing entry of data into a 21 CFR Part 11-compliant data capture system provided by the NCI CCR and ensuring data accuracy, consistency and timeliness. The MDASI-BT Survey responses will be entered by study subjects directly into Scribe/Labmatrix. The principal investigator, associate investigators/research nurses and/or a contracted data manager will assist with the data management efforts. All data will have identifiers so that research data can be attributed to an individual human subject participant. All adverse events, including clinically significant abnormal findings on laboratory evaluations, regardless of severity, will be followed until return to baseline or stabilization of event. Such events will be recorded at each examination on the Adverse Event case report forms/worksheets. The investigator will make every attempt to follow all subjects with non-serious adverse events for outcome. 65 Abbreviated Title: GBM Pembro HSPPC Version Date: 03/26/2024 For the time period beginning at treatment initiation through 90 days following cessation of treatment, or 30 days following cessation of treatment if the subject initiates new anticancer therapy, whichever is earlier, any serious adverse event, or follow up to a serious adverse event, including death due to any cause, whether or not related to the study treatments, must be reported. 6.1.1 Exceptions to Data Collection Adverse events that occur after the consent form is signed but before treatment (RT, Pembrolizumab, TMZ) must be collected by the investigator only if they cause the subject to be excluded from the trial. Sites (NCI or participating BTTC sites) will be responsible for entering data collected at their site. Changes resulting from normal growth and development that do not vary significantly in frequency or severity from expected levels are not to be considered adverse events. Examples of this may include, but are not limited to, onset of menses or menopause occurring at a physiologically appropriate time. An abnormal laboratory value will be considered an AE if the laboratory abnormality is characterized by any of the following: Results in discontinuation from the study Is associated with clinical signs or symptoms Requires treatment or any other therapeutic intervention Is associated with death or another serious adverse event, including hospitalization. Is judged by the Investigator to be of significant clinical impact If any abnormal laboratory result is considered clinically significant, the investigator will provide details about the action taken with respect to the test drug and about the patient’s outcome. End of study procedures: Data will be stored according to HHS, FDA regulations and NIH Intramural Records Retention Schedule as applicable. Loss or destruction of data: Should we become aware that a major breach in our plan to protect subject confidentiality and trial data has occurred, this will be reported expeditiously per requirements in section 7.2.1. 6.1.2 Source Documentation Timeframes The following information will be entered into a 21 CFR Part 11-compliant data capture system provided by the NCI CCR and Scribe/Labmatrix within the indicated timeframes. In addition, the source documents should be provided to the BTTC Coordinating Center’s Research Nurse at secure fax: 240-541-4432, encrypted email, or Secure Email and File Transfer within the indicated timeframe. The MDASI-BT responses will be entered by study subjects directly into Scribe/LabMatrix. Data Set / Source Documents Schedule for Submission Regulatory Documents (as described in the BTTC Operations Manual)Prior to Step 1 of registration 66 Abbreviated Title: GBM Pembro HSPPC Version Date: 03/26/2024 Data Set / Source Documents Schedule for Submission Registration Form (eligibility checklist) Within 24 hours of signing Informed Consent (Step 1 registration) Following surgery and confirmation of diagnosis (Step 2 registration) Prior to end of RT in order to randomize subject (Step 3 registration) Copy of signed & dated Informed Consent w/ HIPAA Authorization Within 24 hours of signing Informed Consent (Step 1 registration) Pathology Report (from the most recent pre- registration diagnostic biopsy or surgery)At time of Step 2 of registration Baseline MDASI – BT Questionnaire Within 14 days (+ 3 working days) after enrollment Screening/Baseline Source Documents At time of registration (step 1 or 2, as applicable) Other Source Documents With Participant Status Updates Form 6.1.3 Database Entry Timeframes The following data should be entered into a 21 CFR Part 11-compliant data capture system provided by the NCI CCR and Scribe/Labmatrix within the specified timeframes. Source documentation will be kept at the participating site. Sites (NCI or participating BTTC sites) will be responsible for entering data collected at their site. 67 Abbreviated Title: GBM Pembro HSPPC Version Date: 03/26/2024 Data Set Schedule for Data Entry Screening data Within 14 days of Step 1 Registration Baseline data No later than 14 days after Day 1 of radiation (RT cycle) Treatment (Course/Cycle) Data (To include treatment, response, AE, and clinical evaluation information)Course initiation case report form (CRF) no later than 7 days after the cycle begins All other course/cycle CRFs must be entered no later than 21 days after the cycle is complete Off Treatment Data Within 21 days after the: last date of any modality of protocol treatment; or, study discontinuation visit. Follow-up (Survival) Data (To include post-protocol treatment and long- term follow up survival data) Note: Long-term follow up is required every 8- 16 weeks for two years until patient is off study.No later than 21 days after follow up visit or survival call or post-treatment medication begins. Non-Treatment Data (May include Quality of Life questionnaires (MDASI-BT), Specimen Tracking information, Pathology Specimen Submission, etc.)Within 10 days after each scheduled assessment, event, or activity Off Study Data No later than 21 days after the date the patient is removed from the study. 6.1.4 Confidentiality All documents, investigative reports, or information relating to the patient are strictly confidential. Any source documents submitted to the BTTC Coordinating Center with protected health information or personally identifiable information (e.g. patient’s name) must be sent via Secure Email and File Transfer (SEFT) or secure fax. For NIH only, documents can also be sent via hand-delivery or encrypted email. 6.1.5 Safety Data All patients receiving study agents will be evaluated for safety. The safety parameters include all laboratory tests and hematological abnormalities, CNS observations, physical examination findings, and spontaneous reports of adverse events reported to the investigator by patients. Life-threatening toxicities that are unexpected and assessed to be possibly related to the study agent/s should be reported immediately. 68 Abbreviated Title: GBM Pembro HSPPC Version Date: 03/26/2024 Information about all adverse events, whether volunteered by the subject, discovered by investigator questioning, or detected through physical examination, laboratory test or other means, will be collected and recorded on the Adverse Event Case Report Form and followed as appropriate. Medical conditions/diseases present before starting study treatment are only considered adverse events if they worsen after starting study treatment (any procedures specified in the protocol). Adverse events occurring before starting study treatment but after signing the informed consent form are recorded on the Baseline Evaluations Case Report Form. 6.1.6 Data Monitoring All submitted data will be monitored by the BTTC Clinical Research Nurse specifically assigned to this protocol. Requests for correction of data deficiencies will be sent via emailed to the Institutional Coordinator. Any major deficiencies will be corrected by telephone and email communication. All data will be monitored for completeness. Key parameters such as drug dosages including attenuations and escalations, toxicity documentation and tumor measurements will be analyzed. All data deficiencies will be corrected within two weeks. 6.2 DATA SHARING PLANS 6.2.1 Human Data Sharing Plan What data will be shared? I will share human data generated in this research for future research as follows: Coded, linked data in an NIH-funded or approved public repository. Coded, linked data in another public repository. Coded, linked data in BTRIS (automatic for activities in the Clinical Center) Coded, linked or identified data with approved outside collaborators under appropriate agreements. How and where will the data be shared? Data will be shared through: An NIH-funded or approved public repository: clinicaltrials.gov. BTRIS (automatic for activities in the Clinical Center) Approved outside collaborators under appropriate individual agreements. Publication and/or public presentations. When will the data be shared? Before publication. At the time of publication or shortly thereafter. 6.2.2 Genomic Data Sharing Plan Unlinked genomic data will be deposited in public genomic databases such as dbGaP in compliance with the NIH Genomic Data Sharing Policy. 69 Abbreviated Title: GBM Pembro HSPPC Version Date: 03/26/2024 6.3 RESPONSE C RITERIA 6.3.1 Definitions 6.3.1.1 Evaluable for toxicity: All patients will be evaluable for toxicity from the time of their first treatment with Pembrolizumab and/or HSPPC-96. 6.3.1.2 Evaluable for objective response: Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response.