Yan to cover page. Typographical error corrected in Section 11 for inclusion criterion on KPS score from 60 to 70%. Changed wording from “recurrent” to “progressive” (Sections 8, 9, 11, 12, and 15). Removed the prior chemotherapy exclusion criterion (Section 11). Amended version 5 20160517 for IRB AMD010 Updated eligibility criterion on pregnancy testing to within 72 hours prior to leukapheresis (Section 11). Amended version 6 20160 519 for IRB AMD 011 Clarified diff erence between Td booster and pre- conditioning by adding route of administration as well as changed booster for ALL subjects (Sections 6, 9, 10, & 12); Allowed subjects that transition to a higher grade glioma to continue on vaccines monthly during SOC XRT/TMZ (Sections 6, 8, 9, 12, and 15 ); Updated immune monitoring blood work and PT-PhI-II v05.22.12 Duke Cancer Institute Page 3 CONFIDENTIAL biomarker testing and removed urine sampling (Sections 6, 8, 9 12, & 15); Added genomic analyses (Sections 8 , 9, 12, and 15); Added MRS for 2HG measurements (Section s 6, 8, 9, 12 & 15); Changed wording from specifically study coordinator to study team (Section 9); Included standard language for leukapheresis preparation (Section 12); Increased t he dexamethasone from 2 mg to 4 mg max (Section 12); clarified KPS and physical exam to occur during standard BTC visit with the Td pre - conditioning (Section 12); clarified tumor sampling for IHC analysis (Section 12); added language regarding antihistamine usage (Section 12 ); Included SOC language for XRT/TMZ and adjuvant TMZ in the appendices as a reference (Sections 18.4 & 18.5). Amended version 7 20160 808 for IRB AMD01 5 Adjusted timin g of immune monitoring and genomic proteomic analysis in those who’ve transformed to a higher grade (Sections 6, 9.4, and 12); Clarified the description of study procedure following consent (Section 9 ); Clarified pregnancy testing and MRIs in table of events as well as pathology testing (Section 12); Corrected error in timing of vaccine #1 (Section 12); allowed for every 3 month MRI in low grade setting (Section 9 and 12); Updated screening examination to match current practice and updated location of paper CRFs (Section 12); and Corrected error that vaccine #3 is actually given on day 29 not day 30 (Sections 6, 9, and 12). Amended version 8 2016 1128 for IRB AMD0 23 Formatted for FDA electronic submission; Changed the lead study coordinator and regulatory coordinator; Reformatted Table 2: Screening and On-Study Tests and Procedures (Section 12); Clarified that vaccine will be given on day 22 (+2), not day 21 (+/ -2) of monthly cycles of TMZ because vaccine cannot be given on the same day as TMZ (Section 6, throughout ); Clarified that Single- Voxel MR will be d one before Td booster (Section 6, Section 9.5); Removed requirement that l eukapheresis be performed within 2 weeks of consent (Sect ion 9.1, Section 12); Corrected guidelines for dose delay, reduction , and discontinuation to fit 21- day TMZ , not standard 5- day TMZ (Section 18.5.2) ; Grade 3 subjects receiving RT/TMZ can delay TMZ more than a week without coming off study (Section 18.5.1); Corrected CTQA to the new name OARC (Section 4, Section 14.2); Immunization mixture will be given half in right groin and half in left groin for each vaccine (Section 9.1, Section 10.4.2, Table 2 ); Changed SOC abbreviation to standard of care, not Safety Oversight Committee (Section 13.3) Amended version 9 2017010 6 for IRB AMD027 Added additional MRS time points (Sections 6, 9.1, 9.5, 12); Correct ed MRS data acquisition time from 30 minutes to PT-PhI-II v05.22.12 Duke Cancer Institute Page 4 CONFIDENTIAL 1-2 hours (Section 9.5); Baseline MRS is before PEP IDH1M vaccine #1 (Section 9.5) Amended version 10 201701 27 for IRB AMD030 Removed recommendation that the needle be 25 gauge for injection of study vaccine because it is too narrow a bore for the vaccine (Section 10.4.2); Added that EMLA ® cream, or equivalent topical analgesic, can be offered to subjects who experience local pain at the injection site (Section 12.8.2); Corrected the number of patients to 24 in the Study Schema (Section 6); Testing of leukapheresis blood for HIV, hepatitis, and syphilis was re-moved (Section 12.8.2 ) Amended version 11 20170 215 for IRB AMD03 5 Added immune monitoring time point at vaccine #6 (Section s 6, 9.1, and 12) Amended version 12 20170223 for IRB AMD03 7 Changed Princip al Investigator (title page, Section 13.2.1 ) Amended version 13 20171011 for IRB AMD054 Primary objective wording changed from “proportion” to “percentage” (Sections 8 and 15.4.1) ; Changed wording of the timing of the Td from “12- 24 hours” before vaccine #1 to “one day ” before (Sections 6, 9.1, 10.4.1, and 12); Clarified documentation of review of aggregate summary of AE information (Section 13.1.1) ; Added that providers will take pictures of the injection site at clinic visits at pre-op time point and at other time points at discretion of physician (Section s 9 and 12); Added collection of research blood at end of vaccine treatm ent (1 month after vaccine #15 or time the subject comes off study , whichever comes first ) (Section 12): Changed total enrollment from 24 to 28, keeping the number of evaluable subjects that will receive at least 6 vaccines at 20 (Section s 6 and 15.4.2 ) Pro00054746: RESIST Study Version: 20171011 PT-PhI-II v05.22.12 Duke Cancer Institute Page 2 CONFIDENTIAL 1 TABLE OF CONTENTS 1 TABLE OF CONTENTS ................................................................................................................ 2 2 LIST OF FIGURES ........................................................................................................................