5 3 LIST OF TABLES .......................................................................................................................... 5 4 LIST OF ABBREVIATIONS ........................................................................................................... 6 5 PROTOCOL SYNOPSIS AND SUMMARY .................................................................................. 9 6 STUDY SCHEMA ........................................................................................................................ 10 7 BACKGROUND AND SIGNIFICANCE ....................................................................................... 11 7.1 Study Disease ......................................................................................................................... 11 7.2 Study Agents ........................................................................................................................... 12 7.2.1 PEP IDH1M .......................................................................................................................... 12 7.2.2 GM-CSF .......................................................................................................................... 12 7.2.3 Montanide ISA 51 (Incomplete Freund’s Adjuvant) ........................................................ 12 7.2.4 Tetanus -diphtheria toxoid (Td) ........................................................................................ 12 7.2.5 Pre-clinical experience .................................................................................................... 14 7.2.6 Clinical experience .......................................................................................................... 16 7.3 Study Purpose and Rationale ................................................................................................. 17 7.3.1 Temozolomide, Lymphopenia, and Homeostatic Proliferation ....................................... 17 7.3.2 Peptide Vaccines for Cancer ........................................................................................... 19 7.3.3 Summary of Study Purpose/Rationale ............................................................................ 20 8 OBJECTIVES AND ENDPOINTS ............................................................................................... 21 9 INVESTIGATIONAL PLAN .......................................................................................................... 22 9.1 Study Design ........................................................................................................................... 22 9.1.1 Definition of Unacceptable Toxicity ................................................................................. 23 9.1.2 Concomitant Medications ................................................................................................ 23 9.2 Rationale for Selection of Dose, Regimen, and Treatment Duration ...................................... 23 9.3 Rationale for Correlative Studies ............................................................................................ 23 9.4 Rationale for Genomic Proteomic Analyses ........................................................................... 24 9.5 Single -Voxel MR Spectroscopy ............................................................................................... 24 9.6 Definition of Evaluable Subjects, On Study, and End of Study ............................................... 25 9.7 Early Study Termination .......................................................................................................... 25 10 STUDY DRUG ............................................................................................................................. 26 10.1 Names, Classification, and Mechanism of Action ............................................................... 26 10.2 Packaging and Labeling ...................................................................................................... 26 10.3 Supply, Receipt, and Storage ............................................................................................. 26 10.4 Dispensing, Preparation and Administration ....................................................................... 26 10.4.1 Td ................................................................................................................................ 26 10.4.2 PEP IDH1M Vaccine with GM- CSF and Montanide ISA 51 ............................................ 26 Pro00054746: RESIST Study Version: 20171011 PT-PhI-II v05.22.12 Duke Cancer Institute Page 3 CONFIDENTIAL 10.5 Compliance and Accountability ........................................................................................... 27 10.6 Disposal and Destruction ....................................................................................................