45 13.1. Table, Listing, and Figure Format ........................................................................................ 45 13.1.1. General ......................................................................................................................... 45 13.1.2. Headers ......................................................................................................................... 45 13.1.3. Display Titles ................................................................................................................ 46 13.1.4. Column Headers ............................................................................................................ 46 13.1.5. Body of the Data Display ............................................................................................... 46 13.1.6. Footnotes ...................................................................................................................... 49 14. QUALITY CONTROL ............................................................................... 50 15. INDEX OF TABLES, LISTINGS, AND FIGURES ...................................... 51 16. APPENDICES ............................................................................................ 52 17. APPENDIX 1 - STUDY EVENT SCHEDULE: STAGE 1 ............................ 53 18. APPENDIX 2 - STUDY EVENT SCHEDULE: STAGE 2 ............................ 56 19. APPENDIX 3 – KARNOFSKY PERFORMANCE SCALE .......................... 59 20. APPENDIX 4 – MODIFIED RANO CRITERIA FOR RESPONSE ASSESSMENT ...................................................................................................... 60 21. APPENDIX 5 – RECIST CRITERIA FOR RESPONSE ASSESSMENT (VERSION 1.1) ...................................................................................................... 61 22. APPENDIX 6 – OVERALL RESPONSE ASSESSMENT AT VISIT (RECIST) 62 23. APPENDIX 7 – ASSIGNMENT OF BEST OVERALL RESPONSE WHEN CONFIRMATION OF CR/PR IS REQUIRED ....................................................... 63 DocuSign Envelope ID: B3F56764-C440-4885-BA44-7578C4A73DB3 Stemline Therapeutics, Inc. Protocol: STML- 701-0114 Version 3.0, 10-JUL-2015 (Amendment 2) Statistical Analysis Plan Page 7 of 63 1. GLOSSARY OF ABBREVIATIONS Abbreviation Description AA anaplastic astrocytoma AE adverse event AG anaplastic glioma ALT alanine aminotransferase ANC absolute neutrophil count ANCOVA analysis of covariance ANOVA analysis of variance aPTT activated partial thrombopastin time AST aspartate aminotransferase ATC Anatomical Therapeutic Chemical BMI body mass index BSG brainstem glioma CI confidence interval CNS central nervous system CR complete response CSC cancer stem cell CT computed tomography CTCAE Common Terminology Criteria for Adverse Events CTL cytotoxic T lymphocyte CV coefficient of variation DC dendritic cell DDC Duration of disease control DR duration of response ECG electrocardiogram eCRF electronic case report form ELISPOT enzyme-linked immunosorbent spot FDA Food and Drug Administration DocuSign Envelope ID: B3F56764-C440-4885-BA44-7578C4A73DB3 Stemline Therapeutics, Inc. Protocol: STML- 701-0114 Version 3.0, 10-JUL-2015 (Amendment 2) Statistical Analysis Plan Page 8 of 63 Abbreviation Description FLAIR fluid-attenuated inversion recovery GAA glioma-associated antigen GBM glioblastoma multiforme GCP Good Clinical Practice GM-SCF granulocyte macrophage-colony stimulating factor HLA human leukocyte antigen ICF Informed Consent Form ICH International Conference on Harmonization IDMC Independent Data Monitoring Committee IFN interferon- γ IL interleukin IL-13Rα2 interleukin-13 receptor alpha 2 protein chain INR International Normalized Ratio mITT Modified intent- to-treat ITT intent- to-treat IVRS Interactive Voice Randomization System IWRS Interactive Web Randomization System KPS Karnofsky performance status Max maximum MedDRA Medical Dictionary for Regulatory Activities MHC major histocompatibility complex Min minimum n number of patients with an observation N number of patients in the dataset or population N/A not applicable NCI-CTCAE National Cancer Institute – Common Terminology for Adverse Events ORR objective response rate OS overall survival DocuSign Envelope ID: B3F56764-C440-4885-BA44-7578C4A73DB3 Stemline Therapeutics, Inc. Protocol: STML- 701-0114 Version 3.0, 10-JUL-2015 (Amendment 2) Statistical Analysis Plan Page 9 of 63 Abbreviation Description OS-12 percent of patients alive 12 months after the initiation of SL-701 therapy PBMC peripheral blood mononuclear cells poly-ICLC poly-inosinic-poly-cytidylic acid stabilized with poly-lysine and carboxymethyl cellulose PD progressive disease PFS progression-free survival PFS-12 percent of patients alive and progression-free 12 months after the initiation of SL-701 therapy PFS-6 percent of patients alive and progression-free 6 months after the initiation of SL-701 therapy PP Per protocol PR partial response PT preferred term RANO Response Assessment in Neuro-Oncology RECIST Response Evaluation Criteria in Solid Tumors RLT regimen limiting toxicity RT radiotherapy SAE serious adverse event SAP Statistical Analysis Plan SC Subcutaneous SD stable disease SE standard error SI Standard International System of Units SOC system organ class SOP Standard Operating Procedure SS safety s et STDV standard deviation TAA tumor-associated antigen TEAE treatment-emergent adverse event DocuSign Envelope ID: B3F56764-C440-4885-BA44-7578C4A73DB3 Stemline Therapeutics, Inc. Protocol: STML- 701-0114 Version 3.0, 10-JUL-2015 (Amendment 2) Statistical Analysis Plan Page 10 of 63 Abbreviation Description TLF table, listing and figure TMZ Temozolomide ULN upper limit of normal VEGF vascular endothelial growth factor VEGFR vascular endothelial growth factor receptor WHODrug World Health Organization Drug DocuSign Envelope ID: B3F56764-C440-4885-BA44-7578C4A73DB3 Stemline Therapeutics, Inc. Protocol: STML- 701-0114 Version 3.0, 10-JUL-2015 (Amendment 2) Statistical Analysis Plan Page 11 of 63 2. PURPOSE The purpose of this statistical analysis plan (SAP) is to ensure that the data listings, summary t ables and figures which will be produced, and the statistical methodologies that will be used, are complete and appropriate to allow valid conclusions regarding the study objectives. 2.1. RESPONSIBILITIES TCM Groups will perform the statistical analyses and is responsible for the production and qual ity control of all tables, figures and listings. 2.2. TIMING OF ANALYSES The primary analysis of safety and efficacy data is planned after all patients in both Stage 1 a nd Stage 2 have completed the final study visit (including survival follow up) or have termi nated early from the study. DocuSign Envelope ID: B3F56764-C440-4885-BA44-7578C4A73DB3 Stemline Therapeutics, Inc. Protocol: STML- 701-0114 Version 3.0, 10-JUL-2015 (Amendment 2) Statistical Analysis Plan Page 12 of 63 3.