Do not make unauthorized copies. The secondary endpoint of ORR will be analyzed using Pearson’s chi -square test. Overall response rate (ORR) is defined as the proportion of patients who have prolonged stable disease or a partial or complete response to therapy according to RECIST 1.1. ORR will be reviewed 6 months after treatment with Vigil. The secondary analysis of all secondary endpoints will be conducted using two-sided tests at the alpha=0.05 level of significance. 8.1.3 Sensitivity Analyses of the Primary Endpoint Five sensitivity analyses of the primary endpoint will be conducted using each of the following modifications to the definition of PFS: • If the disease recurrence/progression assessment involves more than one date, the latest date will be used as the event date. • If disease recurrence or death occurs right after missing data for a scheduled radiographic disease assessment (including missing the assessment or assessment results in an unevaluable status for overall response per RECIST 1.1), the patient will be censored at the date of the last radiographic disease assessment. • If a patient receives non -protocol treatment for Ewing’s Sarcoma, the patient will be treated as having progression at the date of the last radiographic disease assessment. • Patients missing baseline disease assessment will be treat ed as having progression at the date of randomization. • For equivocal findings of recurrence (e.g., very small and uncertain new lesions; cystic changes or necrosis in existing les ions) for whom treatment continues until the next scheduled assessment, and if recurrence is confirmed at the next scheduled assessment, the date of recurrence should be the earlier date when recurrence was suspected. 8.1.4 Sensitivity Analysis of Overall Survival A sensitivity analysis of OS will be conducted in which subjects who are crossed over to Vigil therapy will be censored at the time of crossover. 8.1.5 Subgroup Analyses of the Primary (PFS) and Key Secondary Endpoints (OS, ORR) Subgroup analyses will be conducted in the following subsets of the ITT population: • Race / ethnicity • Study site / region Statistical Analysis Plan IND 014205 Ph III Ewing’s Sarcoma Vigil ± Irinotecan +Temozolomide CL-SAP-00001 Version: 03 Page 12 of 19 Confidential and proprietary information of Gradalis, Inc. Effective: 05-DEC-2018 It is the user’s responsibility to verify adequate training before executing a document. Do not make unauthorized copies. • Age group ( <15 years (low), ≥15 years (high) ) • Gender • Number of doses received (≤median number of doses administered, >median number of doses administered) • Number of lines of prior treatments including chemotherapy and radiation • At time of diagnosis: localized vs. metastatic disease • At time of diagnosis: skeletal vs. extraskeletal • At time of diagnosis: tumor volume/burden (<100ml or 8cm vs >100ml or 8cm) • Response to frontline therapy (CR vs. PR vs.