SD vs. progressive disease) • Time to first recurrence: <2 years, > 2 years Safety Analyses Safety endpoints include all adverse events (CTCAE version 5.0), laboratory safety assessments, and physical examination findings. Interim Analysis An interim analysis for efficacy, futility, and potential sample size re-estimation will be conducted by an independent data monitoring committee (IDMC) when 40 PFS events have been achieved (60% information fraction). Based on the Lan-DeMets method for group sequential trials using O’Brien-Fleming boundaries (Reboussin, DeMets et al. 2000), the levels of significance for the interim and final analyses are alpha=0.00762 and alpha=0.0476, respectively. Based on the results of the interim analysis, the IDMC will make one of the following four recommendations to the sponsor: • Terminate the study for efficacy (p<0.00762 at the interim analysis); • Continue the study as planned; • Increase the sample size to 120 events; • Terminate the study for futility. Provided that the IDMC does not recommend terminating the study early for efficacy, the conditional power of the planned final analysis at 67 events will be computed using the methodology of (Harrington 2001) (Jennison and Turnbull 2000), under the assumption that the observed hazard ratio at the interim analysis represents the true effect. In terms of the HR observed at the interim analysis, these rules can be translated (approximately) as follows: • If the HR is less than 0.43, terminate for efficac y • If the HR is in the range from 0.43 to 0.51, continue as planned. • If the HR is in the range from 0.51 to 0.61 (i.e., conditional power in the range from 50% to 80%), increase the sample size to 120 events. • If the HR is greater than 0.61 (i.e., conditional power less than 50%), terminate for futility. Statistical Analysis Plan IND 014205 Ph III Ewing’s Sarcoma Vigil ± Irinotecan +Temozolomide CL-SAP-00001 Version: 03 Page 13 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.