8.3.4. Progression-Free Survival (PFS) Progression-free survival (PFS) is defined as the time from the date of the first injecti on of SL-701 to the date of disease progression or death from any cause, whichever occurs first. PFS times will be derived using procedure dates from the “Tumor Assessment” CRF pages or, if needed, the date of death from the “Notice of Death” CRF page. The date of progression will be the earliest of the dates that triggered the assessment of PD. PFS will be calculated for all patient s regardless of whether the patient discontinued study drug or received another anti-cancer therapy prior to progression. Patients who have not progressed or died at the time of the analysis will be censored at the date of their latest tumor assessment (ie, using the relevant RANO or RECIST criteria) or surv ival assessment. If a patient has no evaluable post- treatment tumor response data and the patient’s vital status is unknown at the time of analysis, the patient will be censored at Day 0 (ie, will be excl uded from the Kaplan-Meier analysis). The distribution of PFS in the mITT, ITT and PP Populations will be displayed by presenting the survival distribution function estimated using the Kaplan-Meier methodology as a function of tim e as assessed by the modified RANO criteria. The median PFS and its associated two-sided 95% CI (Brookmeyer and Crowley, 1982) will also be provided. 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 34 of 63 A sensitivity analysis will estimate PFS in both Stages 1 and 2 in the mITT, ITT and PP Populations as described above but will use RECIST rather than the modified RA NO criteria for assessing tumor response. 8.3.5. Progression-Free Survival at 6 and 12 Months (PFS-6 and PFS-12) Progression free survival at 6 and 12 months (PFS-6 and PFS-12) is defined as the proportion of patients who are alive and progression-free at 6 and 12 months after the initiation of SL-701 therapy. All analyses estimating PFS-6 and PFS-12 will use the mITT, ITT and PP Populations and the modified RANO criteria. PFS-6 and PFS-12 will be estimated by using an exact binomial proportion and by the Kaplan- Meier methodology. When estimating PFS-6 and PFS-12 by binomial proportion, all patients in the mITT, ITT and PP populations will be included in the proportion’s denominator. A patient’s disease will be considered to have progressed by 6 months if the patient meets any of the following criteria:  Died prior to Week 24  Had confirmed PD by Week 24  Had a last evaluable assessment of PD (i.e., among Weeks 8, 16, and 24)  Had an unknown vital status at Week 24. An exact two-sided 95% confidence interval (CI) for PFS-6 and PFS-12 will be computed using the method of Clopper and Pearson (Clopper and Pearson 1934). A sensitivity analysis of PFS-6 and PFS-12will be performed using Kaplan-Meier methodology. Patients will be considered to have progressed either if they had a confirmed assessment of PD or have died prior to Week 24. For patients who had confirmed PD, the patient’s survival time will be calculated using the date of the first event that triggered the assessment of PD. For patient s who died before Week 24, the date of death from the “Notice of Death” CRF page will be used to calculate their survival times. If patient did not have a confirmed diagnosis of PD but had an unknown vital status at Week 24, the patient’s survival time will be censored at the ti me at which the patient was last known to be alive. For these patients, the date of the last tumor response assessment or the date of collection of clinical laboratory samples, whichever is later, w ill be used to calculate survival time. If a patient survives at 6 months and does not have a diagnosis of confirmed PD, the patient’s survival time will be censored at the time of the last tumor response assessment. The distribution of PFS-6 and PFS-12 in the mITT , ITT and PP Populations will be displayed by presenting the survival distribution function estimated using the Kaplan-Meier methodology as a function of time. The survival probability and a two-sided 95% CI will be reported for PFS- 6 and PFS-12 using the standard error derived from the Greenwood formula (Kalbfleisch and Prentice 1980). 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 35 of 63 For the purpose of PFS-6 calculation, PFS status obtained between days 167-198 will be considered the 6th-month assessment and for PFS-12 the status obtained between days 350- 380 will be considered the 12th month. 8.3.6. Overall Survival (OS) Overall survival (OS) is defined as the time from the initiation of SL-701 therapy to the date of death from any cause. OS will be estimated using Kaplan-Meier methodology and the Treated Population. Any patient not known to have died at the time of analysis will be censored based on the last recorded date that the patient was known to be alive. This date is the latest of t he last know tumor assessment, last date of collection of clinical laboratory or vital sign data, or the l ast date of telephone contact with the patient. The distribution of OS will be displayed by presenting the survival distribution function estimat ed using the Kaplan-Meier methodology as a function of time. The median value of OS and its two- sided 95% CI will also be provided. For the purpose of survival analysis, survival status obtained between days 350-380 will be considered the 12th-month assessment) 8.4. EXPLORATORY ENDPOINTS AND ANALYSES 8.4.1. Correlation between DR and DDC with OS Duration of response and duration of disease control may be evaluated as appropriate in exploratory analyses 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 36 of 63 9.