EFFICACY 8.1. TUMOR RESPONSE ASSESSMENTS The primary criteria for assessing tumor response will be the modified Radiologic Assessment f or Neuro-oncology (RANO) criteria (Wen 2010) (see Appendix 4). The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) (see Appendix 5) will be used in certain secondary and sensitivity analyses of tumor response. 8.1.1. Modified RANO Criteria The modified RANO criteria use a combination of radiographic measurements and clinical fact ors (e.g., changes in a patient’s neurological status) to assess response to therapy. Measurable disease is defined as contrast-enhancing lesions with clearly defined margins by MRI or CT scan with 2 perpendicular diameters of at least 10 mm each. Non-measurable disease is defined by lesions that are one dimensional, or have maximal perpendicular diameters less than 10 mm, or have margins that are not clearly defined. The categories of response assessment for the RANO criteria include: Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD).The criteria defining each of the 4 response categories are shown in Appendix 4. Post-treatment assessments of radiographic response (CR, PR, SD) are made by comparing the sum of the products of the maximal cross-sectional enhancing diameters of up to 5 measurable lesions with the corresponding sum of products measured at baseline. In contrast, assessments of progressive disease are made by comparing the sum of the products of the maximal cross-sectional enhancing diameters with the corresponding sum of products at baseline (ie, if there was no response) or at the previous best response. Changes in non-measurable lesions will by noted by the investigator as having decreased, increased or remain unchanged. Patients without measureable disease cannot respond and can only achieve SD as the best radiographic outcome. Patients without measureable disease will be excluded from assessments that require assessment of response (OR R and DR). An analysis of disease control and duration of disease control (SD+PR+CR) will be conducted on the ITT/mITT/PPP populations. The modified RANO criteria require that a response (CR, PR, SD) be confirmed by a subsequent scan that occurs at least 4 weeks later. In the absence of a confirming scan at least 4 weeks later , assessments of either CR or PR will be considered only SD. When calculating variables that involve time- to-response/disease (e.g., DR, OS, PFS), the response or progression date will be defined as the date that the criteria were first met for response or progression, respect ively. In addition to the modified RANO criteria, information will be collected on the patient’s functional status using the Karnofsky Performance Scale (KPS) scores, and concomitant medications, including corticosteroid use. The KPS score (Appendix 3), a commonly used scale for rating a patient’s capacity to function under the burden of his disease, will be used to provi de consistency in this assessment across sites. 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 31 of 63 8.2. PRIMARY EFFICACY ENDPOINTS AND ANALYSES The primary efficacy variable will be overall survival at 12 months (OS-12) a. This variable wi ll be analyzed for each stage separately. 8.2.1. Primary Analysis of Overall Survival at 12 Months (OS-12) OS-12 is defined as the percentage of patients surviving at 12 months after the first injection of SL - 701. Should a patient’s vital status at 12 months be unknown, the patient will be considered to be deceased when estimating OS-12. This approach is a conservative one and assumes that patient loss is related to mortality. Analyses of OS-12 will use the mITT, ITT and PPP Populations. Survival status obtained between days 350-380 will be considered the 12th-month assessment. For Stage 1, an exact one-sample binomial test with a one-sided, type I error rate of 2.5 % will assess whether OS-12 is > 25%. An exact two-sided 90% confidence interval (CI) for OS-12 will be computed using the method of Clopper and Pearson (Clopper and Pearson 1934). For Stage 2, an exact one-sample binomial test with a one-sided, type I error rate of 2.5% will assess whether OS-12 is > 25%. An exact two-sided 90% confidence interval (CI) for OS-12 will be computed using the method of Clopper and Pearson (Clopper and Pearson 1934). 8.2.2. Sensitivity Analyses of OS-12 A sensitivity analysis will be carried out on the primary endpoint, using Kaplan-Meier methodology to estimate OS-12 . If a patient’s vital status is unknown at 12 months, the patient’s survival time will be censored at the time at which the patient was last known to be alive (i .e., using the later of the last tumor response assessment or the last collection date of lab sampl es). Two-sided 90% CIs will be reported for the survival probability at 12 months (OS-12) using the standard error derived from the Greenwood formula (Kalbfleisch and Prentice 1980). The Kaplan- Meier analysis will be performed using the Treated Population. 8.3. SECONDARY EFFICACY ENDPOINT(S) AND ANALYSES Descriptive statistics will be used to summarize all secondary efficacy endpoints. No inferent ial testing will be performed and no adjustments will be made for multiplicity. For analyses of dat a from both Stage 1 and Stage 2, t wo-sided 95% CIs will be reported for key descriptive statistics as noted below.