Clinical trial NCT02113982
Conditions: Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Acute Myeloid Leukemia (AML)
Sponsor: Stemline Therapeutics, Inc.
Start date: 2014-09-01; Completion date: 2020-03-12
Enrollment: 138 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
This is a 4-stage, non-randomized, open-label, dose escalation and expansion, multicenter study. A cycle of therapy is 21 days. Stage 1 was a dose-escalation stage. During Stages 2-4, patients are treated at the MTD or maximum tested dose at which multiple DLTs are not observed during Stage 1.

Detailed description:
Study 0114 is a multi-stage, non-randomized, open-label, multicenter study of Tagraxofusp in First line and Relapsed/Refractory (R/R) Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) and Acute Myeloid Leukemia (AML) patients divided into 4 stages.

Each study stage has its own unique objectives and patient population, with Stage 1 representing the dose escalation phase and Stage 3 the pivotal phase.

In Stages 1 and 2, both patients with BPDCN (first-line and R/R) and AML were enrolled; Stage 3 enrolled previously untreated (first-line) BPDCN patients only. A separate stage, Stage 4, enrolled First-line and R/R BPDCN patients to further characterize safety and efficacy of Tagraxofusp.

The primary study objectives are reported below by stage:

Stage 1: to determine the Maximum Tolerated Dose (MTD) (or Maximum Tested Dose, MTeD where multiple DLTs were not observed) of Tagraxofusp administered at the following dose levels 7, 9, 12, 16 µg/kg/day

Stage 2: cohort expansion to determine the efficacy and safety of Tagraxofusp at the MTD selected in Stage 1

Stage 3 (pivotal): to determine the efficacy and safety of Tagraxofusp in patients with First-line BPDCN

Stage 4: to further characterize the efficacy and safety of Tagraxofusp in patients with both First-line and R/R BPDCN

Arms: arm 1: Intervention: Tagraxofusp arm 2: Intervention: Tagraxofusp arm 3: Intervention: Tagraxofusp
Interventions: intervention 1: Tagraxofusp
Intervention descriptions: intervention 1: None

Protocol documents:
Prot_000.pdf: 
SL-401 Diphtheria Toxin Interleukin-3 Fusion Protein 
Stemline Therapeutics, Inc. 
Protocol STML-401-0114 
Amendment 12 (FINAL): 17 January 2019 
1 
CONFIDENTIAL 
SL-401 in Patients with Acute Myeloid Leukemia or Blastic Plasmacytoid 
Dendritic Cell Neoplasm 
Sponsor: 
Stemline Therapeutics, Inc. 
750 Lexington Avenue, 11th Floor 
New York, NY 10022 
Study Product:  
SL-401 
Protocol Number: 
STML-401-0114 
IND Number: 
 
Study Contacts: 
Issue Date: 
17 January 2019 
CONFIDENTIAL – PROPRIETARY INFORMATION 
The confidential information in this document is the property of Stemline Therapeutics, Inc. It is understood that this 
information will not be disclosed to any third party, in any form, without prior written authorization from Stemline 
Therapeutics, Inc. 
NCT #: NCT02113982


SL-401 Diphtheria Toxin Interleukin-3 Fusion Protein 
Stemline Therapeutics, Inc. 
Protocol STML-401-0114 
Amendment 12 (FINAL): 17 January 2019 
2 
CONFIDENTIAL 
PROTOCOL APPROVAL SIGNATURE 
Protocol Title: 
SL-401 in Patients with Acute Myeloid Leukemia or Blastic Plasmacytoid 
Dendritic Cell Neoplasm 
Protocol Number: 
STML-401-0114 
This study will be conducted in compliance with the clinical study protocol (and amendments), 
International Council for Harmonisation (ICH) guidelines for current Good Clinical Practice (GCP) and 
applicable regulatory requirements. Compliance with GCP standards provides public assurance that the 
rights, safety, and well-being of trial subjects are protected, consistent with the principles that have their 
origin in the Declaration of Helsinki. 


SL-401 Diphtheria Toxin Interleukin-3 Fusion Protein 
Stemline Therapeutics, Inc. 
Protocol STML-401-0114 
Amendment 12 (FINAL): 17 January 2019 
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CONFIDENTIAL 
INVESTIGATOR PROTOCOL AGREEMENT 
SL-401 in Patients with Acute Myeloid Leukemia or Blastic Plasmacytoid 
Dendritic Cell Neoplasm 
I hereby agree to: 
•
Conduct the study as outlined in this protocol with reference to national/local regulations and
current International Council for Harmonisation / Good Clinical Practice guidelines.
•
Discuss and agree upon any modification to the protocol with Stemline Therapeutics, Inc. or
representatives hereof.
•
Fully co-operate with monitoring and auditing and allow access to all documentation by authorized
individuals representing Stemline Therapeutics, Inc. or Health authorities.
Protocol Version / Date: 
Amendment 12: 17 January, 2019 
To be signed by Principal Investigator: 
Print Name 
Signature 
Date 
Institution 


SL-401 Diphtheria Toxin Interleukin-3 Fusion Protein 
Stemline Therapeutics, Inc. 
 
Protocol STML-401-0114 
Amendment 12 (FINAL): 17 January 2019 
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CONFIDENTIAL 
Table of Contents 
1 
Protocol Synopsis .............................................................................................................. 11 
2 
Abbreviations and Definitions .......................................................................................... 24 
3 
Introduction and Study Rationale ..................................................................................... 27 
3.1 
Blastic Plasmacytoid Dendritic Cell Neoplasm ........................................................ 27 
3.2 
Acute Myeloid Leukemia ......................................................................................... 29 
3.2.1 
First-line Therapy.............................................................................................. 29 
3.2.2 
Second-line Therapy ......................................................................................... 30 
3.2.3 
Third-line Therapy ............................................................................................ 30 
3.3 
Targeting Cancer Stem Cells .................................................................................... 30 
3.4 
IL-3 Receptor (IL-3R) Over-Expression in AML .................................................... 31 
3.5 
Mechanism of Action of SL-401 .............................................................................. 32 
3.6 
Preclinical Studies ..................................................................................................... 33 
3.7 
SL-401 Clinical Studies ............................................................................................ 37 
3.7.1 
Study 50047 ...................................................................................................... 37 
3.7.2 
Current Study (STML-401-0114) ..................................................................... 38 
3.8 
Discussion and Rationale for Current Study ............................................................. 39 
4 
Study Objectives ............................................................................................................... 42 
4.1 
Primary Objectives.................................................................................................... 42 
4.2 
Secondary Objectives................................................................................................ 42 
4.3 
Exploratory Objectives ............................................................................................. 43 
5 
Patient Selection ................................................................................................................ 43 
5.1 
Study Population ....................................................................................................... 43 
5.2 
Patient Inclusion Criteria .......................................................................................... 43 
5.3 
Patient Exclusion Criteria ......................................................................................... 45 
5.4 
Replacement of Patients ............................................................................................ 46 
6 
Investigational Plan ........................................................................................................... 46 
6.1 
Dose and Schedule Rationale.................................................................................... 46 
6.2 
Overall Study Design ................................................................................................ 47 


SL-401 Diphtheria Toxin Interleukin-3 Fusion Protein 
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Protocol STML-401-0114 
Amendment 12 (FINAL): 17 January 2019 
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6.2.1 
Stage 1: Dose Escalation ................................................................................... 47 
6.2.2 
Stages 2-4 .......................................................................................................... 49 
6.3 
Study Duration .......................................................................................................... 51 
6.4 
Study Completion ..................................................................................................... 51 
7 
Study Treatment Identification, Administration, and Schedule ........................................ 51 
7.1 
Product Manufacturing and Characterization ........................................................... 51 
7.2 
Recommended Medications Per Institutional Guidelines/Practices ......................... 52 
7.3 
Allowed Medications/Therapies ............................................................................... 52 
7.4 
Prohibited Medications/Therapies ............................................................................ 52 
7.5 
SL-401....................................................................................................................... 52 
7.5.1 
SL-401 Description and Storage ....................................................................... 52 
7.5.2 
Dose, Schedule and Duration of Treatment ...................................................... 52 
7.5.3 
SL-401 Premedication and Dose Preparation and Administration ................... 53 
7.5.4 
Patient Monitoring Procedures During the SL-401 Dosing Period .................. 54 
7.5.5 
Dose Delays/Modifications and Management Procedures for Toxicities 
Associated with SL-401 .................................................................................... 54 
7.6 
Treatment Discontinuation........................................................................................ 55 
7.6.1 
Criteria for Treatment Discontinuation ............................................................. 55 
7.6.2 
Procedures and Follow-up after Treatment Discontinuation ............................ 56 
8 
Study Procedures .............................................................................................................. 57 
8.1 
Patient Selection........................................................................................................ 57 
8.2 
Medical History ........................................................................................................ 57 
8.3 
Disease Confirmation (Patients with BPDCN in Stages 2-4) ................................... 58 
8.4 
Prior and Concomitant Medication ........................................................................... 58 
8.5 
ECOG Performance Status ....................................................................................... 58 
8.6 
Physical Examination................................................................................................ 58 
8.7 
Vital Signs ................................................................................................................. 58 
8.8 
Electrocardiograms ................................................................................................... 58 
8.9 
Clinical Laboratory Tests .......................................................................................... 58 
8.10 
Urine or Serum Pregnancy Test ................................................................................ 59 


SL-401 Diphtheria Toxin Interleukin-3 Fusion Protein 
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Protocol STML-401-0114 
Amendment 12 (FINAL): 17 January 2019 
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8.11 
Vision Assessment .................................................................................................... 59 
8.12 
Tumor Assessments and Disease Response Assessment .......................................... 59 
8.12.1 
Stage 1 ............................................................................................................... 59 
8.12.2 
Stage 2, Patients with AML .............................................................................. 60 
8.12.3 
Patients with BPDCN (Stages 2-4) ................................................................... 61 
8.13 
Pharmacokinetic Studies ........................................................................................... 63 
8.14 
Immunogenicity Studies ........................................................................................... 64 
9 
Schedule of Events ............................................................................................................ 65 
9.1 
Study Day -14 to -4: Screening ................................................................................. 65 
9.2 
Study Day -1 to 0: Procedures Prior to Start of Treatment ....................................... 65 
9.3 
Cycle 1 ...................................................................................................................... 66 
9.3.1 
Study Days 1 – 5 (Up to Study Day 10 if Infusion(s) Held): Pre-Infusion ...... 66 
9.3.2 
Study Days 1 – 5 (Up to Study Day 10 if Infusion(s) Held): Infusion ............. 66 
9.3.3 
Study Day 8 ±3 Days, or 3 ±3 Days after Completion of Infusions if Infusion(s) 
Held ................................................................................................................... 67 
9.3.4 
Study Day 15 ±3 Days ...................................................................................... 67 
9.3.5 
Study Day 21 ±7 Days: End of Cycle ............................................................... 67 
9.3.6 
Study Day 28 ±3 Days, Then Every 7 ±3 days: Delayed End of Cycle for Toxicity 
Resolution Only if Required ............................................................................. 68 
9.4 
Cycles 2 – 6 ............................................................................................................... 68 
9.4.1 
Days 1 – 5 (Up to Day 10 if Infusion(s) Held): Pre-Infusion ........................... 68 
9.4.2 
Days 1 – 5 (Up to Day 10 if Infusion(s) Held): Infusion .................................. 69 
9.4.3 
Day 8 ±3 Days, or 3 ±3 Days after Completion of Infusions if Infusion(s) Held69 
9.4.4 
Day 15 ±3 Days ................................................................................................ 69 
9.4.5 
Day 21 ±7 Days: End of Cycle ......................................................................... 69 
9.4.6 
Day 28 ±3 Days, Then Every 7 ±3 days: Delayed End of Cycle for Toxicity 
Resolution Only if Required ............................................................................. 70 
9.5 
End of Treatment ...................................................................................................... 71 
9.6 
Safety Monitoring: Through 30 Days after Last Infusion ........................................ 71 
9.7 
Survival Monitoring: Approximately Every 90 Days after End of Treatment until 
Study Completion ..................................................................................................... 71 


SL-401 Diphtheria Toxin Interleukin-3 Fusion Protein 
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Protocol STML-401-0114 
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9.8 
Schedules of Events .................................................................................................. 71 
10 Adverse Events and Safety Evaluation ............................................................................. 80 
10.1 
Definitions................................................................................................................. 81 
10.1.1 
Adverse Event (AE) .......................................................................................... 81 
10.1.2 
Serious Adverse Event (SAE) ........................................................................... 81 
10.2 
Period of Observation ............................................................................................... 82 
10.3 
Pre-existing Conditions ............................................................................................. 83 
10.4 
Pregnancy .................................................................................................................. 83 
10.5 
Documentation and Reporting of Adverse Events by Investigator .......................... 84 
10.6 
Assessment of Causal Relationship to SL-401 ......................................................... 85 
10.7 
Grading of Adverse Event Severity .......................................................................... 86 
11 Excluded Prior and Concomitant Medications and Therapy ............................................ 87 
12 Statistical Analysis ............................................................................................................ 87 
12.1 
General Considerations ............................................................................................. 87 
12.2 
Populations for Analysis ........................................................................................... 88 
12.3 
Determination of Sample Size .................................................................................. 88 
12.4 
Demographics and Baseline Characteristics ............................................................. 89 
12.5 
Analyses of Safety Data ............................................................................................ 89 
12.6 
Analysis of Efficacy Data in First-Line BPDCN ...................................................... 90 
12.6.1 
Order of Statistical Analyses of Efficacy .......................................................... 90 
12.6.2 
Response Rate ................................................................................................... 91 
12.6.3 
Duration of Response ........................................................................................ 91 
12.6.4 
Bridge to SCT ................................................................................................... 92 
12.6.5 
Progression-free Survival.................................................................................. 92 
12.6.6 
Overall Survival ................................................................................................ 92 
12.6.7 
Exploratory and Subgroup Analyses ................................................................ 92 
12.7 
Additional Efficacy Analyses ................................................................................... 92 
12.8 
Pharmacokinetic and Immunogenicity Analyses ...................................................... 93 
12.9 
Blinding..................................................................................................................... 93 


SL-401 Diphtheria Toxin Interleukin-3 Fusion Protein 
Stemline Therapeutics, Inc. 
 
Protocol STML-401-0114 
Amendment 12 (FINAL): 17 January 2019 
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12.10 Interim Analyses ....................................................................................................... 93 
12.11 Final Analysis ........................................................................................................... 93 
12.12 Study Oversight Committees .................................................................................... 93 
13 Emergency Procedures ...................................................................................................... 94 
13.1 
Emergency Contact ................................................................................................... 94 
13.2 
Emergency Identification of Investigational Products .............................................. 94 
13.3 
Emergency Treatment ............................................................................................... 94 
14 Ethical and Regulatory Considerations ............................................................................. 94 
14.1 
Good Clinical Practice .............................................................................................. 94 
14.2 
Delegation of Investigator Responsibilities .............................................................. 94 
14.3 
Patient Information and Informed Consent............................................................... 95 
14.4 
Confidentiality .......................................................................................................... 95 
14.5 
Protocol Amendments ............................................................................................... 96 
14.6 
IRB/IEC Approval and Reporting ............................................................................ 96 
14.7 
Closure of the Study.................................................................................................. 96 
14.8 
Record Retention ...................................................................................................... 97 
14.9 
Liability and Insurance ............................................................................................. 97 
14.10 Financial Disclosure.................................................................................................. 97 
14.11 Study Monitoring and Auditing ................................................................................ 97 
14.11.1 Study Monitoring and Source Data Verification .............................................. 97 
14.11.2 Study Documentation........................................................................................ 98 
14.11.3 Site Audits ......................................................................................................... 99 
14.12 Documentation and Use of Study Findings .............................................................. 99 
14.12.1 Documentation of Study Findings .................................................................... 99 
14.12.2 Use of Study Findings ....................................................................................... 99 
15 References ....................................................................................................................... 101 
16 Appendices ...................................................................................................................... 107 
16.1 
Appendix A. Tumor Response Criteria for Patients with AML ............................. 107 
16.2 
Appendix B. Tumor Response Criteria for Patients with BPDCN ......................... 108 


SL-401 Diphtheria Toxin Interleukin-3 Fusion Protein 
Stemline Therapeutics, Inc. 
 
Protocol STML-401-0114 
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16.3 
Appendix C. Modified Severity Weighted Assessment Tool ................................. 110 
16.4 
Appendix D. ECOG Performance Status ................................................................ 111 
16.5 
Appendix E. CLS Management Guidance .............................................................. 112 
 


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Protocol STML-401-0114 
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List of Tables in the Text 
Table 1: Immunophenotypic Marker Expression in BPDCN .................................................. 28 
Table 2: Completed SL-401 Repeat-Dose Toxicity Studies, Investigator-sponsored IND ..... 34 
Table 3: Completed SL-401 Repeat-Dose Toxicity Studies with SL-401, Stemline IND ...... 34 
Table 4: Recommended ELZONRIS Dose Modifications ...................................................... 55 
Table 5: Study Events Schedule for Cycle 1 (Study Day -14 to Study Day 21): Stage 1 (All Pts) 
& Stage 2 (AML Pts) ........................................................................................... 72 
Table 6: Study Events Schedule for Cycles 2-6 and Subsequent Cycles: Stage 1 (All Pts) & Stage 
2 (AML Pts) ......................................................................................................... 74 
Table 7: Study Events Schedule for Cycles 1 & 2 (Study Day -14 to Study Day 21): BPDCN 
Patients in Stages 2-4 ........................................................................................... 76 
Table 8: Study Events Schedule for Cycles 3-6 and Subsequent Cycles: Stages 2-4 (BPDCN 
Patients) ................................................................................................................ 78 
Table 9: Time Points for Pharmacokinetic Blood Draws and ECGs ....................................... 80 
 
List of Figures in the Text 
Figure 1: Schematic of SL-401 Construction .......................................................................... 32 
 


SL-401 Diphtheria Toxin Interleukin-3 Fusion Protein 
Stemline Therapeutics, Inc. 
 
Protocol STML-401-0114 
Amendment 12 (FINAL): 17 January 2019 
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CONFIDENTIAL 
1 
Protocol Synopsis 
Name of Finished Product: 
SL-401 Injection frozen solution (1 mg/mL) / SL-401 for Injection lyophilized powder, for solution 
(1 mg/mL) 
SL-401 Injection frozen solution (1mg/mL) was approved by the Food and Drug Administration 
(FDA) on 21 December 2018 for the treatment of BPDCN in adults and in pediatric patients 2 years 
and older under the name ELZONRIS (tagraxofusp-erzs). 
Name of Active Ingredient: 
SL-401 (tagraxofusp-erzs) 
Study Title: 
SL-401 in Patients with Acute Myeloid Leukemia or Blastic Plasmacytoid Dendritic Cell Neoplasm 
Protocol Number: 
STML-401-0114 
Study Phase: 
1 / 2 
Primary Objectives: 
Stage 1 (completed):  
• 
Determine the maximum tolerated dose (MTD), or the maximum tested dose where multiple 
dose-limiting toxicities (DLTs) are not observed, of SL-401. 
Stage 2 (completed): 
• 
Determine the efficacy of SL-401 in patients with blastic plasmacytoid dendritic cell neoplasm 
(BPDCN), as assessed by objective response rate (ORR). 
• 
Characterize the safety profile of SL-401 at the MTD or maximum tested dose in both patients 
with acute myeloid leukemia (AML) and BPDCN. 
Stage 3 (completed): 
• 
Determine the complete response (CR) rate (i.e., CR + CR [clinical] with minimal residual 
skin abnormality [CRc]) in patients with first-line BPDCN. 
• 
Characterize the safety profile of SL-401 in patients with first-line BPDCN. 
Stage 4: 
• 
Further characterize the efficacy of SL-401 in first-line and relapsed/refractory (R/R) patients 
with BPDCN following the completion of Stage 2 and Stage 3, respectively, as assessed by the 
rate of CR (CR + CR with incomplete blood count recovery [CRi] + CRc). 
• 
Further characterize the safety profile of SL-401 among first-line and R/R patients with 
BPDCN. 
• 
Characterize the efficacy and safety of a lyophilized formulation of SL-401 among R/R and 
first-line patients with BPDCN. 
Secondary Objectives: 


SL-401 Diphtheria Toxin Interleukin-3 Fusion Protein 
Stemline Therapeutics, Inc. 
 
Protocol STML-401-0114 
Amendment 12 (FINAL): 17 January 2019 
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• 
Determine the CR rate (i.e., CR + CRi + CRc) for Stage 1 and Stage 2, and ORR for Stage 3 
patients.  
• 
Estimate duration of response (DOR), progression-free survival (PFS), and overall survival 
(OS) in patients with BPDCN. 
• 
Enable preliminary characterization of the estimated ORR in patients with R/R AML, 
including in subsets of patients with R/R AML based on pre-treatment blast count, 
cytogenetics, or CD123 measurement. 
• 
Estimate duration of response, PFS, and OS in patients with AML. 
• 
Characterize the pharmacokinetics (PK) and immunogenicity of SL-401. 
Exploratory Objectives: 
Exploratory objectives are to characterize expression of the interleukin-3 receptor (IL-3R)/CD123 (and 
other potentially relevant stem cell and disease markers) on leukemia cells in peripheral blood and 
bone marrow (when feasible), to evaluate potential changes in IL-3R/CD123 (and other potentially 
relevant marker) expressing populations over time, and preliminary correlation of baseline IL-
3R/CD123 (and other potentially relevant marker) expression and clinical efficacy (including response 
rates). 
Study Design: 
This is a 4-stage, non-randomized, open-label, dose escalation and expansion, multicenter study. A 
cycle of therapy is 21 days. A Data Safety Review Committee (DSRC), which will include Sponsor 
representatives, will be established to review the accruing safety data and make safety decisions during 
the study, including dose escalations in Stage 1. 
Stage 1: Dose Escalation (completed) 
During Stage 1, approximately 9-24 patients will be treated with SL-401 Injection at doses of 7, 9, 12, 
or 16 µg/kg/day for 5 consecutive days every 21 days. The 16 µg/kg/day dose will be evaluated only in 
patients with AML. Evaluation of higher doses (in increments of 25% or less) in AML patients may be 
attempted pending evaluation of the safety/tolerability of the 16 µg/kg/day dose level (these 
evaluations would be attempted to identify an MTD and will be guided by the criteria [stipulated 
below] defining safety/tolerability of all dose levels). 
Cohorts of 3-6 patients will be treated at each dose level. All patients within a cohort must complete 
the first cycle of therapy before patients from a new cohort receive SL-401 Injection at the next higher 
dose. No intra-patient dose escalation is allowed. The first cohort of patients will receive SL-401 at a 
dose of 7 µg/kg/day. After all patients in this cohort complete the first cycle of therapy, the dose for the 
second cohort of patients will increase by 29% to 9 µg/kg/day, conditional on the DLT rules described 
below. Similarly, after all patients in the second cohort complete the first cycle of therapy, the dose for 
the third cohort of patients will increase by 33% to 12 µg/kg/day, conditional on the DLT rules 
described below. Finally, after all patients in the third cohort complete the first cycle of therapy, the 
dose for the fourth cohort of patients, consisting only of patients with AML, will increase by 33% to 16 
µg/kg/day, conditional on the DLT rules described below. 
During Stage 1, DLT is defined as any of the following during the first cycle of therapy: 
• 
Any treatment-emergent Grade 4 transaminase or creatine phosphokinase (CPK) elevation, 
regardless of duration or relationship to SL-401. 
• 
Any treatment-emergent Grade 4 hematologic toxicity (unrelated to persistent leukemia) 
lasting >21 days after the last infusion of SL-401. 
• 
Any treatment-emergent Grade ≥3 non-hematologic toxicity (unrelated to persistent leukemia), 
with the exception of Grade 3 laboratory toxicities that resolve to Grade ≤1 or baseline ≤21 
days after the last infusion of SL-401, or the following Grade 3 toxicities if they resolve to 


SL-401 Diphtheria Toxin Interleukin-3 Fusion Protein 
Stemline Therapeutics, Inc. 
 
Protocol STML-401-0114 
Amendment 12 (FINAL): 17 January 2019 
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CONFIDENTIAL 
Grade ≤1 or baseline ≤21 days after the last infusion of SL-401: arthralgia, myalgia, fever 
responding to treatment, nausea and/or vomiting (excluding cases that require tube feeding, 
TPN or hospitalization) or diarrhea associated with suboptimal prophylaxis or treatment. 
Beginning with the dose level 7 µg/kg/day of SL-401 Injection, a decision to allow treatment at the 
next higher dose level will depend on the number of patients who experience a DLT during the first 
cycle. If none of the initial 3 patients treated (0/3) experiences a DLT, then dose escalation will 
proceed and 3 new patients will be treated at the next higher dose of 9 µg/kg/day. If one of the initial 3 
patients treated (1/3) experiences a DLT, the cohort will be expanded to include up to an additional 3 
patients treated at the same dose 7 µg/kg/day. If only one patient (1/6) from this expanded cohort 
experiences a DLT, then 3 new patients will be treated at the next higher dose 9 µg/kg/day. Expansion 
of the 9 µg/kg/day cohort to 6 patients, if necessary, will follow the same rules as the 7 µg/kg/day 
cohort. The same DLT rules will also apply to the 12 µg/kg/day and 16 µg/kg/day (AML specific) 
cohorts. 
In the event that 2 (or more) patients within a cohort have a DLT, then the MTD will be exceeded and 
further dose escalation will not occur. The MTD is defined as the dose preceding the dose level at 
which two patients experience a DLT during treatment Cycle 1. The MTD will be used in Stages 2-4 of 
the study. If the highest planned treatment dose is completed and determined to be safe and the MTD is 
not exceeded, the available PK and safety data will be reviewed to assess whether further dose 
escalation is justified. A patient who does not complete the first cycle of treatment for reasons other 
than the occurrence of DLT will be replaced by another patient who will receive the same dose 
regimen. 
In the event that a DLT occurs in two patients treated at the 7 µg/kg/day dose level, 5 µg/kg/day will be 
considered by the DSRC as an alternative starting dose. In this event, a new cohort of 3 patients will 
receive 5 µg/kg/day for the first cycle. The same DLT rules will apply to this dose level. If two or more 
patients experience a DLT at the 5 µg/kg/day dose level, the study will be halted. 
Stage 1 is complete, with the MTD of SL-401 determined to be 12 µg/kg/day in R/R AML and a 
maximum tested dose of SL-401 of 12 µg/kg/day in BPDCN. (An MTD was not determined in 
BPDCN.) 
Stages 2-4: Safety Expansion and Efficacy Assessment: 
During Stages 2-4, patients will be treated at the MTD or maximum tested dose at which multiple 
DLTs are not observed during Stage 1, or a lower dose with potentially the most favorable risk/benefit 
profile.  
SL-401 will be supplied as SL-401 Injection frozen solution (1 mg/mL) as described in Section 7.5. A 
lyophilized formulation (SL-401 for Injection, lyophilized powder, for solution; 1 mg/mL) also will be 
supplied. All patients enrolled in Stage 4 (both R/R and first-line) subsequent to completion of 
enrollment in Stage 3 will receive the lyophilized formulation of SL-401. Note that when the 
lyophilized formulation is introduced, patients who start treatment with SL-401 Injection frozen 
solution will continue to receive this dosage form throughout the study. 
At the time of Protocol Amendment 11, only Stage 4 is open for enrollment. 
Tumor Assessments During Stages 2-4 
Patients with AML (Stage 2 only) 
Assessment of the anti-tumor activity of SL-401 in patients with AML will be assessed by the 
Investigator as a secondary endpoint using the criteria in Section 16.1, Appendix A. The following 


SL-401 Diphtheria Toxin Interleukin-3 Fusion Protein 
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Protocol STML-401-0114 
Amendment 12 (FINAL): 17 January 2019 
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assessments will be performed at baseline within 14 days prior to the first administration of SL-401 
and thereafter for determination of tumor response for patients with AML in Stage 2, as follows:  
• 
Bone marrow aspirates (± biopsy) 21 (±7) days after the start of Cycles 1 and 2. Patients with 
evidence of bone marrow involvement prior to study treatment will also have bone marrow 
evaluations following Cycles 4 and 6 and then every 3 months from Months 6-12; every 6 months 
from 12 to 24 months; and every 12 months thereafter until there is evidence of relapsed or 
progressive disease. If the Cycle 1 (Day 21 [±7]) bone marrow examination is empty (i.e., 
hypocellular) or inadequate, a bone marrow examination should be repeated in 7 (±7) days to 
document response. If additional time is required to complete the repeat examination, consultation 
with the Medical Monitor is required. If CD123 flow cytometry or IHC stain assessment was 
performed on the bone marrow aspiration (± biopsy), the results should be recorded in the 
electronic case report form (eCRF).  
• 
Collection of peripheral blood samples for determination of blasts 21 (±7) days after the start of 
Cycles 1 and 2. Patients with evidence of peripheral blasts at baseline will also have peripheral 
blood samples collected 21 (±7) days after the start of Cycles 1 and 2 and 21 (±7) days after the 
start of every 2nd cycle thereafter (Cycles 4, 6, etc.) until there is evidence of relapsed or 
progressive disease. 
Patients with BPDCN (Stages 2-4) 
Standardized assessment of potential sites of disease involvement (including skin, lymph nodes, blood, 
bone marrow, and visceral organs) and consistently-defined response criteria will be utilized.  
The BPDCN diagnosis will be made or confirmed during screening by the pathology laboratories at the 
investigative sites. Subsequent to enrollment, pathology material will be submitted for review by the 
central pathologist for confirmation of the BPDCN diagnosis. 
Tumor response will be assessed by the Investigators for all patients with BPDCN, with the 
Investigator’s assessment to be used in the primary analysis. As a supportive assessment, tumor 
response will be assessed by an Independent Review Committee (IRC). Tumor response will be 
assessed using the Tumor Response Criteria for Patients with BPDCN presented in Section 16.2, 
Appendix B. All patients will also be followed for duration of response and survival. The following 
assessments will be performed at baseline within 14 days prior to the first administration of SL-401 
and thereafter for determination of tumor response for patients with BPDCN: 
• 
Bone marrow aspirates (± biopsy) samples 21 (±7) days after the start of Cycles 1 and 2. Patients 
with evidence of bone marrow involvement prior to study treatment will also have bone marrow 
evaluations following Cycles 4 and 6 and then every 3 months from Months 6-12; every 6 months 
from 12 to 24 months; and every 12 months thereafter until there is evidence of relapsed or 
progressive disease. 
• 
If the Cycle 1 (Day 21 [±7]) bone marrow examination is empty (i.e., hypocellular) or 
inadequate, a bone marrow examination should be repeated in 7 (±7) days to document 
response. If additional time is required to complete the repeat examination, consultation with 
the Medical Monitor is required. If CD123 flow cytometry or IHC stain assessment was 
performed on the bone marrow aspiration (± biopsy), the results should be recorded in the 
eCRF.  


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• 
Skin assessments, including photographs, for patients with skin involvement, and determination of 
skin disease burden using the Modified Severity Weighted Assessment Tool (mSWAT) (see 
Section 16.3, Appendix C) 21 (±7) days after the start of Cycles 1 and 2 and 21 (±7) days after the 
start of every 2nd cycle thereafter (Cycles 4, 6, etc.) until there is evidence of relapsed or 
progressive disease. Refer to the separate mSWAT Manual for instructions regarding the 
quantitation of malignant lesions via the mSWAT and response assessment in skin. 
• 
In situations in which there is substantial reduction of skin lesions (especially when 
accompanied by disappearance of BPDCN from bone marrow or other sites), a skin biopsy is 
required. The mSWAT guidance states: “A biopsy of normal appearing skin is unnecessary to 
assign a complete response. However a skin biopsy should be performed of a representative 
area of the skin if there is any question of residual disease (persistent erythema or pigmentary 
change) where otherwise a complete response would exist” (Olsen et al. 2011). 
• 
Computed tomography (CT) scans of index lesions 21 (±7) days after the start of Cycles 2, 4 and 
6 and 21 (±7) days after the start of every 4th cycle thereafter (for patients with baseline evidence of 
lymph node or visceral disease) until there is evidence of relapsed or progressive disease. For 
patients with no baseline evidence of lymph node or visceral BPDCN involvement, subsequent 
scans should be performed at the end of Cycle 2 (±7 days; or at time of disease progression (PD) if 
PD occurs prior to end of Cycle 2), 21 (±7) days after the start of Cycle 6, and at Investigator’s 
discretion thereafter. Baseline CT scans should be full-body (chest/ abdomen/pelvis), whereas 
follow-up scans should document response of index lesions (Cheson et al. 2007). 
• 
Collection of peripheral blood samples for determination of blasts 21 (±7) days after the start of 
Cycles 1 and 2. Patients with evidence of peripheral blasts at baseline will also have peripheral 
blood samples collected 21 (±7) days after the start of Cycles 1 and 2 and 21 (±7) days after the 
start of every 2nd cycle thereafter (Cycles 4, 6, etc.) until there is evidence of relapsed or 
progressive disease. 
Study Centers: 
This study will be conducted at up to 10 study centers. 
Inclusion Criteria: 
1. The patient has a diagnosis of AML (Protocol Stage 1 or 2) or BPDCN (Protocol Stages 1-4) 
according to World Health Organization (WHO) classification (AML; excluding acute 
promyelocytic leukemia [APL, FAB M3]) or confirmed by hematopathology (BPDCN) (Facchetti 
et al. 2008). 
2. The patient must meet one of the following (a) or (b) or (c):  
(a) Has evidence of persistent or recurrent AML (Protocol Stages 1 or 2) in the peripheral blood 
and/or bone marrow that is refractory to, or has relapsed from, their most recent prior line of 
treatment. 
• 
A prior line of treatment is considered an induction regimen if it involves an approved or 
investigational cytotoxic chemotherapy agent, biological agent, and/or hypomethylating 
agent administered alone or in a combination regimen, with the intent to induce robust 
cytoreduction (i.e., CR).  
• 
The previous induction regimen may have been a stem cell transplant (SCT) with intent to 
induce a CR.  


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• 
Consolidation and/or maintenance (including SCT) may have been given in CR/CRi, but 
are not counted as a line of treatment. 
• 
Hydroxyurea will not be considered a prior line of treatment. 
(b) Has previously untreated AML (Protocol Stages 1 and 2) and is considered to be at high risk 
for disease progression and/or is unlikely to derive more than transient benefit from standard 
therapy by having at least one of the following: 
• 
Treatment-related AML, except if it is associated with favorable cytogenetics (e.g., 
inversion 16, t[16;16], t[8;21], t[15;17]). 
• 
AML with antecedent hematological disease (e.g., myelodysplastic syndrome [MDS], 
myelofibrosis, polycythemia vera) and not a candidate for SCT in their current disease 
state. 
(c) Has histological and/or cytological evidence of BPDCN by pathologic assessment at the 
investigative site according to WHO classification (Facchetti et al. 2008) by a pathologist with 
expertise in hematologic malignancies, that can be measured for treatment response and is 
either: 
• 
Previously untreated (i.e., first-line) (Protocol Stages 2-4). 
• 
Persistent or recurrent in the peripheral blood, bone marrow, spleen, lymph nodes, skin, or 
other sites after previous treatment with at least 1 line of systemic therapy for BPDCN, e.g., 
stem cell transplant or chemotherapy (Protocol Stages 1, 2, and 4). A pathology specimen 
must be available for central pathology review for all BPDCN patients enrolled in Stages 2-
4.  
3. The patient is ≥18 years old. 
4. The patient has an ECOG performance score (PS) of 0-2. 
5. The patient has adequate baseline organ function, including cardiac, renal, and hepatic function: 
• 
Left ventricular ejection fraction (LVEF) ≥institutional lower limit of normal as measured 
by multigated acquisition (MUGA) scan or 2-dimensional (2-D) echocardiography 
(ECHO) within 28 days prior to start of therapy and no clinically significant abnormalities 
on a 12-lead electrocardiogram (ECG) 
• 
Serum creatinine ≤1.5 mg/dL (133 µmol/L) 
• 
Serum albumin ≥3.2 g/dL (32 g/L) (please note that albumin infusions are not permitted in 
order to enable eligibility) 
• 
Bilirubin ≤1.5 mg/dL (26 µmol/L) 
• 
Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 times the upper limit 
of normal (ULN) 
6. If the patient is a woman of child bearing potential (WOCBP), she has had a negative serum or 
urine pregnancy test within 1 week prior to treatment. 
7. The patient has signed informed consent prior to initiation of any study-specific procedures or 
treatment. 
8. The patient is able to adhere to the study visit schedule and other protocol requirements, including 
follow-up for survival assessment. 
9. The patient (male and female) agrees to use acceptable contraceptive methods for the duration of 
time on the study, and continue to use acceptable contraceptive methods for 2 months after the last 
infusion of SL-401. 


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Exclusion Criteria: 
1. The patient has a diagnosis of APL (FAB M3). 
2. The patient has persistent clinically significant toxicities Grade ≥2 from previous chemotherapy 
(excluding alopecia, nausea, fatigue, and liver function tests [as mandated in the inclusion 
criteria]).  
3. The patient has received treatment with chemotherapy, wide-field radiation, or biologic therapy 
within 14 days of study entry. 
4. The patient has received treatment with another investigational agent within 14 days of study entry. 
5. The patient has previously received treatment with SL-401. 
6. The patient has an active malignancy and/or cancer history (excluding AML, BPDCN, or 
antecedent MDS) that may confound the assessment of the study endpoints. Patients with a past 
cancer history (within 2 years of entry) with substantial potential for recurrence and/or ongoing 
active malignancy must be discussed with the Sponsor before study entry. Patients with the 
following neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ, cervical 
intraepithelial neoplasia, organ-confined prostate cancer with no evidence of progressive disease. 
7. The patient has clinically significant cardiovascular disease (e.g., uncontrolled or any New York 
Heart Association Class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial 
infarction, unstable angina or stroke within 6 months prior to study entry, uncontrolled 
hypertension or clinically significant arrhythmias not controlled by medication). 
8. The patient has uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive 
pulmonary disease, pulmonary hypertension) that in the opinion of the Investigator would put the 
patient at significant risk for pulmonary complications during the study. 
9. The patient has known active or suspected central nervous system (CNS) leukemia. If suspected, 
CNS leukemia should be ruled out with relevant imaging and/or examination of cerebrospinal 
fluid. 
10. The patient is receiving immunosuppressive therapy – with the exception of low-dose prednisone 
(≤10 mg/day) – for treatment or prophylaxis of graft-versus-host disease (GVHD). If the patient 
has been on immunosuppressive treatment or prophylaxis for GVHD, the treatment(s) must have 
been discontinued at least 14 days prior to study treatment and there must be no evidence of Grade 
≥2 GVHD. 
11. The patient has uncontrolled intercurrent illness including, but not limited to, uncontrolled 
infection, disseminated intravascular coagulation, or psychiatric illness/social situations that would 
limit compliance with study requirements. 
12. The patient is pregnant or breast feeding. 
13. The patient has known positive status for human immunodeficiency virus or active or chronic 
Hepatitis B or Hepatitis C. 
14. The patient is oxygen-dependent. 
15. The patient has any medical condition which in the opinion of the Investigator places the patient at 
an unacceptably high risk for toxicities. 
16. The patient has AML and requires more than 1g per day of hydroxyurea. (Hydroxyurea is 
permitted at doses of 1g per day or less). 


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Investigational Product, Dose, and Mode of Administration: 
SL-401 is a novel protein comprised of recombinant human interleukin-3 (IL-3) genetically fused to 
truncated diphtheria toxin protein. SL-401 targets the IL-3R, which is over-expressed on the cancer 
stem cells (CSCs) and/or tumor bulk of a variety of leukemias and hematopoietic malignancies, 
including BPDCN and AML, relative to normal hematopoietic stem cells and other hematopoietic 
cells.  
A cycle of therapy is 21 days. SL-401 Injection is provided as an intravenous (IV) injectable and 
administered as a 15-minute IV infusion for the first 5 consecutive days of a 21-day cycle; refer to the 
Pharmacy Manual for details regarding SL-401 preparation and administration. The first cycle of 
SL-401 must be administered in the inpatient setting, with hospitalization beginning the day of the first 
infusion of SL-401 and ending 24 hours after the last infusion of SL-401. Subsequent cycles of SL-401 
can be administered in the inpatient setting or in a suitable outpatient ambulatory care setting that is 
equipped for intensive monitoring of patients with hematopoietic malignancies undergoing treatment, 
per the discretion of the Investigator and institutional guidelines and capabilities. Patients will be 
monitored for at least 4 hours following the administration of each infusion of SL-401. 
Patients who benefit from treatment and do not have evidence of clinically significant progressive 
disease may receive repeated cycles of SL-401 even if a response, in the judgment of the Investigator, 
is not attained. Patients should continue to receive SL-401 as long as they may be benefiting from 
treatment, according to the Investigator; no maximum duration of therapy has been set.  
Patients will receive the following premedications approximately 60 minutes before each SL-401 
infusion: 
• 
Acetaminophen 650 mg (or equivalent dose of paracetamol) orally (PO) 
• 
Diphenhydramine 50 mg IV (or equivalent dose of another H1-histamine antagonist) 
• 
Methylprednisolone 50 mg IV (or an equivalent dose of another corticosteroid) 
• 
Ranitidine 50 mg IV (or an equivalent dosage of another H2-histamine antagonist) 
During the dosing period for each cycle, individual SL-401 infusions may be delayed to allow for 
toxicity resolution, as detailed in Section 7.5.5. 
During the first cycle, patients will receive a starting dose according to their dosing cohort in Stage 1, 
or the dose carried into Stages 2-4. Potential dose modifications for subsequent cycles relative to the 
prior cycle dose will be based on the severity and resolution of toxicities. Dose reductions should be 
discussed with the medical monitor on a case by case basis. 
Procedures During Dosing Period: 
During each cycle, testing and procedures that may result in withholding of a scheduled SL-401 
infusion, largely based on unresolved manifestations of fluid retention and/or other relevant acute 
toxicities during daily dosing, are described in Table 5, Table 6, Table 7, and Table 8 in Section 9.8. 
Withhold SL-401 infusion if any of the following occur: 
• 
Body temperature ≥38°C 
• 
Heart rate ≥130 or ≤40 bpm 
• 
Systolic blood pressure (BP) ≥160 or ≤80 mmHg 
• 
Serum creatinine >1.8 mg/dL (159 µmol/L) 
• 
Serum albumin  
o In settings in which albumin is reduced to 3.0-3.5 g/dL (30-35 g/L) or by ≥0.5 g/dL 
(5 g/L) below the level at the start of the cycle, withhold SL-401 infusion and 
administer albumin 25 g IV daily or every 12 hours as clinically feasible until serum 


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albumin is both ≥3.5 g/dL and not reduced by ≥0.5 g/dL from the level at the start of 
the cycle prior to resuming treatment with SL-401 in the same cycle. 
o In settings in which albumin is reduced to <3.0 g/dL (30 g/L) or by more than 1.0 g/dL 
(10 g/L) below the level at the start of the cycle (i.e., from 4.3 g/dL to 3.2 g/dL), 
withhold SL-401 infusions for the duration of that particular cycle. Albumin should be 
administered until the albumin level is at least above 3.5g/dL. Consultation with the 
Medical Monitor is advised. 
o Dosing in the next cycle may resume if albumin remains at 3.5 g/dL without additional 
albumin infusions. 
• 
AST >5 times the ULN or ALT >5 times the ULN (SL-401 will be withheld for remainder of 
study cycle) 
• 
Increase in body weight by ≥1.5 kg over pre-treatment weight on the prior treatment day. 
Refer to Section 7.5.5 for dose modifications/delays.  Management procedures for capillary leak 
syndrome (CLS) and associated symptoms are provided in Section 16.5, Appendix E. 
Concomitant Medications: 
Recommended Medications Per Institutional Guidelines/Practices: 
It is recommended that patients receive the following types of prophylactic therapies/regimens per 
institutional guidelines/practices:  
• 
Antibacterial: ciprofloxacin, levofloxacin, or an equivalent antibiotic 
• 
Antifungal: fluconazole, voriconazole, or an equivalent antifungal 
• 
Antiviral: acyclovir, valacyclovir or an equivalent antiviral 
Allowed Medications/Therapies: 
All patients may receive supportive care measures as clinically indicated, including prophylactic 
antibiotics, antihistamines, antiemetics, albumin, fluids (hydration), and supportive measures. Patients 
may receive growth factor support and/or blood product transfusions as per the discretion of their 
physician. 
Albumin 25 g IV daily should be administered if serum albumin is between 3.0-3.5 g/dL (30-35 g/L) 
on days that dosing occurs or if it is <3.0 g/dL (30 g/L) on days when treatment has been withheld or in 
the immediate post-treatment period. The Investigator has discretion with regard to frequency of 
administration. 
Prohibited Medications/Therapies: 
An enrolled patient may not receive investigational or approved anticancer or anti-leukemia agents, 
including cytotoxic chemotherapy agents, hypomethylating agents (5-azacytadine, decitabine or 
others), or anticancer tyrosine kinase inhibitors (including imatinib, ruxolitinib, sorafenib and others) 
or therapeutic monoclonal antibodies. Hydroxyurea may be administered (however its use should be 
discussed with the Medical Monitor). 
Assessments: 
Assessments for safety, efficacy, and biological effects will be performed according to the schedules 
outlined in Table 5, Table 6, Table 7, and Table 8 in Section 9.8. 
Safety Assessments: 
Safety assessments include DLTs, adverse events (AEs), serious adverse events (SAEs), physical 
examinations, vital sign measurements, clinical laboratory evaluations, and reasons for treatment 
discontinuation due to toxicity. In addition, patients will be monitored for changes in visual acuity and 
color vision and post-transplantation veno-occlusive disease (VOD). 


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The AE reporting period for a patient treated in the study begins with the initiation of SL-401 and is 
continuous through 30 days after the last SL-401 infusion. All AEs that occur in treated patients during 
the AE reporting period specified in the protocol must be reported to the Sponsor, whether or not the 
event is considered related to SL-401. Any known untoward event that occurs beyond the AE reporting 
period that the Investigator assesses as related to SL-401 should also be reported as an AE. 
Efficacy Assessments: 
For BPDCN patients, a global assessment paradigm is to be followed for determination of baseline 
disease and subsequent response evaluations, with all potential disease sites assessed during Screening, 
including the bone marrow (via aspirate and/or biopsy when an aspirate is not available), blood (via 
clinical laboratory testing for blasts and hematologic parameters), skin (via visual examination with 
determination of skin disease burden using mSWAT), lymph nodes, liver, spleen, and other viscera 
(via CT), and lymph nodes, liver, spleen, and other viscera (via physical examination). Positive sites of 
disease identified during screening MUST be followed during the study in every response evaluation. 
(Disease in organs that were disease-positive at screening are to be assessed, documented and recorded 
in the clinical database, even if the disease disappeared in subsequent response evaluations.) Sites with 
no evidence of disease during Screening must be documented as such and an assessment that baseline 
disease is not present are to be adequately documented in source and recorded in the clinical database; 
thereafter, these sites need not be followed, unless there is evidence of PD. 
Efficacy endpoints include ORR, CR rate, duration of response, PFS, and OS. Stem cell transplantation 
rate following SL-401 therapy and subsequent disease assessments will also be evaluated. Among 
patients with BPDCN in Stages 2-4, patients with a central pathologist-confirmed diagnosis of BPDCN 
who received at least one SL-401 infusion will be considered evaluable for the primary analysis of 
efficacy.  
See Study Design for a description of efficacy assessments for patients with AML. 
Pharmacokinetic (PK) Studies: 
An intensive schedule for collection of blood samples after specific infusions during Cycles 1 and 3 of 
SL-401 will be used to determine plasma concentrations of SL-401. Plasma concentration data over 
time will be used to characterize the PK disposition of SL-401, to assess any change in the PK 
properties of SL-401 during the 5-day course of treatment or between cycles of treatment, and relate 
the PK characteristics of SL-401 to immunogenicity, toxicity, and disease activity. The nominal blood 
sampling time schedule is summarized in Table 9.  
Immunogenicity Studies: 
Blood samples will be collected for the detection of SL-401 reactive antibodies. 
Cardiac Assessments: 
All patients will have 12-lead ECGs performed according to the schedule in Table 9 in Section 9.8. All 
ECGs will be analyzed by a central facility. 
Statistical Methods: 
Analysis Populations: 
Safety analysis will be performed on the population of patients who have received any amount of study 
treatment. The primary population for the analysis of efficacy will be the modified intent-to-treat 
(mITT) population, consisting of those patients who have received at least one dose of study drug. For 
BPDCN patients, an additional criterion for mITT patients will be a confirmed diagnosis based on 
central pathology review. BPDCN patients in the mITT population will be said to be evaluable. 
Additional efficacy analyses will be performed on a per-protocol (PP) population, consisting of those 
patients who are in the mITT population, are compliant with all major aspects of the protocol, and have 
received a minimum of 2 cycles of study treatment. 


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Sample Size: 
The sample size was originally planned to be approximately 40-50 patients with BPDCN, including 
approximately 40 first-line patients planned to be treated with the optimal SL-401 dose as determined 
in the completed Stage 1 of this study (12 µg/kg/day). In addition, up to approximately 36 patients with 
relapsed/refractory AML were planned to be enrolled in Stage 2 of the study.  
After the maximum number of patients with first-line BPDCN in Stage 3 were enrolled, subsequent 
first-line BPDCN patients that meet eligibility criteria will be enrolled in Stage 4. Furthermore, any 
patient with R/R BPDCN enrolled in this study on or after 26 October, 2016, will be allocated to Stage 
4. Enrollment will continue in Stage 4 to ensure continued access to SL-401 for BPDCN patients in a 
clinical trial setting; up to approximately 145 patients (including ~95 BPDCN patients) may be 
enrolled.  
Analysis Conventions: 
Analyses will be performed on all patients who received any quantity of SL-401 (i.e., all treated 
patients). 
Summaries will be grouped by disease (BPDCN and AML). For data from BPDCN patients, further 
categories for summarization will consist of line of therapy (first-line, R/R, and total) and dose 
(12 µg/kg/day and all doses). Efficacy endpoints will be summarized separately for Stage 3 patients, 
with an additional summary for all first-line and R/R BPDCN patients across all stages. 
Continuous (non-survival related) data will be summarized using descriptive statistics: number of 
observations (n), mean, standard deviation (SD), median, minimum, and maximum. Time to event data 
will be summarized using frequency and percentage of events and censored observations. Kaplan-
Meier analysis will be performed to estimate the 25th percentile, median, and 75th percentile for time to 
events with corresponding two-sided 95% confidence intervals.  


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Unless otherwise stated, confidence intervals, when presented, will be constructed at the 2-sided 95% 
level. For binomial variables, 95% confidence intervals will be constructed using the Clopper Exact 
method instead of normal approximation. 
Data listings will present all data collected on eCRFs by study drug dose, center, Stage of study 
enrollment, and patient number.  
Safety: 
Safety data analysis will be performed primarily on the pool of first-line BPDCN patients treated with 
the 12 µg/kg/day dose level, with additional summaries for patients with R/R BPDCN and across the 
pool of all BPDCN patients. Separate safety tabulations will be produced for patients with AML, 
patients who are treated with the lyophilized formulation of SL-401, and an overall pool of all enrolled 
patients. 
Treatment-emergent AEs through 30 days after last SL-401 infusion will be summarized by 
MedDRA™ Version 13.1 (or higher) System Organ Class and preferred term. The incidences and 
percentages of patients experiencing each AE preferred term will be summarized with descriptive 
statistics. AEs will also be summarized by National Cancer Institute Common Terminology Criteria for 
Adverse Events (NCI-CTCAE), Version 4.03 (or higher) grade and by causality (relationship to study 
treatment). Dose-limiting toxicities, Grade ≥3 AEs, SAEs, and AEs resulting in dose modification or 
treatment discontinuation will also be summarized by preferred term. 
Laboratory results will be classified according to NCI-CTCAE, Version 4.03 (or higher). Laboratory 
results not corresponding to an NCI-CTCAE term will not be graded. Incidences of laboratory 
abnormalities will be summarized with descriptive statistics. 
Vital signs and physical examination results will be summarized with descriptive statistics. 
Efficacy: 
Efficacy assessments include CR rate (i.e., CR + CRi + CRc), DOR, ORR, PFS, and OS. Efficacy 
analyses will focus on patients with first-line BPDCN, treated at the 12 µg/kg/day dose level. The 
analysis of efficacy of SL-401 in these patients will be performed to address several objectives, based 
on data from the different stages of the study. Descriptive statistical analysis will be performed for 
patients with R/R disease and for AML patients, with the extent of efficacy data used for these analyses 
dependent on data maturity and need for regulatory submission. 
Analyses by stage are intended as follows. Stage 3 will provide the pivotal results for a potential 
registrational submission in first-line BPDCN patients as assessed by rate of CR+CRc. Stage 1 and 2 
results will be presented, similar to the interim analysis as noted in Section 12.10. Stage 4 results will 
be presented separately and may be used to further assess consistency across drug formulations, 
dependent on the extent of available data. 
The primary evidence of efficacy will be derived from an analysis of the rate of CR+CRc, as assessed 
by the Investigator, in patients in Stage 3, accompanied by an evaluation of the durability of these CRs 
as a key secondary endpoint. A formal statistical analysis will first be performed for the primary 
efficacy endpoint to test the hypothesis that the rate of CR+CRc in first-line patients in Stage 3 exceeds 
the lower benchmark value of 10%. The primary analysis will be performed when all patients in Stage 
3 have been followed for a minimum of 6 months or discontinued treatment, whichever occurs first. In 
addition, the durability of CR will be evaluated; refer to Section 12.6.3 for analysis methods for 
duration. 
A number of additional secondary analyses will then be performed, to further evaluate the rate of CR in 
other stages of the study and to assess additional efficacy parameters in support of the primary analysis 
results. The analyses of all secondary endpoints will be descriptive, with summaries of secondary 
endpoints to be evaluated and presented in the following order of importance (as noted above, these 


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analyses will be performed on data from first-line BPDCN patients treated at the 12 µg/kg/day dose 
level): 
1. Bone-marrow CR (BMCR) and DOR for Stage 3 
2. CR rate and DOR for Stages 1 and 2 
3. CR rate and DOR for pooled data from Stages 1, 2, 3, and 4 
4. ORR and DOR for Stages 1 and 2 
5. ORR and DOR for pooled data from Stages 1, 2, 3, and 4 
6. Proportion of patients who receive SCT based on pooled data from Stages 1, 2, 3 and 4 
7. PFS for Stages 1, 2, 3, and 4 
8. OS for Stages 1, 2, 3, and 4 
Study Oversight: Monitoring and Review Committees: 
The conduct and evaluation of the study will include a DSRC, IRC, and a central pathologist. A charter 
detailing the operations of each group will be written.  
Stage 1 (completed): 
During Stage 1 and the initial portions of Stage 2, decisions regarding DLT determination, dose 
escalation and cohort progression will be made by a DSRC whose membership includes Sponsor 
representatives and study Investigators.  
Stages 2-4 (enrollment completed in Stages 2 and 3): 
In Stages 2-4 of the study, the DSRC will conduct a safety data review on an every 1-2-month basis. 
Periodic safety reviews will be conducted by the Sponsor. 
A central pathologist will confirm histopathological BPDCN diagnosis. Tumor response will be 
assessed by the Investigators for all patients with BPDCN, with the Investigator’s assessment to be 
used in the primary analysis. As a supportive assessment, tumor response was also evaluated by an IRC 
on a pre-specified subset of patients. 
 


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2 Abbreviations and Definitions 
AE 
Adverse Event 
ALL 
Acute Lymphoid Leukemia 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Transaminase 
AML 
Acute Myeloid Leukemia 
ANC 
Absolute Neutrophil Count 
APL 
Acute Promyelocytic Leukemia 
Ara-C 
Cytosine Arabinoside 
AST 
Aspartate Transaminase 
BM 
Bone Marrow 
BMA 
Bone Marrow Aspiration 
BMCR 
Bone Marrow Complete Response 
BP 
Blood Pressure 
BPDCN 
Blastic Plasmacytoid Dendritic Cell Neoplasm 
BSA 
Body Surface Area 
BTD 
Breakthrough Therapy Designation 
BUN 
Blood Urea Nitrogen 
CBC 
Complete Blood Count 
CLS 
Capillary Leak Syndrome 
CML 
Chronic Myeloid Leukemia 
CNS 
Central Nervous System 
CPK 
Creatine Phosphokinase 
CR 
Complete Response 
CRc 
CR [Clinical] with Minimal Residual Skin Abnormality  
CRi 
Complete Response with Incomplete Bone Marrow Recovery  
CSC 
Cancer Stem Cell 
CT 
Computed Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 


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DLT 
Dose-Limiting Toxicity 
DSRC 
Data Safety Review Committee 
DT 
Diphtheria Toxin 
ECG 
Electrocardiogram 
ECHO 
Echocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic Case Report Form 
EDTA 
Ethylenediamine Tetraacetic Acid 
FDA 
Food and Drug Administration 
GLP 
Good Laboratory Practice 
GVHD 
Graft Versus Host Disease 
HIPAA 
Human Insurance Portability Accountability Act 
IB 
Investigator Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
ICU 
Intensive Care Unit 
IHC 
Immunohistochemistry 
IND 
Investigational New Drug Application 
IRC 
Independent Review Committee 
IL-3 
Interleukin-3 
IL-3R 
Interleukin-3 Receptor 
INR 
International Normalized Ratio 
IV 
Intravenous Administration 
LDH 
Lactate Dehydrogenase 
LFT 
Liver function test 
LVEF 
Left Ventricular Ejection Fraction 
MDS 
Myelodysplastic Syndrome 
mITT 
Modified intent-to-treat 
mSWAT 
Modified Severity Weighted Assessment Tool 


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MTD 
Maximum Tolerated Dose 
MUGA 
Multigated Acquisition Scan 
NCI 
National Cancer Institute 
ORR 
Objective Response Rate 
OS 
Overall Survival 
PD 
Progressive Disease 
pDCs 
Plasmacytoid Dendritic Cells 
PK 
Pharmacokinetics 
PFS 
Progression-free Survival 
PO 
Orally 
PP 
Per-protocol 
PR 
Partial Response 
PS 
Performance Status 
PT 
Prothrombin Time 
PTT 
Partial Thromboplastin Time 
RBC 
Red Blood Cell 
R/R 
Relapsed/Refractory 
rIL2 
Recombinant Interleukin-2 
SAE 
Serious Adverse Event 
SCT 
Stem Cell Transplant 
SD 
Stable Disease 
SGOT 
Serum Glutamic Oxaloacetic Transaminase 
SGPT 
Serum Glutamic Pyruvic Transaminase 
TEAE 
Treatment-emergent adverse event 
TLS 
Tumor Lysis Syndrome 
ULN 
Upper Limit of Normal 
VOD 
Veno-occlusive disease 
WHO 
World Health Organization 
WOCBP 
Women of Childbearing Potential 


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3 Introduction and Study Rationale 
3.1 
Blastic Plasmacytoid Dendritic Cell Neoplasm 
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an uncommon hematological 
malignancy characterized by the clonal proliferation of malignant plasmacytoid dendritic cells 
(pDCs) (Facchetti et al. 2003). This neoplasm was originally recognized as a distinct entity in 
1994 (Adachi et al. 1994) and the uncertainty regarding its histogenesis was reflected by the 
multiplicity of terms that were previously used for its designation, including agranular CD4+ 
natural killer cell leukemia (Brody et al. 1995), blastic natural killer leukemia/lymphoma 
(DiGiuseppe et al. 1997), and agranular CD4+/CD56+ hematodermic neoplasm (Petrella et al 
2002; Herling et al. 2007). In 2001, the World Health Organization (WHO) classification of 
tumors of hematopoietic and lymphoid tissue proposed the term blastic natural killer (NK) cell 
lymphoma on the basis of the blastic cytology, and the expression of CD56 in the absence of 
other lineage specific markers. The relationship of BPDCN to pDCs was hypothesized first by 
Lucio et al. (1999) and subsequently confirmed by several studies (Petrella et al. 2002; Jacob et 
al. 2003; Reichard et al. 2005; Urosevic et al. 2005; Chaperot et al. 2004; Bene et al. 2003). The 
term BPDCN was introduced in 2008 by the updated WHO classification (4th edition) (Facchetti 
et al. 2008).  
BPDCN most commonly affects middle-aged and older patients and is approximately 3.5-fold 
more common in men than women. The median age at diagnosis is 66 years and is lower for 
women than men. The true incidence and prevalence of BPDCN, like many other rare diseases 
without definitive and/or effective therapy, is not precisely known. However, based on a 
published report (Wang et al. 2012), BPDCN may constitute approximately 0.44% of the 
incident cases of hematologic cancers annually, or approximately 700 and 1,000 incident cases 
annually in the United States (US) and Europe, respectively, based on published data of 
hematologic cancer cases. 
BPDCN cells show an immature “blastic” appearance; the diagnosis rests upon the 
demonstration of CD4 and CD56 expression, together with markers more restricted to PDC (such 
as CD123 [or the interleukin-3 receptor; IL-3R]) and negativity for lymphoid, NK and myeloid 
lineage-associated antigens. Immunophenotypic markers frequently, variably and infrequently 
expressed in BPDCN are detailed in Table 1 (Chaperot et al. 2001, Facchetti et al. 2008, 
Garnache-Ottou et al. 2009, Herling et al. 2007, Marafioti et al. 2008, Shi et al 2014, Zheng et al. 
2012). The diagnosis of BPDCN is enabled by comprehensive evaluation of overall clinical 
manifestations, the morphologic appearance of blasts on skin, marrow or other biopsy, and a 
characteristic immunophenotypic profile, as indicated in Table 1.  


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Table 1: Immunophenotypic Marker Expression in BPDCN 
Immunophenotypic Marker 
Description 
Frequently expressed in BPDCN 
 
CD4, CD56, CD123 (IL-R3α) 
Widely recognized BPDCN markers with significant expression in 
substantial majority of BPDCN cases. 
TCL1(TCL1A) (T cell 
leukemia/lymphoma) 
Lymphoid marker, expressed in majority of BPDCN (and also normal 
pDCs); also expressed in B- and T-cell ALL. 
BDCA-2/CD303 
Dendritic cell marker frequently expressed in BPDCN and 
infrequently expressed in other acute leukemias. 
BDCA-4/Neuropilin-1 
Dendritic cell marker frequently expressed in BPDCN; may also be 
expressed in other acute leukemias. 
CD2AP (CD2-associated protein) 
Adaptor protein frequently expressed in pDCs and BPDCN and 
infrequently expressed in other acute leukemias. 
CD45-RA 
T-lymphoid marker, frequently expressed in BPDCN; may also be 
expressed in acute lymphoid malignancies. 
Variably expressed in BPDCN 
 
HLA-DR 
Myeloid precursor with variable expression in BPDCN; may also be 
expressed in acute myeloid leukemias. 
Infrequently expressed in BPDCN 
 
CD11c, MPO (myeloperoxidase) 
Myeloid markers, negative in majority of BPDCN cases. 
CD79a 
B-lymphoid marker, negative in majority of BPDCN cases. 
CD3 
T-lymphoid marker, negative in majority of BPDCN cases. 
 
The clinical features and evolution of BPDCN are homogeneous, primarily consisting of 
2 patterns (Brody et al. 1995; Herling et al. 2007; Reichard et al. 2005; Petrella et al. 2005; 
Petrella et al. 1999; Suzuki et al. 2005; Assaf et al. 2007). The first pattern (90% of cases) is 
characterized by an indolent onset dominated by cutaneous lesions followed by tumor 
dissemination. The second pattern shows features of an acute leukemia with systemic 
involvement from the outset, and multiple skin nodules are frequently present (Suzuki et al. 
2005). BPDCN most typically presents with skin lesions, as well as extracutaneous malignant 
disease in the bone marrow, blood, lymph nodes, spleen, and other organs. Despite the frequent 
appearance of a somewhat indolent clinical presentation at the outset, the course of BPDCN is 
highly aggressive and the median survival is approximately 12-14 months (Herling et al. 2007; 
Jacob et al. 2003; Petrella et al. 2005; Bekkenk et al. 2004; Feuillard et al. 2002). The disease 
also almost always results in a terminal leukemic phase with proliferation of BPDCN blasts in 
the bone marrow and peripheral blood, leading to decreased blood cell counts with resultant 
infections, bleeding, and invariably death.  


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There is currently no standard of care, nor an effective treatment regimen, for BPDCN (Riaz et 
al. 2014). Previously untreated (first-line) BPDCN patients are typically treated with 
combination chemotherapy regimens generally used for lymphoma or acute leukemia, often 
requiring dose reductions or elimination of anthracyclines due to the predominance of elderly 
patients with this disease. There are only a few large studies (over 40 patients) reported in the 
literature; the most recent and largest, with over 80 patients, reported a 56% response rate in 
first-line BPDCN with combination chemotherapy, but response criteria were not elucidated. 
Median overall survival (OS) from diagnosis is only 8 to 14 months, with elderly patients being 
at the lower end of this range. Allogeneic stem cell transplant, mostly reserved for younger 
patients in first complete response (CR) with good performance status, has also been employed 
but only when patients’ disease state and overall physical condition permit. Furthermore, the 
literature for the treatment of relapsed/refractory (R/R) BPDCN is scattered, limited and 
inconsistent in the way that clinical benefit is measured and presented, and management beyond 
first-line is usually not described in the larger retrospective case studies; of 7 published studies 
involving ≥10 patients, there is only one documented response to ≥2 lines of therapy. 
3.2 
Acute Myeloid Leukemia 
Acute Myeloid Leukemia (AML) is characterized by the uncontrolled proliferation of immature 
myeloid cells in the bone marrow and peripheral blood, resulting in the development of anemia, 
neutropenia, and thrombocytopenia, and associated complications such as serious infections, 
bleeding, and fatigue. The American Cancer Society (2013) estimates there will be 
approximately 14,590 new cases of AML in the United States during 2013, with an estimated 
10,370 deaths due to the disease. The median age at diagnosis is 67 years, and 5-year survival 
across all ages, treatments, and other prognostic subgroups is 24% (National Cancer Institute 
2013). The WHO classification of AML incorporates morphology, cytogenetics, molecular 
genetics, and immunologic markers to define clinically relevant disease entities that are 
universally applicable and prognostically valid with therapeutic implications (Bennett et al. 
1976; Brunning et al. 2001; Cheson et al. 1990; Cheson et al. 2007). 
3.2.1 First-line Therapy 
Initial treatment of AML is divided into induction chemotherapy and post-response, 
consolidation therapy. To optimize potential for durable response, patients frequently receive 
some form of consolidation therapy, which is routinely given to patients age <60 and generally 
involves multiple courses of intensive chemotherapy or stem cell transplant (SCT) (Dohner et al. 
2010). Consolidation therapy is often given only once, or not given at all, to patients who are 
>60 years old. Tolerance of the induction and consolidation phases is directly related to patient 
characteristics such as age, the presence or absence of comorbidities, and performance status. 
Strategies for consolidation are generally based on the risk of relapse, with higher risk patients 
receiving more aggressive therapy. Current first-line induction treatments for AML among 
eligible patients include chemotherapy drugs such as cytarabine, daunorubicin, and 


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mitoxantrone. Post-response therapies include dose-intensified cytarabine, and autologous or 
allogeneic SCT. 
Although CR rates after standard first-line induction therapy in AML are relatively high, certain 
subgroups of patients with AML often cannot tolerate treatment strategies which optimize the 
probability of durable responses, or have a high risk of relapse even when available standard 
therapies are administered. Consequently, National Comprehensive Cancer Network Guidelines 
(2013) recommend that AML patients with an antecedent hematologic disease (e.g., 
myelodysplasia, myelofibrosis, polycythemia vera), age >60 years, or unfavorable cytogenetics 
(e.g., deletion of 5 or 7 and >3 abnormalities) are appropriate candidates for clinical studies with 
novel agents early in their disease (i.e., as first-line therapy). 
3.2.2 Second-line Therapy 
Approximately 70% of patients who receive first-line therapy and achieve a first CR would be 
expected to experience recurrent disease, and a subset of patients who do not derive benefit from 
first-line therapy would also be candidates for subsequent treatment. In second-line AML, while 
there are currently no approved treatments, typical therapies include additional chemotherapy, 
often cytarabine at various dosages and regimens. Unless allogeneic SCT can be performed, 
patients with R/R AML have a poor prognosis; relatively few patients are eligible for SCT due to 
donor unavailability, advanced age, and significant morbidity with reinduction efforts (Forman 
and Rowe, 2013). 
3.2.3 Third-line Therapy 
Following failure of second-line therapy, patients often have depressed bone marrow function 
and are no longer optimal candidates for additional chemotherapy. There are currently no 
approved treatments for third-line AML, although therapeutic options include supportive care, 
cytarabine based combinations, and investigational therapies (e.g., hypomethylating agents). 
Many of these therapies impart serious toxicities – including cytopenias – that may compound 
the complications of AML itself, and, in particular, heavily-pretreated AML. Importantly, no 
currently available treatments have been shown to extend survival in this setting. The median OS 
for AML patients after failure of second-line treatment, based on two large series, is 1.5 months 
(Giles et al. 2005; Keating et al. 1989). 
3.3 
Targeting Cancer Stem Cells 
The field of cancer stem cells (CSCs) is a new area of cancer biology that may fundamentally 
alter the approach to oncology drug development. CSCs have been identified in virtually all 
major tumor types, including leukemia and cancers of the brain, breast, colon, prostate, and 
pancreas (Jordan et al. 2006). CSCs are the highly malignant “seeds” of a tumor that self-renew 
and generate more mature cells that comprise the bulk of the tumor, or “the tumor bulk.” As 
such, CSCs appear to be responsible for tumor initiation, propagation, and metastasis. Many of 
the characteristics of CSCs, such as their slow growth, anti-cell death mechanisms, and presence 


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of multi-drug resistance proteins, may enable CSCs to resist therapeutic agents traditionally used 
to treat cancer. This may be due to the many challenging characteristics of CSCs, including slow 
growth, presence of multi-drug resistance proteins, anti-cell death mechanisms, and increased 
activity of cellular mechanisms that repair damaged deoxyribonucleic acid. CSCs are particularly 
resistant to chemotherapy, radiation, or targeted therapy relative to tumor bulk. 
CSCs have also been shown to increase, as a percentage of total tumor cells, as a result of 
exposure to a traditional therapy (Bao et al. 2006; Hermann et al. 2008). Consistent with their 
pivotal role in the development of tumors and relapse, higher amounts of CSCs in patient tumors 
as a percentage of their entire cancer appear to correlate with poor prognosis. CSC fractions 
greater than 3.5% and 1% of the entire cancer correlate with poor survival outcomes in patients 
with AML and brain cancer, respectively (van Rhenen et al. 2005; Zeppernick et al. 2008). 
3.4 
IL-3 Receptor (IL-3R) Over-Expression in AML  
The alpha subunit of the IL-3R (IL-3 α receptor = IL-3Rα, also called multi-colony stimulating 
factor) is a type I transmembrane glycoprotein belonging to the cytokine receptor superfamily; 
all the members of this superfamily are characterized by a conserved region homologous to the 
fibronectin type III domain. The IL-3R is a heterodimer of α (CD123) and β chains; (the β chain 
is shared by IL-3, IL-5, and granulocyte macrophage-colony stimulating factor receptors). The 
receptor, found on pluripotent progenitor cells, induces tyrosine phosphorylation within the cell 
and promotes proliferation and differentiation within the hematopoietic cell lines. 
IL-3R is over-expressed on AML blasts and CSCs relative to normal hematopoietic stem cells 
(Jordan et al. 2000; Jordan et al. 2006; Tehranchi et al. 2010). CD34+/38- CSCs strongly express 
IL-3R, whereas IL-3R is virtually undetectable on normal CD34+/38- hematopoietic stem cells 
(Jordan et al. 2000; Jordan et al. 2006). The differential expression of IL-3R between malignant 
and normal stem cells provides a potential opportunity for a therapeutic window in which to 
target CSCs with an IL-3R-targeted therapy (e.g., SL-401), while minimizing toxicity to normal 
bone marrow including normal hematopoietic stem cells.  
In addition to AML, IL-3R has also been shown to be differentially expressed on other 
hematological cancers, including BPDCN, myelodysplastic syndrome (MDS), chronic myeloid 
leukemia (CML), acute lymphoid leukemia (ALL), hairy cell leukemia, Hodgkin’s disease, and 
certain aggressive non-Hodgkin’s lymphomas (e.g., follicular cell, mantle cell, and Burkitt’s 
lymphomas) (Tehranchi et al. 2010; Aldinucci et al. 2005; Munoz et al. 2001; Aldinucci et al. 
2002; Black et al. 2003; Frolova et al. 2010). Moreover, IL-3R is also over-expressed on CSCs 
of multiple hematologic malignancies, including CML, MDS, and T-cell ALL (Jordan et al. 
2006; Tehranci et al. 2010; Florian et al. 2006; Lhermitte et al. 2006).  
A higher percentage of IL-3R-expressing CSCs within a patient’s tumor relates to poor outcome 
(Vergez et al. 2011). In particular, AML patients with IL-3R-expressing CSCs that comprise 
≥3.5% of their entire leukemia have a worse prognosis than patients with IL-3R-expressing 
CSCs that comprise <3.5% of their entire leukemia (van Rhenen et al. 2005). Interestingly, IL-


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3R-rich pDCs have been found to be increased in the bone marrow of patients with multiple 
myeloma and appear to contribute to disease aggressiveness and resistance to treatment 
(Chauhan et al. 2009). These findings further validate that IL-3R is an important oncology target 
in multiple hematologic cancer indications. 
3.5 
Mechanism of Action of SL-401  
Diphtheria toxin (DT) IL-3 fusion protein (designated SL-401 by Stemline Therapeutics, Inc. 
[“Stemline”]) is a novel biologic targeted therapy directed to the IL-3R. SL-401 is comprised of 
recombinant human IL-3 genetically fused to a truncated DT, in which the binding domain of DT 
has been replaced with IL-3. As depicted in Figure 1, the IL-3 domain of SL-401 is able to target 
the agent to leukemia blasts and CSCs that over-express IL-3R, leading to receptor-mediated 
endocytosis and localization of SL-401 to early endosomes. The translocation domain of DT 
changes conformation in the acidic environment of the endosome, and the RXRR motif (residues 
191-194) located between the catalytic and translocation domains of DT is cleaved by endosomal 
furin. The translocation domain of DT then inserts into the endosomal membrane. As the TAT-
like domain of DT (residues 201-230) interacts with cytosolic Hsp90 and thioredoxin reductase, 
the catalytic domain (A fragment) unfolds, is reduced, and translocates to the cytosol. Upon 
release into the cytosol, the A fragment refolds and catalytically inactivates cellular protein 
synthesis by ADP-ribosylating the diphthamide residue in domain IV of EF2, leading to 
apoptosis (Yamaizumi et al. 1978; Deng et al. 2008; FitzGerald et al. 1989; Perentesis et al. 
1992; Louie et al. 1997; Ratts et al. 2005; Thorburn et al. 2004).  
Figure 1: Schematic of SL-401 Construction 
 
The manner by which SL-401 kills cells is distinct from that of available cancer therapeutics. 
First, SL-401 is a targeted therapy directed to the IL-3R that is present on CSCs and/or tumor 
bulk, but not on normal hematopoietic stem cells. Second, SL-401 utilizes a payload that is not 
cell cycle-dependent. Therefore, it is designed to kill not just highly proliferative tumor bulk, but 
also relatively quiescent CSCs. Lastly, SL-401 utilizes a payload that may not be subject to 
multi-drug resistance mechanisms typically used by CSCs to evade traditional therapies. The 
payload also kills cells in a manner that is distinct from that of other available therapies, which is 
another reason why SL-401 may be an effective addition to the therapeutic armamentarium 
against hematologic malignancies. 
 
Trans- 
location 
SL-401 DNA 


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3.6 
Preclinical Studies 
In vitro and in vivo activity against both leukemia blasts (i.e., tumor bulk) and CSCs of a variety 
of human leukemia cell lines and primary leukemia cells from patients has been demonstrated 
using SL-401 (designated as DT388IL3 [Diphtheria Toxin Interleukin-3 Fusion Protein] in these 
earlier studies) (Angelot-Delettre et al. 2011; Alexander et al. 2000; Frankel et al. 2000).  
Potent cytotoxicity against leukemic cells in vitro in a dose-dependent fashion was demonstrated 
for SL-401, with IC50 (concentration that inhibits the growth of 50% of leukemia cells) values in 
the low picomolar range. Notably, and in contrast, normal bone marrow progenitor cells were 
relatively insensitive. Anti-CSC activity was also exhibited. In particular, SL-401 inhibited long-
term AML colony formation, an assay for stem cell activity, compared with normal human bone 
marrow. Additionally, engraftment and growth (i.e., tumorigenicity) of AML cells was reduced 
relative to normal human bone marrow, when these cells were treated ex vivo and reimplanted 
into immunodeficient mice, which also indicates anti-tumor activity at the level of the CSC 
(Frankel et al. 2000). Treatment of severe combined immunodeficiency mice also significantly 
reduced engraftment of AML (Feuring-Buske et al. 2002). AML engraftment was reduced by an 
average of 83% (range, 14–100) and 57% (range, 0–98) after 4 and 12 weeks, respectively (n = 
6). Leukemia was not detected in 2 of 6 mice 12 weeks after SL-401 treatment. Repeating 
treatment every 4 weeks enhanced its effectiveness (Black et al. 2003; Frankel et al. 2000). 
The cytotoxicity of SL-401 relates to the level of IL-3R expression on leukemia cells in vitro 
(Frankel et al. 2000). In studies performed to date, leukemia cells with high surface expression of 
IL-3R have been exquisitely sensitive to SL-401, with IC50 values ranging from 1-28 pM, 
whereas low cellular expression of IL-3R has been associated with higher IC50 values, i.e., 
∼1400 pM (Frankel et al. 2000). Even so, SL-401 plasma concentrations exceeding the entire 
range of IC50 values have been readily achievable in patients receiving SL-401 at doses below 
the maximum tolerated dose in a Phase 1-2 study described in Section 3.7.  
In addition to being active against AML cells, very potent activity against BPDCN cells was 
demonstrated. In preclinical studies, the IC50 values against BPDCN cell lines derived from 
patients and primary tumor cells from BPDCN patients were in the femtomolar (i.e., 10-15 M) 
range, which is perhaps the most sensitive tumor cell type to any specific cancer therapeutic 
known (Chauhan et al. 2009). 
Interestingly, the bone marrows of patients with multiple myeloma have been demonstrated to 
contain high quantities of IL-3R-expressing pDCs. These pDCs have since been shown to 
augment the growth of multiple myeloma and contribute to drug resistance, suggesting that 
killing pDCs may confer clinical benefit in patients with multiple myeloma (Chauhan et al. 
2009). Indeed, SL-401 has been recently been demonstrated to possess potent activity against 
multiple myeloma cell lines and primary tumor samples, which appears to be related to both 
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To support the Phase 1/2 clinical study conducted under the Investigator-sponsored 
investigational new drug application (IND), repeat-dose toxicity studies with SL-401 were 
conducted in mice and cynomolgus monkeys. The study designs are summarized in Table 2. 
Table 2: Completed SL-401 Repeat-Dose Toxicity Studies, Investigator-sponsored IND 
Study Type and Duration 
Dose Level(s) 
Dose Regimen 
Mice 
 
 
5-day efficacy study, survival data 
2 µg (≈ 100 µg/kg) 
IP injection daily for 5 days 
14-day toxicity study 
0.5, 1, 2, 2.5, 3, 3.5, 5, 7, 10 µg 
(≈ 25, 50, 100, 125, 150, 175, 
250, 350, 500 µg/kg) 
IP injection 3 times a week for 2 weeks 
(6 doses) 
Monkeys 
 
 
14-day toxicity study 
40, 60, 100 µg/kg 
IV injection every other day (6 doses) 
14-day toxicity study 
100, 150 µg/kg 
IV injection every other day (6 doses) 
 
Stemline has conducted two non-Good Laboratory Practice (GLP) toxicity studies in 
cynomolgus monkeys and one GLP 5-Day toxicity study in cynomolgus monkeys with a 3-week 
recovery period to confirm target organs of toxicity with SL-401. The study designs are 
summarized in Table 3. Note that the doses described in the table and subsequent summary are 
doses of SL-401. 
Table 3: Completed SL-401 Repeat-Dose Toxicity Studies with SL-401, Stemline IND 
Study 
Number 
Study Title 
Number of 
Animals 
Study Type and 
Duration 
 Dose 
Level(s) 
Dose 
Regimen 
Noteworthy Findings 
2231-
001 
SL-401: An 
Intravenous 
Dose Range 
Finding Study in 
Cynomolgus 
Monkeys 
6; 2/sex/group 
Non-GLP; 5 
days 
40, 60, 80 
µg/kg 
IV 
injection 
daily 
During the study, on Day 5, 
the male at 80 µg/kg/day 
was euthanized in extremis, 
due to SL-401-related 
clinical signs. Based on 
clinical observations as well 
as clinical laboratory values 
the maximum tolerated dose 
(MTD) of SL-401 was 
determined to be 60 
µg/kg/day when given as an 
intravenous slow bolus 
injection daily for 
5 consecutive days. 


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Study 
Number 
Study Title 
Number of 
Animals 
Study Type and 
Duration 
 Dose 
Level(s) 
Dose 
Regimen 
Noteworthy Findings 
2231-
004 
SL-401: An 
Intravenous Pilot 
Dose 
Confirmation 
Study in 
Cynomolgus 
Monkeys 
4; 1/sex/group 
Non-GLP; 5 
days 
30, 60 
µg/kg 
IV 
injection 
daily 
Evidence of sporadic 
inflammation and hepatic 
effects in both sexes at both 
dose levels. Based on 
clinical observations as well 
as clinical laboratory values 
and chemistries the 60 
µg/kg/day dose was well-
tolerated when given as an 
intravenous slow bolus 
injection daily for 5 
consecutive days. 
2231-
002 
SL-401: A 5-
Day Intravenous 
Toxicity Study 
in Cynomolgus 
Monkeys with a 
3-Week 
Recovery Period 
26; Terminal: 
3/sex/group; 
Recovery: 
2/sex/dose 
group 
GLP; 5 days 
with a 3-week 
recovery period 
Control, 
30, 60 
µg/kg 
IV 
injection 
daily 
One female administered 60 
µg/kg/day was euthanized 
in extremis on Day 6, prior 
to the scheduled necropsy. 
The cause of moribundity 
was severe necrosis of renal 
cortical tubules (kidneys). 
Additional dose-related and 
test article-related 
microscopic changes were 
present in brain choroid 
plexus, kidneys, liver, and 
thymus. 
 
Three toxicity studies were conducted with SL-401 at doses ranging from 30 µg/kg/day to 
80 µg/kg/day daily for 5 days. Assessment of toxicity was based on mortality, clinical 
observations, body weights, clinical pathology, and in one study histopathology. The main 
SL-401 related findings noted were as follows: 
• Dose-dependent clinical signs of decreased activity, hunched posture, and sparse hair 
were observed in males and females at all dose levels. Additionally, signs of decreased 
appetite were exhibited by all 3 females and one male (dose 60 µg/kg/day), as were 
reductions in body weight in males (5-9%) at all dose levels and respective decreases of 6 
and 7% in females receiving doses of 80 and 40 µg/kg/day. 
• Dose-related test article related findings were observed in clinical pathology parameters; 
increased liver enzymes (aspartate transaminase [AST] and alanine transaminase [ALT]) 
in both sexes of all dose groups after the first dose; sporadic evidence of renal injury 
(increased urea nitrogen and/or creatinine) in both sexes at all dose levels by after the 
fifth dose interval; sporadic/inconsistent effects on neutrophils, platelet, and/or 
reticulocyte counts, mostly at a dose of 80 µg/kg/day; and mild serum protein alterations 
in both sexes at all dose levels (increased globulin with decreased albumin). 


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• Dose-related microscopic changes were present in brain choroid plexus, kidneys, liver, 
and thymus of animals treated with SL-401 at dose levels of 30 µg/kg/day and 
60 µg/kg/day. Inflammation/necrosis degeneration of the choroid plexus was present in 
terminal males and females at doses of 30 and 60 µg/kg/day and in recovery males and 
females at 60 µg/kg/day. Degeneration/necrosis of renal cortical tubules in the kidneys 
was present in females at 30 and 60 µg/kg/day as well as terminal males at 60 µg/kg/day. 
Kidneys were within normal limits in all recovery animals. Minimal centrilobular 
hepatocellular necrosis and mild vacuolation (centrilobular or diffuse) were present in the 
livers of terminal males at 60 µg/kg/day. Livers were within normal limits in all recovery 
animals. The thymus of one recovery male at 60 µg/kg/day was reduced in size compared 
to controls. This finding correlated microscopically to generalized lymphoid depletion.  
• Toxicokinetic data in male and female cynomolgus monkeys demonstrated a half-life of 
approximately 0.5 hour after an intravenous bolus dose. The systemic plasma 
concentrations of SL-401 following doses of 40, 60, or 80 μg/kg/day showed a 
corresponding (reasonably proportional) increase in systemic exposure across the doses. 
There was no effect of pre-existing low level anti-DT specific antibodies. There was no 
accumulation. Comparison of the first to fifth dose sequence showed there were no 
appreciable changes in the toxicokinetic exposure profile and there were no notable 
gender differences in exposure.  
• From data collected and evaluated during these 3 studies, it appears that the maximum 
tolerated dose (MTD) of SL-401 is between 30 and 60 µg/kg/day, when given as an 
intravenous slow bolus injection daily for 5 consecutive days. 
Based on the collective data from three toxicology studies conducted with SL-401, the kidney, 
liver, and blood vessel manifestations observed were highly consistent with previous toxicity 
studies. Inflammation and necrosis of epithelial cells lining the choroid plexus was consistent 
with previous toxicity studies using DT388IL3. However, severe brain hemorrhage was not 
observed with SL-401. The highest non-severely toxic dose from the combined toxicity studies 
in monkeys evaluating SL-401 ranged from 30 µg/kg/day to 60 μg/kg/day, which is equivalent to 
9 µg/kg/day to 20 µg/kg/day in humans based on the body surface area (BSA) normalization 
method. A dose of 7.07 µg/kg/day for 5 days was well-tolerated in the previous DT388IL3 
clinical study, described in Section 3.7. Therefore, given the non-human primate toxicity results 
from DT388IL3 together with the full clinical safety database and the confirmatory target organ 
toxicity findings in 3 additional non-human primate studies with SL-401, the starting clinical 
dose was selected to be 7 µg/kg/day. Furthermore, based on the previous clinical study, the 
maximum clinical dose was anticipated to be 12 μg/kg/day for a 5-day consecutive regimen. 


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3.7 
SL-401 Clinical Studies 
3.7.1 Study 50047 
The safety and efficacy of SL-401 was evaluated in Study 50047, a multicenter, open-label, dose 
escalation Phase 1/2 study, in which enrolled patients had R/R adult AML, de novo AML unfit 
for chemotherapy, high-risk MDS, CML, or BPDCN (Frankel et al. 2014). 
 
 Recruitment occurred at 5 study centers, 4 
in the US and one in Canada. The primary study objective was to determine the MTD, 
recommend a dose for subsequent disease-directed studies, and document dose-limiting toxicities 
(DLTs) of escalating doses of a single cycle of SL-401 as a 15-minute IV infusion under two 
different regimens: every other day for up to 6 doses (Regimen A) or daily for up to 5 doses 
(Regimen B). The study also characterized the pharmacokinetic (PK) properties (using a non-
specific biological assay to measure the plasma concentrations of SL-401) and immune 
responses associated with these regimens and determined the relationship between disease 
response and patient disease burden. Follow-up information on adverse events (AEs), laboratory 
parameters, and OS was also collected during the study. 
Ninety-two patients were enrolled and treated with SL-401 in the study; 70 patients had AML 
(including 59 with R/R disease), 12 patients had BPDCN, and the remainder had MDS or CML. 
The MTD for Regimen A was not identified. The MTD for Regimen B was 16.6 µg/kg/day with 
hypoalbuminemia and edema, manifestations of capillary leak syndrome (CLS), as the DLT at 
the 22.1 µg/kg/day dose level. Regimen B at a dose of 12.5 µg/kg/day appeared to have the most 
favorable risk/benefit profile, with a low incidence of DLTs and multiple major tumor responses. 
Hypoalbuminemia (any Grade = 58.7%; Grade ≥3 = 0%) and transaminase elevation (any Grade 
= 50%; Grade ≥3 = 25%) were the most common Grade ≥3 AE attributed to SL-401, however 
almost all episodes were transient. Time courses of liver function tests (LFTs) and albumin 
among the patients treated with Regimen B indicate that LFT elevations tended to peak 
approximately two weeks after the first infusion of SL-401, while albumin levels, supported by 
the administration of albumin to patients with serum albumin falling below 3 g/dL, reached a 
minimum approximately one week after the first infusion. In most cases, levels of the laboratory 
parameters resolved to near baseline levels by 14-28 days after the first infusion. Other AEs 
commonly (i.e., any Grade in ≥15% of patients) attributed to SL-401 included fever (any Grade 
= 29.3%; Grade ≥3 = 1.1%), hypocalcemia (any Grade = 25.0%; Grade ≥3 = 0%), edema (any 
Grade = 18.5%; Grade ≥3 = 3.3%), and nausea (any Grade = 16.3%; Grade ≥3 = 0%). 
A single cycle of SL-401 was associated with single agent activity in patients with R/R AML, 
including 2 durable CRs of 8 and >25 months duration and 5 partial responses (PRs). OS also 
appeared to be improved among the most heavily pretreated AML patients compared with 
historical survival results. Specifically, in AML patients who had progression through at least 
two previous therapies (i.e., third-line or greater; n = 35), the median OS was 3.6 months, more 
than double the historical median OS of 1.5 months (Giles et al. 2005). Multiple durable 


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objective responses were also observed among the patients with BPDCN. Among 9 BPDCN 
patients treated with 12.5 μg/kg/day who were evaluable for response, there were 5 CRs 
(durations of 3, >3, 5, >7, and >20 months) and 2 PRs yielding a response rate of 78% 
(two patients treated with 12.5 μg/kg/day and one patient treated with 9.4 μg/kg/day were not 
evaluable for response). 
3.7.2 Current Study (STML-401-0114) 
Stage 1 of STML-401-0114 employed a traditional 3+3 design and has been completed. A total 
of 23 patients were enrolled in Stage 1, of whom 9 had BPDCN and 14 had R/R AML. SL-401 
was investigated at doses of 7, 9, 12, and 16 μg/kg/day IV for up to 5 consecutive days every 21 
days (i.e., a multi-cycle regimen). (Only patients with AML received SL-401 at doses of 9 and 
16 μg/kg/day.) The maximum tested dose of SL-401 in patients with BPDCN was 12 μg/kg/day; 
an MTD was not identified in BPDCN.  
A complete summary of all AEs attributed to SL-401, including DLTs seen in Stage 1 of the 
study, is available in the most recent version of the SL-401 Investigator Brochure.  
An analysis of safety data available through 28 July, 2016, for 26 patients with BPDCN showed 
that, overall, 24 (92%) patients have experienced at least 1 treatment-emergent adverse event 
(TEAE), with 22 (85%) patients experiencing at least 1 ≥Grade 3 TEAE. The most common 
TEAE was transaminase elevation (either ALT increased [62%] or AST increased [58%]). 
Overall, 17 (65%) patients have experienced ALT increased and/or AST increased, with these 
events also being the most common ≥Grade 3 TEAE (each 54%), treatment-related TEAE 
(54%), and treatment-related ≥Grade 3 TEAE (50%). Transaminase elevations were largely 
transient and not dose-limiting.  
Other most commonly reported TEAEs, regardless of relationship to study drug, were nausea 
and peripheral edema (each 46%); fatigue, hypoalbuminemia, and pyrexia (each 42%); chills 
(35%); and anemia and hyperglycemia (each 31%). 
The frequency and type of TEAEs were similar between the 12 µg/kg/day and 7 µg/kg/day dose 
groups, with no indication of dose-relationship. 
Twelve (46%) of 26 patients experienced at least 1 serious adverse event (SAE). The only SAEs 
reported for >1 patient were CLS, pyrexia, and respiratory failure (each 2 patients). 
Please consult the most recent SL-401 Investigator Brochure for comprehensive and up-to-date 
information concerning the safety profile associated with SL-401.  
An interim analysis of efficacy data was performed on 32 patients with BPDCN enrolled in the 
study through 29 August, 2016. Findings from this analysis, based on the Investigators’ 
assessment of response, showed that of the 32 BPDCN patients evaluable for response, 
regardless of line or dose, the objective response rate (ORR) was 84%, and the CR rate (i.e., 
CR +CR with incomplete blood count recovery [CRi] + CR [clinical] with minimal residual skin 
abnormality [CRc]) was 56%. Of the 19 first-line patients (all doses) evaluable for response, the 
ORR was 95%, and the CR rate was 74%. Of the 16 first-line patients treated at 12 µg/kg/day 


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evaluable for response, the ORR was 100%, and the CR rate was 81%. Analysis of progression-
free survival (PFS) showed that of the 16 evaluable first-line patients treated at 12 µg/kg/day, 
11 were progression-free. This included 5 patients receiving ongoing SL-401 therapy for ~1-14+ 
months, all in CR (n=3) or PR (n=2), and 6 patients who sustained a remission while on SL-401 
(CR [n=5]; PR [n=1]) and were then successfully bridged to SCT following ~2-6 months of SL-
401 therapy; these patients have remained relapse-free up to 16.0+ months post-first SL-401 dose 
and up to 10.2+ months post-SCT. Median PFS had not been reached.  
Of the 13 R/R patients evaluable for response, the ORR was 69%, and the CR rate was 31%.  
3.8 
Discussion and Rationale for Current Study 
The rationale for clinical development of SL-401 for patients with AML or BPDCN is based on 
the high expression of the IL-3R on AML and BPDCN blasts, the potent preclinical activity of 
SL-401 against AML and BPDCN cells, the clinical responsiveness observed to date with 
SL-401, in BPDCN in particular, and the unmet medical need for these indications. 
Clinical results with SL-401 indicate that the agent can be safely administered to patients with de 
novo AML, R/R AML, or BPDCN, with clinical benefit in terms of disease response and 
extended survival. While 16.6 μg/kg/day for 5 consecutive days was determined to be the MTD 
in Study 50047 and a safe starting dose for subsequent studies, the starting dose selected for this 
Phase 1/2 study, 7 μg/kg/day (similar to the lowest tested dose for this regimen (7.07 μg/kg/day) 
in Study 50047), allowed for an initial abbreviated (3 dose level) dose escalation/confirmation 
stage to an expected maximum tested dose (12 μg/kg/day) that appears to have the most 
favorable risk/benefit profile.  
The SL-401 drug product used in the current study is manufactured using a commercial-scale 
process that will provide study material for all pivotal studies. Consequently, the purpose of the 
initial stage of the current study was to bridge the existing Phase 1/2 experience utilizing the 
earlier SL-401 drug product to SL-401 made using a commercial-scale manufacturing process. 
These initial clinical data will confirm the safety and activity of SL-401 from the commercial 
scale. Furthermore, the current study will generate clinical experience in which administration of 
multiple cycles of SL-401 can be evaluated in patient populations that may derive additional 
clinical benefit beyond administration of a single cycle.  
The LFT and albumin findings from SL-401 in Study 50047 indicate that most patients with 
clinically meaningful changes in these parameters following administration of SL-401 would be 
expected to recover to near baseline levels by 3-4 weeks following the initiation of therapy. 
These results therefore support administration of cycles every 3 weeks with the allowance to 
delay the start of a subsequent cycle to allow toxicity resolution. This has been confirmed during 
Stage 1 of the current study, where the majority of patients have been able to receive multiple 
cycles of SL-401 despite transaminase elevations and hypoalbuminemia during Cycle 1. CLS 
was the principal DLT in Study 50047 and in the current study. Similarly, CLS is an event 
associated with treatment with approved doses of denileukin diftitox (Ontak®), a Food and Drug 


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Administration (FDA)-approved treatment for patients with persistent or recurrent cutaneous T-
cell lymphoma whose malignant cells express the IL-2 receptor. Treatment of patients with SL-
401 at doses below those in which multiple cases of severe CLS were observed in Study 50047 is 
one element by which the risk of this SL-401-associated toxicity will be minimized in the current 
study. 
During Study 50047, risk mitigation measures for CLS were implemented. These included 
premedication (e.g., an H1-histamine antagonist, acetaminophen, and a corticosteroid); 
administration of IV albumin if serum albumin decreased to <3 g/dL; and a diuretic regimen 
(e.g., furosemide) if patients experienced >10% weight gain (with no hypotension) concurrent 
with the administration of a basal parenteral hydration to maintain intravascular volume. In the 
peri-treatment period, vital signs, weight, serum electrolytes, and albumin were monitored. 
Similar measures have been incorporated into the current study, as described in Section 7.5.4. 
Additional precautions, including a requirement that patients have a normal cardiac ejection 
fraction at study entry, and requiring withholding of treatment in the setting of albumin 
reductions or weight increases during the dosing period, similar to recommendations concerning 
the optimal administration of denileukin diftitox, have also been implemented (McCann et al. 
2012, Olsen et al. 2001, Prince et al. 2009). 
Denileukin diftitox also is associated with loss of visual acuity, usually with loss of color vision, 
with or without retinal pigment mottling. Recovery was reported in some of the affected patients; 
however, most patients reported persistent visual impairment. This finding is considered related 
to the IL-2 component of denileukin diftitox. Although SL-401 targets IL-3R rather than IL-2R, 
patients will be monitored for potential vision loss in this study. 
SL-401 was granted Breakthrough Therapy Designation (BTD) by the US FDA for the treatment 
of BPDCN in August 2016. In October 2016, the Sponsor conducted an interim analysis of 
efficacy data from 32 patients with BPDCN enrolled in this study between 06 October, 2014, and 
29 August, 2016. A meeting was held with FDA on 20 December, 2016, to review the results of 
this interim analysis and discuss the continued development of SL-401 for treatment of BPDCN. 
As an outcome of that meeting, the following changes were made by Amendment 9: 
• Enrollment of patients with AML is closed. 
• Enrollment of patients with BPDCN is ongoing. 
- Any patient with first-line BPDCN enrolled in this study on or after 26 October, 
2016, is included in Stage 3; a sufficient number of patients will be enrolled to ensure 
10 evaluable patients are included, with evaluable patients being those with a 
diagnosis of BPDCN, as confirmed via central pathology review who received at least 
1 dose of SL-401. These patients will constitute a standalone pivotal cohort for 
confirmation of efficacy of SL-401 in first-line BPDCN; for reference in this 


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protocol, this cohort will be designated Stage 3. The primary endpoint for this pivotal 
cohort is the CR rate. 
- Any patients with R/R BPDCN enrolled in this study on or after 26 October, 2016, 
are allocated to Stage 4. After the maximum number of planned first-line BPDCN 
patients are enrolled in Stage 3, any additional first-line BPDCN patients are to be 
enrolled in Stage 4. BPDCN patients enrolled in Stage 4 subsequent to completion of 
enrollment in Stage 3 will receive the lyophilized formulation of SL-401 for 
Injection.  
- Enrollment will continue in Stage 4 until the study enrollment cap is reached. 
• The total study sample size is increased to up to 120 patients (including ~70 patients with 
BPDCN) in order to adequately assess efficacy and safety of SL-401 in patients with 
BPDCN in a clinical study setting. 
• The inclusion/exclusion criteria for patients with BPDCN and SL-401 dose and treatment 
schedule are the same across Stages 2-4, with the exception that only first-line BPDCN 
patients are eligible for Stage 3.  
• Safety monitoring to assess visual acuity and color vision, which are potential class 
toxicities of immunotoxins, and follow-up to determine whether treatment with SL-401 
alters the risk of veno-occlusive disease (VOD) after subsequent SCT have been added. 
Other study procedures and evaluations are the same across Stages 2-4.  
Key elements included in Protocol Amendment 10 are as follows: 
• The total study sample size is increased to up to 130 patients (including ~80 patients with 
BPDCN) in order to ensure continued access to SL-401 for BPDCN patients in a clinical 
study setting. 
• Updated enrollment status. 
• Updated guidance for toxicity management, including CLS management, to continue 
reducing the risk of severe CLS and other SL-401-associated toxicities.  
• Updates to reflect agreements and requests made by the FDA, including agreements on 
the primary efficacy endpoint for Stage 3.  
Protocol Amendment 11 provides for additional BPDCN patients to be enrolled in Stage 4. 
Protocol Amendment 12 provides details on the timing of analyses of duration of response and 
overall survival for all cohorts, as well as modifications to certain procedures based on the 
approved package insert and follow up requirement for patients who received stem cell 


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transplant following treatment with SL-401, to identify engraftment delays or failures. SL-401 
Injection frozen solution (1mg/mL) was approved by the Food and Drug Administration (FDA) 
on 21 December 2018 for the treatment of BPDCN in adults and in pediatric patients 2 years and 
older under the name ELZONRIS (tagraxofusp-erzs). 
4 Study Objectives 
4.1 
Primary Objectives 
Stage 1 (completed):  
• Determine the maximum tolerated dose (MTD), or the maximum tested dose where 
multiple dose-limiting toxicities (DLTs) are not observed, of SL-401. 
Stage 2 (completed enrollment): 
• Determine the efficacy of SL-401 in patients with BPDCN, as assessed by ORR. 
• Characterize the safety profile of SL-401 at the MTD or maximum tested dose in both 
patients with AML and BPDCN. 
Stage 3 (completed enrollment): 
• Determine the CR rate (i.e., CR + CRc) in patients with first-line BPDCN. 
• Characterize the safety profile of SL-401 in patients with first-line BPDCN. 
Stage 4: 
• Further characterize the efficacy of SL-401 in R/R and first-line patients with BPDCN 
following the completion of Stage 2 and Stage 3, respectively, as assessed by the rate of 
CR (i.e., CR + CRi + CRc). 
• Further characterize the safety profile of SL-401 among first-line and R/R patients with 
BPDCN. 
• Characterize the efficacy and safety of a lyophilized formulation of SL-401 among first-
line and R/R patients with BPDCN.  
4.2 
Secondary Objectives 
The secondary objectives are to:  
• Determine the CR rate (i.e., CR + CRi + CRc) for Stage 1 and Stage 2, and ORR for 
Stage 3 patients. 
• Estimate duration of response (DOR), PFS, and OS in patients with BPDCN. 


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• Enable preliminary characterization of the estimated ORR in patients with R/R AML, 
including in subsets of patients with R/R AML based on pre-treatment blast count, 
cytogenetics, or CD123 measurement. 
• Estimate DOR, PFS, and OS in patients with AML. 
• Characterize the pharmacokinetics (PK) and immunogenicity of SL-401. 
4.3 
Exploratory Objectives 
Exploratory objectives are to characterize expression of IL-3R/CD123 (and other potentially 
relevant stem cell and disease markers) on leukemia cells in peripheral blood and bone marrow 
(when feasible), to evaluate potential changes in IL-3R/CD123 (and other potentially relevant 
marker) expressing populations over time, and preliminary correlation of baseline IL-3R/CD123 
(and other potentially relevant marker) expression and clinical efficacy (including response 
rates). 
5 
Patient Selection 
5.1 
Study Population 
Patients with BPDCN or AML are to be enrolled in this study; refer to Section 5.2 and Section 
5.3 for details. 
5.2 
Patient Inclusion Criteria 
To be included in the study, a patient must meet the following criteria: 
1. The patient has a diagnosis of AML (Protocol Stages 1 and 2) or BPDCN (Protocol 
Stages 1-4) according to WHO classification (AML; excluding acute promyelocytic 
leukemia [APL, FAB M3]) or confirmed by hematopathology (BPDCN) (Facchetti et al. 
2008).  
2. The patient must meet one of the following (a) or (b) or (c):  
(a) Has evidence of persistent or recurrent AML (Protocol Stages 1 and 2) in the 
peripheral blood and/or bone marrow that is refractory to, or has relapsed from, their 
most recent prior line of treatment.  
• A prior line of treatment is considered an induction regimen if it involves an 
approved or investigational cytotoxic chemotherapy agent, biological agent, 
and/or hypomethylating agent administered alone or in a combination regimen, 
with the intent to induce robust cytoreduction (i.e., CR).  
• The previous induction regimen may have been a SCT with intent to induce a CR.  
• Consolidation and/or maintenance (including SCT) may have been given in 
CR/CRi, but are not counted as a line of treatment. 


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• Hydroxyurea will not be considered a prior line of treatment. 
(b) Has previously untreated AML (Protocol Stages 1 and 2) and is considered to be at 
high risk for disease progression and/or is unlikely to derive more than transient 
benefit from standard therapy by having at least one of the following: 
• Treatment-related AML, except if it is associated with favorable cytogenetics 
(e.g., inversion 16, t[16;16], t[8;21], t[15;17]), and not a candidate for SCT in 
their current disease state. 
• AML with antecedent hematological disease (e.g., MDS, myelofibrosis, 
polycythemia vera) and not a candidate for SCT. 
(c) Has histological and/or cytological evidence of BPDCN by pathologic assessment at 
the investigative site according to WHO classification (Facchetti et al. 2008) by a 
pathologist with expertise in hematologic malignancies, that can be measured for 
treatment response and is either: 
• Previously untreated (i.e., first-line) (Protocol Stages 2-4). 
• Persistent or recurrent in the peripheral blood, bone marrow, spleen, lymph nodes, 
skin, or other sites after previous treatment with at least 1 line of systemic therapy 
for BPDCN, e.g., stem cell transplant or chemotherapy (Protocol Stages 1, 2, and 
4). A pathology specimen must be available for central pathology review for all 
BPDCN patients enrolled in Protocol Stages 2-4.  
3. The patient ≥18 years old.  
4. The patient has an Eastern Cooperative Oncology Group (ECOG) performance status 
(PS) of 0-2. 
5. The patient has adequate baseline organ function, including cardiac, renal, and hepatic 
function: 
• LVEF ≥institutional lower limit of normal as measured by multigated acquisition 
(MUGA) scan or 2-dimensional (2-D) echocardiography (ECHO) within 28 days 
prior to start of therapy and no clinically significant abnormalities on a 12-lead 
electrocardiogram (ECG) 
• Serum creatinine ≤1.5 mg/dL (133 µmol/L) 
• Serum albumin ≥3.2 g/dL (32 g/L) (please note that albumin infusions are not 
permitted in order to enable eligibility) 
• Bilirubin ≤1.5 mg/dL (26 µmol/L) 
• AST and ALT ≤2.5 times the upper limit of normal (ULN) 


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6. If the patient is a woman of child bearing potential (WOCBP), she has had a negative 
serum or urine pregnancy test within 1 week prior to treatment. 
7. The patient has signed informed consent prior to initiation of any study-specific 
procedures or treatment. 
8. The patient is able to adhere to the study visit schedule and other protocol requirements, 
including follow-up for survival assessment. 
9. The patient (male and female) agrees to use acceptable contraceptive methods for the 
duration of time on the study, and continue to use acceptable contraceptive methods for 
2 months after the last infusion of SL-401. 
5.3 
Patient Exclusion Criteria 
A patient will not be included in the study if any of the following criteria are met: 
1. The patient has a diagnosis of APL (FAB M3). 
2. The patient has persistent clinically significant toxicities Grade ≥2 from previous 
chemotherapy (excluding alopecia, nausea, fatigue, and liver function tests [as mandated 
in the inclusion criteria]). 
3. The patient has received treatment with chemotherapy, wide-field radiation, or biologic 
therapy within 14 days of study entry. 
4. The patient has received treatment with another investigational agent within 14 days of 
study entry. 
5. The patient has previously received treatment with SL-401. 
6. The patient has an active malignancy and/or cancer history (excluding AML, BPDCN, or 
antecedent MDS) that may confound the assessment of the study endpoints. Patients with 
a past cancer history (within 2 years of entry) with substantial potential or recurrence 
and/or ongoing active malignancy must be discussed with the Sponsor before study entry. 
Patients with the following neoplastic diagnoses are eligible: non-melanoma skin cancer, 
carcinoma in situ, cervical intraepithelial neoplasia, organ-confined prostate cancer with 
no evidence of progressive disease. 
7. The patient has clinically significant cardiovascular disease (e.g., uncontrolled or any 
New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled angina, 
history of myocardial infarction, unstable angina or stroke within 6 months prior to study 
entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by 
medication). 
8. The patient has uncontrolled, clinically significant pulmonary disease (e.g., chronic 
obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the 
Investigator would put the patient at significant risk for pulmonary complications during 
the study. 


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9. The patient has known active or suspected central nervous system (CNS) leukemia. If 
suspected, CNS leukemia should be ruled out with relevant imaging and/or examination 
of cerebrospinal fluid. 
10. The patient is receiving immunosuppressive therapy – with the exception of low-dose 
prednisone (≤10 mg/day) – for treatment or prophylaxis of graft-versus-host disease 
(GVHD). If the patient has been on immunosuppressive treatment or prophylaxis for 
GVHD, the treatment(s) must have been discontinued at least 14 days prior to study 
treatment and there must be no evidence of Grade ≥2 GVHD.  
11. The patient has uncontrolled intercurrent illness including, but not limited to, 
uncontrolled infection, disseminated intravascular coagulation, or psychiatric 
illness/social situations that would limit compliance with study requirements. 
12. The patient is pregnant or breast feeding.  
13. The patient has known positive status for human immunodeficiency virus or active or 
chronic Hepatitis B or Hepatitis C. 
14. The patient is oxygen-dependent. 
15. The patient has any medical condition which in the opinion of the Investigator places the 
patient at an unacceptably high risk for toxicities. 
16. The patient has AML and requires more than 1g per day of hydroxyurea. (Hydroxyurea is 
permitted at doses of 1g per day or less). 
5.4 
Replacement of Patients 
At the discretion of the Sponsor, additional patients may be enrolled to supplement patient data 
compromised due to premature study dropout or other reasons. 
6 Investigational Plan 
6.1 
Dose and Schedule Rationale 
Under an 
 the MTD of SL-401 as a daily × 5 regimen in a 
Phase 1/2 dose escalation study was determined to be 16.6 μg/kg/day. The principal DLTs 
consisted of hypoalbuminemia and edema (i.e., CLS), and the incidences of DLTs were 2 of 
2 patients at the 22.12 µg/kg/day dose level, 1 of 8 patients at the 16.6 µg/kg/day dose level, and 
1 of 18 patients at the 12.5 µg/kg/day dose level. The LFT and albumin results from the 
Investigator-sponsored study investigating SL-401 indicate that most patients with clinically 
meaningful changes in these parameters following administration of SL-401 would be expected 
to recover to near baseline levels by 3-4 weeks following the initiation of therapy. These results 
therefore support administration of cycles every 3 weeks with the allowance to delay the start of 
a subsequent cycle to allow toxicity resolution. Furthermore, a single cycle of SL-401 
demonstrated single agent activity in patients with R/R AML or BPDCN, with the majority of 
major responses occurring at the 12.5 μg/kg/day dose level. Therefore, the risk/benefit profile of 


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SL-401 appeared to be most favorable at the 12.5 µg/kg/day dose level, and this is the expected 
dose that will be used in future studies of SL-401 as a single-agent given on multiple cycles 
(every 3 weeks). 
The present study serves to bridge the early Phase 1/2 clinical experience with SL-401 produced 
using an earlier process to SL-401 made using a commercial-scale manufacturing process. Given 
the results from the SL-401 Phase 1/2 study (Study 50047), it was anticipated that the starting 
dose for Stage 2 of the present study would be 12 µg/kg/day. However, in the interest of 
optimizing patient safety and thoroughly evaluating the commercial-scale SL-401, the dose 
escalation in Stage 1 of the study began 2 dose levels below, or 7 µg/kg/day, which was the 
lowest tested dose for this regimen (7.07 μg/kg/day) in the Phase 1/2 study evaluating SL-401 
(Study 50047).  
6.2 
Overall Study Design 
This is a 4-stage, non-randomized, open-label, dose escalation and expansion, multicenter study. 
A cycle of therapy is 21 days. A Data Safety Review Committee (DSRC), which will include 
Sponsor representatives, will be established to review the accruing safety data and make safety 
decisions during the study, including dose escalations in Stage 1.  
6.2.1 Stage 1: Dose Escalation 
During Stage 1, approximately 9-18 patients will be treated with SL-401 at doses of 7, 9, 12, or 
16 µg/kg/day for 5 consecutive days every 21 days. The 16 µg/kg/day dose will be evaluated 
only in patients with AML. Evaluation of higher doses (in increments of 25% or less [i.e., at 
20 µg /kg/day and 25 µg /kg/day levels]) in AML patients may be attempted pending evaluation 
of the safety/tolerability of the 16 µg/kg/day dose level; these evaluations would be attempted to 
identify an MTD and will be guided by the criteria (stipulated below) defining safety/tolerability 
of all dose levels. 
Three to 6 patients will be treated at each dose level. All patients within a cohort must complete 
the first cycle of therapy before patients from a new cohort receive SL-401 at the next higher 
dose. No intra-patient dose escalation is allowed. The first cohort of patients will receive SL-401 
at a dose of 7 µg/kg/day. After all patients in this cohort complete the first cycle of therapy, the 
dose for the second cohort of patients will increase by 29% to 9 µg/kg/day, conditional on the 
DLT rules described below. The dose for the third cohort of patients will increase by 33% to 12 
µg/kg/day, conditional on the DLT rules described below. Finally, after all patients in the third 
cohort complete the first cycle of therapy, the dose for the fourth cohort of patients, consisting 
only of patients with AML, will increase by 33% to 16 µg/kg/day, conditional on the DLT rules 
described below. 


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During Stage 1, DLT is defined as any of the following during the first cycle of therapy: 
(a) Any treatment-emergent Grade 4 transaminase or creatine phosphokinase (CPK) 
elevation, regardless of duration or relationship to SL-401. 
(b) Any treatment-emergent Grade 4 hematologic toxicity (unrelated to persistent leukemia) 
lasting >21 days after the last infusion of SL-401. 
(c) Any treatment-emergent Grade ≥3 non-hematologic toxicity (unrelated to persistent 
leukemia), with the exception of Grade 3 laboratory toxicities that resolve to Grade ≤1 or 
baseline ≤21 days after the last infusion of SL-401, or the following Grade 3 toxicities if 
they resolve to Grade ≤1 or baseline ≤21 days after the last infusion of SL-401: 
arthralgia, myalgia, fever responding to treatment, nausea and/or vomiting (excluding 
cases that require tube feeding, TPN or hospitalization) or diarrhea associated with 
suboptimal prophylaxis or treatment. 
SL-401-related toxicities are AEs that are considered by the Investigator to be either possibly, 
probably or definitely related to investigational SL-401 (Please refer to protocol Section 10.6 for 
more thorough guidance as to the assessment of “relatedness” in the context of investigational 
anticancer therapy).  It should be noted that although the cycle length is 21 days, cycle duration 
may extend beyond 21 days in the setting of AEs, which are detailed in Section 7.5.5.  Specific, 
reversible AEs resulting in a prolongation of Cycle 1 to 28 days will not necessitate a dose-
reduction for subsequent cycles and will not be considered DLTs if they occur during Cycle 1. 
Beginning with the dose level 7 µg/kg/day of SL-401, a decision to allow treatment at the next 
higher dose level will depend on the number of patients who experience a DLT during the first 
cycle. If none of the initial 3 patients treated (0/3) experiences a DLT, then dose escalation will 
proceed and 3 new patients will be treated at the next higher dose of 9 µg/kg/day. If one of the 
initial 3 patients treated (1/3) experiences a DLT, the cohort will be expanded to include up to an 
additional 3 patients treated at the same dose 7 µg/kg/day. If only one patient (1/6) from this 
expanded cohort experiences a DLT, then 3 new patients will be treated at the next higher dose 9 
µg/kg/day. Expansion of the 9 µg/kg/day cohort to 6 patients, if necessary, will follow the same 
rules as the 7 µg/kg/day cohort. The same DLT rules will also apply to the 12 µg/kg/day and 16 
µg/kg/day (AML specific) cohorts. 
In the event that 2 patients within a cohort have a DLT, then the MTD will be exceeded and 
further dose escalation will not occur. The MTD is defined as the dose preceding the dose level 
at which 2 patients experience a DLT during treatment Cycle 1. The MTD will be used in Stages 
2-4 of the study. If the highest planned treatment dose is completed and determined to be safe 
and the MTD is not exceeded, the available PK and safety data will be reviewed to assess 
whether further dose escalation is justified. A patient who does not complete the first cycle of 
treatment for reasons other than the occurrence of DLT will be replaced by another patient who 
will receive the same dose regimen. 


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In the event that a DLT occurs in 2 patients treated at the 7 µg/kg/day dose level, 5 µg/kg/day 
will be considered by the DSRC as an alternative starting dose. In this event, a new cohort of 
3 patients will receive 5 µg/kg/day for the first cycle. The same DLT rules will apply to this dose 
level. If 2 or more patients experience a DLT at the 5 µg/kg/day dose level, the study will be 
halted. 
Stage 1 is complete, with the MTD of SL-401 determined to be 12 µg/kg/day in R/R AML and a 
maximum tested dose of SL-401 of 12 µg/kg/day in BPDCN. (An MTD was not determined in 
BPDCN.) 
6.2.2 Stages 2-4 
During Stages 2-4, patients will be treated at the MTD or maximum tested dose at which 
multiple DLTs are not observed during Stage 1, or a lower dose with potentially the most 
favorable risk/benefit profile. At the time of Protocol Amendment 11, only Stage 4 is open for 
enrollment. 
SL-401 will be supplied as SL-401 Injection frozen solution (1 mg/mL) as described. A 
lyophilized formulation (SL-401 for Injection, lyophilized, powder, for solution; 1 mg/mL) also 
will be supplied. All patients enrolled in Stage 4 (both first-line and R/R) subsequent to 
completion of enrollment in Stage 3 will receive the lyophilized formulation of SL-401. Note 
that when the lyophilized formulation is introduced, patients who start treatment with SL-401 
Injection frozen solution will continue to receive this dosage form throughout the study. 
6.2.2.1 Patients with AML (Stage 2 only) 
The primary objective for patients with AML enrolled in Stage 2 is to characterize the safety 
profile of SL-401 at the MTD or maximum tested dose in patients with AML. Assessment of the 
anti-tumor activity of SL-401 in patients with AML will be assessed by the Investigator as a 
secondary endpoint using the criteria in Section 16.1, Appendix A. The following assessments 
will be performed at baseline within 14 days prior to the first administration of SL-401 and 
thereafter for determination of tumor response for these patients, as follows:  
• Bone marrow aspirates (± biopsy) 21 (±7) days after the start of Cycles 1 and 2. 
Patients with evidence of bone marrow involvement prior to study treatment will also 
have bone marrow evaluations following Cycles 4 and 6 and then every 3 months from 
Months 6-12; every 6 months from 12 to 24 months; and every 12 months thereafter until 
there is evidence of relapsed or progressive disease. If the Cycle 1 (Day 21 [±7]) bone 
marrow examination is empty (i.e., hypocellular) or inadequate, a bone marrow 
examination should be repeated in 7 (±7) days to document response. If additional time is 
required to complete the repeat examination, consultation with the Medical Monitor is 
required. If CD123 flow cytometry or IHC stain assessment was performed on the bone 
marrow aspiration (± biopsy), the results should be recorded in the electronic case report 
forms (eCRFs).  


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• Collection of peripheral blood samples for determination of blasts 21 (±7) days after the 
start of Cycles 1 and 2. Patients with evidence of peripheral blasts at baseline will also 
have peripheral blood samples collected 21 (±7) days after the start of Cycles 1 and 2 and 
21 (±7) days after the start of every 2nd cycle thereafter (Cycles 4, 6, etc.) until there is 
evidence of relapsed or progressive disease. 
6.2.2.2 Patients with BPDCN (Stages 2-4) 
Standardized assessment of potential sites of disease involvement (including skin, lymph nodes, 
blood, bone marrow, and visceral organs) and consistently-defined response criteria will be 
utilized.  
The BPDCN diagnosis will be made or confirmed during Screening by the pathology 
laboratories at the investigative sites. Subsequent to enrollment, pathology material will be 
submitted for central pathology review for confirmation of the BPDCN diagnosis. 
Tumor response will be assessed by the Investigators for all patients with BPDCN, with the 
Investigator’s assessment to be used in the primary analysis. As a supportive assessment, tumor 
response will be assessed by an Independent Review Committee (IRC) in a pre-specified subset 
of patients. Tumor response will be assessed using the Tumor Response Criteria for Patients with 
BPDCN presented in Section 16.2, Appendix B. All patients will also be followed for DOR and 
survival. The following assessments will be performed at baseline within 14 days prior to the 
first administration of SL-401 and thereafter for determination of tumor response for patients in 
Stages 2-4: 
• Bone marrow aspirates (± biopsy) samples 21 (±7) days after the start of Cycles 1 and 
2. Patients with evidence of bone marrow involvement prior to study treatment will also 
have bone marrow evaluations following Cycles 4 and 6 and then every 3 months from 
Months 6-12; every 6 months from 12 to 24 months; and every 12 months thereafter until 
there is evidence of relapsed or progressive disease. 
• If the Cycle 1 (Day 21 [±7]) bone marrow examination is empty (i.e., hypocellular) or 
inadequate, a bone marrow examination should be repeated in 7 (±7) days to 
document response. If additional time is required to complete the repeat examination, 
consultation with the Medical Monitor is required. If CD123 flow cytometry or IHC 
stain assessment was performed on the bone marrow aspiration (± biopsy), the results 
should be recorded in the eCRF.  
• Skin assessments, including photographs, for patients with skin involvement, and 
determination of skin disease burden using mSWAT (see Section 16.3, Appendix C) 
21 (±7) days after the start of Cycles 1 and 2 and 21 (±7) days after the start of every 2nd 
cycle thereafter (Cycles 4, 6, etc.) until there is evidence of relapsed or progressive 
disease. Refer to the separate mSWAT Manual for instructions regarding the quantitation 
of malignant lesions via the mSWAT and response assessment in skin. 


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• In situations in which there is substantial reduction of skin lesions (especially when 
accompanied by disappearance of BPDCN from bone marrow or other sites), a skin 
biopsy is required. The mSWAT guidance states: “A biopsy of normal appearing skin 
is unnecessary to assign a complete response. However a skin biopsy should be 
performed of a representative area of the skin if there is any question of residual 
disease (persistent erythema or pigmentary change) where otherwise a complete 
response would exist” (Olsen et al. 2011).  
• CT scans of index lesions 21 (±7) days after the start of Cycles 2, 4 and 6 and 
21 (±7) days after the start of every 4th cycle thereafter (for patients with baseline 
evidence of lymph node or visceral disease) until there is evidence of relapsed or 
progressive disease. For patients with no baseline evidence of lymph node or visceral 
BPDCN involvement, subsequent scans should be performed at the end of Cycle 2 (±7 
days; or at time of disease progression (PD) if PD occurs prior to end of Cycle 2), 21 (±7) 
days after the start of Cycle 6, and at Investigator’s discretion thereafter. Baseline CT 
scans should be full-body (chest/ abdomen/pelvis), whereas follow-up scans should 
document response of index lesions (Cheson et al. 2007). 
• Collection of peripheral blood samples for determination of blasts 21 (±7) days after the 
start of Cycles 1 and 2. Patients with evidence of peripheral blasts at baseline will also 
have peripheral blood samples collected 21 (±7) days after the start of Cycles 1 and 2 and 
21 (±7) days after the start of every 2nd cycle thereafter (Cycles 4, 6, etc.) until there is 
evidence of relapsed or progressive disease. 
6.3 
Study Duration 
Patient enrollment is expected to occur over a 52-month period, with follow-up continuing for a 
minimum of 12 months on each patient. Total study duration is expected to be approximately 60 
months. Please consult Section 7.6.2 regarding recommended procedures and follow-up after 
treatment discontinuation. 
6.4 
Study Completion 
The study is considered complete when sufficient information is available to enable assessment 
of the primary endpoint and selected secondary endpoints. The Study Completion date will be 
the date beyond which study data are no longer entered into the primary database (this study 
completion date generally precedes the date on which the database lock occurs by several 
weeks/months). 
7 
Study Treatment Identification, Administration, and Schedule 
7.1 
Product Manufacturing and Characterization 
Refer to the Investigator Brochure (IB) for full details of product manufacturing and 
characterization. 


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7.2 
Recommended Medications Per Institutional Guidelines/Practices 
It is recommended that patients receive the following types of prophylactic therapies/regimens 
per institutional guidelines/practices:  
• Antibacterial: ciprofloxacin, levofloxacin, or an equivalent antibiotic 
• Antifungal: fluconazole, voriconazole, or an equivalent antifungal 
• Antiviral: acyclovir, valacyclovir or an equivalent antiviral 
7.3 
Allowed Medications/Therapies 
All patients may receive supportive care measures as clinically indicated, including prophylactic 
antibiotics, antihistamines, antiemetics, albumin, fluids (hydration), and supportive measures. 
Patients may receive growth factor support and/or blood product transfusions as per the 
discretion of their physician. 
Albumin 25 g IV daily should be administered if serum albumin is between 3.0-3.5 g/dL (30-35 
g/L) on days that dosing occurs or if it is <3.0 g/dL (30 g/L) on days when treatment has been 
withheld or in the immediate post-treatment period. The Investigator has discretion with regard 
to frequency of administration per product and institutional guidelines.  
7.4 
Prohibited Medications/Therapies 
Please refer to Section 11 regarding investigational or approved anticancer agents prohibited 
during study participation. 
7.5 
SL-401 
7.5.1 SL-401 Description and Storage 
SL-401 is a novel biologic fusion protein comprised of recombinant human IL-3 genetically 
fused to truncated diphtheria toxin protein. SL-401 targets the IL-3R, which is over-expressed on 
the CSCs and/or tumor bulk of a variety of leukemias and hematopoietic malignancies, including 
BPDCN and AML, relative to normal hematopoietic stem cells and other hematopoietic cells.  
SL-401 drug product is prepared in two formulations and dosage forms.  
• SL-401 Injection is a non-preserved, sterile, liquid dosage form supplied in sterile 2 mL 
glass vials containing 1 mL of sterile SL-401 solution (1 mg/vial) and should be stored 
frozen at -20°C (±5°C).  
• SL-401 for Injection is a non-preserved, sterile, powder for solution supplied in sterile 
3 mL glass vials and should be stored at -20°C (±5°C). 
Documentation stating the product’s expiry date will be provided with each shipment. 
7.5.2 Dose, Schedule and Duration of Treatment 
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• In Stage 1, SL-401 is administered at escalating doses of at 7, 9, 12, or 16 µg/kg/day.  
• In Stages 2-4, all patients will receive SL-401 at a dose of 12 µg/kg/day. 
The dose of SL-401 will be dependent upon the patient’s baseline body weight in kg (day of 
initial infusion for Cycle 1). This dose will be recalculated if there is a 10% (or greater) change 
in body weight from baseline. The aliquot is calculated from the µg/kg dose × patient weight in 
kg (including one decimal place; all patient doses are calculated in µg/kg body weight). Dose 
changes should only occur once a cycle has been completed. Intra-cycle dose modifications will 
not be permitted.  
Patients who benefit from treatment and do not have evidence of clinically significant 
progressive disease may receive repeated cycles of SL-401 even if a response, in the judgment of 
the Investigator, is not attained. Patients will continue to receive SL-401 as long as they may be 
benefiting from treatment, according to the Investigator; until the study is completed. No 
maximum duration of therapy has been set.  
7.5.3 SL-401 Premedication and Dose Preparation and Administration 
7.5.3.1 Premedication 
Patients will receive the following premedication approximately 60 minutes before each SL-401 
infusion: 
• Acetaminophen 650 mg (or equivalent dose of paracetamol) orally (PO) 
• Diphenhydramine 50 mg intravenously (IV) (or equivalent dose of another H1-histamine 
antagonist) 
• Methylprednisolone 50 mg IV (or an equivalent dose of another corticosteroid) 
• Ranitidine 50 mg IV (or an equivalent dosage of another H2-histamine antagonist) 
7.5.3.2 SL-401 Dosage Preparation 
SL-401 is prepared for administration by the pharmacy. The total per-patient dose is calculated 
based on patient body weight in kilograms (kg) including one decimal place, and the patient’s 
assigned dose (µg/kg dose × patient weight in kg, including one decimal place [example: 7 µg/kg 
× 70.3kg]). The dose of SL-401 will be dependent upon the patient’s baseline body weight in kg 
(day of initial infusion for Cycle 1). This dose will be recalculated if there is a 10% (or greater) 
change in body weight from baseline. Additional dose preparation supplies and instructions for 
both SL-401 formulations utilized in this study are described in detail within the Pharmacy 
Manual  
7.5.3.3 Inpatient and Outpatient Setting for Dose Administration 
The first cycle of SL-401 must be administered in the inpatient setting, with hospitalization 
beginning the day of the first infusion of SL-401 (or a prior day) and ending approximately 
24 hours after the last infusion of SL-401. Subsequent cycles of SL-401 can be administered in 


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the inpatient setting or in a suitable outpatient ambulatory care setting that is equipped for 
intensive monitoring of patients with hematopoietic malignancies undergoing treatment, per the 
discretion of the Investigator and institutional guidelines and capabilities. Patients will be 
monitored for at least 4 hours following the administration of each infusion of SL-401. 
7.5.4 Patient Monitoring Procedures During the SL-401 Dosing Period 
To assess relevant acute toxicities, testing and procedures summarized below are to be performed 
and results are to be reviewed prior to each scheduled SL-401 infusion (refer to Section 9.8 
Table 5, Table 6, Table 7, and Table 8 for more detail):  
• Vital signs including blood pressure, heart rate, respiration rate, body temperature, and 
pulse oximetry:  
o During daily dosing (usually Days 1, 2, 3, 4 and 5):  
 immediately prior to infusion,  
 immediately after completion of infusion, and  
 30, 60, and 240 minutes post-infusion. 
o Days 8, 15, and 21. 
• Diagnostic blood tests during daily dosing (usually Days 1, 2, 3, 4 and 5) and Days 8, 15, 
and 21 as follows: 
o Hematology: complete blood count (CBC) with differential, platelet count; 
o Serum Electrolytes and Chemistry: sodium, potassium, bicarbonate, chloride, 
blood urea nitrogen (BUN), creatinine, glucose, alanine aminotransferase (ALT), 
albumin, alkaline phosphatase (ALP), aspartate aminotransferase, (AST), 
bilirubin (total, direct, and indirect), calcium, creatine phosphokinase (CPK), 
magnesium, lactate dehydrogenase (LDH), phosphate, total protein, uric acid; 
o Coagulation: prothrombin time (PT) or International Normalized Ratio (INR), and 
activated partial thrombin time (aPTT). 
• Routine urinalysis on Day 1 (prior to SL-401 infusion), and Days 8, 15, and 21.  
7.5.5 Dose Delays/Modifications and Management Procedures for Toxicities Associated with 
SL-401 
During the dosing period for each cycle, individual SL-401 infusions may be delayed to allow 
for toxicity resolution. Details are presented in Table 4. 
Monitor vital signs and check albumin, transaminases, and creatinine prior to preparing each 
dose of ELZONRIS. 


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Table 4: Recommended ELZONRIS Dose Modifications 
Parameter 
Severity Criteria 
Dose Modification 
Serum albumin  
Serum albumin < 3.5 g/dL or reduced ≥ 
0.5 g/dL from value measured prior to 
initiation of the current cycle 
See CLS Management Guidelines 
(Appendix E) 
Body weight  
Body weight increase ≥ 1.5 kg over 
pretreatment weight on prior treatment day 
See CLS Management Guidelines 
(Appendix E) 
Aspartate 
aminotransferase 
(AST) or alanine 
aminotransferase 
(ALT)  
ALT or AST increase > 5 times the upper 
limit of normal  
Withhold SL-401 until transaminase 
elevations are ≤ 2.5 times the upper 
limit of normal. 
Serum creatinine  
Serum creatinine > 1.8 mg/dL (159 
micromol/L) or creatinine clearance < 60 
mL/minute 
Withhold SL-401 until serum 
creatinine resolves to ≤ 1.8 mg/dL (159 
micromol/L) or creatinine clearance ≥ 
60 mL/minute. 
Systolic blood 
pressure 
Systolic blood pressure ≥ 160 mmHg or ≤ 80 
mmHg 
Withhold SL-401 until systolic blood 
pressure is < 160 mmHg or > 80 
mmHg. 
Heart rate  
Heart rate ≥ 130 bpm or ≤ 40 bpm 
Withhold SL-401 until heart rate is 
< 130 bpm or > 40 bpm. 
Body temperature  
Body temperature ≥ 38°C 
Withhold SL-401 until body 
temperature is < 38°C. 
Hypersensitivity 
reactions 
Mild or moderate 
Withhold SL-401 until resolution of 
any mild or moderate hypersensitivity 
reaction. Resume ELZONRIS at the 
same infusion rate. 
Severe or life-threatening 
Discontinue SL-401 permanently. 
 
Dose reductions should be discussed with the medical monitor on a case by case basis.  
7.6 
Treatment Discontinuation 
7.6.1 Criteria for Treatment Discontinuation 
SL-401 treatment may be discontinued for any of the following reasons:  
• Patient withdrawal of consent  
• Occurrence of unacceptable toxicity, including DLT 
• SL-401 related anaphylaxis or Grade ≥3 hypersensitivity reaction  
• Requirement for >1 dose reduction unless there is evidence of AML/BPDCN response 
(beyond Cycle 1), in which case additional dose reductions are permitted, however these 


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reductions must be discussed with the Medical Monitor and documented in the context of 
ongoing AML/BPDCN response 
• Disease recurrence/progression 
• Intercurrent illness that prevents further administration of SL-401 
• Patient non-compliance 
• Occurrence of pregnancy 
• Investigator’s decision 
The reason for SL-401 discontinuation and the date of discontinuation should be recorded in the 
eCRF. 
In settings in which there is preliminary but not conclusive evidence of disease progression 
(i.e., new skin lesions of indeterminate etiology, new lymph nodes ≤1.5cm, modest increase in 
bone marrow blast percentage subsequent to an initial marked reduction, appearance of new blast 
population on bone marrow evaluation by means of flow cytometry or other molecular 
methodology without increase in blast percentage consistent with PD), additional SL-401 cycles 
may be administered, provided that the Investigator documents that the evidence of potential 
disease progression is inconclusive and that the overall risk/benefit assessment favors additional 
investigational therapy. Additional SL-401 may also be administered in situations of mixed 
response BPDCN in which response/progression is not consistent between a given patient’s 
disease sites, provided that the Investigator documents that the overall risk/benefit assessment 
favors additional investigational therapy. In such situations, it is essential that relevant findings 
and assessments are documented, and that areas of potential disease progression are followed 
closely on subsequent assessments. 
7.6.2 Procedures and Follow-up after Treatment Discontinuation 
The evaluation during which the Investigator determines that SL-401 will be discontinued should 
be considered the End of Treatment Evaluation; all tests and procedures for the End of Treatment 
Evaluation are listed in Table 6 and Table 8 (in Section 9.8). In addition, patients should be 
followed for a minimum of 30 days after the last infusion of SL-401 for assessment of AEs 
(including potential new AEs and potential change/resolution of existing AEs).  
If the patient is in CR/PR at the time of discontinuation, disease assessments should continue to 
be performed as described in Section 8.12 on an every 6-week basis (±1 week) through 6 months 
post-C1D1 and then on an every 90-day basis or until, in the judgment of the Investigator, there 
is evidence of relapsed or progressive disease. Beyond the End of Treatment Evaluation and 30-
day follow up (safety/AE assessment), it is requested that subsequent follow-up occur 
approximately every 90 days for survival status. (If the patient is in CR/PR at the time of 
discontinuation, disease assessments should continue to be performed as described in Section 
8.12 on an every 6-week basis (±1 week) through 6 months post-C1D1 and then on an every 90-
day basis or until, in the judgment of the Investigator, there is evidence of relapsed or 


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progressive disease. Patients who undergo SCT will be followed for the occurrence of VOD and 
engraftment delay or failure as part of survival monitoring. 
If the patient discontinues SL-401 treatment and also withdraws consent for collection of future 
information, no further evaluations should be performed and no additional data should be 
collected as part of the study. The Sponsor will only retain and use any data collected before 
withdrawal of consent. 
Please consult Section 6.4 for recommendations concerning ongoing follow-up of patients alive 
with or without evidence of disease progression at the time of Study Completion/assessment of 
primary and critical secondary endpoints. 
8 
Study Procedures 
8.1 
Patient Selection 
Patients with BPDCN or R/R AML who have previously received at least one line of therapy for 
their disease, previously untreated AML that is considered high risk for disease progression, and 
who otherwise meet the inclusion/exclusion criteria will be recruited for enrollment into the 
study. Patients will be advised of the clinical protocol by the Investigator. If the patient is 
interested and is potentially eligible for participation in the study, he/she will be provided with 
the ICF to review and sign. The ICF includes a detailed explanation of the study design and the 
potential risks and benefits of treatment. Patients who agree to participate in the study will be 
provided with a copy of the signed consent form; the original signed consent document will be 
filed in the patient’s medical record. Only eligible and consenting patients will be entered into 
the study. 
Patients will be screened by the site’s Investigator or study nurse/coordinator prior to study 
entry. All patients enrolled on the study will be entered into a patient registration log at each site. 
Each screened patient will be assigned a sequential patient/study screening number with digits 
indicating site number and patient study number (e.g., XX-YYY, where XX denotes site number 
and YYY denotes patient study number as assigned at screening). Original screening records and 
source documents should be kept for all patients, including those who fail to meet the patient 
eligibility requirements and any completed eCRFs should be retained for monitoring and 
auditing. Each patient’s data obtained from subsequent evaluations should be recorded and 
evaluated in the source documents and eCRF. Prior to treatment, the Investigator will re-confirm 
patient eligibility criteria and assignment of the correct patient study number. 
8.2 
Medical History 
Medical history includes current and past medical conditions and smoking history, date of AML 
or BPDCN diagnosis, prior AML/BPDCN treatment, response to prior treatment, and date of 
relapse, if applicable. Information concerning any prior malignant diagnoses with particular 
focus on cytotoxic therapies received for prior malignancies (i.e., dates/duration of anthracycline 
for prior breast cancer) is to be collected whenever feasible. 


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8.3 
Disease Confirmation (Patients with BPDCN in Stages 2-4) 
For patients with BPDCN enrolled in Stages 2-4, the BPDCN diagnosis will be made or 
confirmed during Screening by the pathology laboratories at the investigative sites. Subsequent 
to enrollment, pathology material will be submitted for review by the central pathologist for 
confirmation of the BPDCN diagnosis. 
Pathology material will consist of pathology slides (or tissue blocks) and associated pathology 
reports for all organ sites evaluated for BPDCN via histopathology/ cytopathology. In situations 
in which submission of slides or blood smears is considered not feasible, submission of 
representative electronic images of histopathology will be permitted. Pathology submission will 
also include reports of all immunohistochemistry evaluations for BPDCN and other hematologic-
malignancy-associated markers, and reports of flow cytometry performed on bone marrow 
aspirate (or blood if applicable) for BPDCN and other hematologic-malignancy-associated 
markers. Submission of scatter-plots of flow cytometric evaluation is strongly encouraged.  
8.4 
Prior and Concomitant Medication 
Medications taken within 28 days prior to screening and throughout the study are to be collected 
and recorded. 
8.5 
ECOG Performance Status 
See Section 16.4 for a scoring guide. 
8.6 
Physical Examination 
Physical examination includes evaluation by body system and height (at screening only). 
8.7 
Vital Signs 
Vital signs include temperature, heart rate, respiration rate, pulse oximetry, and blood pressure. 
Collection should occur after the patient has been sitting for 3-5 minutes.  
8.8 
Electrocardiograms 
All patients will have a 12-lead ECG performed at the screening visit and pre-treatment visit 
(Study Day 0 or 1), as well as Day 21 (±3 days), and Day 28 (±3 days) only if delayed end of 
cycle) of each cycle. During the days when patients are undergoing PK sampling (during Cycle 
1, infusions 1 and 5; Cycle 3, infusions 1 and 5), an ECG will be performed at 3 distinct time 
points (triplicates) within 5 minutes prior to each PK sample collection pre-infusion and at 30 
and 60 minutes post-infusion (see Table 9 in Section 9.8). An ECG should be performed after 
patient is supine for 5 minutes. All ECGs will be analyzed by a central facility. 
8.9 
Clinical Laboratory Tests 
The following assessments should be done per the visit schedule and processed by the local 
laboratory: 


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• Hematology: Minimally, scheduled hematology collections should include white blood 
cell (WBC) count, differential white cell count (lymphocytes, monocytes, basophils, 
eosinophils, neutrophils), red blood cell (RBC) count, hematocrit, hemoglobin and 
platelet count. 
• Serum albumin: May be a component of the serum chemistry panel. See Appendix E for 
management of changes in albumin values.  
• Serum electrolytes and chemistry: Sodium, potassium, bicarbonate, chloride, blood urea 
nitrogen (BUN), creatinine, glucose, ALT, albumin, ALP, AST, bilirubin (total, direct, 
and indirect), calcium, CPK, magnesium, LDH, phosphate, total protein, and uric acid. 
• Coagulation parameters: PT and/or INR, aPTT. 
• Urinalysis: Appearance, color, pH, specific gravity, ketones, leukocytes, protein, glucose, 
bilirubin, urobilinogen, and occult blood. 
8.10 
Urine or Serum Pregnancy Test 
A urine or serum pregnancy test will be performed within 1 week prior to treatment for WOCBP 
who are not on acceptable birth control measures. The pregnancy test should be performed at the 
clinical research site and processed by the local laboratory. 
8.11 
Vision Assessment 
All patients will be questioned regarding any changes in visual acuity and/or color vision. 
Patients who have experienced any ≥Grade 2 study drug-related changes in vision (NCI CTCAE 
v4.03 Grade) will have an ophthalmologic consultation and/or examination performed. In the 
event any abnormalities are detected, the patient will be followed up as per the recommendations 
of the consulting ophthalmologist. Management of treatment-related ocular disorders with 
inflammatory characteristics should include corticosteroid eye drops and/or other measures, as 
indicated by an ophthalmologist. In the setting of persistent study drug-related ocular disorders 
≥Grade 2, consultation with the study’s Medical Monitor is required. 
8.12 
Tumor Assessments and Disease Response Assessment 
8.12.1 Stage 1 
All patients must have a baseline (pre-treatment) bone marrow aspirate (± biopsy) and peripheral 
blood sample within 14 days prior to the first administration of SL-401. In addition, patients with 
BPDCN must have a baseline skin assessment (with biopsies and/or for patients with skin 
involvement) and full-body CT scan within 14 days prior to the first administration of SL-401. 
Subsequent assessments for response will be performed on the following schedules until, in the 
judgment of the Investigator, there is evidence of relapsed or progressive disease: 
• All patients in Stage 1: bone marrow aspirates (± biopsy) 21 (±7) days after the start of 
Cycles 1 and 2, and thereafter at a schedule determined by the Investigator in 
consultation with the Sponsor. If the Cycle 1 (Day 21 [±7]) bone marrow examination is 
empty (i.e., hypocellular) or inadequate, a bone marrow examination should be repeated 


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in 7 (±7) days to document response. If additional time is required to complete the repeat 
examination, consultation with the Medical Monitor is required. If CD123 flow 
cytometry or IHC stain assessment was performed on the bone marrow aspiration (± 
biopsy), the results should be recorded in the eCRF. 
• BPDCN patients: skin assessments (with biopsies and/or photographs for patients with 
skin involvement) 21 (±7) days after the start of Cycles 1 and 2 and 21 (±7) days after the 
start of every 2nd cycle thereafter (Cycles 4, 6, etc.). CT scans of index lesions 21 (±7) 
days after the start of Cycles 2 and 4 and 21 (±7) days after the start of every 4th cycle 
thereafter (approximately every 12 weeks). 
Tumor response will be assessed by the Investigator using the criteria in Section 16.1, 
Appendix A (AML), and Section 16.2, Appendix B (BPDCN). 
8.12.2 Stage 2, Patients with AML 
The following disease assessments will be performed at baseline within 14 days prior to the first 
administration of SL-401 and thereafter for determination of tumor response for patients with 
AML in Stage 2, as follows. Note that all sites of disease identified at baseline are to be followed 
thereafter for determination of disease response.  
• Bone marrow aspirates (± biopsy) 21 (±7) days after the start of Cycles 1 and 2. 
Patients with evidence of bone marrow involvement prior to study treatment will also 
have bone marrow evaluations following Cycles 4 and 6 and then every 3 months from 
Months 6-12; every 6 months from 12 to 24 months; and every 12 months thereafter until 
there is evidence of relapsed or progressive disease. If the Cycle 1 (Day 21 [±7]) bone 
marrow examination is empty (i.e., hypocellular) or inadequate, a bone marrow 
examination should be repeated in 7 (±7) days to document response. If additional time is 
required to complete the repeat examination, consultation with the Medical Monitor is 
required. If CD123 flow cytometry or IHC stain assessment was performed on the bone 
marrow aspiration (± biopsy), the results should be recorded in the eCRF.  
• The Cycle 1-2 Day 21 (±7 days) bone marrow assessment should occur on Day 21 
(±7 days) even in the setting of patients receiving SL-401 over 6-10 days (as opposed 
to 5 consecutive days) or in the setting of patients receiving less than 5 doses in a 
cycle. 
• Collection of peripheral blood samples for determination of blasts 21 (±7) days after the 
start of Cycles 1 and 2. Patients with evidence of peripheral blasts at baseline will also 
have peripheral blood samples collected 21 (±7) days after the start of Cycles 1 and 2 and 
21 (±7) days after the start of every 2nd cycle thereafter (Cycles 4, 6, etc.) until there is 
evidence of relapsed or progressive disease. 
Assessment of the anti-tumor activity of SL-401 in patients with AML will be assessed by the 
Investigator on an exploratory basis using the criteria in Section 16.1, Appendix A.  


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8.12.3 Patients with BPDCN (Stages 2-4) 
A global assessment paradigm is to be followed, with all potential disease sites assessed during 
screening, including the bone marrow (via aspirate and biopsy), blood (via clinical laboratory 
testing for blasts and hematologic parameters), skin (via visual examination and photography, 
with determination of skin disease burden using mSWAT), lymph nodes, liver, spleen, and other 
viscera (via CT), and lymph nodes, liver, spleen, and other viscera (via physical examination). 
Positive sites of disease identified during screening must be followed during the study in every 
response evaluation. (Disease in organs that were disease-positive at screening are to be 
assessed, documented, and recorded in the clinical database, even if the disease disappeared in 
subsequent response evaluations.) Sites with no evidence of disease during Screening must be 
documented as such and an assessment that baseline disease is not present are to be adequately 
documented in source and recorded in the clinical database; thereafter, these sites need not be 
followed, unless there is evidence of PD. 
The following disease assessments will be performed at baseline within 14 days prior to the first 
administration of SL-401 and thereafter for determination of tumor response for patients in 
Stages 2-4, as follows. Note that all sites of disease identified at baseline are to be followed 
thereafter for determination of disease response. 
• Bone marrow aspirates (± biopsy) samples 21 (±7) days after the start of Cycles 1 and 
2. Patients with evidence of bone marrow involvement prior to study treatment will also 
have bone marrow evaluations following Cycles 4 and 6 and then every 3 months from 
Months 6-12; every 6 months from 12 to 24 months; and every 12 months thereafter until 
there is evidence of relapsed or progressive disease. 
• If the Cycle 1 (Day 21 [(±7]) bone marrow examination is empty (i.e., hypocellular) 
or inadequate, a bone marrow examination should be repeated in 7 (±7) days to 
document response. If additional time is required to complete the repeat examination, 
consultation with the Medical Monitor is required. If CD123 flow cytometry or IHC 
stain assessment was performed on the bone marrow aspiration (± biopsy), the results 
should be recorded in the eCRF.  
• The Cycle 1-2 Day 21 (±7 days) bone marrow assessment should occur on Day 21 
(±7 days) even in the setting of patients receiving SL-401 over 6-10 days (as opposed 
to 5 consecutive days) or in the setting of patients receiving less than 5 doses in a 
cycle. 
• Skin assessments, including photographs, for patients with skin involvement, and 
determination of skin disease burden using mSWAT (see Section 16.3, Appendix C) 21 
(±7) days after the start of Cycles 1 and 2 and 21 (±7) days after the start of every 2nd 
cycle thereafter (Cycles 4, 6, etc.) until there is evidence of relapsed or progressive 
disease.  


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• Photographs: Body region(s) where skin lesions are present will be photographed. 
Digital images/photographs may be collected by the Sponsor or its representatives 
during routine monitoring visits. Care should be taken to ensure that patients cannot 
be identified from these images. Refer to the separate Photography Guidelines for 
detailed photography instructions. 
• Quantification of skin disease burden via the mSWAT: Quantification of skin 
disease burden via the mSWAT (Section 16.3, Appendix C) is required at the time of 
each skin assessment. Refer to the separate mSWAT Manual for instructions 
regarding the quantitation of malignant lesions via the mSWAT and response 
assessment in skin. 
• Skin biopsies: In situations in which there is substantial reduction of skin lesions 
(especially when accompanied by disappearance of BPDCN from bone marrow or 
other sites), a skin biopsy is required. The mSWAT guidance states: “A biopsy of 
normal appearing skin is unnecessary to assign a complete response. However a skin 
biopsy should be performed of a representative area of the skin if there is any 
question of residual disease (persistent erythema or pigmentary change) where 
otherwise a complete response would exist” (Olsen et al. 2011).  
• CT scans of index lesions 21 (±7) days after the start of Cycles 2, 4 and 6 and 
21 (±7) days after the start of every 4th cycle thereafter (for patients with baseline 
evidence of lymph node or visceral disease) until there is evidence of relapsed or 
progressive disease. For patients with no baseline evidence of lymph node or visceral 
BPDCN involvement, subsequent scans should be performed at the end of Cycle 2 (±7 
days; or at time of disease progression (PD) if PD occurs prior to end of Cycle 2), 21 (±7) 
days after the start of Cycle 6, and at Investigator’s discretion thereafter. Baseline CT 
scans should be full-body (chest/ abdomen/pelvis), whereas follow-up scans should 
document response of index lesions (Cheson et al. 2007). 
• During Stages 2-4, subsequent to the end of Cycle 2, imaging at intervals less 
frequent than those stipulated above may be permitted when required by local 
regulations; however, this must be reviewed with the Medical Monitor (or designee). 
• For patients in Stages 2-4, electronic copies of all baseline and subsequent CT scans 
will be submitted to a central archive (scans are to be submitted regardless of the 
presence/absence of BPDCN-related abnormalities). 
• Collection of peripheral blood samples for determination of blasts 21 (±7) days after the 
start of Cycles 1 and 2. Patients with evidence of peripheral blasts at baseline will also 
have peripheral blood samples collected 21 (±7) days after the start of every 2nd cycle 
thereafter (Cycles 4, 6, etc.) until there is evidence of relapsed or progressive disease. 


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Tumor response will be assessed by the Investigators for all patients with BPDCN, with the 
Investigator’s assessment to be used in the primary analysis. As a supportive assessment, tumor 
response was also evaluated by an IRC on a pre-specified subset of patients. Tumor response will 
be assessed using the Tumor Response Criteria for Patients with BPDCN presented in Section 
16.2, Appendix B. All patients will also be followed for DOR and survival until study 
completion. 
8.13 
Pharmacokinetic Studies 
An intensive schedule for collection of blood samples after specific infusions during Cycle 1 and 
3 of SL-401 will be used to determine plasma concentrations of SL-401. During Stage 1 and 
early portions of Stage 2, PK assessment was conducted on samples for all patients.  
The concentration of SL-401 in plasma samples will be determined by a sensitive and specific 
sandwich enzyme-linked immunosorbent assay method at a contract laboratory according to 
industry GLP bioanalytical practices. Plasma concentration data over time will be used to 
characterize the PK disposition of SL-401, to assess any change in the PK properties of SL-401 
during the 5-day course of treatment or between cycles of treatment, and relate the PK 
characteristics of SL-401 to immunogenicity, toxicity, and disease activity. 
Collectively, the SL-401 plasma concentration-time data will be analysed by conventional 
noncompartmental PK methods to define the fundamental PK properties of SL-401. 
Furthermore, if supported by the adequacy of the data, a population PK model will be developed, 
in which the effects of various potentially relevant co-variants (i.e., gender, age, IL-3R 
expression, immunogenicity) on relevant PK parameters, will be evaluated. Sample collection 
requires that the actual date and time (24-hour clock) that the SL-401 treatment begins (start of 
infusion, SOI) and ends (end of infusion, EOI) will be recorded as will be the date and time (24-
hour clock time) of all blood samples.  
Detailed instructions for collecting, processing, storing, and shipping the samples are provided in 
a separate procedure manual.
 
 
Blood samples will be collected into ethylenediamine tetraacetic acid (EDTA) tubes (lavender 
top, at least 6mL each); upon collection the samples should be inverted gently several times to 
ensure adequate mixing of the EDTA anticoagulant and whole blood. Within approximately 
30 minutes of collection, samples should be centrifuged in a refrigerated centrifuge to separate 
the plasma. An aliquot of the plasma (>1 mL) will be transferred to a clean tube, tightly sealed, 
labelled appropriately and stored frozen at -70 C or below prior to analysis in the validated 
immunoassay.  
Samples will be collected immediately prior to the start of the infusion of SL-401, immediately 
after end of infusion (time recorded), then 15, 30, 45, 60, 90, 120, 180 and 240 minutes after the 
completion of the infusion (see Table 9 in Section 9.8). It is recognized that it is not always 
possible to obtain the specimens at the precise time points specified above, although it requested 


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that sites make every effort to do so; it is essential that the precise time of infusion and times of 
subsequent pharmacokinetic sampling be recorded diligently.  
The nominal blood sampling time schedule is summarized in Table 9 (in Section 9.8) for the 
following SL-401 treatment days: 
• Cycle 1, infusion 1 (i.e., Study Day 1). 
• Cycle 1, infusion 5 (i.e., usually Study Day 5). 
• Cycle 3, infusion 1 (i.e., Day 1 of Cycle 3). 
• Cycle 3, infusion 5 (i.e., usually Day 5 of Cycle 3). 
8.14 
Immunogenicity Studies 
Peripheral blood samples (10 mL) will be collected (serum red top tube, no additive) for the 
detection and characterization of SL-401 reactive antibodies according to the following schedule: 
• Cycle 1: Day 1 (pre-infusion), Day 15 (±3 days), and Day 21 (±3 days). 
• Cycle 2, 3, 4, 5, or 6: Day 1 (pre-infusion) and Day 21 (±3 days). Note: A separate Day 1 
(pre-infusion) sample does not need to be drawn if the Day 21 sample from the prior 
cycle has been drawn no more than 24 hours prior to the first infusion of the next cycle to 
be given. In that case, the data for the Day 21 sample may be used both as the Day 21 
sample for the prior infusion as well as the Day 1 (pre-infusion) sample, avoiding the 
necessity to draw 2 blood samples in close proximity. 
• A blood sample for immunogenicity studies will be collected between 16 weeks and 
20 weeks after the last SL-401 dose. 
• If there are clinical manifestations suggesting either an infusion related reaction or drug 
hypersensitivity, an immunogenicity sample should be obtained. 
• If infusions are held (postponed) for any reason, an immunogenicity sample must be 
collected within 3 ±3 days after completion of the last SL-401 infusion for the cycle. 
 
Detailed instructions for collecting, processing, storing, and shipping the samples will be 
provided in a separate procedure manual. 
In the setting of detection of SL-401 reactive antibodies, plasma from corresponding specimens 
will be evaluated for SL-401 levels (PK analysis). Plasma from patients without SL-401 reactive 
antibodies would then be utilized as a control for this PK analysis.  


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Following the required immunogenicity and pharmacokinetic evaluations, if additional serum or 
plasma is available, this serum and/or plasma may be used for evaluation of other relevant 
markers (for example IL-3 levels) if considered appropriate by the Sponsor or Investigator. 
9 
Schedule of Events 
The study schedule of events is summarized in Table 5, Table 6, Table 7, and Table 8 (in 
Section 9.8). 
9.1 
Study Day -14 to -4: Screening 
The following evaluations will be performed on Study Day -14 to -4 to determine the patient’s 
eligibility for the study and in anticipation of study treatment.  
All Patients, All Study Stages: 
• Informed Consent  
• Inclusion / Exclusion criteria 
• Medical history, including prior therapy and concomitant medications 
• ECOG performance status 
• Physical examination 
• Urine or serum pregnancy test 
• Vital signs and weight 
• 12-lead ECG 
• ECHO or MUGA scan (within 28 days prior to start of first cycle of study treatment) 
• Clinical laboratory tests: hematology, serum electrolytes and chemistry (including 
albumin), coagulation parameters, and urinalysis 
• Bone marrow aspiration (± biopsy) within 14 days prior to start of first cycle of study 
treatment. If CD123 flow cytometry or IHC stain was performed on the bone marrow 
aspirations (± biopsy), the results should be recorded in the eCRF.  
Patients with BPDCN Only 
• Full-body CT scan (chest/abdomen/pelvis) within 14 days prior to start of first cycle of 
study treatment 
• Skin assessment within 14 days prior to start of first cycle of study treatment (including 
quantification using mSWAT) 
Investigators will maintain a confidential log of all patients who have been screened for 
participation in the study whether or not the patient was eligible for study participation. 
9.2 
Study Day -1 to 0: Procedures Prior to Start of Treatment 
All Patients, All Study Stages: 
• Concomitant medication assessment 
• Physical examination 


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• Vital signs and weight 
• 12-lead ECG 
• Clinical laboratory tests: hematology, serum electrolytes and chemistry (including 
albumin) 
9.3 
Cycle 1 
9.3.1 Study Days 1 – 5 (Up to Study Day 10 if Infusion(s) Held): Pre-Infusion 
All Patients, All Study Stages: 
• Inpatient admission (Study Day 1) 
• Vital signs and weight (pre-treatment weight should be recorded on each day for which 
an SL-401 infusion is planned) 
• AE and SAE monitoring 
• Clinical laboratory tests: hematology, serum electrolytes and chemistry (including 
albumin), coagulation parameters, and urinalysis 
• Collection of peripheral blood for immunogenicity (infusion 1) and PK sampling 
(infusions 1 and 5) immediately prior to the start of the infusion 
• 12-lead ECG each day of infusion (Infusions 1 and 5 of Cycles 1 and 3 will be triplicates 
at the specified timepoints) 
• Diphenhydramine 50 mg IV 60 minutes prior to infusion 
• Acetaminophen 650 mg PO (or equivalent dose of paracetamol) 60 minutes prior to 
infusion 
• Methylprednisolone 50 mg IV (or an equivalent dose of another corticosteroid) 
60 minutes prior to infusion 
• Ranitidine 50 mg IV (or an equivalent doses of another H2-histamine antagonist) 
60 minutes prior to infusion 
9.3.2 Study Days 1 – 5 (Up to Study Day 10 if Infusion(s) Held): Infusion 
All Patients, All Study Stages: 
• 12-lead ECG (infusions 1 and 5) performed at 3 distinct time points (triplicates) within 5 
minutes prior to each PK sample collection at 30 and 60 minutes post-infusion 
• Collection of peripheral blood for PK sampling (infusions 1 and 5) collected immediately 
after end of infusion (time recorded), then 15, 30, 45, 60, 90, 120, 180 and 240 minutes 
after the completion of the infusion 
• 15-minute IV infusion of SL-401 at required dose  
• Vital signs: immediately after completion of infusion and 30, 60, and 240 minutes post-
infusion 
• Monitoring for at least 4 hours 
• AE and SAE monitoring 


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9.3.3 Study Day 8 ±3 Days, or 3 ±3 Days after Completion of Infusions if Infusion(s) Held 
All Patients, All Study Stages: 
• Concomitant medication assessment 
• Physical examination 
• Vital signs and weight 
• Clinical laboratory tests: hematology, serum electrolytes and chemistry (including 
albumin), coagulation parameters, and urinalysis 
• AE and SAE monitoring 
9.3.4 Study Day 15 ±3 Days 
All Patients, All Study Stages: 
• Concomitant medication assessment 
• Physical examination 
• Vital signs and weight 
• Clinical laboratory tests: hematology, serum electrolytes and chemistry (including 
albumin), coagulation parameters, and urinalysis 
• AE and SAE monitoring 
9.3.5 Study Day 21 ±7 Days: End of Cycle 
Note: The end-of-cycle evaluations (Day 21 or thereafter) may also serve as the pre-infusion 
evaluations for the subsequent cycles; with the exception of vital signs, these do not need to 
be duplicated on successive days unless there is an abnormality or other clinically relevant 
reason for repeat evaluation. 
All Patients, All Study Stages: 
• Concomitant medication assessment 
• ECOG performance status 
• Physical examination 
• Vital signs and weight 
• 12-lead ECG 
• Clinical laboratory tests: hematology, serum electrolytes and chemistry (including 
albumin), coagulation parameters, and urinalysis 
• Tumor response assessment: bone marrow aspiration (± biopsy) and peripheral blood 
sample (AML and BPDCN). If the Cycle 1 (Day 21 [±7]) bone marrow examination is 
empty (i.e., hypocellular) or inadequate, a bone marrow examination should be repeated 
in 7 (±7) days to document response. If additional time is required to complete the repeat 
examination, consult with the Medical Monitor. If CD123 flow cytometry or IHC stain 
was performed on the bone marrow aspirations (± biopsy), then the results should be 
recorded in the eCRF. 


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• Collection of peripheral blood (serum) for immunogenicity  
• Monitoring for changes in visual acuity and color vision 
• AE and SAE monitoring 
Patients with BPDCN Only: 
• Tumor response assessment: skin, including mSWAT 
9.3.6 Study Day 28 ±3 Days, Then Every 7 ±3 days: Delayed End of Cycle for Toxicity 
Resolution Only if Required 
All Patients, All Study Stages: 
• Concomitant medication assessment 
• ECOG performance status 
• Vital signs and weight 
• 12-lead ECG 
• Clinical laboratory tests: hematology, serum electrolytes and chemistry (including 
albumin), coagulation parameters, and urinalysis 
• AE and SAE monitoring 
9.4 
Cycles 2 – 6 
Note: The end-of-cycle evaluations (Day 21 or thereafter) may also serve as the pre-infusion 
evaluations for the subsequent cycles; with the exception of vital signs, these do not need to 
be duplicated on successive days unless there is an abnormality or other clinically relevant 
reason for repeat evaluation. 
9.4.1 Days 1 – 5 (Up to Day 10 if Infusion(s) Held): Pre-Infusion 
All Patients, All Study Stages: 
• Inpatient admission (Day 1) or treatment at a suitable outpatient facility 
• Vital signs and weight 
• AE and SAE monitoring 
• Clinical laboratory tests: hematology, serum electrolytes and chemistry (including 
albumin), coagulation parameters, and urinalysis 
• 12-lead ECG each day of infusion (Infusions 1 and 5 of Cycles 1 and 3 will be triplicates 
at the specified timepoints) 
• Collection of peripheral blood (plasma) for PK sampling (Cycle 3 only, infusions 1 and 
5) immediately prior to the start of the infusion 
• Diphenhydramine 50 mg IV 60 minutes prior to infusion 
• Acetaminophen 650 mg (or equivalent dose of paracetamol) PO 60 minutes prior to 
infusion 
• Methylprednisolone 50 mg IV (or an equivalent dose of another corticosteroid) 60 
minutes prior to infusion 


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• Ranitidine 50 mg IV (or an equivalent doses of another H2-histamine antagonist) 60 
minutes prior to infusion 
9.4.2 Days 1 – 5 (Up to Day 10 if Infusion(s) Held): Infusion 
All Patients, All Study Stages: 
• 12-lead ECG (Cycle 3 only, infusions 1 and 5) performed at 3 distinct time points 
(triplicates) within 5 minutes prior to each PK sample collection at 30 and 60 minutes 
post-infusion 
• Collection of peripheral blood (plasma) for PK sampling (Cycle 3 only, infusions 1 and 
5) collected immediately after end of infusion (time recorded), then 15, 30, 45, 60, 90, 
120, 180 and 240 minutes after the completion of the infusion 
• 15-minute IV infusion of SL-401 at required dose  
• Vital signs: immediately after completion of infusion and 30, 60, and 240 minutes post-
infusion 
• Monitoring for at least 4 hours 
• AE and SAE monitoring 
9.4.3 Day 8 ±3 Days, or 3 ±3 Days after Completion of Infusions if Infusion(s) Held 
All Patients, All Study Stages: 
• Concomitant medication assessment 
• Physical examination 
• Vital signs and weight 
• Clinical laboratory tests: hematology, serum electrolytes and chemistry (including 
albumin), coagulation parameters, and urinalysis 
• AE and SAE monitoring 
9.4.4 Day 15 ±3 Days 
All Patients, All Study Stages: 
• Concomitant medication assessment 
• Physical examination 
• Vital signs and weight 
• Clinical laboratory tests: hematology, serum electrolytes and chemistry (including 
albumin), coagulation parameters, and urinalysis 
• AE and SAE monitoring 
9.4.5 Day 21 ±7 Days: End of Cycle 
Note: The end-of-cycle evaluations (Day 21 or thereafter) may also serve as the pre-infusion 
evaluations for the subsequent cycles; with the exception of vital signs, these do not need to be 
duplicated on successive days unless there is an abnormality or other clinically relevant reason 
for repeat evaluation. 


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All Patients, All Study Stages: 
• Concomitant medication assessment 
• ECOG performance status 
• Physical examination 
• Vital signs and weight 
• 12-lead ECG 
• Clinical laboratory tests: hematology, serum electrolytes and chemistry (including 
albumin), coagulation parameters, and urinalysis 
• Collection of peripheral blood for immunogenicity (serum)  
• Monitoring for changes in visual acuity and color vision 
• AE and SAE monitoring 
Patients with BPDCN Only: 
• Tumor response assessment: CT scan of index lesions as follows: 
• Stage 1: Cycles 2 and 4 and every 4th cycle thereafter.  
• Stages 2-4 with baseline BPDCN involving lymph nodes or viscera: Cycles 2, 4, and 
6 and following every 4th cycle thereafter. Without baseline BPDCN involving lymph 
nodes or viscera: Cycles 2, 6 and at Investigator’s discretion thereafter. 
• Tumor response assessment: skin (Cycles 2, 4, and 6, and every 2 cycles thereafter), 
including mSWAT 
Stages 2-4 
• Tumor response assessment: bone marrow aspiration (± biopsy). Bone marrow will be 
collected subsequent to Cycles 2, 4 and 6 and then every 3 months from Months 6-12; 
every 6 months from 12 to 24 months; and every 12 months thereafter until there is 
evidence of relapsed or progressive disease. If CD123 flow cytometry or IHC stain was 
performed on the bone marrow aspirations (± biopsy), the results should be recorded in 
the eCRF. 
• Collection of peripheral blood samples for determination of blasts 21 (±7) days after the 
start of Cycle 2, and, for patients with evidence of peripheral blasts at baseline, 21 (±7) 
days after the start of Cycles 1 and 2 and 21 (±7) days after the start of every 2nd cycle 
thereafter (Cycles 4, 6, etc.) until there is evidence of relapsed or progressive disease. 
9.4.6 Day 28 ±3 Days, Then Every 7 ±3 days: Delayed End of Cycle for Toxicity Resolution 
Only if Required 
All Patients, All Study Stages: 
• Concomitant medication assessment 
• ECOG performance status 
• Vital signs and weight 


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• 12-lead ECG 
• Clinical laboratory tests: hematology, serum electrolytes and chemistry (including 
albumin), coagulation parameters, and urinalysis 
• AE and SAE monitoring 
9.5 
End of Treatment 
All Patients, All Study Stages: 
• ECOG performance status 
• Physical examination 
• Vital signs and weight 
• Monitoring for changes in visual acuity and color vision 
9.6 
Safety Monitoring: Through 30 Days after Last Infusion 
All Patients, All Study Stages: 
• AE and SAE monitoring 
• Survival status 
9.7 
Survival Monitoring: Approximately Every 90 Days after End of Treatment until Study 
Completion 
Patients in PR/CR at End of Treatment: 
• Survival status and response/disease progression status, continuing until 
assessments of the primary and secondary objectives are completed for all 
patients; survival status may be performed by telephone contact.  
• Patients who undergo SCT will be followed for the occurrence of VOD and 
delayed or failed engraftment as part of survival monitoring. 
9.8 
Schedules of Events 
The study schedule of events is summarized in Table 5, Table 6, Table 7, and Table 8. 
 


SL-401 Diphtheria Toxin Interleukin-3 Fusion Protein 
Stemline Therapeutics, Inc. 
 
Protocol STML-401-0114 
Amendment 12 (FINAL): 17 January 2019 
 
72 
CONFIDENTIAL 
Table 5: Study Events Schedule for Cycle 1 (Study Day -14 to Study Day 21): Stage 1 (All Pts) & Stage 2 (AML Pts) 
Tests and Observations 
Study Day   
-14 to -4 
Cycle 1 
Study Day   
-1 to 0 
Study Days 1-5 (Up to Study 
Day 10 if Infusion(s) Held) 
SL-401 Treatment 
Study Day 
8±3(q) and 
15±3 
Study Day 
21±7 
Study Day 28±7, 
Then Every 7±3 days 
 
Screening 
Pre- 
treatment 
Pre-Infusion 
Infusion 
End of Cycle 
Delayed End of Cycle 
for Toxicity Resolution 
Only if Required 
Informed consent form 
X 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
Medical history including prior therapy, 
concomitant medications  
X 
 
 
 
 
 
 
Concomitant Medications 
 
X 
 
 
X 
X 
X 
ECOG performance status 
X 
 
 
 
 
X 
X 
Physical examination 
X 
X 
 
 
X 
X 
 
Pregnancy test (a) 
X 
 
 
 
 
 
 
Vital signs and weight(b) 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG(c) 
X 
X 
X  
X (Infusions 1, 5) 
 
X 
X 
ECHO or MUGA scan(d) 
X 
 
 
 
 
 
 
Hematology(e) 
X 
X 
X 
 
X 
X 
X 
Serum electrolytes(f) 
X 
X 
X 
 
X 
X 
X 
Serum albumin(g) 
X 
X 
X 
 
X 
X 
X 
Serum chemistry(h) 
X 
X 
X 
 
X 
X 
X 
Coagulation parameters: PT/INR, aPTT 
X 
 
X 
 
X 
X 
X 
Urinalysis(i)  
X 
 
X (Infusion 1) 
 
X 
X 
X 
Tumor response assessment: Bone marrow 
aspiration ± biopsy(j) 
X 
 
 
 
 
X 
 
Tumor response assessment: CT scan(k) 
X 
 
 
 
 
 
 
Tumor response assessment: Skin, including 
biopsies and/or photographs(l) 
X 
 
 
 
 
X 
 
Tumor response assessment: Peripheral blood 
 
 
 
 
 
X 
 
Administration of premeds (m) 
 
 
X 
 
 
 
 
SL-401 administration(n) 
 
 
 
X 
 
 
 
Pharmacokinetic sampling(o)  
 
 
X (Infusions 1, 5)  X (Infusions 1, 5) 
 
 
 
Immunogenicity sampling(p)  
 
 
X (Infusion 1) 
 
X (Day 15) 
X 
 
AE and SAE monitoring 
 
 
X 
X 
X 
X 
X 
 


SL-401 Diphtheria Toxin Interleukin-3 Fusion Protein 
Stemline Therapeutics, Inc. 
 
Protocol STML-401-0114 
Amendment 12 (FINAL): 17 January 2019 
 
73 
CONFIDENTIAL 
(a) Urine or serum pregnancy test must be performed within 1 week prior to treatment in women of childbearing potential. 
(b) Vital signs should be performed after patient is sitting for 3-5 minutes. If during dosing period, vital signs should be taken immediately prior to infusion, immediately after 
completion of infusion, and 30, 60, and 240 minutes post-infusion. 
(c) All patients will have a 12-lead ECG performed at the screening visit and pre-treatment visit, as well as Day 21 (and Day 28 only if delayed end of cycle) of each cycle. 
During the days when patients are undergoing PK sampling (Cycle 1, infusions 1 and 5; Cycle 3, infusions 1 and 5), an ECG will be performed at 3 distinct time points 
(triplicates) within 5 minutes prior to each PK sample collection pre-infusion and at 30 and 60 minutes post-infusion (see (p) and Table 9). 
(d) MUGA or 2-D ECHO to quantify left ventricular ejection fraction (LVEF). Must be completed within 28 days prior to start of first cycle of study treatment.  
(e) To be collected prior to SL-401 infusion if during dosing period. Hematology includes White blood cell (WBC) count, differential white cell count, red blood cell count, 
hematocrit, hemoglobin and platelet count. 
(f) To be collected prior to SL-401 infusion if during dosing period. Electrolytes include sodium, potassium, bicarbonate, chloride, blood urea nitrogen (BUN), and creatinine.  
(g) To be collected prior to SL-401 infusion if during dosing period. Serum albumin may be a component of the chemistry panel (h). See protocol for administration of albumin if 
serum albumin decreases during treatment days or in the immediate post-treatment period. 
(h) To be collected prior to SL-401 infusion if during dosing period. Serum electrolytes and chemistry: Sodium, potassium, bicarbonate, chloride, blood urea nitrogen (BUN), 
creatinine, glucose, alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase, (AST), bilirubin (total, direct, and indirect), calcium, 
creatine phosphokinase (CPK), magnesium, lactate dehydrogenase (LDH), phosphate, total protein, uric acid 
(i) To be collected prior to SL-401 infusion if during dosing period. Urinalysis includes appearance, color, pH, specific gravity, ketones, leukocytes, protein, glucose, bilirubin, 
urobilinogen, and occult blood.  
(j) Morphology and differential WBC/blast count on aspirate. Baseline must be performed within 14 days prior to the first administration of SL-401. Subsequent bone marrow 
aspirates (± biopsy) will be performed 21 (±7) days after the start of Cycles 1 and 2, and at the Investigator’s discretion thereafter until there is evidence of relapsed or 
progressive disease. If the Cycle 1 (Day 21 [±7]) bone marrow aspirate (±biopsy) is empty, hypocellular, or inadequate, a bone marrow examination should be repeated within 
7 (±7) days to document response. During Stage 2, AML patients will also have bone marrow evaluations following Cycles 4 and 6, and at the Investigator’s discretion prior 
to end of treatment and thereafter. If CD123 flow cytometry or IHC stain was performed on the bone marrow aspirations (± biopsy), the results should be recorded in the 
eCRF. 
(k) BPDCN patients only. Baseline must be performed within 14 days prior to the first administration of SL-401. Subsequent CT scans will be performed 21 (±3) days after the 
start of Cycle 2 and 4 and 21 (±7) days after the start of every 4th cycle thereafter until there is evidence of relapsed or progressive disease. Baseline CT scans should be full-
body, whereas follow-up scans should document response of index lesions. 
(l) BPDCN patients only, with biopsies and/or photographs for patients with skin involvement. Baseline must be performed within 14 days prior to the first administration of Sl-
401. Subsequent skin assessments will be performed 21 (±3) days after the start of Cycles 1 and 2 and 21 (±7) days after the start of every 2nd cycle thereafter (Cycles 4, 6, 
etc.) until there is evidence of relapsed or progressive disease. 
(m) Refer to protocol Section 7.5.3.1 – Premedication 
(n) Following treatment with premedication, SL-401 will be administered as a 15-minute infusion for the first 5 consecutive days of a 21-day cycle. Individual SL-401 infusions 
may be delayed to allow for toxicity resolution, all infusions should be completed within 10 days and fewer than 5 infusions are permitted in settings of incipient CLS or 
hepatotoxicity. Patients must be monitored for 4 hours post infusion. 
(o) Plasma samples (6 mL each) will be collected immediately prior to the start of the infusion of SL-401, immediately after end of infusion (time recorded), then 15, 30, 45, 60, 
90, 120, 180, and 240 minutes after completion of the infusion during infusions 1 (i.e., Study Day 1) and 5 (i.e., Study Day 5) (see (c) and Table 9). 
(p) Blood samples (10 mL) will be collected for the detection of SL-401 reactive antibodies according on Day 1 (pre-infusion), Day 15, and Day 21 (if patient is to receive 
Cycle 2, can be Day 1, pre-infusion for Cycle 2). If infusions are held, please collect a sample within 3±3 days after the last SL-401 infusion(s) of the cycle.  


SL-401 Diphtheria Toxin Interleukin-3 Fusion Protein 
Stemline Therapeutics, Inc. 
 
Protocol STML-401-0114 
Amendment 12 (FINAL): 17 January 2019 
 
74 
CONFIDENTIAL 
Table 6: Study Events Schedule for Cycles 2-6 and Subsequent Cycles: Stage 1 (All Pts) & Stage 2 (AML Pts)  
Tests and Observations 
Cycle 2+ 
End of 
Treatment 
Safety: 
Through 
30 Days 
After Last 
Infusion 
Survival: 
Every 90 
Days After 
Last Infusion 
Days 1-5 (Up to Day 10 if 
Infusion(s) Held) 
SL-401 Treatment 
Day 
8±3(q) and 
15±3 
Day 
21±3 
Day 28±3, Then Every 
7±3 days 
Pre-Infusion 
Infusion 
End of Cycle 
Delayed End of Cycle 
for Toxicity Resolution 
Only if Required 
Medical history including prior therapy, 
concomitant medications  
 
 
 
 
 
 
 
 
Concomitant Medications 
 
 
X 
X 
X 
 
 
 
ECOG performance status 
 
 
 
X 
X 
X 
 
 
Physical examination 
 
 
X 
X 
 
X 
 
 
Vital signs and weight(a) 
X 
X 
X 
X 
X 
X 
 
 
12-lead ECG(b) 
X 
X (Cycle 3, 
Infusions 1, 5) 
 
X 
X 
 
 
 
Hematology(c) 
X 
 
X 
X 
X 
 
 
 
Serum electrolytes(d) 
X 
 
X 
X 
X 
 
 
 
Serum albumin(e) 
X 
 
X 
X 
X 
 
 
 
Serum chemistry(f) 
X 
 
X 
X 
X 
 
 
 
Coagulation parameters: PT/INR, aPTT 
X 
 
X 
X 
X 
 
 
 
Urinalysis(g) 
X 
(Infusion 1) 
 
X 
X 
X 
 
 
 
Tumor response assessment: Bone marrow 
aspiration ± biopsy(h) 
 
 
 
  X (h)  
 
 
 
 
Tumor response assessment: CT scan(i) 
 
 
 
X  
 
 
 
 
Tumor response assessment: skin, including 
biopsies and/or photographs(j) 
 
 
 
X 
 
 
 
 
Tumor response assessment: peripheral blood 
 
 
 
X(k) 
 
 
 
 
Administration of premeds (l) 
X 
 
 
 
 
 
 
 
SL-401 administration(m) 
 
X 
 
 
 
 
 
 
Pharmacokinetic sampling(n) 
X (Cycle 3, 
Infusions 1, 5) 
X (Cycle 3, 
Infusions 1, 5) 
 
 
 
 
 
 
Immunogenicity sampling(o) 
X 
(Infusion 1) 
 
 
X 
 
 
 
 
AE and SAE monitoring 
X 
X 
X 
X 
X 
 
X 
 
Long-term follow-up(p) 
 
 
 
 
 
 
X 
X 
 


SL-401 Diphtheria Toxin Interleukin-3 Fusion Protein 
Stemline Therapeutics, Inc. 
 
Protocol STML-401-0114 
Amendment 12 (FINAL): 17 January 2019 
 
75 
CONFIDENTIAL 
(a) Vital signs should be performed after patient is sitting for 3-5 minutes. If during dosing period, vital signs should be taken immediately prior to infusion, immediately after 
completion of infusion, and 30, 60, and 240 minutes post-infusion. 
(b) All patients will have a 12-lead ECG performed at the screening visit and pre-treatment visit, as well as Day 21 (and Day 28 only if delayed end of cycle) of each cycle. 
During the days when patients are undergoing PK sampling (Cycle 1, infusions 1 and 5; Cycle 3, infusions 1 and 5), an ECG will be performed at 3 distinct time points 
(triplicates) within 5 minutes prior to each PK sample collection pre-infusion and at 30 and 60 minutes post-infusion (see footnote (n) and Table 9). 
(c) To be collected prior to SL-401 infusion if during dosing period. Hematology includes White blood cell (WBC) count, differential white cell count, red blood cell count, 
hematocrit, hemoglobin and platelet count. 
(d) To be collected prior to SL-401 infusion if during dosing period. Electrolytes include sodium, potassium, bicarbonate, chloride, blood urea nitrogen (BUN), and creatinine.  
(e) To be collected prior to SL-401 infusion if during dosing period. Serum albumin may be a component of the chemistry panel (f). See protocol for administration of albumin if 
serum albumin decreases during treatment days or in the immediate post-treatment period. 
(f) To be collected prior to SL-401 infusion if during dosing period. Serum electrolytes and chemistry: Sodium, potassium, bicarbonate, chloride, blood urea nitrogen (BUN), 
creatinine, glucose, alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase, (AST), bilirubin (total, direct, and indirect), calcium, 
creatine phosphokinase (CPK), magnesium, lactate dehydrogenase (LDH), phosphate, total protein, uric acid 
(g) To be collected prior to SL-401 infusion if during dosing period. Urinalysis includes appearance, color, pH, specific gravity, ketones, leukocytes, protein, glucose, bilirubin, 
urobilinogen, and occult blood.  
(h) Morphology and differential WBC/blast count on aspirate. Bone marrow aspirates (± biopsy) will be performed 21 (±7) days after the start of Cycle 2, and, in Stage 1, at the 
Investigator’s discretion prior to end of treatment and thereafter until there is evidence of relapsed or progressive disease. During Stage 2, AML patients will also have bone 
marrow evaluations following Cycles 4 and 6 and then every 3 months from Months 6-12; every 6 months from 12 to 24 months; and every 12 months thereafter until there is 
evidence of relapsed or progressive disease. If CD123 flow cytometry or IHC stain was performed on the bone marrow aspirations (± biopsy), the results should be recorded 
in the eCRF. 
(i) BPDCN patients only. Baseline must be performed within 14 days prior to the first administration of SL-401. In Stage 1, subsequent CT scans will be performed 21 (±7) days 
after the start of Cycle 2 and 4 and 21 (±7) days after the start of every 4th cycle thereafter until there is evidence of relapsed or progressive disease. Baseline CT scans should 
be full-body, whereas follow-up scans should document response of index lesions. 
(j) BPDCN patients only, with biopsies and/or photographs for patients with skin involvement. Baseline must be performed within 14 days prior to the first administration of SL-
401. Subsequent skin assessments will be performed 21 (±7) days after the start of Cycles 1 and 2 and 21 (±7) days after the start of every 2nd cycle thereafter (Cycles 4, 6, 
etc.) until evidence of relapsed or progressive disease. Quantification of disease burden via the mSWAT is required at the time of each skin assessment. 
(k) Patients with evidence of peripheral blasts at baseline will have peripheral blood samples collected 21 (±7) days after the start of Cycles 1 and 2 and 21 (±7) days after the 
start of every 2nd cycle thereafter (Cycles 4, 6, etc.) until there is evidence of relapsed or progressive disease. 
(l) Refer to protocol Section 7.5.3.1 – Premedication 
(m) Following treatment with premedication, SL-401 will be administered as a 15-minute infusion for the first 5 consecutive days of a 21-day cycle. Individual SL-401 infusions 
may be delayed to allow for toxicity resolution; all infusions should be completed within 10 days and fewer than 5 infusions are permitted in settings of incipient CLS or 
hepatotoxicity. Patients must be monitored for 4 hours post infusion. 
(n) Plasma samples (6 mL each) will be collected immediately prior to the start of the infusion of SL-401, immediately after end of infusion (time recorded), then 15, 30, 45, 60, 
90, 120, 180, and 240 minutes after the start of the infusion during infusions 1 (i.e., Day 1) and 5 (i.e., Day 5) of Cycle 3 (see footnote (b) and Table 9).  
(o) Blood samples (10 mL) will be collected for the detection of SL-401 reactive antibodies according on Day 1 (pre-infusion), Day 15, and Day 21 (if patient is to receive 
additional cycles, can be Day 1, pre-infusion for next cycle). If infusions are held, please collect a sample within 3±3 days the last SL-401 infusion(s) of the cycle. 
(p) After the follow-up visit, patients will then be followed every 90 days for survival status. The survival follow-up may be by telephone contact. If the patient is in CR/PR at the 
time of discontinuation, disease assessments should continue to be performed as described in Section 8.11 on an every 6-week basis (±1 week) through 6 months post-C1D1 
and then on an every 90-day basis or until, in the judgment of the Investigator, there is evidence of relapsed or progressive disease.  


SL-401 Diphtheria Toxin Interleukin-3 Fusion Protein 
Stemline Therapeutics, Inc. 
 
Protocol STML-401-0114 
Amendment 12 (FINAL): 17 January 2019 
 
76 
CONFIDENTIAL 
Table 7: Study Events Schedule for Cycles 1 & 2 (Study Day -14 to Study Day 21): BPDCN Patients in Stages 2-4 
Tests and Observations 
Study Day   
-14 to -4 
Cycles 1 & 2 
Study Day 
-1 to 0 
Cycle Days 1-5 (Up to Study 
Day 10 if Infusion(s) Held) 
SL-401 Treatment 
Study Day 
8±3(q) and 
15±3 
Cycle Day 
21±7 
Cycle Day 28±7, 
Then Every 7±3 days 
 
Screening 
Pre- 
treatment 
Pre-Infusion 
Infusion 
End of Cycle 
Delayed End of Cycle 
for Toxicity Resolution 
Only if Required 
Informed consent form 
X 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
Medical history including prior therapy, 
concomitant medications  
X 
 
 
 
 
 
 
Concomitant Medications 
 
X 
 
 
X 
X 
X 
ECOG performance status 
X 
 
 
 
 
X 
X 
Physical examination 
X 
X 
 
 
X 
X 
 
Pregnancy test (a) 
X 
 
 
 
 
 
 
Vital signs and weight(b) 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG(c) 
X 
X 
X  
X (Infusions 1, 5) 
 
X 
X 
ECHO or MUGA scan(d) 
X 
 
 
 
 
 
 
Hematology(e) 
X 
X 
X 
 
X 
X 
X 
Serum electrolytes(f) 
X 
X 
X 
 
X 
X 
X 
Serum albumin(g) 
X 
X 
X 
 
X 
X 
X 
Serum chemistry(h) 
X 
X 
X 
 
X 
X 
X 
Coagulation parameters: PT/INR, aPTT 
X 
 
X 
 
X 
X 
X 
Urinalysis(i)  
X 
 
X (Infusion 1) 
 
X 
X 
X 
Tumor response assessment: Bone marrow 
aspiration ± biopsy(j) 
X 
 
 
 
 
X 
 
Tumor response assessment: CT scan(k) 
X 
 
 
 
 
X (Cycle 2) (k) 
 
Tumor response assessment: Skin, including 
biopsies and/or photographs(l) 
X 
 
 
 
 
X 
 
Tumor response assessment: Peripheral blood  
 
 
 
 
 
X 
 
Administration of premeds (m) 
 
 
X 
 
 
 
 
SL-401 administration(n) 
 
 
 
X 
 
 
 
Pharmacokinetic sampling(o)  
 
 
X (Infusions 1, 5)  X (Infusions 1, 5) 
 
 
 
Immunogenicity sampling(p)  
 
 
X (Infusion 1) 
 
X 
(C1D15 only) 
X 
 
Vision assessment 
X 
 
 
 
 
X 
 
AE and SAE monitoring 
 
 
X 
X 
X 
X 
X 


SL-401 Diphtheria Toxin Interleukin-3 Fusion Protein 
Stemline Therapeutics, Inc. 
 
Protocol STML-401-0114 
Amendment 12 (FINAL): 17 January 2019 
 
77 
CONFIDENTIAL 
(a) Urine or serum pregnancy test must be performed within 1 week prior to treatment in women of childbearing potential. 
(b) Vital signs should be performed after patient is sitting for 3-5 minutes. If during dosing period, vital signs should be taken immediately prior to infusion, immediately after 
completion of infusion, and 30, 60, and 240 minutes post-infusion. 
(c) All patients will have a 12-lead ECG performed at the screening visit and pre-treatment visit, as well as Day 21 (and Day 28 only if delayed end of cycle) of each cycle. 
During the days when patients are undergoing PK sampling (Cycle 1, infusions 1 and 5; Cycle 3, infusions 1 and 5), an ECG will be performed at 3 distinct time points 
(triplicates) within 5 minutes prior to each PK sample collection pre-infusion and at 30 and 60 minutes post-infusion (see (p) and Table 9). 
(d) MUGA or 2-D ECHO to quantify left ventricular ejection fraction (LVEF). Must be completed within 28 days prior to start of first cycle of study treatment.  
(e) To be collected prior to SL-401 infusion if during dosing period. Hematology includes White blood cell (WBC) count, differential white cell count, red blood cell count, 
hematocrit, hemoglobin and platelet count. 
(f) To be collected prior to SL-401 infusion if during dosing period. Electrolytes include sodium, potassium, bicarbonate, chloride, blood urea nitrogen (BUN), and creatinine.  
(g) To be collected prior to SL-401 infusion if during dosing period. Serum albumin may be a component of the chemistry panel (h). See protocol for administration of albumin if 
serum albumin decreases during treatment days or in the immediate post-treatment period. 
(h) To be collected prior to SL-401 infusion if during dosing period. Serum electrolytes and chemistry: Sodium, potassium, bicarbonate, chloride, blood urea nitrogen (BUN), 
creatinine, glucose, alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase, (AST), bilirubin (total, direct, and indirect), calcium, 
creatine phosphokinase (CPK), magnesium, lactate dehydrogenase (LDH), phosphate, total protein, uric acid 
(i) To be collected prior to initial SL-401 infusion of the cycle. Urinalysis includes appearance, color, pH, specific gravity, ketones, leukocytes, protein, glucose, bilirubin, 
urobilinogen, and occult blood.  
(j) Morphology and differential WBC/blast count on aspirate. Baseline must be performed within 14 days prior to the first administration of SL-401. For BPDCN patients in 
Stages 2-4, subsequent bone marrow aspirates (± biopsy) will be performed 21 (±7) days after the start of Cycles 1 and 2. If the Cycle 1 (Day 21 [±7]) bone marrow aspirate 
(± biopsy) is empty, hypocellular, or inadequate, a bone marrow examination should be repeated within 7 (±7) days to document response. If CD123 flow cytometry stain was 
performed on the bone marrow aspirations (± biopsy), the results should be recorded in the eCRF.  
(k) Baseline CT must be performed within 14 days prior to the first administration of SL-401. For patients with baseline evidence of lymph node or visceral disease involvement, 
subsequent Stages 2-4 CT scans will be performed 21 (±7) days after the start of Cycles 2, 4 and 6, and 21 (±7) days after the start of every 4th cycle thereafter (approximately 
every 12 weeks) until there is evidence of relapsed or progressive disease. For patients with no baseline evidence of lymph node or visceral BPDCN involvement, subsequent 
scans should be performed at the end of Cycle 2 (±7 days; or at time of disease progression if PD occurs prior to end of Cycle 2), 21 (±7) days after the start of Cycle 6, and at 
Investigator’s discretion thereafter. Baseline CT scans should be full-body, whereas follow-up scans should document response of index lesions. 
(l) For patients with skin involvement. Baseline must be performed within 14 days prior to the first administration of Sl-401. Subsequent skin assessments will be performed 21 
(±7) days after the start of Cycles 1 and 2 and 21 (±7) days after the start of every 2nd cycle thereafter (Cycles 4, 6, etc.) until there is evidence of relapsed or progressive 
disease. Quantification of skin disease burden via the mSWAT instrument is required at the time of each skin assessment.  
(m) Refer to protocol Section 7.5.3.1 – Premedication and Administration 
(n) Following treatment with premedication, SL-401 will be administered as a 15-minute infusion for the first 5 consecutive days of a 21-day cycle. Individual SL-401 infusions 
may be delayed to allow for toxicity resolution; all infusions should be completed within 10 days and fewer than 5 infusions are permitted in settings of incipient CLS or 
hepatotoxicity. Patient must be monitored for 4 hours post infusion. 
(o) Plasma samples (6 mL each) will be collected immediately prior to the start of the infusion of SL-401, immediately after end of infusion (time recorded), then 15, 30, 45, 60, 
90, 120, 180, and 240 minutes after completion of the infusion during infusions 1 (i.e., Study Day 1) and 5 (i.e., Study Day 5) of Cycles 1 & 3 (see Table 9).  
(p) Blood samples (10 mL) will be collected for the detection of SL-401 reactive antibodies on Day 1 (pre-infusion), Day 15, and Day 21 (if patient is to receive Cycle 2, can be 
Day 1, pre-infusion for Cycle 2). If infusions are held, please collect a sample within 3±3 days after completion of the last SL-401 infusion of the cycle. 


SL-401 Diphtheria Toxin Interleukin-3 Fusion Protein 
Stemline Therapeutics, Inc. 
 
Protocol STML-401-0114 
Amendment 12 (FINAL): 17 January 2019 
 
78 
CONFIDENTIAL 
Table 8: Study Events Schedule for Cycles 3-6 and Subsequent Cycles: Stages 2-4 (BPDCN Patients) 
Tests and Observations 
Cycle 3+ 
End of 
Treatment 
Safety: 
Through 
30 Days 
After Last 
Infusion 
Survival: 
Every 90 
Days After 
Last Infusion 
Days1-5 (Up to Day 10 if 
Infusion(s) Held) 
SL-401 Treatment 
Day 
8±3(q) and 
15±3(q) 
Day 
21±7 
Day 28±7, Then Every 
7±3 days 
Pre-Infusion 
Infusion 
End of Cycle 
Delayed End of Cycle 
for Toxicity Resolution 
Only if Required 
Medical history including prior therapy, 
concomitant medications  
 
 
 
 
 
 
 
 
Concomitant Medications 
 
 
X 
X 
X 
 
 
 
ECOG performance status 
 
 
 
X 
X 
X 
 
 
Physical examination 
 
 
 
X 
 
X 
 
 
Vital signs and weight(a) 
X 
X 
 
X 
X 
X 
 
 
12-lead ECG(b) 
X 
X (Cycle 3, 
Infusions 1, 5) 
 
X 
X 
 
 
 
Hematology(c) 
X 
 
X 
X 
X 
 
 
 
Serum electrolytes(d) 
X 
 
X 
X 
X 
 
 
 
Serum albumin(e) 
X 
 
X 
X 
X 
 
 
 
Serum chemistry(f) 
X 
 
X 
X 
X 
 
 
 
Coagulation parameters: PT/INR, aPTT 
X 
 
X 
X 
X 
 
 
 
Urinalysis(g) 
X (Infusion 1) 
 
X 
X 
X 
 
 
 
Tumor response assessment: Bone marrow 
aspiration ± biopsy(h) 
 
 
 
 X(i) 
 
 
 
 
Tumor response assessment: CT scan(i) 
 
 
 
X 
 
 
 
 
Tumor response assessment: skin, including 
biopsies and/or photographs(j) 
 
 
 
X 
 
 
 
 
Tumor response assessment: peripheral blood 
 
 
 
X(k) 
 
 
 
 
Administration of premeds (l) 
X 
 
 
 
 
 
 
 
SL-401 administration(m) 
 
X 
 
 
 
 
 
 
Pharmacokinetic sampling(n) 
X (Cycle 3, 
Infusions 1, 5) 
X (Cycle 3, 
Infusions 1, 5) 
 
 
 
 
 
 
Immunogenicity sampling(o) 
X (Infusion 1) 
 
 
X 
 
 
 
 
Vision assessment 
 
 
 
 
X 
X 
 
 
AE and SAE monitoring 
X 
X 
X 
X 
X 
 
X 
 
Long-term follow-up(p) 
 
 
 
 
 
 
X 
X 


SL-401 Diphtheria Toxin Interleukin-3 Fusion Protein 
Stemline Therapeutics, Inc. 
 
Protocol STML-401-0114 
Amendment 12 (FINAL): 17 January 2019 
 
79 
CONFIDENTIAL 
(a) Vital signs should be performed after patient is sitting for 3-5 minutes. If during dosing period, vital signs should be taken immediately prior to infusion, immediately after 
completion of infusion, and 30, 60, and 240 minutes post-infusion. 
(b) All patients will have a 12-lead ECG performed at the screening visit and pre-treatment visit, as well as Day 21 (and Day 28 only if delayed end of cycle) of each cycle. 
During the days when patients are undergoing PK sampling (Cycle 1, infusions 1 and 5; Cycle 3, infusions 1 and 5), an ECG will be performed at 3 distinct time points 
(triplicates) within 5 minutes prior to each PK sample collection pre-infusion and at 30 and 60 minutes post-infusion (see (m) and Table 9). 
(c) To be collected prior to SL-401 infusion if during dosing period. Hematology includes White blood cell (WBC) count, differential white cell count, red blood cell count, 
hematocrit, hemoglobin and platelet count. 
(d) To be collected prior to SL-401 infusion if during dosing period. Electrolytes include sodium, potassium, bicarbonate, chloride, blood urea nitrogen (BUN), and creatinine.  
(e) To be collected prior to SL-401 infusion if during dosing period. Serum albumin may be a component of the chemistry panel (f). See protocol for administration of albumin if 
serum albumin decreases during treatment days or in the immediate post-treatment period. 
(f) To be collected prior to SL-401 infusion if during dosing period. Serum electrolytes and chemistry: Sodium, potassium, bicarbonate, chloride, blood urea nitrogen (BUN), 
creatinine, glucose, alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase, (AST), bilirubin (total, direct, and indirect), calcium, 
creatine phosphokinase (CPK), magnesium, lactate dehydrogenase (LDH), phosphate, total protein, uric acid 
(g) To be collected prior to initial SL-401 infusion of the cycle. Urinalysis includes appearance, color, pH, specific gravity, ketones, leukocytes, protein, glucose, bilirubin, 
urobilinogen, and occult blood.  
(h) Morphology and differential WBC/blast count on aspirate. In Stages 2-4, patients with evidence of bone marrow involvement prior to study will have bone marrow 
evaluations following Cycles 4 and 6 and then every 3 months from Months 6-12; every 6 months from 12 to 24 months; and every 12 months thereafter until there is 
evidence of relapsed or progressive disease. If CD123 flow cytometry stain was performed on the bone marrow aspirations (± biopsy), the results should be recorded in the 
eCRF. 
(i) Baseline CT must be performed within 14 days prior to the first administration of SL-401. For patients with baseline evidence of lymph node or visceral disease involvement, 
subsequent Stages 2-4 CT scans will be performed 21 (±7) days after the start of Cycles 1, 2, 4 and 6, and 21 (±7) days after the start of every 4th cycle thereafter 
(approximately every 12 weeks) until there is evidence of relapsed or progressive disease. For patients with no baseline evidence of lymph node or visceral BPDCN 
involvement, subsequent scans should be performed at the end of Cycle 2 (±7 days; or at time of disease progression if PD occurs prior to end of Cycle 2), 21 (±7) days after 
the start of Cycle 6, and at Investigator’s discretion thereafter. Baseline CT scans should be full-body, whereas follow-up scans should document response of index lesions. 
(j) For patients with skin involvement. Baseline must be performed within 14 days prior to the first administration of Sl-401. Subsequent skin assessments will be performed 21 
(±7) days after the start of Cycles 1 and 2 and 21 (±7) days after the start of every 2nd cycle thereafter (Cycles 4, 6, etc.) until there is evidence of relapsed or progressive 
disease. Quantification of skin disease burden via the mSWAT instrument is required at the time of each skin assessment. 
(k) Peripheral blood samples will be collected 21 (±7) days after the start of Cycles 1 and 2 and, for patients with evidence of peripheral blasts at baseline, 21 (±7) days after the 
start of every 2nd cycle thereafter (Cycles 4, 6, etc.) until there is evidence of relapsed or progressive disease. 
(l) Refer to protocol Section 7.5.3.1 – Premedication and Administration 
(m) Following treatment with premedication, SL-401 will be administered as a 15-minute infusion for the first 5 consecutive days of a 21-day cycle. Individual SL-401 infusions 
may be delayed to allow for toxicity resolution; all infusions should be completed within 10 days and fewer than 5 infusions are permitted in settings of incipient CLS or 
hepatotoxicity. Patient must be monitored for 4 hours post infusion. 
(n) Plasma samples (6 mL each) will be collected immediately prior to the start of the infusion of SL-401, immediately after end of infusion (time recorded), then 15, 30, 45, 60, 
90, 120, 180, and 240 minutes after the start of the infusion during infusions 1 (i.e., Day 1) and 5 (i.e., Day 5) of Cycles 1 & 3 (see Table 9).  
(o) Blood samples (10 mL) will be collected for the detection of SL-401 reactive antibodies on Day 1 (pre-infusion), Day 15, and Day 21 (if patient is to receive additional cycles, 
can be Day 1, pre-infusion for next cycle). If infusions are held, please collect a sample within 3±3 days after the last SL-401 infusion of the cycle. 
(p) After the follow-up visit, patients will then be followed every 90 days for survival status. The survival follow-up may be by telephone contact. If the patient is in CR/PR at the 
time of discontinuation, disease assessments should continue to be performed as described in Section 8.12 on an every 6-week basis (±1 week) through 6 months post-C1D1 
and then on an every 90-day basis or until, in the judgment of the Investigator, there is evidence of relapsed or progressive disease. Patients who undergo SCT will be 
followed for the occurrence of VOD and delayed or failed engraftment as part of survival monitoring. 
(q) For Cycles 5 and beyond (Stages 2-4), the Day 8 and 15 concomitant medication and AE evaluations may be conducted via telephone and the laboratory evaluations may be 
performed at local laboratories for patients who live a considerable distance from the study center. 


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Table 9: Time Points for Pharmacokinetic Blood Draws and ECGs 
Time Point 
Cycle: Day/Dose 
Cycle 1: 
Day 1/Infusion 1 
Cycle 1: 
Day 5/Infusion 5 
Cycle 3: 
Day 1/Infusion 1 
Cycle 3: 
Day 5/Infusion 5 
ECG 
PK 
ECG 
PK 
ECG 
PK 
ECG 
PK 
Pre-Infusion 
X 
X 
X 
X 
X 
X 
X 
X 
Immediately After End of 
Infusion (time recorded) 
 
X 
 
X 
 
X 
 
X 
15 Minutes Post-Infusion 
 
X 
 
X 
 
X 
 
X 
30 Minutes Post-Infusion 
X 
X 
X 
X 
X 
X 
X 
X 
45 Minutes Post-Infusion 
 
X 
 
X 
 
X 
 
X 
60 Minutes Post-Infusion 
X 
X 
X 
X 
X 
X 
X 
X 
90 Minutes Post-Infusion 
 
X 
 
X 
 
X 
 
X 
120 Minutes Post-Infusion 
 
X 
 
X 
 
X 
 
X 
180 Minutes Post-Infusion  
 
X 
 
X 
 
X 
 
X 
240 Minutes Post-Infusion 
 
X 
 
X 
 
X 
 
X 
ECGs will be performed at 3 distinct time points (triplicates) within 5 minutes prior to each PK sample 
collection at the time points indicated. 
10 Adverse Events and Safety Evaluation 
The AE reporting period for a patient treated in the study begins with the initiation of SL-401 
and is continuous through 30 days after the last SL-401 infusion. All AEs that occur in treated 
patients during the AE reporting period specified in the protocol must be reported to the Sponsor 
or designee, whether or not the event is considered related to SL-401. Any known untoward 
event that occurs beyond the AE reporting period that the Investigator assesses as related to SL-
401 should also be reported as an AE. 
All patients should be monitored per institutional guidelines for at least 4 hours following the 
administration of each infusion of SL-401. The Principal Investigator, who is a physician, or 
medical staff responsible for study conduct and safety evaluations, should be available during the 
administration SL-401 and follow-up to assess, treat, or report as necessary any AE or serious 
adverse event (SAE) that may occur. 


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10.1 
Definitions 
All observed or volunteered AEs regardless of suspected causal relationship to SL-401 will be 
reported as described below. 
10.1.1 Adverse Event (AE) 
An AE is any untoward medical occurrence in a study patient who is administered a medicinal 
product (drug or biologic); the event may or may not have a causal relationship with the 
medicinal product. Examples of AEs include, but are not limited to the following: 
• Clinically significant symptoms and signs including: 
o Worsening of signs and symptoms of the disease under study; disease progression 
without worsening of signs and symptoms as assessed by bone marrow aspiration or 
other methods should not be reported as AEs. 
o Signs and symptoms resulting from drug overdose, abuse, misuse, withdrawal, 
sensitivity, dependency, interaction, or toxicity. 
o All possibly related and unrelated illnesses, including the worsening of a preexisting 
illness. 
o Injury or accidents. Note that if a medical condition is known to have caused the 
injury or accident (hip fracture from a fall secondary to dizziness), the medical 
condition (dizziness) and the outcome of the accident (hip fracture from a fall) should 
be reported as 2 separate AEs. 
• Abnormalities in physiological testing or physical examination findings that require 
clinical intervention or further investigation (beyond ordering a repeat confirmatory test). 
• Laboratory abnormalities that meet any of the following (Note: merely repeating an 
abnormal test, in the absence of any of the below conditions, does not constitute an AE. 
Any abnormal test result that is determined to be an error does not require reporting as an 
AE): 
o Test result that is associated with accompanying symptoms 
o Test result that requires additional diagnostic testing or medical/surgical intervention 
o Test result that leads to significant additional concomitant drug treatment or other 
therapy 
o Test result that is considered to be an AE by the Investigator or Sponsor 
Note that VOD, engraftment delay or failure occurring post-SCT and any changes in visual 
acuity and/or color vision will be followed as adverse events of special interest. 
10.1.2 Serious Adverse Event (SAE) 
An AE that meets one or more of the following criteria/outcomes is classified as serious: 
• Results in death; 
• Is life-threatening (at immediate risk of death); 
• Requires admittance to the hospital or prolongation of existing hospitalization; 


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• Results in persistent or significant disability/incapacity; 
• Results in congenital anomaly/birth disfigurements among the offspring of the patients;  
• Events with medical significance or needing medical intervention to prevent the 
occurrence of any of the above events. 
Medical judgment should be exercised in deciding whether expedited reporting is appropriate in 
other situations, such as important medical events that may not be immediately life-threatening 
or result in death or hospitalization, but may jeopardize the patient or may require intervention to 
prevent one of the other outcomes listed in the definition above. Serious also includes any other 
event that the Investigator or Sponsor judges to be serious, or which is defined as serious. 
Adverse events associated with inpatient hospitalization, or prolongation of an existing 
hospitalization, are considered serious. Any initial admission, even if the duration is less than 
24 hours is considered serious. In addition, any transfer within the hospital to an acute/intensive 
care unit is considered serious. However, the following hospitalizations should not be considered 
serious: 
• Hospitalization or prolonged hospitalization in the absence of precipitating clinical AEs 
as follows: 
o Admission for treatment of preexisting condition not associated with the development 
of a new AE or with a worsening of the preexisting condition 
o Administrative admission (e.g., for a yearly physical exam) 
o Protocol-specified admission during the study (e.g., admission for SL-401 treatment) 
o Preplanned treatments or surgical procedures 
o Admission exclusively for the administration of blood products 
Progression of the disease under study (including signs and symptoms of progression) should not 
be reported as SAEs unless the outcome is fatal during the study or within the safety reporting 
period. If the disease under study has a fatal outcome during the study or within the safety 
reporting period, then the event leading to death must be recorded as an AE and as a SAE with 
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 
Grade 5. PD is NOT an SAE; however some sequelae of disease progression (i.e., pain, 
thrombocytopenia) may be reported as AEs or SAEs (generally not related to investigational 
therapy). 
The onset date of an SAE is defined as the date on which the event initially met serious criteria 
(e.g., the date of admission to a hospital). The end date is the date on which the event no longer 
met serious criteria (e.g., the date the patient was discharged from a hospital) or upon death. 
10.2 
Period of Observation 
Clinical signs and symptoms, and AEs (regardless of relationship to study treatment) will be 
collected continuously from the first day of SL-401 treatment to 30 days following the last 
infusion of SL-401. All SAEs and AEs judged to be related to study treatment will be collected 
throughout the follow-up period. 


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Conditions that the patient experienced prior to SL-401 treatment should be recorded in the 
patient medical history section of the eCRF. All the AEs should be followed-up until the 
symptoms dissipate or become stable even if AEs continue beyond the period of observation. 
AEs unresolved at the end of the observation period will be considered “ongoing” with an 
undetermined outcome; however, if after the period of observation completes but prior to the 
completion of the study, additional outcome information becomes available, it will be reported. 
The severity of the signs, symptoms, or AEs should be determined using the NCI CTCAE, 
Version 4.03. A complete CTCAE list can be downloaded at 
http://evs.nci.nih.gov/ftp1/CTCAE/About.html. 
All clinically meaningful abnormal test results should be retested. Abnormal test results that are 
difficult to associate with the study drug should be followed until normalized or until the 
abnormity could be clearly attributed to another cause. Abnormal test results should not be 
reported as AEs unless they meet the criteria outlined in Section 10.1.1. 
10.3 
Pre-existing Conditions 
A pre-existing condition will not be reported as an AE unless the condition worsens by at least 
one CTCAE grade during the study. The pre-existing condition, however, must be recorded in 
the screening eCRF as a pre-existing condition and all related concomitant medication 
administered for the condition recorded in the baseline (prior) concomitant medication eCRF.  
10.4 
Pregnancy 
WOCBP and men with partners of childbearing potential must be using an adequate method of 
contraception to avoid pregnancy throughout the study and for up to 2 months after the study in 
such a manner that the risk of pregnancy is minimized. WOCBP include any female who has 
experienced menarche and who has not undergone successful surgical sterilization 
(hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal 
(defined as amenorrhea ≥12 consecutive months; or women on hormone replacement therapy 
with documented serum follicle-stimulating hormone level ≥35 mIU/mL). Even women who are 
using oral, implanted, or injectable contraceptive hormones or mechanical products, such as an 
intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, 
are practicing abstinence, or whose partner is sterile (e.g., vasectomy), should be considered to 
be of childbearing potential. 
WOCBP must have a negative serum or urine pregnancy test during Screening within 1 week 
prior to dosing. If the pregnancy test is positive, the patient must not receive study therapy and 
must not be enrolled in the study. 
Sexually active WOCBP must use an effective method of birth control during the course of the 
study, in a manner such that the risk of failure is minimized. 


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Prior to study enrollment, WOCBP must be advised of the importance of avoiding pregnancy 
during study participation and the potential risk factors for an unintentional pregnancy. This 
information will be included in the ICF that must be signed by the patient.  
In addition, all WOCBP or fertile men with partners of childbearing potential should be 
instructed to contact the Investigator immediately if they suspect they or their partner might be 
pregnant (e.g., missed or late menstrual period) at any time during study participation. 
If following initiation of study treatment, it is subsequently discovered that a patient is pregnant 
or may have been pregnant at the time of exposure to study therapy, including during at least 2 
months after product administration, study therapy will be permanently discontinued in an 
appropriate manner. Exceptions to discontinuation may be considered for life threatening 
conditions only after consultation with the Sponsor and Medical Monitor or as otherwise 
specified in this protocol. The Investigator must immediately notify the Sponsor and Medical 
Monitor of this event. 
Protocol-required procedures for study discontinuation and follow-up must be performed on the 
patient unless contraindicated by pregnancy (e.g., x-ray studies). Other appropriate pregnancy 
follow-up procedures should be considered if indicated. In addition, the Investigator must report 
to the Sponsor follow-up information regarding the course of the pregnancy, including perinatal 
and neonatal outcome. Infants should be followed for a minimum of 8 weeks postpartum. 
10.5 
Documentation and Reporting of Adverse Events by Investigator 
The Investigator is to report all directly observed AEs as well as those spontaneously reported by 
the patient using concise medical terminology. In addition, each patient will be questioned about 
AEs at each clinic visit following initiation of treatment. The question asked will be “Since your 
last clinic visit have you had any health problems?” or a similar non-leading question to assess 
health status. 
The AE reporting period for this study begins upon initiation of SL-401 treatment and ends 
30 days after the last infusion of SL-401. All AEs are to be reported on the AE eCRFs.  
All AEs that occur in study patients during the AE reporting period specified in the protocol 
must be reported to the Sponsor or designee, whether or not the event is considered study 
treatment-related. In addition, any untoward event that occurs beyond the AE reporting period 
that the Investigator assesses as related to the investigational product should also be reported as 
an AE. 
Each AE is to be classified by the Investigator as serious or non-serious. This classification of 
the gravity of the event determines the reporting procedures to be followed. If a SAE occurs, 
reporting will follow local and international regulations, as appropriate. 
For any event that meets one of the SAE criteria, the Investigator 
 
Safety within 24 hours of the knowledge of the occurrence. To report the SAE, the SAE form is 
to be completed electronically in the electronic data capture (EDC) system for the study. When 


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the form is completed, 
 personnel will be notified electronically and will retrieve 
the form. If the event meets serious criteria and it is not possible to access the internet, an email 
to should be sent to 
 or a call made 
to the 
 
 within 24 hours of awareness. When the 
EDC system becomes available, the SAE information must be entered within 24 hours of the 
system becoming available. 
Each SAE should be followed until resolution, or until such time as the Investigator determines 
its cause or determines that, it has become stable.  
Within 24 hours of receipt of follow-up information, the Investigator must update the SAE form 
electronically in the EDC system for the study and submit any supporting documentation (e.g., 
subject discharge summary or autopsy reports) to 
 via fax or e-mail. If it 
is not possible to access the EDC system, refer to the procedures outlined above for initial 
reporting of SAEs. 
The Sponsor will report AEs, which are unexpected and reported as serious and associated with 
use of the study drug, to the US Food and Drug Administration (FDA) and all participating 
clinical sites. For events, which are fatal or life threatening, unexpected, and associated with use 
of the investigational product, a 7-Day Alert Report will be submitted to the FDA within 7 
calendar days of receipt of the SAE information. For all other events that are serious, 
unexpected, and associated with the use of the investigational medicinal product, a written report 
will be made no more than 15 calendar days from the date the Sponsor learns of the event. 
Reports of delayed or failed engraftment post-SCT will be reported as 15-day safety reports.  
10.6 
Assessment of Causal Relationship to SL-401 
In this study, the investigational medicinal product is SL-401. The relationship of an AE to the 
investigational product should be classified using the following guidelines: 
• Related: A temporal relationship exists between the event onset and administration of SL-
401. It cannot be readily explained by the patient’s clinical state, intercurrent illness, or 
concomitant therapies. In case of cessation or reduction of the dose, the event abates or 
resolves and reappears upon rechallenge. This includes events that are considered 
possibly, probably, or definitely related to SL-401.  


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• Not Related: Evidence exists that the AE has an etiology other than the study drug (e.g., 
pre-existing condition, underlying disease, intercurrent illness, or concomitant 
medication). This includes events that are considered probably not or not related to SL-
401. It should be emphasized that ineffective study drug treatment should not be 
considered as causally related in the context of AE reporting (in other words, disease 
progression is not considered an AE; however some sequelae of disease progression may 
be reported as AEs and should generally be reported as AEs not related to investigational 
therapy). 
An Investigator who is qualified in medicine must make the determination of relationship to the 
investigational product for each AE. The Investigator should decide whether, in his or her 
medical judgment, there is a reasonable possibility that the event may have been caused by the 
investigational product. The following factors for study drug relationship should be referenced 
when making a determination of “related” or “not related.” 
• The temporal sequence from study drug administration: The event should occur after the 
study drug is given. The length of time from study drug exposure to event should be 
evaluated in the clinical context of the event. 
• Underlying, concomitant, intercurrent diseases: Each report should be evaluated in the 
context of the natural history and course of the disease being treated and any other disease 
the subject may have. 
• Concomitant medication: The other medications the subject is taking or the treatment the 
subject receives should be examined to determine whether any of them might be 
recognized to cause the event in question. 
• Known response pattern for this class of study drug: Clinical and/or preclinical data may 
indicate whether a particular response is likely to be a class effect. 
• Exposure to physical and/or mental stresses: The exposure to stress might induce adverse 
changes in the recipient and provide a logical and better explanation for the event. 
• The pharmacology and PK of the study drug: the known pharmacologic properties 
(absorption, distribution, metabolism, and excretion) of the study drug should be 
considered. 
10.7 
Grading of Adverse Event Severity 
To report AEs on the eCRFs, the Investigator will use the severity grading as described in NCI-
CTCAE, Version 4.03. 
Every effort should be made by the Investigator to assess the AE according to CTCAE criteria. If 
the Investigator is unable to assess severity because the term is not described in NCI-CTCAE 
Version 4.03, severity of MILD, MODERATE, SEVERE, LIFE-THREATENING, or DEATH 
may be used to describe the maximum intensity of the AE. For purposes of consistency, these 
intensity grades are defined as follows: 
• Mild (Grade 1): does not interfere with patient’s usual function 


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• Moderate (Grade 2): interferes to some extent with patient’s usual function 
• Severe (Grade 3): interferes significantly with patient’s usual function 
• Life-threatening (Grade 4): results in immediate risk of patient’s death 
• Death (Grade 5): results in patient’s death 
Note the distinction between the severity and the seriousness of an AE. A severe event is not 
necessarily a serious event. For example, a headache may be severe (interferes significantly with 
patient’s usual function) but would not be classified as serious unless it met one of the criteria for 
serious events. 
It is requested that when reporting AEs for which potentially redundant CTCAE terms exist, 
Investigators utilize the more clinically-oriented terminology (for example, “anemia” is 
preferable to “hemoglobin decreased”). 
It is also requested that in the setting of a hypersensitivity reaction or suspected hypersensitivity 
reaction considered by the Investigator to be related to investigational therapy, that Investigators 
report both the specific symptoms associated with the reaction (i.e., “urticaria,” ”chills,” 
“dyspnea,” etc.) and also report the appropriate term indicating the hypersensitivity reaction 
(“allergic reaction,” or “infusion related reaction” or “anaphylaxis” if appropriate [General 
Disorders and Immune System Disorders; CTCAE v4.x, pages 23 and 26]). 
11 Excluded Prior and Concomitant Medications and Therapy  
An enrolled patient may not receive investigational or approved anticancer or anti-leukemia 
agents, including cytotoxic chemotherapy agents, hypomethylating agents (5-azacytadine, 
decitabine or others), or anticancer tyrosine kinase inhibitors (including imatinib, ruxolitinib, 
sorafenib and others) or therapeutic monoclonal antibodies. Hydroxyurea may be administered 
(however its use should be discussed with the Medical Monitor). 
12 Statistical Analysis 
12.1 
General Considerations 
Study STML-401-0114 contains patients with both AML and first-line and R/R BPDCN. The 
current development strategy for SL-401 is to first pursue marketing authorization for an 
indication in first-line BPDCN patients, with potential additional indications in R/R BPDCN 
and/or AML, depending on the study results. Therefore, this statistical analysis section will focus 
primarily on the first-line BPDCN indication, with generally similar analytical approaches to be 
taken with the other potential indications upon achievement of sufficient data. 
Analyses will be performed on all patients who received any quantity of SL-401 (i.e., all treated 
patients). The baseline value for a given variable is defined as the last measurement for the 
variable prior to the first infusion of SL-401. Study Day 1 for each individual patient is defined 
as the date the patient receives their first infusion of SL-401. 


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Unless otherwise stated, all analyses will be performed using SAS Version 9 and all hypothesis 
tests will be conducted at a two-sided significance level of 0.05 or at a one-sided significance 
level of 0.025. P-values will be presented with 3 decimals and p-values that are less than 0.001 
will be presented as <0.001. Selected data summaries will be presented by disease (BPDCN and 
AML), with the primary data presentations provided for data from patients with BPDCN. For 
data from BPDCN patients, further categories for summarization will consist of line of therapy 
(first-line, R/R, and total) and dose (12 µg/kg/day and all doses). Efficacy endpoints will be 
summarized separately for Stage 3 patients, with an additional summary for all first-line and R/R 
BPDCN patients across all study stages. Stage 4 will be analyzed separately. 
Continuous (non-survival related) data will be summarized using descriptive statistics: number 
of observations (n), mean, standard deviation (SD), median, minimum, and maximum. Time to 
event data will be summarized using frequency and percentage of events and censored 
observations. Kaplan-Meier analysis will be performed to estimate the 25th percentile, median, 
and 75th percentile for time to events with corresponding two-sided 95% confidence intervals.  
Unless otherwise stated, confidence intervals, when presented, will be constructed at the 2-sided 
95% level. For binomial variables, 95% confidence intervals will be constructed using the 
Clopper Exact method instead of normal approximation. 
Data listings will present all data collected on eCRFs by study drug dose, center, Stage of study 
enrollment, and patient number.  
12.2 
Populations for Analysis 
Safety analysis will be performed on the population of patients who have received any amount of 
study treatment. The primary population for the analysis of efficacy will be the modified intent-
to-treat (mITT) population, consisting of those patients who are eligible based on screening 
criteria, and have received at least one dose of study drug. For BPDCN patients an additional 
criterion for mITT patients will be a confirmed diagnosis based on central pathology review. 
BPDCN patients in the mITT population will be said to be evaluable. Additional efficacy 
analyses will be performed on a per-protocol (PP) population, consisting of those patients who 
are in the mITT population, are compliant with all major aspects of the protocol, and have 
received a minimum of 2 cycles of study treatment.  
12.3 
Determination of Sample Size 
The sample size was originally planned to be approximately 40-50 patients with BPDCN, 
including approximately 40 first-line patients planned to be treated with the optimal SL-401 dose 
as determined in the completed Stage 1 of this study (12 µg/kg/day). In addition, up to 
approximately 36 patients with R/R AML were planned to be enrolled in Stage 2 of the study.  
In Stage 3, a sufficient number of patients were enrolled to ensure 10 evaluable patients were 
included, with evaluable patients being those with a diagnosis of BPDCN, as confirmed via 


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central pathology review who received at least 1 dose of SL-401. The sample size allocated for 
Stage 3 is intended to satisfy specific statistical criteria established by the Sponsor at the request 
of the US FDA.
 
 
 
The 
primary efficacy analysis for Stage 3 compares the lower bound of a two-sided 95% Clopper 
Exact confidence interval surrounding the observed CR rate to a clinically meaningless value of 
10%. Statistical significance is determined if the lower bound of this confidence interval falls 
above the rate of 10%. Assuming a CR rate of at least 60%, a sample size of a minimum of 10 
first-line BPDCN patients provides at least 90% power for this the primary efficacy assessment. 
 
 
 
 
To avoid possible selection bias, all first-line BPDCN patients enrolled in this time period are 
included in the Stage 3 analysis. This sample size also ensures there are 10 patients in the PP 
analysis population. 
After the maximum number of patients with first-line BPDCN in Stage 3 were enrolled, 
subsequent first-line BPDCN patients are enrolled in Stage 4. Furthermore, any patient with R/R 
BPDCN enrolled in this study on or after 26 October, 2016, will be allocated to Stage 4. 
Enrollment will continue in Stage 4 up until enrollment of up to approximately 145 patients or 
prior termination of the study. 
12.4 
Demographics and Baseline Characteristics 
Demographic (e.g., gender, age, race) and baseline characteristics (e.g., ECOG performance 
status, height, weight, and prior therapy) will be summarized by SL-401 dose group with 
descriptive statistics.  
12.5 
Analyses of Safety Data 
Safety assessments include DLTs, AEs, SAEs, physical examinations, vital sign measurements, 
ECGs, clinical laboratory evaluations, and reasons for treatment discontinuation due to toxicity. 
Safety data analysis will be performed primarily on the pool of first-line BPDCN patients treated 
with the 12 µg/kg/day dose level, with additional summaries across all BPDCN patients, patients 
with R/R disease and the pool of all BPDCN patients. Separate safety tabulations will be 
produced for patients with AML, patients who are treated with the lyophilized formulation of 
SL-401, and an overall pool of all enrolled patients. 


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Treatment-emergent AEs through 30 days after last SL-401 infusion will be summarized by 
MedDRA™ Version 13.1 (or higher) System Organ Class and preferred term. The incidences 
and percentages of patients experiencing each AE preferred term will be summarized with 
descriptive statistics. AEs will also be summarized by National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03 (or higher) grade and by 
causality (relationship to study treatment). Dose-limiting toxicities, ≥Grade 3 AEs, SAEs, and 
AEs resulting in dose modification or treatment discontinuation will also be summarized by 
preferred term.  
Laboratory results will be classified according to NCI-CTCAE, Version 4.03. Laboratory results 
not corresponding to an NCI-CTCAE term will not be graded. Incidences of laboratory 
abnormalities will be summarized with descriptive statistics. 
Vital signs, physical examination results, and ECGs will be summarized with descriptive 
statistics. 
12.6 
Analysis of Efficacy Data in First-Line BPDCN 
Efficacy assessments include CR rate (i.e., CR + CRi + CRc), DOR, ORR, PFS, and OS. The 
following sections refer specifically to patients with first-line BPDCN, treated at the 
12 µg/kg/day dose level. The following sub-sections refer specifically to patients with first-line 
BPDCN, treated at the 12 µg/kg/day dose level. The analysis of efficacy of SL-401 in these 
patients will be performed to address several objectives, based on data from the different stages 
of the study. 
Analyses by stage are intended as follows. Stage 3 will provide the pivotal results for a potential 
registrational submission in first-line BPDCN patients as assessed by rate of CR+CRc. Stage 1 
and 2 results will be presented, similar to the interim analysis as noted in Section 12.10. Stage 4 
results will be presented separately and may be used to assess consistency across drug 
formulations. 
12.6.1 Order of Statistical Analyses of Efficacy 
The primary evidence of efficacy will be derived from an analysis of the rate of CR+CRc, as 
assessed by the Investigator, in patients in Stage 3, accompanied by an evaluation of the 
durability of these CRs as a key secondary endpoint. A formal statistical analysis will first be 
performed for the primary efficacy endpoint to test the hypothesis that the rate of CR in first-line 
patients in Stage 3 exceeds the lower benchmark value of 10%. The primary analysis will be 
performed when all patients in Stage 3 have been followed for a minimum of 3 cycles or 
discontinued treatment, whichever occurs first. In addition, the durability of CR will be 
evaluated; refer to Section 12.6.3 for analysis methods for duration.  
A number of additional secondary analyses will then be performed, to further evaluate the rate of 
CR in other stages of the study and to assess additional efficacy parameters in support of the 
primary analysis results. The analyses of all secondary endpoints will be descriptive, with 


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summaries of secondary endpoints to be evaluated and presented in the following order of 
importance (as noted above, these analyses will be performed on data from first-line BPDCN 
patients treated at the 12 µg/kg/day dose level): 
1. Bone-marrow CR (BMCR) and DOR for Stage 3  
2. CR rate and DOR for Stages 1 and 2 
3. CR rate and DOR for pooled data from Stages 1, 2, 3, and 4 
4. ORR and DOR for Stages 1 and 2 
5. ORR and DOR for pooled data from Stages 1, 2, 3, and 4 
6. Proportion of patients who receive SCT based on pooled data from Stages 1, 2, 3 and 4 
7. PFS for Stages 1, 2, 3, and 4 
8. OS for Stages 1, 2, 3, and 4 
Response will be assessed using International Working Group (IWG) criteria for AML (for 
patients with AML) (Cheson et al. 2003) and a modified version of the Revised Response 
Criteria for Malignant Lymphoma (for patients with BPDCN) (Cheson et al. 2007). Disease 
response in skin will be assessed using the weighted BSA/modified Severity Weighted 
Assessment tool (mSWAT) score (for patients with BPDCN) (Olsen et al. 2011). For the patients 
with BPDCN, assessment of response and disease progression will include evaluation of all sites 
of disease involvement at baseline, which may include skin, lymph nodes, spleen, liver, 
peripheral blood, and bone marrow. Up to 6 of the largest dominant nodes or nodal masses 
should be identified as index lesions for radiographic response assessments. Response criteria for 
AML and BPDCN are summarized in Sections 16.1 and 16.2, respectively, and the mSWAT 
template is presented in Section 16.3.  
12.6.2 Response Rate 
For rates of response, including CR and ORR, as appropriate, two-sided 95% Clopper Exact 
confidence intervals around the response rate will be presented. For CR+CRc in first-line 
patients in Stage 3, statistical significance at the one-sided 0.025 will be declared if the lower 
bound of this confidence interval exceeds the lower clinical benchmark level of 10%. An 
analysis of the rate of bone-marrow CR (BMCR) will also be performed, by pooling data from 
patients who had either CR or PR with complete bone-marrow response (reduction to <5% blast 
cells), as a proportion of all patients with marrow disease (≥ 5% blast cells) at baseline.  
12.6.3 
Duration of Response 
DOR is defined as the time from when measurement criteria are first met for CR/CRi/CRc 
(whichever is recorded first) until the date that the criteria for relapse after CR/CRi/CRc is met. 


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For patients who receive bone marrow transplant after CR/CRi/CRc is observed, duration of 
response will include time to disease relapse post-transplant. Patients who are lost to follow-up 
or who do not relapse after CR/CRi/CRc as of the cut-off for analysis will be censored at the date 
of last radiologic assessment while on study. The same definition will be used for ORR, with the 
obvious modification that data from patients with either CR or PR will be included. 
Analysis of duration of response will be performed by Kaplan-Meier time to event analysis to 
estimate the 25th percentile, median, and 75th percentile of times to event, number, and 
percentage of events, censored observations, and appropriate confidence intervals. Additional 
descriptive analysis will be performed separately for patients who do and do not receive bone 
marrow transplant. 
12.6.4 Bridge to SCT 
The proportion of patients who become eligible and receive SCT will be analyzed, using the data 
from Stage 1-4. Patients may receive SCT subsequent to CR or PR; therefore, this analysis will 
be performed by response category as well as overall.  
12.6.5 Progression-free Survival 
Progression-free survival is defined as the time from the date of first infusion of SL-401 to the 
date of progressive disease (PD) or death from any cause, whichever occurred first. The 
distribution for progression free survival will be estimated by Kaplan-Meier methodology. 
12.6.6 Overall Survival 
OS is defined as the time from the date of first infusion of SL-401 to the date of death from any 
cause. The distribution for OS will be estimated by Kaplan-Meier methodology. 
12.6.7 Exploratory and Subgroup Analyses 
Exploratory and subgroup analyses may be performed to assess the influence of demographic 
and baseline characteristics on the rate of CR. In general, the exploratory and subgroup analyses 
will use the pooled data from first-line BPDCN patients from Stages 1, 2, 3, and 4. 
12.7 
Additional Efficacy Analyses 
Analysis of efficacy data from patients with R/R disease at study entry will be performed for all 
such patients, pooled Stage 1 and 2, using descriptive methods similar to those intended for the 
analysis of first-line BPDCN patients. Data from patients enrolled into Stage 4 will be presented 
separately; response data from the pool of Stages 3 and 4 may also be presented to augment the 
results from the pivotal Stage 3. A pooled, descriptive analysis of R/R patients across Stages 1, 2, 
and 4 will be performed. 
Additional efficacy analysis, including assessments of CR, DOR, and ORR, may be performed 
on patients treated with the lyophilized formulation of the SL-401 product. Analysis will be 
performed separately for R/R and first-line BPDCN patients. Efficacy for patients with AML 
will be analysed separately upon achievement of sufficient data. 


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Efficacy data from first-line BPDCN patients treated with an initial dose other than 12 µg/kg/day 
dose level will be summarized. 
12.8 
Pharmacokinetic and Immunogenicity Analyses 
Planned PK and immunogenicity analyses will be described in separate analysis plans. 
12.9 
Blinding 
This is an open-label study. 
12.10 Interim Analyses 
In Stages 2-4 of the study, the DSRC will conduct a safety data review on an every 1-2-month 
basis.  
An informal interim analysis was performed on efficacy data from Stages 1 and 2 
 
 (see Section 3.7.2). This analysis was 
performed on the 32 patients enrolled in the study through 29 August, 2016; note that no further 
enrollment of first-line BPDCN patients occurred until October, 2016. 
 
 
12.11 Final Analysis 
The final safety and efficacy analyses will be performed upon study completion. Study 
completion is the date in which every patient who is alive had at least 12 months of follow up 
data. 
12.12 Study Oversight Committees 
Study conduct will be monitored by the following oversight committees: a DSRC and an IRC. 
The roles of these committees are outlined briefly as follows, and will also be delineated in detail 
in designated committee charters.  
• The DSRC includes Sponsor representatives and study Investigators. The DSRC will 
review cumulative safety data and make decisions regarding DLT determination, dose 
escalation, and cohort progression during Stage 1. The DSRC may also make other 
recommendations pertinent to patient safety, both in Stage 1 and Stages 2-4, and will 
periodically review data during Stages 2-4 on an every 1-2-month basis. 
• Tumor response will be assessed by the Investigators for all patients with BPDCN, with 
the Investigator’s assessment to be used in the primary analysis. A central pathologist 
will confirm histopathological BPDCN diagnosis. As a supportive assessment, tumor 
response was also evaluated by an IRC on a pre-specified subset of patients in Stages 2-4. 
The IRC will be comprised of clinicians with expertise in hematologic and/or 
dermatologic malignancies who are not involved in the clinical study, and will review 


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data as reported by the Investigators for the assessment of response. It is anticipated that 
the IRC will meet several times per year. 
13 Emergency Procedures  
13.1 
Emergency Contact 
In emergencies, the Investigator should contact the Medical Monitor by telephone at the number 
listed on the title page of the protocol. 
13.2 
Emergency Identification of Investigational Products 
Since this is an open-label study, the investigational treatment and patient number will be 
identified on the package labeling. 
13.3 
Emergency Treatment 
During a patient’s participation in the study, the Investigator and/or institution should ensure that 
adequate medical care is provided to a patient for any AEs, including clinically significant 
laboratory values, related to the study. 
14 Ethical and Regulatory Considerations  
14.1 
Good Clinical Practice 
As the Sponsor of this clinical study, Stemline Therapeutics Inc. has the overall responsibility for 
the conduct of the study, including assurance that the study meets the requirements of applicable 
regulatory authorities. Stemline will maintain compliance with the FDA Code of Federal 
Regulations, ICH Guideline E6, Declaration of Helsinki, and Good Clinical Practice (GCP) 
Guidelines. The study must receive approval from an Institutional Review Board (IRB) or 
Independent Ethics Committee (IEC) prior to commencement. The Investigator will conduct all 
aspects of this study in accordance with applicable national, state, and local laws of the pertinent 
regulatory authorities. 
The Sponsor is responsible for ensuring IRB approvals are obtained, providing Investigators with 
information required to conduct the study, ensuring proper investigative site monitoring, 
verifying that appropriate patient informed consent is obtained, submitting an IND application to 
FDA, and ensuring that the IRB and regulatory agencies are promptly informed of significant 
new information regarding the study. 
14.2 
Delegation of Investigator Responsibilities 
The Investigator must ensure that all persons assisting with the study are adequately informed 
about the protocol, any amendments to the protocol, the study treatments, and their study-related 
duties and functions. The Investigator should maintain a list of sub-investigators and other 
appropriately qualified persons to whom he or she has delegated significant study-related duties. 


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14.3 
Patient Information and Informed Consent 
Before being admitted to the clinical study, the patient must consent to participate after the 
nature, scope, and possible consequences of the clinical study have been explained in a language 
understandable to him or her. An Informed Consent Form (ICF) that includes information about 
the study will be prepared and given to the patient. This document will contain all ICH, GCP, 
and locally required regulatory elements. The ICF must specify who informed the patient about 
the study and be approved by the Institution’s IRB. Copies of the ICF used in the study must 
contain the IRB-approval stamp (if applicable) and version date. The Investigator must keep the 
original executed ICF including the patients’ signatures and the signing dates properly stored in a 
secured location at the study site. 
After reading the informed consent document, the patient must give consent in writing. The 
written informed consent will be obtained prior to conducting any study-related procedures or 
tests. The patient’s consent must be confirmed at the time of consent by the dated signature of 
the person conducting the informed consent discussions. If the patient agrees to participate in the 
study, the patient and the Investigator must sign both copies of the ICF. An original copy of the 
signed consent document must be given to the patient or the patient’s legally authorized 
representative. The signed ICF must be available for verification by the Sponsor’s designated 
monitors or regulatory authorities. 
The date of the signed ICF will also be noted in the patient’s medical chart. Patients should be 
informed of new information learned during the study, which may affect their decision to 
continue participation in the study. The Investigator should inform the patient’s primary 
physician about the patient’s participation in the study if the patient has a primary physician and 
if the patient agrees to the primary physician being informed. 
14.4 
Confidentiality 
The Investigator(s) and the Sponsor or its authorized representative will preserve the 
confidentiality of all patients and donors participating in the study, in accordance with GCP, 
local regulations and to the extent applicable the Health Insurance Portability and Accountability 
Act of 1996 (“HIPAA”). 
Patient names will not be supplied to the Sponsor or its authorized representative. Only the 
patient study numbers and (if permitted by the institution) patient initials will be recorded in the 
eCRF, and if the patient name appears on any other document (e.g., pathologist report), it must 
be obliterated before a copy of the document is supplied to the Sponsor or its authorized 
representative. Study findings stored on a computer will be stored in accordance with local data 
protection laws. Patients will be told that representatives of the Sponsor, its authorized 
representative, IRB or IEC, or regulatory authorities may inspect their medical records to verify 
the information collected, and that all personal information made available for inspection will be 
handled in strictest confidence and in accordance with local data protection law. The Investigator 
will maintain a personal patient identification list (patient numbers with the corresponding 


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patient names) to enable records to be identified. 
14.5 
Protocol Amendments 
Any changes that affect patient safety or welfare will be submitted to the IRB/IEC and 
Regulatory Authority (where applicable) for approval prior to implementation. The Investigator 
and the Sponsor must approve all amendments. No amendment will be implemented until 
approved and signed by all parties. Exceptions to this are when the Investigator considers that the 
patient’s safety is compromised. 
Once the study has started, amendments should be made only in exceptional cases. The changes 
then become part of the study protocol. 
14.6 
IRB/IEC Approval and Reporting 
The Investigator must obtain appropriate IRB/IEC approval prior to study initiation. A copy of 
the written approval from the IRB and a copy of the approved ICF should be sent to the Sponsor 
or its delegate. It is also necessary to submit a list of the IRB members (including their Institution 
affiliations, gender makeup, and occupations) or supply a statement from the IRB specifying that 
the membership complies with applicable regulations. 
The study protocol, ICF, the IB, available safety information, patient recruitment procedures 
(e.g., advertisements), information about payments and compensation available to the patients 
and documentation evidencing the Investigator’s qualifications should be submitted to the 
IRB/IEC for ethical review and approval according to local regulations, prior to the study start. 
The written approval should identify all documents reviewed by name and version. 
Any changes to the protocol must be approved by the Sponsor in writing unless the change is 
proposed to assure safety of the patient. In the non-emergent setting, following agreement on the 
proposed changes, an amendment to the protocol will be submitted by the Sponsor to the IRB for 
approval prior to implementation of the change. Any change made emergently must be 
documented in the patient's medical record. 
If required by legislation or the IRB/IEC, the Investigator must submit to the IRB/IEC: 
• Information on serious or unexpected AEs as soon as possible; 
• Periodic reports on the progress of the study. 
14.7 
Closure of the Study 
The Sponsor, its authorized representative, or the Investigator has the right to close this study at 
any time. The IRB/IEC must be informed, if required by legislation. Should the study be closed 
prematurely, all unused SL-401 will be reconciled with dispensing records, documented, and, if 
directed by the Sponsor, destroyed at the study site after completion of accountability by the site 
monitor. 


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14.8 
Record Retention 
The Sponsor will maintain copies of correspondences, records of shipment and disposition of 
study drug, adverse effects, and other records related to the clinical study and the signed 
Investigator agreements. Patient records must be retained even if the patient has died. 
Study documents must be retained by the Investigator for a minimum of 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the investigational product. These documents 
should be retained for a longer period, however, if required by the applicable regulatory 
requirements or by an agreement with the Sponsor. It is the responsibility of the Sponsor to 
inform the Investigator when storage of these documents is no longer required. The Investigator 
should contact the Sponsor if the site’s archiving arrangements change at any time. 
14.9 
Liability and Insurance 
Liability and insurance provisions for this study are provided in the Investigator’s contract with 
Stemline. 
14.10 Financial Disclosure 
Prior to study initiation the Investigator will be asked to sign a clinical trial agreement. All 
Investigators will be required to sign a Financial Disclosure Form in accordance with 21 CFR 
Part 54; Financial Disclosure by Clinical Investigators. 
14.11 Study Monitoring and Auditing 
All aspects of the study will be carefully monitored by the Sponsor or its designee for 
compliance to applicable government regulations with respect to current good clinical practice 
and current standard operating procedures. Monitoring functions will be performed in 
compliance with 21CFR§812.43(d) and 21CFR§812.46. Direct access to the on-site study 
documentation and medical records must be ensured by the Investigator. 
14.11.1 Study Monitoring and Source Data Verification 
The Investigator is responsible for the validity of all data collected at the site and must accept the 
various monitoring procedures employed by the Sponsor. The purpose of monitoring is to verify 
the rights and well-being of human patients are protected; that study data are accurate, complete, 
and verifiable with source data; that the study is conducted in compliance with the protocol, GCP 
and the applicable regulatory requirements. 
Sites will be monitored to identify and reconcile any differences between the completed eCRFs 
and medical records, and review source documents for accuracy, completeness, and legibility. 
The monitor will review completed data forms and study documentation for accuracy, 
completeness, and protocol compliance. In addition, the Sponsor will evaluate any protocol 
deviations and take corrective action as necessary. 


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The Sponsor will review significant new information, including unanticipated AEs and ensure 
that such information is provided to all reviewing IRBs. This information will also be provided 
to the FDA, other regulatory authorities, and Investigators worldwide in accordance with local 
regulations. The monitor’s responsibilities include site visits, review of eCRFs, source 
documents and results, and ensuring clear communication between Investigators and the 
Sponsor. 
The monitor will query any missing or spurious data with the Investigator, which should be 
resolved in a timely manner. A monitoring log will be maintained recording each visit, the 
reason for the visit, the monitor’s signature, and Investigator’s or designee’s confirmation 
signature. 
14.11.2 Study Documentation 
The Investigator must provide the Sponsor with the following documents prior to enrollment and 
maintain the accuracy of these documents throughout the course of the study. 
• Completed and signed Form 1572. 
• All applicable country-specific regulatory forms. 
• Current signed and dated curricula vitae for the Investigator, sub-investigators, and other 
individuals having significant Investigator responsibility who are listed on the Form 1572 
or equivalent, or the clinical study information form. 
• Copy of the current medical license of the principal Investigator, any sub-investigators 
and any other individuals having significant responsibility as listed in the Form 1572. 
• A financial disclosure form for the Principal Investigator and any other persons listed in 
the Form 1572. 
• Copy of the IRB/IEC approval letter for the protocol and informed consent. All 
advertising, recruitment, and other written information provided to the patient must be 
approved by the IRB/IEC. Written assurance of continuing approval (at least annually) as 
well as a copy of the annual progress report submitted to the IRB/IEC must also be 
provided to the Sponsor. 
• Copy of the IRB/IEC-approved informed consent document. 
• A list of the IRB/IEC members or a FWA/DHHS number. 
• Copy of the protocol sign-off page signed by the Investigator. 
• Fully executed Clinical Trial Agreement including budget. 
• A written document containing the name, location, certification number, and date of 
certification of each laboratory to be used for laboratory assays and those of other 
facilities conducting tests. This document should be returned along with the laboratory 
director’s curricula vitae and active medical license. A list of normal laboratory values 


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and units of measure for all laboratory tests required by the protocol is to be provided. 
The sites will also be asked to maintain a Delegation of Authority Log, pharmacy logs, 
temperature logs, patient identification log and monitoring visit logs during this study. 
14.11.3 Site Audits 
For the purpose of compliance with Good Clinical Practices (GCP) and regulatory agency 
guidelines, it may be necessary for Sponsor authorized Quality Assurance personnel and/or 
authorized personnel from a regulatory agency to conduct an audit/inspection of an 
Investigational site. These site reviews may be planned or spontaneous and occur at any stage 
during the study. The purpose of an audit is to assess the quality of data with regard to accuracy, 
adequacy, and consistency, and to assure that studies are in accordance with GCP, protocol, and 
regulatory agency guidelines. 
The Investigator should promptly notify the Sponsor or its authorized representative of any 
audits by any regulatory authorities and promptly forward copies of any audit reports received to 
the Sponsor or its authorized representative. 
Electronic data systems will be in accordance with applicable aspects of 21 CFR Part 11, ICH 
Guidelines, GCP, and HIPAA. 
14.12 Documentation and Use of Study Findings 
14.12.1 Documentation of Study Findings 
Source documentation will be maintained to document the treatment and study course of a 
patient and to substantiate the integrity of the study data submitted for review to regulatory 
agencies. Source documentation for Stemline studies will include, but not be limited to, 
worksheets, hospital and/or clinic or office records documenting patient visits including study 
and other treatments or procedures, medical history and physical examination information, 
laboratory and special assessments results, drug accountability records, and medical 
consultations (as applicable). 
Laboratory and diagnostic reports including but not limited to: local laboratory hematology and 
chemistry results, bone marrow biopsy reports, bone marrow aspirate reports, photographs (de-
identified), ECHO readings, and MUGA readings may be collected by the study monitor during 
the course of the study. Every effort should be made by the site to de-identify personal patient 
information from these reports and replace the information with the patient’s study identification 
number.  
14.12.2 Use of Study Findings 
All information concerning the product, as well as any matter concerning the operations of the 
Sponsor, such as clinical indications for the drug, its formula, methods of manufacture, and other 
scientific data relating to it, that have been provided by the Sponsor and are unpublished, are 
confidential and must remain the sole property of the Sponsor. The Investigator will agree to use 
the information only for the purposes of carrying out this study and for no other purpose unless 


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prior written permission from the Sponsor is obtained. The Sponsor has full ownership of the 
eCRFs completed as part of the study. 
All publications and presentations of the results of the Study are governed by the applicable 
provisions of the Clinical Trial Agreement between the Sponsor and the institution. By signing 
the study protocol, the Investigator agrees that the results of the study may be used for the 
purposes of national and international registration, publication, and information for medical and 
pharmaceutical professionals by the Sponsor. If necessary, the authorities will be notified of the 
Investigator’s name, address, qualifications, and extent of involvement in the study. The 
Investigator may not publish or present any information on this study without the express written 
approval of the Sponsor. Additionally, the Sponsor may, for any reason, withhold approval for 
publication or presentation. If the Investigator is to be an author of a publication manuscript 
prepared by the Sponsor, the Sponsor will allow the Investigator 30 days for full review of the 
manuscript before publication. Such manuscript or materials should be provided for Sponsor 
review only after the final database is available. 
 


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16 Appendices 
16.1 
Appendix A. Tumor Response Criteria for Patients with AML 
Response 
Location 
Criteria 
Complete 
Remission (CR) 
Marrow 
• 
Normalization of blast percentage (≤5%) 
• 
No detectable Auer rods 
Peripheral Blood 
• 
Normalization neutrophil count (≥1,000/µL) and platelet count 
(≥100,000/µL) 
• 
Absence of leukemic blasts 
Extramedullary 
• 
No extramedullary disease (CNS or soft tissue) 
CR with 
incomplete blood 
count recovery 
(CRi) 
Marrow 
• 
Normalization of blast percentage (≤5%) 
Peripheral Blood 
• 
Incomplete recovery of neutrophil and/or platelet count 
• 
Absence of leukemic blasts 
Extramedullary 
• 
No extramedullary disease (CNS or soft tissue) 
Partial Remission 
(PR) 
Marrow 
• 
Decrease by ≥50% in blast percentage to 5 - 25% or to ≤5% with 
Auer rods present 
Peripheral Blood 
• 
Normalization neutrophil count (≥1,000/µL) and platelet count 
(≥100,000/µL) 
Stable Disease 
(SD) 
 
• 
Failure to achieve at least a PR, but no evidence of progression for 
at least 8 weeks 
Relapse after 
CR/CRi 
Marrow 
• 
Blast percentage >5% (if no peripheral blasts, then confirmation 
aspirate required ≥1 week later) 
Relapse after PR 
Marrow 
• 
Blast percentage ≥25% (if no peripheral blasts, then confirmation 
aspirate required ≥1 week later) 
Progressive 
Disease (PD) 
Marrow 
• 
≥50% increase in blasts from baseline 
Peripheral Blood 
One or more of the following: 
• 
≥50% decrease from peak remission levels in platelets or 
granulocytes; 
• 
Reduction in hemoglobin concentration by at least 2 g/dL; 
• 
Transfusion dependence 
Source: Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the international working group for diagnosis, 
standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. 
J Clin Oncol 2003;21:4642-4649. 


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16.2 
Appendix B. Tumor Response Criteria for Patients with BPDCN 
Response 
Location 
Criteria 
Complete 
Response (CR) 
Marrowb 
• 
Normalization of blast percentage (≤5%) b 
Peripheral Blood 
• 
Normalization of neutrophil count (≥1,000/µL) and platelet count 
(≥100,000/µL) 
• 
Absence of leukemic blasts 
Skina 
• 
100% clearance of all skin lesions from baseline; no new lesions 
in patients without lesions at baselinea 
Nodal Masses 
• 
Regression to normal size on CT 
Spleen, Liver 
• 
Not palpable, nodules disappeared 
CR with 
incomplete blood 
count recovery 
(CRi) 
Marrowb 
• 
Normalization of blast percentage (≤5%) b 
Peripheral Blood 
• 
Incomplete recovery of neutrophil and/or platelet count 
• 
Absence of leukemic blasts 
Skina 
• 
100% clearance of all skin lesions from baseline; no new lesions 
in patients without lesions at baselinea  
Nodal Masses 
• 
Regression to normal size on CT 
Spleen, Liver 
• 
Not palpable, nodules disappeared 
CR [clinical] with 
minimal residual 
skin abnormality 
(CRc) 
Marrowb 
• 
Normalization of blast percentage (≤5%) b 
Peripheral Blood 
• 
Normalization of neutrophil count (≥1,000/µL) and platelet count 
(≥100,000/µL) 
• 
Absence of leukemic blasts 
Skina 
• 
Marked clearance of all skin lesions from baseline; residual 
hyperpigmentation or abnormality with BPDCN identified on 
biopsy (or no biopsy performed) a 
Nodal Masses 
• 
Regression to normal size on CT 
Spleen, Liver 
• 
Not palpable, nodules disappeared 
Partial Response 
(PR) 
Marrowb 
• 
Decrease by ≥50% in blast percentage to 5 − 25% b 
Peripheral Blood 
• 
Normalization of neutrophil count (≥1,000/µL) and platelet count 
(≥100,000/µL) 
Skina 
• 
50% − <100% clearance of all skin lesions from baseline; no new 
lesions in patients without lesions at baselinea 
Nodal Masses 
• 
≥50% decrease in SPD of up to 6 largest dominant masses; no 
increase in size of other nodes 
Spleen, Liver 
• 
≥50% decrease in SPD of nodules (for single nodule in greatest 
transverse diameter); no increase in size of liver or spleen 
Stable Disease 
(SD) 
 
• 
Failure to achieve at least a PR, but no evidence of progression for 
at least 8 weeks 
Relapse after 
CR/CRi/CRc 
Marrowb 
• 
Blast percentage >5% (if no peripheral blasts, then confirmation 
aspirate required ≥1 week later) b 
Peripheral Blood 
• 
Presence of leukemic blasts 
Skina 
• 
Increase in skin score greater than the sum of nadir plus 50% 
baseline scorea 
Nodal Masses 
• 
Appearance of a new lesion(s) >1.5 cm in any axis, ≥50% increase 
from nadir in SPD of more than one node, or ≥50% increase from 
nadir in longest diameter of a previously identified node >1 cm in 
short axis 
Spleen, Liver 
• 
>50% increase from nadir in the SPD of any previous lesions 


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Relapse after PRc 
Marrowb 
• 
Blast percentage ≥25% (if no peripheral blasts, then confirmation 
aspirate required ≥1 week later) b 
Skina 
• 
Increase in skin score greater than the sum of nadir plus 50% 
baseline scorea 
Nodal Masses 
• 
Appearance of a new lesion(s) >1.5 cm in any axis, ≥50% increase 
from nadir in SPD of more than one node, or ≥50% increase from 
nadir in longest diameter of a previously identified node >1 cm in 
short axis 
Spleen, Liver 
• 
>50% increase from nadir in the SPD of any previous lesions 
Progressive 
Disease (PD) c 
Marrowb 
• 
≥50% increase in blasts from baseline (and blast percentage >5%)b 
Peripheral Blood 
One or more of the following: 
• 
≥50% decrease from peak remission levels in platelets or 
granulocytes; 
• 
Reduction in hemoglobin concentration by at least 2 g/dL; 
• 
Transfusion dependence 
Skina 
One or more of the following: 
• 
≥25% increase in skin disease from baselinea 
• 
Any new tumors in patients without tumors at baseline 
Nodal Masses 
• 
Appearance of a new lesion(s) >1.5 cm in any axis, ≥50% increase 
from nadir in SPD of more than one node, or ≥50% increase from 
nadir in longest diameter of a previously identified node >1 cm in 
short axis 
Spleen, Liver 
• 
>50% increase from nadir in the SPD of any previous lesions 
Source: Cheson BD, Pfistner B, Juweid ME, et al. The International Harmonization Project on Lymphoma. 
Revised response criteria for malignant lymphoma. J Clin Oncol 2007;25:579-586. 
Abbreviations: CT, computed tomography; SPD, sum of the product of the diameters. 
All parameters detailed above (including bone marrow, blood, skin [including mSWAT quantification], lymph 
nodes and viscera) are to be assessed both at baseline and stipulated subsequent timepoints. Responses are 
determined via comparison to baseline values (or post-treatment nadir values as stipulated in the above table).  
a The percentage of clearance or increase in skin disease is calculated using the Modified Severity Weighted 
Assessment Tool (mSWAT), which is provided in Section 16.3/Appendix C. Detailed guidance and examples 
regarding the calculation of an mSWAT assessment based on the size and nature of a patient’s skin lesions are 
provided in a separate document.  
b In settings in which there is a change in the blast population on bone marrow evaluation by means of flow 
cytometry or other molecular methodology without a similar degree of change in the morphologic blast 
percentage, the morphologic percentage should be utilized to determine response/progression; however the 
findings from flow cytometry (or other molecular methodology) should be recorded as part of the study record.  
c In settings in which there is preliminary but not conclusive evidence of disease progression (i.e., new skin 
lesions of indeterminate etiology, new lymph nodes ≤1.5cm, modest increase in bone marrow blast percentage 
subsequent to an initial marked reduction, appearance of new blast population on bone marrow evaluation by 
means of flow cytometry or other molecular methodology without increase in blast percentage consistent with 
PD), additional SL-401 cycles may be administered, provided that the Investigator documents that the evidence 
of potential disease progression is inconclusive and that the overall risk/benefit assessment favors additional 
investigational therapy. Additional SL-401 may also be administered in situations of mixed response BPDCN in 
which response/progression is not consistent between a given patient’s disease sites, provided that the 
Investigator documents that the overall risk/benefit assessment favors additional investigational therapy. In such 
situations, it is essential that relevant findings and assessments are documented, and that areas of potential disease 
progression are followed closely on subsequent assessments. 
 


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16.3 
Appendix C. Modified Severity Weighted Assessment Tool 
Body Region 
%BSA in Body 
Region 
Assessment of Involvement in Patient’s Skin 
Patcha 
Plaqueb 
Tumorc 
Head 
7 
 
 
 
Neck 
2 
 
 
 
Anterior trunk 
13 
 
 
 
Arms 
8 
 
 
 
Forearms 
6 
 
 
 
Hands 
5 
 
 
 
Posterior trunk 
13 
 
 
 
Buttocks 
5 
 
 
 
Thighs 
19 
 
 
 
Legs 
14 
 
 
 
Feet 
7 
 
 
 
Groin 
1 
 
 
 
Subtotal of weighted BSA 
 
 
 
Weighting factor 
× 1 
× 2 
× 4 
Weighted subtotal 
 
 
 
Note: mSWAT score equals summation of weighted subtotals.  
Abbreviations: BSA, body surface area; mSWAT, modified Severity Weighted Assessment Tool. Detailed 
guidance and examples regarding the calculation of an mSWAT assessment based on the size and nature of a 
patient’s skin lesions are provided in a separate document. 
aAny size lesion without induration or significant elevation above the surrounding uninvolved skin; poikiloderma 
may be present. 
bAny size lesion that is elevated or indurated; crusting, ulceration, or poikiloderma may be present. 
cAny solid or nodular lesion ≥1 cm in diameter with evidence of deep infiltration in the skin and/or vertical 
growth. 
 
 


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16.4 
Appendix D. ECOG Performance Status 
Grade 
Description 
0 
ABLE TO CARRY OUT ALL NORMAL ACTIVITIES WITHOUT RESTRICTION. 
1 
RESTRICTED IN PHYSICALLY STRENUOUS ACTIVITY BUT AMBULATORY AND ABLE 
TO CARRY OUT WORK OF A LIGHT OR SEDENTARY NATURE. 
2 
AMBULATORY AND CAPABLE OF ALL SELF-CARE BUT UNABLE TO CARRY OUT ANY 
WORK ACTIVITIES: UP AND ABOUT MORE THAN 50% OF WAKING HOURS. 
3 
CAPABLE OF LIMITED SELF-CARE; CONFINED TO BED OR CHAIR MORE THAN 50% OF 
WAKING HOURS. 
4 
COMPLETELY DISABLED; CANNOT CARRY ON SELF-CARE; TOTALLY CONFINED TO 
BED OR CHAIR. 


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16.5 
Appendix E. CLS Management Guidance 
Time of Presentation 
CLS 
Sign/Symptom 
Recommended 
Action 
ELZONRIS Dosing 
Management 
Prior to first dose of 
ELZONRIS in cycle 1  
Serum albumin < 3.2 g/dL  
Administer ELZONRIS when serum albumin ≥ 3.2 g/dL. 
During ELZONRIS dosing 
Serum albumin < 3.5 g/dL  
Administer 25g intravenous albumin (q12h or more 
frequently as practical) until serum albumin is ≥ 3.5 g/dL 
AND not more than 0.5 g/dL lower than the value measured 
prior to dosing initiation of the current cycle. 
Interrupt ELZONRIS 
dosing until the 
relevant CLS 
sign/symptom has 
resolved1. 
Serum albumin reduced by ≥ 0.5 g/dL 
from the albumin value measured prior 
to ELZONRIS dosing initiation of the 
current cycle 
 
A predose body weight that is 
increased by ≥ 1.5 kg over the previous 
day’s predose weight 
Administer 25g intravenous albumin (q12h or more 
frequently as practical), and manage fluid status as 
indicated clinically (e.g., generally with intravenous fluids 
and vasopressors if hypotensive and with diuretics if 
normotensive or hypertensive), until body weight increase 
has resolved (i.e. the increase is no longer ≥ 1.5 kg greater 
than the previous day’s predose weight). 
 
Edema, fluid overload and/or 
hypotension 
Administer 25g intravenous albumin (q12h, or more 
frequently as practical) until serum albumin is ≥ 3.5 g/dL. 
 
Administer 1 mg/kg of methylprednisolone (or an 
equivalent) per day, until resolution of CLS sign/symptom 
or as indicated clinically. 
 
Aggressive management of fluid status and hypotension if 
present, which could include intravenous fluids and/or 
diuretics or other blood pressure management, until 
resolution of CLS sign/symptom or as clinically indicated.   
 
1  ELZONRIS administration may resume in the same cycle if all CLS signs/symptoms have resolved and the patient did not require measures to treat hemodynamic instability. 
ELZONRIS administration should be held for the remainder of the cycle if CLS signs/symptoms have not resolved or the patient required measures to treat hemodynamic 
instability (e.g. required administration of intravenous fluids and/or vasopressors to treat hypotension) (even if resolved), and ELZONRIS administration may only resume in the 
next cycle if all CLS signs/symptoms have resolved, and the patient is hemodynamically stable. 

SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN  
SL-401 in Patients with Acute Myeloid Leukemia or  Blastic Plasmacytoid 
Dendritic Cell Neoplasm Protocol STML-401-0114  
Protocol Number:  
Protocol Version and Date: 
STML-401-0114  
Amendment 12: 17 January 2019 
Amendment 11: 12 June 2018 
Amendment 10: 27 March 2018 
Amendment 9:  08 February 2017 
Amendment 8: 08 February 2016  
Amendment 7: 11 August 2015  
Amendment 6: 01 December 2014  
Amendment 5: 28 July 2014  
Amendment 4: 06 June 2014  
Amendment 3: 21January 2014  
Amendment 2: 12 November 2013 
Amendment 1: 21 October 2013  
Original:  
26 September 2013 
Name of Test Drug: 
SL-401(ELZONRIS® [Tagraxofusp-erzs]) 
Phase:  
Phase 1/2 
Methodology:  
A 4-part, non-randomized, open-label, dose escalation and 
expansion, multicenter study  
Sponsor: 
Stemline Therapeutics, Inc. 
750 Lexington Avenue 
New York, NY 10022 Tel: 
(646) 502-2310
Fax: (646) 389-0968
Sponsor Representative: 
 
  
Analysis Plan Date:  
19 April 2021  
Analysis Plan Version: 
Final Version 3.0 
Confidentiality Statement 
The information contained herein is confidential and the proprietary property  of Stemline 
Therapeutics, Inc. and any unauthorized use or disclosure  of such information without the prior 
written authorization of  Stemline Therapeutics, Inc. is expressly prohibited. 
NCT #: NCT02113982


Stemline Therapeutics, Inc. 
Statistical Analysis Plan, Protocol STML-401-0114 
19 April 2021, Final Version 3.0 
2 
APPROVAL SIGNATURE PAGE 
Protocol Title: 
SL-401 in Patients with Acute Myeloid Leukemia or Blastic 
Plasmacytoid Dendritic Cell Neoplasm 
Sponsor: 
Stemline Therapeutics, Inc. 
750 Lexington Avenue 
New York, NY 10022 
Protocol Number: 
STML-401-0114 
Document Date / Version: 
19 April 2021 / Final Version 3.0 
Veristat, LLC Author: 
 
Approval Signature 
Job Title 
 
Sponsor Approval 
By signing this document, I acknowledge that I have read the document and approve of the 
planned statistical analyses described herein. I agree that the planned statistical analyses are 
appropriate for this study, are in accordance with the study objectives, and are consistent with 
the statistical methodology described in the protocol, clinical development plan, and all 
applicable regulatory guidances and guidelines. 
I have discussed any questions I have regarding the contents of this document with the 
biostatistical author. 
I also understand that any subsequent changes to the planned statistical analyses, as described 
herein, may have a regulatory impact and/or result in timeline adjustments. All changes to the 
planned analyses will be described in the clinical study report. 
Sponsor Signatory: 
 
Approval Signature 
Job Title 
 
 


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TABLE OF CONTENTS  
1.  Information From the Study Protocol ....................................................................................... 9 
1.1.  Introduction and Objectives ....................................................................................... 9 
1.1.1.  Definitions ................................................................................................. 10 
1.1.2.  Study Objectives ....................................................................................... 11 
1.1.3.  Study Objectives and Definitions Updates ............................................... 12 
1.1.4.  Purpose of this Document ......................................................................... 13 
1.2.  Study Design ............................................................................................................ 13 
1.2.1.  Synopsis of Study Design ......................................................................... 13 
1.2.2.  Randomization Methodology .................................................................... 13 
1.2.3.  Stopping Rules and Unblinding ................................................................ 13 
1.2.4.  Study Procedures....................................................................................... 14 
1.2.5.  Efficacy, Pharmacokinetic, and Safety Parameters .................................. 14 
1.2.5.1. Efficacy Parameters ............................................................................................ 14 
1.2.5.2. Safety Parameters ................................................................................................ 15 
1.2.5.3. Pharmacokinetic and Immunogenicity Parameters ............................................. 15 
2.  Patient Population ................................................................................................................... 17 
2.1.  Population Definitions.............................................................................................. 17 
2.2.  Protocol Violations ................................................................................................... 17 
3.  General Statistical Methods .................................................................................................... 17 
3.1.  Sample Size Justification ......................................................................................... 17 
3.2.  General Methods ...................................................................................................... 18 
3.3.  Computing Environment .......................................................................................... 18 
3.4.  Baseline Definitions ................................................................................................. 19 
3.5.  Methods of Pooling Data.......................................................................................... 19 
3.5.1.  Pooling of Stages 3 and 4 .......................................................................... 19 
3.6. Adjustments for Covariates ....................................................................................... 20 
3.7. Assessment of Clinical Benefit ................................................................................. 20 
3.8.  Efficacy Endpoint Analysis ...................................................................................... 22 
3.8.1.  Primary Endpoint ...................................................................................... 22 
3.8.2.  Secondary Endpoints................................................................................. 22 
3.8.3.  Exploratory Endpoints .............................................................................. 22 
3.9.  Subgroup Analyses ................................................................................................... 22 
3.10.  Withdrawals, Dropouts, Loss to Follow-up ........................................................... 23 
3.11.  Missing, Unused, and Spurious Data ..................................................................... 23 
3.12.  Visit Windows ........................................................................................................ 23 
3.13.  Timing of Analyses ................................................................................................ 23 
3.13.1.  Interim Analyses ..................................................................................... 23 
3.13.2.  Independent Review Committee ............................................................. 24 
3.13.3.  Primary Efficacy, Safety, and Immunogenicity Analysis ....................... 24 


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3.13.4.  Updated Reporting and Stage 4 Analysis ............................................... 24 
4.  Study Analyses ........................................................................................................................ 25 
4.1.  Patient Disposition ................................................................................................... 25 
4.2.  Demographics and Baseline Characteristics ............................................................ 25 
4.3.  Efficacy Evaluation .................................................................................................. 25 
4.3.1.  Response Rate ........................................................................................... 25 
4.3.2.  Duration of Response ................................................................................ 26 
4.3.3.  Bridge to Stem Cell Transplant ................................................................. 26 
4.3.4.  Progression-Free Survival ......................................................................... 27 
4.3.5.  Overall Survival ........................................................................................ 27 
4.3.6.  Exploratory Endpoints .............................................................................. 27 
4.3.6.1. Time to Event Endpoints ..................................................................................... 27 
4.3.6.2. Protocol-Specified Rate of Complete Response ................................................. 28 
4.3.6.3. Additional Analyses ............................................................................................ 28 
4.4.  Safety Analyses ........................................................................................................ 28 
4.4.1.  Study Drug Exposure ................................................................................ 28 
4.4.2.  Adverse Events ......................................................................................... 29 
4.4.2.1. Capillary Leak Syndrome ................................................................................... 30 
4.4.3.  Laboratory Data ........................................................................................ 30 
4.4.4. Vital Signs and Physical Examination ....................................................... 32 
4.4.5. Electrocardiogram ...................................................................................... 32 
4.4.6. Concomitant Medications and Subsequent Treatments ............................. 33 
4.4.7.  Pre-Treatment Medications ....................................................................... 33 
4.5.  Summary of Immunogenicity Parameters ................................................................ 33 
5.  Changes to Planned Analyses ................................................................................................. 34 
5.1.  SAP Version 1.0 (28 April 2017) ............................................................................. 34 
5.2.  Changes from SAP Version 1.0 (28 April 2017) to Version 2.0 ............................. 34 
5.3.  Changes from the SAP Version 2.0 (17 November 2017) to Version  .................... 35 
3.0..................................................................................................................................... 35 
6.  References ............................................................................................................................... 35 
7.  Study Flow Charts ................................................................................................................... 39 
8.  Response Criteria .................................................................................................................... 52 
8.1.  Tumor Response Criteria for Patients with AML .................................................... 52 
8.2.  Tumor Response Criteria for Patients with BPDCN ................................................ 52 
8.3.  Capillary Leak Syndrome FDA Algorithm .............................................................. 55 
 
 
 


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TABLES AND FIGURES INCLUDED IN THE TEXT  
Table 3-1:  
Planned Pooling of Data for Efficacy Analysis at 12 µg/kg/day ..................................... 19
Table 3-2:  
Subgroups and Definitions for Safety Analyses .............................................................. 23
Table 7-1:  
Study Events Schedule for Cycle 1 (Study Day -14 to Study Day 21): Stage 1  
(All Pts) & Stage 2 (AML Pts: Arm A) ........................................................................... 42
Table 7-2:  
Study Events Schedule for Cycles 2-6 and Subsequent Cycles: Stage 1 (All  
Pts) & Stage 2 (AML Pts: Arm A) .................................................................................. 45 
Table 7-3:  
Study Events Schedule for Cycles 1 & 2 (Study Day -14 to Study Day 21):  
BPDCN (Arm B) Patients in Stage 2 .............................................................................. 48 
Table 7-4:  
 
Study Events Schedule for Cycles 3-6 and Subsequent Cycles: Stage 2  
(BPDCN Patients) ........................................................................................................... 51 
Figure 4-1:  
Hy’s Law Candidates Scatterplot .................................................................................... 32 
  
 


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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS  
Abbreviation  
Definition  
AE  
Adverse event  
Allo-SCT  
Allogeneic Hematopoietic Stem Cell Transplantation  
ALT  
Alanine aminotransferase  
AML  
Acute myeloid leukemia  
AST  
Aspartate aminotransferase  
ATC  
Anatomic therapeutic class  
AUC  
Area under the curve  
BLA  
Biological licensing application  
BM  
Bone marrow  
BMCR  
Bone marrow complete response  
BPDCN  
Blastic plasmacytoid dendritic cell neoplasm  
Cmax  
Maximum plasma concentration  
CI  
Confidence interval  
CR  
Complete response  
CRc  
Complete response [Clinical] with minimal residual skin 
abnormality  
CRF  
Case report form  
CRi  
Complete response [Incomplete blood count recovery]  
CSR  
Clinical study report  
CTCAE  
Common Terminology Criteria for Adverse Events  
DLT  
Dose-limiting toxicity  
DOR  
Duration of response  
DT  
Diphtheria toxin  
EBMTG  
The European Blood and Marrow Transplantation Group 
ECOG  
Eastern Cooperative Oncology Group  
ECG  
Electrocardiogram  
eCRF  
Electronic case report form  
FDA  
Food and Drug Administration  
ICH  
International Conference on Harmonisation  
IL-3  
Interleukin-3  
IL-3R  
Interleukin-3 receptor  
IRC  
Independent Review Committee  
IWG  
International Working Group  
hIL-3  
Human interleukin-3  
MedDRA  
Medical Dictionary for Regulatory Activities  


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Abbreviation  
Definition  
mITT  
Modified Intent-to-Treat  
mSWAT  
Modified Severity Weighted Assessment tool 
MTD  
Maximum tolerated dose  
N  
Number  
ORR  
Objective response rate  
OS  
Overall survival  
PCS  
Potentially clinically significant  
PD  
Progressive disease  
PFS  
Progression-free survival  
PK  
Pharmacokinetic  
PR  
Partial response  
R/R  
Relapsed/refractory  
Rel Day  
Relative study day  
RFS  
Relapse-free survival  
SAE  
Serious adverse event  
SAP  
Statistical analysis plan  
SCT  
Stem cell transplant  
SD  
Standard deviation  
SI  
International System of Units  
SOC  
System organ class  
TEAE  
Treatment-emergent adverse event  
TTCR  
Time to complete response (CR + CRc)  
TTP  
Time to progression  
TTR  
Time to response (CR + CRi + CRc + PR)  
ULN  
Upper limit of normal  
US  
United States  
VOD  
Veno-occlusive disease  
WHO  
World Health Organization  
 
  


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1.  
INFORMATION FROM THE STUDY PROTOCOL  
1.1.  
Introduction and Objectives  
The overall purpose of study STML-401-0114 is to support the development of SL-401 
(ELZONRIS® [Tagraxofusp-erzs]; “tagraxofusp”) and assess safety and clinical efficacy of the 
product in treatment of patients with first-line blastic plasmacytoid dendritic cell neoplasm 
(BPDCN), relapsed/refractory (R/R) BPDCN, R/R acute myeloid leukemia (AML), and firstline 
high risk AML. The primary focus of this document is the assessment of efficacy and safety of 
tagraxofusp in first-line BPDCN patients with supporting evidence from the remaining 
populations. Additional analyses will be performed on the R/R BPDCN, R/R AML, and firstline 
high risk AML patients.  
AML is characterized by the uncontrolled proliferation of immature myeloid cells in the bone 
marrow (BM) and peripheral blood, resulting in the development of anemia, neutropenia, and 
thrombocytopenia, and associated complications such as serious infections. The median age at 
diagnosis is 67 years, and 5-year survival across all ages, treatments, and other prognostic 
groups is 24% (National Cancer Institute 2013).   
BPDCN is an uncommon hematological malignancy that is characterized by the clonal 
proliferation of malignant plasmacytoid dendritic cells (Facchetti, et al. 2003). While the disease 
expression of BPDCN is similar to AML, BPDCN was characterized as a distinct cancer type as 
early as 1994 (Adachi, et al. 1994) though little was known of the disease biomarkers until the 
mid-2000s.  
BPDCN most commonly affects middle-aged and older patients and is approximately 3.5-fold 
more common in men than women. The median age at diagnosis is 66 years and is lower for 
women than men. The true incidence and prevalence of BPDCN is not precisely known. 
However, based on a published report (Wang, et al. 2012), BPDCN constitutes approximately 
0.44% of the incident cases of hematologic cancers annually, or approximately 700 and 1,000 
incident cases annually in the United States (US) and Europe, respectively, based on published 
data of hematologic cancer cases.  
The clinical features and evolution of BPDCN consist primarily of 2 patterns (Assaf, et al. 2007; 
Brody, et al. 1995; Herling and Jones 2007; Petrella, et al. 2005; Petrella, et al. 1999; Reichard, 
et al. 2005; Suzuki, et al. 2005). The first pattern (90% of cases) is characterized by an indolent 
onset dominated by cutaneous lesions followed by tumor dissemination. The second pattern 
shows features of an acute leukemia with systemic involvement from the outset, and multiple 
skin nodules are frequently present (Suzuki, et al. 2005). BPDCN most typically presents with 
skin lesions as well as extracutaneous malignant disease in the BM, blood, lymph nodes, spleen, 
and other organs. Despite the frequent appearance of a somewhat indolent clinical presentation 
at the outset, the course of BPDCN is highly aggressive and the median survival is 
approximately 12-14 months (Bekkenk, et al. 2004; Feuillard, et al. 2002; Herling and Jones 
2007; Jacob, et al. 2003; Petrella, et al. 2005). The disease almost always results in a terminal 
leukemic phase with proliferation of BPDCN blasts in the BM and peripheral blood, leading to 
decreased blood cell counts with resultant infections, bleeding, and invariably death.  
Diphtheria toxin (DT) Interleukin-3 (IL-3) fusion protein (tagraxofusp) is a novel biologic 
targeted therapy directed to the IL-3 receptor (IL-3R), a biomarker that is over-expressed on 
AML and BPDCN blasts and cancer stem cells (CSCs) relative to normal hematopoietic stem 


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cells (Jordan, et al. 2006; Jordan, et al. 2000; Tehranchi, et al. 2010). Tagraxofusp is comprised 
of recombinant human IL-3 genetically fused to a truncated DT, in which the native 
receptorbinding domain of DT has been replaced with IL-3. The IL-3 domain of tagraxofusp is 
able to target the agent to cells that over-express IL-3R, leading to receptor-mediated 
endocytosis and localization of tagraxofusp to early endosomes. This allows tagraxofusp to kill 
cells in a distinct manner from other cancer therapeutics. First, tagraxofusp is a targeted therapy 
directed to the IL-3R that is differentially present on tumor bulk and/or CSCs versus normal 
hematopoietic stem cells. Second, tagraxofusp utilizes a payload that is not cell cycle-
dependent. Therefore, it is designed to kill not just highly proliferative tumor bulk, but also 
relatively quiescent CSCs. Tagraxofusp utilizes a payload that may not be subject to multi-drug 
resistance mechanisms typically used by CSCs to evade traditional therapies. The payload also 
kills cells in a manner that is distinct from that of other available therapies, which is another 
reason why tagraxofusp is an effective addition to the therapeutic armamentarium against 
certain hematologic malignancies.  
Tagraxofusp in frozen liquid formulation was approved by the US Food and Drug  
Administration (FDA) in 2019 for treatment of BPDCN in adults and pediatric patients 2 years 
and older based primarily on the efficacy findings from this study, STML-401-0114. STML401-
0114 was designed as a Phase 1/2 dose escalation and expansion study targeting patients with 
BPDCN or AML. Stage 1 (dose escalation) enrolled patients with BPDCN, R/R AML, and 
previously untreated AML considered high risk for progression and/or unfit for standard 
therapy. Stage 2 (expansion) enrolled additional patients with first-line BPDCN, patients with 
R/R BPDCN, and R/R and untreated high risk AML patients. Stage 3 was a confirmatory cohort 
to test pre-specified hypotheses regarding the efficacy of tagraxofusp among first-line BPDCN 
patients in preparation for the biological licensing application (BLA) filing. Stage 4 initiated 
enrollment after August 29, 2016 through January 7, 2019 and included R/R BPDCN patients 
and first-line BPDCN patients enrolled after March 17, 2017. Patients enrolled into Stage 4 
were treated with lyophilized formulation of tagraxofusp. At the time of BLA filing and 
approval limited data were available from Stage 4.   
The purpose of this document is to support an updated report on the clinical efficacy and safety 
of tagraxofusp, emphasizing both the Stage 4 results that were not previously reported and the 
overall conclusions from the duration of the trial.  Emphasis is on the results from BPDCN 
patients. Updated data are included in this report from an additional 44 patients enrolled into 
Stage 4 (42 treated) after the data cut-off for the original clinical study report dated May 09, 
2018.  
1.1.1.  
Definitions  
For the purpose of this document and related analyses:  
• 
Patients who have not received any prior treatment for their disease are considered 
“first-line.”  
• 
Patients who have received any prior treatment, regardless of duration or documentation 
of prior response, are considered “relapsed/refractory,” abbreviated R/R.  
• 
The frozen-liquid formulation of tagraxofusp, abbreviated “frozen”, was approved for 
treatment of BPDCN patients in 2019.   


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• 
The lyophilized formulation of tagraxofusp, abbreviated “lyo”, is considered an 
experimental product.  
1.1.2.  
Study Objectives  
The following objectives are defined in the Study Protocol (Amendment 9, 09 February 2017). 
The response criteria referenced throughout the Study Objectives are provided in Section 8.  
Primary objectives for Stages 1, 2, 3, and 4 are as follows:  
Stage 1: The objectives of Stage 1 are to:   
• 
Determine the maximum tolerated dose (MTD), or the maximum tested dose where 
multiple dose limiting toxicities (DLTs) are not observed, of tagraxofusp.  
Stage 2: The objectives of Stage 2 are to:  
• 
Determine the efficacy of tagraxofusp in patients with BPDCN, as assessed by objective 
response rate (ORR).  
• 
Characterize the safety profile of tagraxofusp at the MTD or maximum tested dose in 
both patients with AML and BPDCN.  
Stage 3: The objectives of Stage 3 are:  
• 
Determine the complete response (CR) rate (ie, CR + CR with incomplete blood count 
recovery [CRi] + CR [clinical] with minimal residual skin abnormality [CRc]) in 
patients with first-line BPDCN.  Note that these objectives are supported by prespecified 
statistical hypotheses and were evaluated using appropriate statistical inference during 
the initial reporting of this study.  
• 
Characterize the safety profile of tagraxofusp in patients with first-line BPDCN.  
Stage 4: The objectives of Stage 4 are to:  
• 
Further characterize the efficacy of tagraxofusp in first-line and R/R patients with 
BPDCN following the completion of Stage 2 and Stage 3 as assessed by the rate of CR 
(CR + CRi + CRc).  
• 
Further characterize the safety profile of tagraxofusp among first-line and R/R patients 
with BPDCN.  
• 
Characterize the efficacy and safety of a lyophilized formulation of tagraxofusp among 
first-line and R/R patients with BPDCN.  
Secondary objectives include:  
• 
Determine the CR rate (CR + CRi + CRc) for Stage 1 and 2 patients, and ORR for Stage 
3 patients.  


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• 
Estimate duration of response (DOR), progression-free survival (PFS) and overall 
survival (OS) in patients with BPDCN.  Note that for patients that received a stem cell 
transplant (SCT), duration of response includes time pre- and post-SCT.  
• 
Enable preliminary characterization of the estimated ORR in patients with R/R AML, 
including subsets of patients with R/R AML categorized by pre-treatment blast counts, 
cytogenetics, or CD123 measurement.  
• 
Estimate DOR, PFS, and OS in patients with AML.  
• 
Characterize the pharmacokinetics (PK) and immunogenicity of tagraxofusp.  
Exploratory objectives are to characterize expression of IL-3R (and other potentially relevant 
stem cell and disease markers) on leukemia cells in peripheral blood and BM, to evaluate 
potential changes in IL-3R (and other potentially relevant markers) expression on populations 
over time, and preliminary correlation of baseline IL-3R (and other potentially relevant markers) 
expression and clinical efficacy (including response rates).  
1.1.3.  
Study Objectives and Definitions Updates  
 
 
 
 
 
An analysis of Stage 1 and Stage 2 first-line 
BPDCN patients was performed to assess the relative clinical benefit of the response 
designations of CR, CRc, and CRi, with benefit defined as duration of response, as defined in 
Section 4.3.2. Durations of response for patients with best responses of CRc and CRi were 
compared to duration of response for patients with best response of CR to assess the likelihood 
that the durations of CR and CRc or CR and CRi would have been derived from the same 
probability distribution. From this analysis, it was determined that the achievement of CRc 
corresponded to a durability of response that is very similar to the durability of CR. Patients 
who attain a response of CRc would be expected to benefit from SL-401 treatment in a similar 
manner as those patients who achieve CR, thereby justifying the inclusion of the category of 
CRc in the primary efficacy analysis of Stage 3. The results of the analysis of comparability of  
CR and CRi did not provide sufficient evidence of similarity. 
 
 
 As a result, the definition of CR has been revised to include both results from 
patients who achieved either CR or CRc .    
In addition to bone marrow clearance and amelioration of other components of disease, the skin 
component of clinical complete response was defined in the protocol to consist of marked 
clearance of all skin lesions from baseline, including only residual hyperpigmentation or 
abnormality with BPDCN identified on biopsy (or no biopsy performed). 
 
 for more specificity in the concept of marked reduction of skin abnormality in the 
context of CRc, and to be consistent with the operational characteristics for this designation 
used by the study investigators, marked reduction in skin manifestation for a response of CRc 
was defined as at least a 75% reduction in the mSWAT score from baseline. Further, residual 
disease was defined as a remaining skin abnormality of 10% mSWAT or less, with this residual 


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consisting of skin hyperpigmentation or other visual abnormality that was not considered by the 
investigator to be active disease. (Section 8.2)  
1.1.4.  
Purpose of this Document  
This statistical analysis plan (SAP) is designed to outline the methods to be used in the analysis 
of study data to answer the study objectives related to Stage 4 and provide additional safety 
summaries related to all enrolled patients. Populations for analysis, data handling rules, 
statistical methods, and formats for data presentation are provided. The statistical analyses and 
summary tabulations described in this SAP will provide the basis for the results sections of an 
updated clinical study report (CSR) for this trial, inclusive of Stage 4 results.  
This SAP will also outline any differences in the currently planned analytical objectives relative 
to those planned in the study protocol.  
1.2.  
Study Design  
1.2.1.  
Synopsis of Study Design  
This study is a non-randomized, open-label, multicenter study divided into 4 stages: dose 
escalation (Stage 1), expansion (Stage 2), pivotal (Stage 3), and supportive efficacy and safety 
(Stage 4). The targeted patient populations are patients with:  
• 
First-line BPDCN for primary efficacy and safety profile of tagraxofusp (Stages 1 to 4).  
• 
R/R BPDCN for supportive efficacy and supportive safety profile of tagraxofusp (Stages 
1, 2 and 4).  
• 
R/R AML and high-risk first-line AML for supportive efficacy and supportive safety 
profile of tagraxofusp (Stages 1 and 2).  
A cycle of therapy consists of administration of tagraxofusp at the identified dose for 5 
consecutive days every 21 days (with the entire cycle duration lasting 21 days). tagraxofusp is 
supplied as tagraxofusp Injection frozen solution (1 mg/mL) for Stages 1, 2, and 3. A 
lyophilized formulation of tagraxofusp (for Injection, lyophilized powder, for solution; 1 
mg/mL) was supplied for dosing in selected patients with AML in Stage 2 and for BPDCN 
patients enrolled in Stage 4 after 17 March 2017.   
Stage 4 is planned to continue enrollment of first-line and R/R BPDCN patients to further 
characterize the efficacy and safety of tagraxofusp and to evaluate the lyophilized formulation in 
a subset of patients. Pooled analysis of Stage 4 data with other stages will be performed at the 
time of the primary analysis of study results.   
1.2.2.  
Randomization Methodology  
As this is a single-agent study, randomization is not applicable.  
1.2.3.  
Stopping Rules and Unblinding  
Tagraxofusp treatment could be discontinued for any of the following reasons:  
• 
Patient withdrawal of consent  


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• 
Occurrence of unacceptable toxicity, including DLT in Stage 1  
• 
Tagraxofusp related anaphylaxis or Grade ≥3 hypersensitivity reaction  
• 
Requirement for >1 dose reduction unless there is evidence of AML/BPDCN response 
(beyond Cycle 1), in which case additional dose reductions are permitted, however these 
reductions must be discussed with the Medical Monitor and documented in the context 
of ongoing AML/BPDCN response  
• 
Disease recurrence/progression  
• 
Intercurrent illness that prevents further administration of tagraxofusp  
• 
Patient non-compliance  
• 
Occurrence of pregnancy  
• 
Investigator’s decision  
The reason for tagraxofusp discontinuation and the date of discontinuation are recorded in the 
electronic case report form (eCRF).  
1.2.4.  
Study Procedures  
The schedules of assessments, as outlined in the study protocol, are provided in Section 7, Table 
7-1, Table 7-2, Table 7-3, and Table 7-4.  
1.2.5.  
Efficacy, Pharmacokinetic, and Safety Parameters  
1.2.5.1.  
Efficacy Parameters  
The primary evidence of efficacy was derived from an analysis of the rate of CR (CR + CRc), 
accompanied by an evaluation of the durability of response (including time pre- and post-SCT, 
for those patients who received SCT), as key secondary endpoints.   
These analyses will be performed on data BPDCN patients treated at the 12 μg/kg/day dose 
level:  
1. Bone marrow CR (BMCR; refer to Section 4.3.1) and duration of BMCR  
2. CR (CR + CRc) rate and duration of CR  
4. ORR (CR + CRc + CRi + partial response [PR]) and duration of objective response  
6. Proportion of patients who receive an SCT   
7. PFS  
8. OS  
Additional exploratory efficacy analyses will be performed on the above endpoints on pooled 
data across Stages and on additional exploratory efficacy parameters. Exploratory efficacy 
parameters will include time to CR (CR + CRc) (TTCR) and time to response (CR + CRc + CRi 


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+ PR) (TTR), time to BMCR, time to progression, and relapse-free survival (RFS).  In addition, 
an exploratory efficacy analysis will be performed to assess the rate and duration of CR + CRc 
+ CRi.  
Bone marrow response will be assessed using International Working Group (IWG) criteria for 
AML (for patients with AML or BPDCN) (Cheson, et al. 2003), skin-related response using a 
weighted BSA/modified Severity Weighted Assessment tool (mSWAT) score (for patients with 
BPDCN) (Olsen, et al. 2011), and lymph node and visceral response using a modified version of 
the Revised Response Criteria for Malignant Lymphoma (for patients with BPDCN) (Cheson, et 
al. 2007). For the patients with BPDCN, assessment of response and disease progression will 
include evaluation of all sites of disease involvement at baseline, which may include BM, skin, 
peripheral blood, lymph nodes, spleen, and liver. Response criteria for AML and BPDCN are 
summarized in Sections 16.1 and 16.2 of the study protocol, Amendment 9. As applicable, up to 
6 of the largest dominant nodes or nodal masses should be identified as index lesions for 
radiographic response assessments. Further detail on the definitions and analysis methods for 
efficacy endpoints are provided in Section 4.3.  
 
 
 
 
 
 
 
 
 
 
  
1.2.5.2.  
Safety Parameters  
Safety evaluations performed during the study included physical examinations, Eastern 
Cooperative Oncology Group (ECOG) performance status, measurement of vital signs, 12-lead 
electrocardiograms (ECGs), clinical laboratory evaluations (hematology, serum chemistry, 
coagulation, and urinalysis), and monitoring of adverse events (AEs) (including treatment 
discontinuation due to AEs), DLTs, and concomitant medications.  
Further details on the definitions and analysis methods for safety endpoints are provided in 
Section 4.3.6.  
1.2.5.3.  
Pharmacokinetic and Immunogenicity Parameters  
Summary of noncompartmental PK parameters and PK exposure response to treatment 
summaries will be described in a separate Modeling and Simulation Plan.  
Summary of immunogenicity parameters, including anti-drug antibodies (further characterized 
for specificity to DT and/or human interleukin-3 [hIL-3]), specific anti-hIL-3 antibodies, and 
tagraxofusp neutralizing antibodies will be performed.    


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Further details on these analyses are provided in Section 4.5.  
 


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2. PATIENT POPULATION  
2.1. Population Definitions  
The following patient populations will be evaluated and used for presentation and analysis of the 
data:  
• 
Modified Intent-to-Treat (mITT) Population: All patients who are eligible based on the 
screening criteria and who received at least 1 dose of tagraxofusp. For BPDCN patients 
to be eligible for mITT they must also have diagnosis of disease based on central 
pathology review to be “Confirmed” or “Inconclusive: Likely BPDCN”. Patients who 
meet the criteria for mITT will be considered “evaluable.” Patients will be grouped 
according to the planned dose level at time of enrollment.  
• 
Immunogenicity Population: All patients enrolled in the study who received at least 1 
dose of tagraxofusp and had sufficient samples to permit immunogenicity analysis.  
• 
Safety Population: All patients enrolled in the study who received at least 1 dose of 
tagraxofusp. Patients will be grouped according to the actual dose level received.  
The mITT population is the primary population for the analysis of efficacy parameters. The 
Immunogenicity population will be used for summary of immunogenicity results. Supportive 
subgroup efficacy analyses will be performed in the mITT population, as described in Section 
3.9. When the subgroup is defined by immunogenicity parameters, the population will be mITT 
patients with sufficient samples collected to permit the respective analysis. The Safety 
population is the primary population for the analysis of safety.  
2.2.  
Protocol Violations  
At the discretion of the Sponsor, major protocol violations, as determined by a review of the 
data prior to database lock and the conduct of statistical analyses described by this document 
(including Stage 3 efficacy analysis). The Sponsor or designee will be responsible for producing 
the final protocol violations file (formatted as a Microsoft Excel file), in collaboration with 
Veristat and the data monitoring group as applicable. This file will be finalized prior to database 
lock.  
All protocol violations will be presented in a data listing.  
3.  
GENERAL STATISTICAL METHODS  
3.1.  
Sample Size Justification  
The sample size was originally planned to be approximately 40-50 patients with BPDCN, 
including approximately 40 previously untreated patients planned to be treated with the 
tagraxofusp dose as determined in the completed Stage 1 of this study (12 µg/kg/day). In 
addition, up to approximately 36 patients with R/R AML were planned to be enrolled in Stage 2 
of the study. These sample sizes were not based on a formal statistical approach but were 
considered reasonable to accomplish study objectives for these phases of the trial.   
In Stage 3, a sufficient number of patients were enrolled to ensure 10 evaluable patients would 
be included, with evaluable patients in the mITT population, defined as patients with a diagnosis 


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of BPDCN, as confirmed via central pathology review, and who received at least 1 dose of 
tagraxofusp. 
 
 
 
 
 
 
The primary efficacy analysis for 
Stage 3 compared the lower bound of a 2-sided 95% Clopper Exact confidence interval (CI) on 
the observed CR rate to a clinically meaningless value of 10%. Assuming a CR rate of at least 
60%, a minimal sample size of 10 first-line BPDCN patients provided at least 90% power for 
the primary efficacy assessment. Due to the criteria for evaluability in the BPDCN mITT 
population requiring central pathology review, 13 first-line BPDCN patients were enrolled in 
Stage 3 between October 26, 2016 and March 17, 2017. Statistical significance was determined 
when the lower bound of this CI fell above the rate of 10%.   
After completion of enrollment of patients with first-line BPDCN in Stage 3, 39 first-line 
BPDCN patients were enrolled in Stage 4 (37 treated with study drug and 2 screen failures) and 
5 R/R BPDCN enrolled in this study after 29 August, 2016 were enrolled in Stage 4.   
3.2.  
General Methods  
All data listings that report an evaluation date will include a relative study day (Rel Day). Pre-
treatment and on-treatment study days are numbered relative to the day of the first dose of study 
drug which is designated as Day 1. The preceding day is Day -1, the day before that is Day -2, 
etc. The last day of study drug is designated with an “L” (eg, Day 26L). Post-treatment study 
days are numbered relative to the last dose and are designated as Day 1P, Day 2P, etc.  
All output will be incorporated into Microsoft Word files, sorted and labeled according to the 
International Council for Harmonisation (ICH) recommendations, and formatted to the 
appropriate page size(s).  
Tabulations will be produced for appropriate demographic, baseline, efficacy, safety and 
immunogenicity parameters. For categorical variables, summary tabulations of the number and 
percentage of patients within each category (with a category for missing data) of the parameter 
will be presented. Two-sided 95% CIs will be computed using the Clopper Exact method. For 
continuous variables, the number of patients, mean, median, standard deviation (SD), minimum, 
and maximum values will be presented. Time-to-event data will be summarized using Kaplan-
Meier methodology using 25th, 50th (median), and 75th percentiles with associated 2-sided 95% 
CIs, as well as percentage of censored observations. Formal statistical hypothesis testing will be 
performed on the primary efficacy endpoint, CR (CR + CRc) rate among all evaluable first-line 
BPDCN patients enrolled in Stage 3, with the hypothesis test performed by comparing the 
lower-bound of a 2-sided 95% Clopper Exact CI to the benchmark of 10%.   
3.3.  
Computing Environment  
All descriptive statistical analyses will be performed using SAS statistical software Version 9.3, 
unless otherwise noted. Medical history and AEs will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA) Version 19.0. Concomitant medications will be coded using 
the World Health Organization (WHO) Drug Dictionary (September, 2016).  


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3.4.  
Baseline Definitions  
For all analyses, baseline will be defined as the most recent measurement prior to the first 
administration of study drug.  
3.5.  
Methods of Pooling Data  
Summaries will be displayed by stage of enrollment and drug formulation for FL BPDCN 
patients treated at 12 µg/kg, for R/R BPDCN at 12 µg/kg and overall, and AML patient groups.   
Efficacy analyses for patients with first-line and R/R BPDCN who received 12 µg/kg will be 
conducted for the patient pools described in Table 3-1.  
Table 3-1:  
Planned Pooling of Data for Efficacy Analysis at 12 µg/kg/day  
Disease and Line 
of Therapy  
FL BPDCN 
RR BPDCN  
Patient Population  
mITT  
mITT  
Stages Included  
1&2  
3  
4  
3&4*  
1&2  
4  
1,2 &4  
CR + Duration  
X  
X  
X  
X  
X   
X   
X   
BMCR + Duration  
  
X  
X  
X  
ORR + Duration  
X  
X  
X  
X  
X   
X   
X  
Percent SCT  
  
X  
X  
X  
  
  
X  
PFS  
  
X  
X  
X  
  
  
X  
OS  
  
X  
X  
X  
X  
TTCR  
  
X  
X  
X  
  
  
  
TTR  
  
X  
X  
X  
  
  
  
TT BMCR  
  
X  
X  
X  
  
  
  
RFS  
  
X  
X  
X  
  
  
  
TTP  
  
X  
X  
X  
  
  
  
Abbreviations: mITT = modified intent to treat population; PP = per protocol population; BPDCN = blastic plasmacytoid 
dendritic cell neoplasm; FL = first-line; R/R = relapsed/refractory; CR = complete response (CR + CRc); BMCR = bone marrow 
complete response; ORR = objective response rate; SCT = stem cell transplant; PFS = progression free survival; OS = overall 
survival; TTCR = time to complete response (CR + CRi + CRc); TTR = time to response (CR + CRi + CRc + PR); TT BMCR = 
time to bone marrow complete response; RFS = relapse free survival; TTP = time to progression..  
^  Per protocol analyses to be performed if protocol violations lead to multiple patients being excluded from the Stage 3 PP 
population.  
*  Stages 3&4 may be pooled if the distributions are determined to be similar, as described in Section 3.5.1.  
3.5.1.  
Pooling of Stages 3 and 4  
Patients with first-line BPDCN in Stages 3 and 4 may be pooled for analysis if the relative 
distributions of CR and duration of CR are determined to be similar to one another and could 
arise from the same underlying distribution. The importance of this determination is to support 
the potential similarities between the frozen liquid formulation and the lyophilized formulation 
of tagraxofusp. If similarities are observed between the stages, pooling will provide increased 
sample size and therefore increased precision of estimates.   


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The assessments for similarity between the Stage 3 and Stage 4 results will proceed as follows:   
1) Comparison of 90% confidence intervals surrounding CR rate, ORR rate, and percent 
SCT to determine similarities of coverage  
2) Permutation test assessing whether the observed percentage difference in CR rate 
between Stage 3 and Stage 4 could occur by chance or if it is indicative of different 
distributions  
3) Permutation test assessing whether the observed differences in duration of CR in Stages  
3 and 4 could occur by chance or if it is indicative of different distributions  
For the permutation tests, the null hypothesis is that Stages 3 and 4 results arise from the same 
distributions.  For each respective parameter, 10,000 replicate datasets (including all 
observations from Stages 3 and 4 first-line BPDCN) will be drawn without replacement and 
summary statistics will be computed to develop the empirical null distribution of possible 
results. The observed result from Stage 3 and Stage 4 will be compared to the empirical null 
distribution. If the observed result falls within the 10th to 90th percentiles, it would be considered 
reasonable that Stages 3 and 4 arose from the same underlying distribution and therefore the 
pooling of the study results are appropriate.  
3.6.  
Adjustments for Covariates  
Due to small sample size, no formal statistical analyses that adjust for possible covariate effects 
are planned. Exploratory subgroup analyses will be performed for descriptive purposes, as 
described in Section 3.9.  
3.7.  
Assessment of Clinical Benefit  
As is noted in the literature, BPDCN is a rare hematologic malignancy that may represent less 
than 1% of cases presenting as AML, and has a multifaceted presentation involving 
manifestation in the BM and skin, and may also involve other organs including lymph nodes 
and other viscera. There are limited prospective data in this rare disease, with no standard of 
care treatment established. It is therefore important to assess the clinical benefit of potential new 
therapies through the analysis and interpretation of multiple clinically relevant endpoints.  
Conventional chemotherapy alone historically has not resulted in long-term remissions in the 
majority of patients with BPDCN (Pemmaraju 2015; Pemmaraju 2014; Pemmaraju 2012); 
however, as noted in the literature, induction remission followed by bridge to stem cell 
transplant (SCT) has been shown to provide long-term remissions in certain patients and has 
been cited as a major, if not the key, therapeutic objective.  
Allogeneic hematopoietic stem cell transplantation (allo-SCT) in BPDCN has been reported to 
be potentially beneficial in select BPDCN patients. Allo-SCT is ideally performed during first 
remission (Aoki, et al. 2015; Kharfan-Dabaja, et al. 2013; Riaz, et al. 2014;  
Roos-Weil, et al. 2013; Shapiro 2015). A large study using data from 86 first-line BPDCN 
patients recruited in the French network of BPDCN demonstrated a median OS for 34 patients 
who received SCT (40%) following CR (autologous SCT, 4 patients; or allo-SCT, 30 patients) 
of 49 months, against OS of 8 months for the 52 patients without SCT (p<0.0001). The 
beneficial effect of SCT appeared to persist independently of age in multivariate analysis (Poret 
2015). The Leukemia and Lymphoma Society in October 2016 stated that allo-SCT may result 


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in remissions that are longer, especially if offered after the first remission, and recommended 
that BPDCN patients be evaluated for SCT as soon as feasible. Dalle and colleagues (Dalle, et 
al. 2010) found that BPDCN patients who had SCT had a median OS of more than 40 months 
versus approximately 12 months for patients who did not receive SCT, and concluded that BM 
transplantation should be considered as a first-line treatment option when feasible. Similar 
results were seen in an analysis of 39 BPDCN patients from the European Blood and Marrow 
Transplantation Group (EBMTG) registry who underwent SCT as reported by Roos-Weil and 
colleagues (Roos-Weil, et al. 2013).  
It is not clear from the literature how many patients with BPDCN are eligible for SCT, but it is 
generally known that candidates for allo-SCT are typically young, have a limited number of 
comorbidities, and have a suitable donor. Although limited data are available, promising results 
also have been seen with autologous SCT (auto-SCT), with 4 year OS and PFS rates of 82% and 
73%, respectively, in a small (n=11) number of patients who underwent auto-SCT in first 
remission (Aoki, et al. 2015).  
Ideally, to optimize the chances of SCT success, a patient ideally needs to be in remission 
following induction therapy and be considered to be ‘fit’ for the procedure based on the SCT 
guidelines. Accordingly, given that BPDCN is largely a disease of the middle aged and elderly, 
therapies that have an acceptable safety profile, are quickly effective, and allow for 
postremission transplantation of older patients with BPDCN are urgently needed and would be 
clinically beneficial (Pemmaraju 2016).  
Control of BPDCN through reduction of blast cells in the BM may allow a patient to be bridged 
to SCT and thus is clinically meaningful, whether manifested as a component of a global CR, ie, 
CR among all compartments of disease present at baseline for patients with marrow disease 
(≥5% blast cells) at baseline, or as a CR in the BM compartment (BMCR) with PR in other non-
BM compartment(s). As noted in the study protocol, a patient with BMCR is defined as having 
a complete BM response (reduction to <5% blast cells), for patients with marrow disease  
(≥5% blast cells) at baseline, with either CR or PR in other non-BM compartments. Marrow 
disease, as in other aggressive hematologic malignancies, is a leading cause of morbidity and 
death in BPDCN and is also the major barrier to resumption of a meaningful quality of life (eg, 
due to the requirement for growth factor support, antibiotics, hospitalizations, etc). Further, 
resolution of disease in the BM, or maintenance of a lack of BM disease from baseline, may 
provide the opportunity for a bridge to SCT (ie, marrow must ideally be grossly disease-free for 
a patient to be considered for SCT), even if there is detectable disease in other compartments of 
BPDCN. Given that bridge to SCT is a major, if not the key, therapeutic objective of BPDCN 
therapy with evidence of long-term benefit in certain patients, we believe that clinically 
meaningful outcomes of induction therapy in BPDCN include either global CR or BMCR (with 
PR in other compartments) that lead to bridge to SCT (Leclerc, et al. 2017).  
The proportion of patients who achieve a response of BMCR and the proportion of patients who 
receive SCT, should therefore, in our view, be considered as part of the overall key endpoints 
that provide evidence of clinical benefit of tagraxofusp in patients with first-line BPDCN. 
(Leclerc, et al. 2017).   
In order to more completely demonstrate the clinical benefit of tagraxofusp, additional 
endpoints will be analyzed in a descriptive, supportive manner, including endpoints related to 
longer-term benefit such as PFS and OS, the proportion of patients who receive SCT and the 
extended duration of effect subsequent to SCT. These additional endpoint analyses will be 


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performed on the pivotal cohort of first-line BPDCN patients from Stage 3, as well as the larger 
pool of data from first-line BPDCN patients across all stages of the trial.   
3.8.  
Efficacy Endpoint Analysis  
3.8.1.  
Primary Endpoint  
The primary evidence of efficacy is an analysis of the rate of CR, accompanied by an evaluation 
of the durability of response, including durability of these CRs, as a key secondary endpoint.   
3.8.2.  
Secondary Endpoints  
Formal hypothesis testing of secondary endpoints is not planned. The analyses of all secondary 
endpoints will be descriptive. The description of analyses to be performed by stage and pooling 
of stages is described in Section 3.5.  Summaries of secondary endpoints to be evaluated and 
presented as follows:  
1. BMCR and duration of BMCR   
2. ORR (CR + CRc + CRi + partial response [PR]) and duration of objective response  
3. Proportion of patients who receive an SCT  
4. PFS  
5. OS  
Further detail on the definitions and analysis methods of primary and secondary efficacy 
endpoints is provided in Section 4.3.  
3.8.3.  
Exploratory Endpoints  
Exploratory endpoints will be assessed to further evaluate efficacy, dependent on the extent of 
data available. These endpoints will include several additional time to event endpoints, 
including TTCR, TTR, time to BMCR, TTP, and RFS. Additional exploratory analysis may 
compare baseline disease severity between Stages and assess the respective impacts of baseline 
disease severity and compartments of disease expression over time on outcome measures such 
as CR rate and ORR. In addition, an exploratory efficacy analysis will be performed to assess 
the rate and duration of CR as defined per the Study Protocol Amendment 9 (09 February 2017), 
including CR + CRc + CRi.  
Further detail on the definitions and analysis methods of exploratory efficacy endpoints is 
provided in Section 4.3.  
3.9.  
Subgroup Analyses  
Efficacy analyses for Stage 4 and pooled Stages 3 and 4 as appropriate, will be summarized 
separately for those bridged to SCT and not bridged to SCT post-treatment. Efficacy analyses 
will also be summarized by baseline disease site (Skin only, Systemic only [Bone Marrow, 
Peripheral Blood, Lymph Node, or Visceral Disease], and Skin and Systemic).    


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Subgroup analyses will be performed for safety parameters in the FL and RR BPDCN 
populations, as specified in the below table.  Subgroup analyses will be presented only when the 
minimum-sized subgroup classification includes at least 10% of the population.  
Table 3-2:  
Subgroups and Definitions for Safety Analyses  
Parameter  
Description  
Age  
<65 vs. ≥65, <75 vs. ≥75 years of age   
Sex  
Male, Female  
BMI  
Obese: >30 kg/m^2  
Overweight: 25-30 kg/m^2  
Normal/Underweight: < 25 kg/m^2  
Eastern Cooperative Oncology Group (ECOG) 
Performance Status  
Baseline score of 0  
Baseline score of 1 or 2  
Subgroup analyses will be performed for the following safety summaries:  
Overview of adverse events (AE)  
Treatment emergent AEs by system organ class (SOC) and preferred term (PT) (occurring in at least 15% of 
population)  
3.10.  
Withdrawals, Dropouts, Loss to Follow-up  
Patients who are withdrawn or discontinue from the study will not be replaced.  
3.11.  
Missing, Unused, and Spurious Data  
In general, there will be no substitutions made to accommodate missing data points. All data 
recorded on the eCRF will be included in data listings that will accompany the CSR.  
When tabulating AE data, partial dates will be handled as follows. If the day of the month is 
missing, the onset day will be set to the first day of the month unless it is the same month and 
year as study treatment. In this case, in order to conservatively report the event as treatment-
emergent, the onset date will be assumed to be the first day of treatment. If the onset day and 
month are both missing, the day and month will be assumed to be January 1, unless the event 
occurred in the same year as the study treatment. In this case, the event onset will be set to the 
first day of treatment in order to conservatively report the event as treatment-emergent. A 
missing onset date will be set to the first day of treatment.  
3.12.  
Visit Windows  
It is expected that all visits should occur according to the protocol schedule. All data will be 
tabulated per the evaluation visit as recorded on the eCRF even if the assessment is outside of 
the visit window. In data listings, the relative day of all dates will be presented (see Section 3.2).  
3.13.  
Timing of Analyses  
3.13.1.  
Interim Analyses  
A preliminary and informal interim analysis was performed on efficacy data from Stages 1 and  
2 
 
 This analysis was performed on the 32 BPDCN patients (19 first-line and 13 R/R) enrolled 


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in the study prior to 29 August, 2016, 3 of whom were treated with tagraxofusp 7 µg/kg/day and 
29 were treated with tagraxofusp 12 µg/kg/day. The ORR, CR rate, PFS, and OS efficacy 
parameters were summarized. Selected safety summaries also were presented.   
Note that no further enrollment of first-line BPDCN patients occurred until October 26, 2016. 
 first-line BPDCN 
patients enrolled on or after October 26, 2016 (with enrollment period later defined as between 
October 26, 2016 and March 17, 2017) will be considered as a separate, pivotal patient cohort 
for statistical analysis, as previously described in Section 1.2.1.   
In Stages 2-4 of the study, the Data Safety Review Committee (DSRC) was to conduct a safety 
data review every 1-2-months.  
3.13.2.  
Independent Review Committee  
An Independent Review Committee (IRC) has been established to review tumor responses and 
duration of response for patients with BPDCN enrolled in Protocol STML-401-0114.    
Response is best assessed by the treating investigator because disease-compartment responses, 
and in particular bone marrow responses, are used in the real-time management of the patient.  It 
is also important to verify to the extent possible that the protocol-specified response criteria 
have been applied objectively and uniformly, therefore the IRC will apply the protocol specified 
response criteria to provide consistent and independent evaluation of tumor responses by cycle 
and overall. The IRC evaluation, which will be considered as supportive to the primary 
assessment of response by the investigator, was performed on 28-29 August 2017, prior to the 
primary efficacy, safety, PK, and immunogenicity analysis. The IRC is governed by a separate 
charter.  
3.13.3.  
Primary Efficacy, Safety, and Immunogenicity Analysis  
The primary analysis of efficacy, safety, and immunogenicity data occurred following the cutoff 
date of 25 September 2017, after all patients enrolled into Stage 3 completed at least 4 cycles of 
treatment with tagraxofusp, have experienced disease progression, or have withdrawn from the 
study. The primary analysis included efficacy, safety, PK, and immunogenicity analysis of 
Stage 3 data. In addition, supporting data from Stages 1 and 2 were analyzed at this time in 
support of the BLA.   
3.13.4.  
Updated Reporting and Stage 4 Analysis  
Following a data cutoff date of 13 March 2020 (database lock), updated reports are planned to 
support the ongoing efficacy and safety of Stages 1, 2, and 3 patients as well as to summarize 
the efficacy and safety of the lyophilized formulation of tagraxofusp, administered in Stage 4. A 
summary of efficacy, safety, PK, and immunogenicity analyses will be presented at this time.   
The Updated Reporting and Stage 4 Analysis is described in this SAP.   
 


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4. STUDY ANALYSES  
4.1. Patient Disposition  
Patient disposition will be tabulated and include the number screened, the number treated in 
total, the number in each patient population for analysis, the number treated in each Stage of the 
study, the number receiving the frozen liquid and lyophilized drug formulation, the number on 
study at the time of data cutoff, the number who withdrew prior to completing the study and 
reason(s) for withdrawal. The summary will be presented by disease and line of therapy (first-
line BPDCN, R/R BPDCN, AML) within Stage.  
A data listing of study completion information, including the reason for premature study 
withdrawal, if applicable, will be presented.  
4.2.  
Demographics and Baseline Characteristics  
Demographics and baseline characteristics will be summarized and presented by disease and 
line of therapy (first-line BPDCN, R/R BPDCN, AML) within Stage. Age, height, and weight 
will be summarized using descriptive statistics (number of patients, mean, standard deviation, 
median, minimum, and maximum). The number and percentage of patients in each gender, 
ethnicity and race category will be presented.   
Medical history and results from baseline screens such as for pregnancy, and smoking status 
will be tabulated. Primary disease history will be summarized including sites and extent of 
disease involvement, molecular markers, mutations, BPDCN baseline diagnosis (type of 
analysis, immunophenotype expression), and time since BPDCN diagnosis. Prior chemotherapy, 
prior immunotherapy, prior radiation therapy, and prior SCT will be summarized.  
Demographic and baseline data for each patient will be provided in data listings.  
4.3.  
Efficacy Evaluation  
Data for all efficacy endpoints will be presented in by-patient listings.  Efficacy summaries will 
be presented by stage of enrollment and line of therapy.  Subgroup analyses will be reported for 
Stage 4 (and Stages 3 and 4 if pooled) according to whether patients were bridged to SCT 
posttreatment and not bridged to SCT post-treatment. Efficacy analyses of responses will also 
be summarized by baseline disease site.    
4.3.1. Response Rate  
Complete response rate will be presented as the number and percentage of patients who 
achieved CR (CR + CRc) after treatment with tagraxofusp.  
Bone marrow CR (BMCR) rate will be measured by pooling data from patients who had either 
CR or PR according to the IWG response criteria, together with BMCR (reduction to ≤5% BM 
blast cells), as a proportion of all patients with marrow disease (>5% BM blast cells) at baseline.  
Objective response rate will be presented as the number and percentage of patients who achieve 
CR (CR + CRc), CRi, or PR after treatment.  
For CR, BMCR, and ORR, 95% Clopper Exact CIs will be presented.  


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Permutation test results for Stage 3 and Stage 4 comparison will be reported as the observed 
results and relative percentile of the empirical null distribution for CR and ORR. Graphical plots 
may be presented.  
4.3.2.  
Duration of Response  
Duration of CR is defined as the time from when the criteria are first met for CR/CRc  
(whichever is recorded first) until the date that the criteria for relapse after CR/CRc are met. 
This could be the occurrence of PD or relapse. In the case that PR or SD follows CR/CRc and 
there is no evidence that response rebounds to CR/CRc, duration of CR will end at the time of 
first reduction of response to below CR/CRc. If CRi follows CR/CRc it will not be considered 
evidence of relapse. For patients who receive SCT after CR/CRc, duration of CR will include 
time to disease relapse post-transplant. Patients who are lost to follow-up or who do not relapse 
after CR/CRc as of the cut-off for analysis will be censored on the latter of the date of last 
treatment with tagraxofusp or date of last disease assessment recorded prior to the analysis 
cutoff date. Permutation test results for Stage 3 and Stage 4 comparison will be reported as the 
observed results and relative percentile of the empirical null distribution. Graphical plots may be 
presented.  
Duration of BMCR is defined as the time from when criteria are first met for BMCR until the 
date that the criteria for relapse are met, including PR, SD, PD, or relapse in bone marrow 
compartment or SD, PD, or relapse in any other disease compartment. Duration of BMCR will 
include time to disease relapse post-transplant. Patients who are lost to follow-up or who do not 
relapse after BMCR as of the cut-off for analysis will be censored on the latter of the date of last 
treatment with tagraxofusp or date of last disease assessment recorded prior to the analysis 
cutoff date.   
Duration of objective response is defined as the time from when criteria are first met for 
CR/CRc, CRi, or PR until the date that the criteria for relapse (including SD, PD, or relapse) 
after CR/CRc/CRi/PR is met. For patients who receive SCT after CR/CRc/CRi/PR, DOR will 
include time to disease relapse post-transplant. Patients who are lost to follow-up or who do not 
relapse after objective response as of the cut-off for analysis will be censored on the latter of the 
date of last treatment with tagraxofusp or date of last disease assessment recorded prior to the 
analysis cut-off date.   
For duration of CR, BMCR, and ORR, a Kaplan-Meier analysis will be applied to estimate the 
25th percentile, median, and 75th percentile of times to event, number and percentage of events 
and censored observations, and appropriate CIs.  
4.3.3. Bridge to Stem Cell Transplant  
The number and proportion of patients who receive SCT subsequent to achieving an 
investigator-determined outcome from tagraxofusp that is deemed by the investigator to enable 
a SCT, will be reported with 95% Clopper-Pearson Exact CIs. Summaries will be performed 
overall and by treatment outcome on tagraxofusp. Permutation test results for Stage 3 and Stage 
4 comparison will be reported as the observed results and relative percentile of the empirical 
null distribution. Graphical plots may be presented.  


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4.3.4. Progression-Free Survival  
Progression-free survival is defined as the time from the date of first infusion of tagraxofusp to 
the date of PD or death from any cause, whichever occurred first. For patients who receive SCT, 
PFS will include time to PD or death post-transplant. Patients who do not progress and are still 
alive at the time of analysis will be censored on the date of last treatment recorded prior to the 
analysis cut-off date. If patients start other anticancer therapies (with the exception of SCT), 
they will be censored at the latter of the date of last treatment with tagraxofusp or date of last 
disease assessment recorded that occurred prior to the start of the new therapy. The distribution 
for PFS will be estimated by Kaplan-Meier methodology and the 25th percentile, median, 75th 
percentile, number and percentage of events and censored observations, and appropriate CIs will 
be presented.  
4.3.5. Overall Survival  
Overall survival is defined as the time from the date of first infusion of tagraxofusp to the date 
of death from any cause. Patients still alive or lost to follow-up at the time of the analysis will 
be censored on the last date known to be alive prior to the analysis cut-off date, as determined 
by in- person visit or telephone contact. The overall distribution for OS will be estimated by 
Kaplan-Meier classical methodology in a similar manner to PFS.  
4.3.6. Exploratory Endpoints  
4.3.6.1.  
Time to Event Endpoints  
Time to CR is defined as the time from initiation of treatment with tagraxofusp to CR (CR, or 
CRc, whichever is achieved first). Only patients who have achieved CR or CRc will be included 
in the analysis. Time to CR will be summarized using descriptive statistics.  
Time to response is defined as the time from initiation of treatment with tagraxofusp to CR (CR 
+ CRc), CRi, or PR, whichever occurs first. Only patients who achieve CR, CRc, CRi, or PR 
will be included in the analysis.  The analysis of TTR will follow the same methods as described 
for TTCR.  
 
follow the same methods as described for TTCR.  
Time to progression is defined as the time from first treatment with study drug disease 
progression. Patients who do not progress or die prior to response will be censored on the date 
of last disease assessment recorded prior to the analysis cut-off date. The distribution for TTP 
will be estimated by Kaplan-Meier methodology and the 25th percentile, median, 75th percentile, 
number and percentage of events and censored observations, and appropriate CIs will be 
presented.  
Relapse free survival (RFS) is defined as the time from CR (CR/CRc) to disease progression or 
death. For patients who receive SCT after CR/CRc, RFS will include time to disease relapse 
post-transplant. Patients who do not achieve CR or die prior to CR will not be included in the 
analysis. Patients who have responded and are alive at the time of analysis will be censored on 
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recorded prior to the analysis cut-off date. The distribution for RFS will be estimated by 
Kaplan-Meier methodology and the 25th percentile, median, 75th percentile, number and 
percentage of events and censored observations, and appropriate CIs will be presented.  
4.3.6.2.  
Protocol-Specified Rate of Complete Response  
The Study Protocol Amendment 9 (09 February 2017)-defined rate and duration of CR, 
inclusive of CR, CRc, and CRi will be summarized by disease and line of therapy (first-line 
BPDCN, R/R BPDCN, AML).  
4.3.6.3.  
Additional Analyses  
Sites and extent of disease involvement, as reported by the investigators, will be listed by Stage 
over time.  For continuous disease measures Stages may be compared using ANOVA 
regression.  Frequencies of categorical disease measures may be compared between Stages 
using chi-square tests of independence.  
For a subset of efficacy parameters, additional supportive analyses may be performed based on 
the IRC-determined assessments of disease response over time. Efficacy parameters may 
include CR rate and ORR, and will be analyzed in a similar manner as was described in Section  
4.3.1 and Section 4.3.2.    
4.4.  
Safety Analyses  
With the exception of Subgroup Analyses (Section 3.9), all safety tabulations will be presented 
by disease (first-line BPDCN, R/R BPDCN, AML) for all patients in the Safety Population by 
stage of enrollment (all doses included).  All safety tabulations will be presented for first-line 
BPDCN patients in the Safety Population who were treated at 12 µg/kg/day by stage of 
enrollment and for those treated with lyophilized formulation of tagraxofusp.    
4.4.1.  
Study Drug Exposure  
Duration of study drug exposure will be calculated as the number of days and number of cycles 
patients were administered study drug.  
𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷 𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷 𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷 𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸𝐸 = 
(𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷 𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷 𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙 𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢 − 𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷 𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷 𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜 
𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢) + 1  
Duration in cycles of drug exposure will be defined the total number of cycles of study drug 
initiated while the patient is on study. Dose modifications, including frequency of dose 
interruptions and dose reductions will be summarized. Total dose administered will be 
summarized overall and by cycle.  
Relative Dose Intensity will be computed using the following definition and summarized by 
disease and line of therapy by stage:  
𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆(𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶 𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴 𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷 
𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅 𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏 𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶) 


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𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅 𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷 𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼𝐼 (%) = 100 ∗ 
  
𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆(𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃 𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷 𝐷𝐷𝐷𝐷𝐷𝐷𝐷𝐷 𝑏𝑏𝑏𝑏𝑏𝑏𝐸𝐸 
𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴𝐴 𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏 𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶) 
Exposure to tagraxofusp will be presented in by-patient data listings.  
4.4.2.  
Adverse Events  
All AEs will be coded using the MedDRA coding system and displayed in tables and data 
listings using system organ class (SOC) and preferred term.  
Analyses of AEs will be performed for those events that are considered treatment-emergent, 
where treatment-emergent is defined per protocol as any AE with onset after the first 
administration of tagraxofusp through 30 days after the last dose of tagraxofusp, or any event 
that was present at baseline but worsened in intensity or was subsequently considered 
drugrelated by the Investigator through 30 days after the last dose of tagraxofusp.  
The number and percentage of patients with any treatment-emergent AE (TEAE), common AEs 
(defined as occurring in ≥10% of the study sample), with any TEAE assessed by the  
Investigator as related to treatment, with TEAE occurring within 24 hours of infusion, with any 
TEAE with severity ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 3, 
with any serious adverse event (SAE), with any AE leading to discontinuation of study 
treatment, with any AE to dose reduction, and with any AE leading to dose interruption will be 
summarized by disease, line of therapy, dose and overall. In these tabulations, each patient will 
contribute only once (ie, the most related occurrence or the most intense occurrence) to each of 
the incidence rates in the descriptive analysis, regardless of the number of episodes.  
Treatment-emergent AEs summarized by patient incidence rates are not tabulated by severity or 
relationship to study treatment; therefore, in such tabulations, a patient contributes only once to 
the count for a given AE SOC or preferred term. For tabulations that include classification by 
relationship to study treatment, AEs with missing relationship will be considered related to 
study drug. For tabulations that include classification by maximum severity grade, AEs with 
missing CTCAE severity will be included in a category for missing severity.  
Incidence of TEAEs occurring within 24 hours of infusion will be summarized by SOC and 
preferred term.  
Analysis of AEs over time will be conducted by presentation of AE incidence by cycle. For this 
analysis, incidence per cycle will be based on the onset of a particular preferred term event 
within the cycle, where onset is indicated by first or repeat occurrence or increase in severity of 
the event within that cycle. This analysis will be conducted for all AEs and for AEs of Grade ≥3 
severity. For AEs of special interest, Kaplan-Meier analyses of time to first occurrence of Grade 
≥2 severity will be conducted for FL BPDCN, R/R BPDCN, and AML patients.  
AESI’s will be determined using MedDRA version 19.0 standardized medical queries (SMQs), 
high-level terms, or preferred terms, as follows:  
• 
Possible hypersensitivity events, based on the SMQ Hypersensitivity (broad search).  


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• 
Vascular capillary leak syndrome (CLS), based on the MedDRA SMQ [to be provided] in 
addition to preferred terms of hypoalbuminaemia, blood albumin decreased, and proteinuria.  
• 
Visual acuity, based on the MedDRA preferred terms of visual acuity reduced, visual acuity 
reduced transiently, visual acuity tests abnormal.  
• 
Post-transplantation veno-occlusive disease, based on the MedDRA preferred terms 
pulmonary veno-occlusive disease and veno-occlusive liver disease.  
• 
Possible drug-induced liver injury events, based on the SMQ drug-related hepatic disorders 
(broad search).  
Summary tables of AESIs produced will report AESI by preferred term, causality, severity 
grade, seriousness, and whether AESI led to discontinuation. These tabulations will be 
completed for all patients, by line of therapy for BPDCN patients, AML patients, and indication. 
AESIs will also be included in data listings.  
4.4.2.1.  
Capillary Leak Syndrome  
In addition to the summaries described in Section 4.4.2, summaries will be provided that 
include:  
• 
Summary of number of CLS events, exposure to tagraxofusp prior to onset of CLS, and 
time to first onset and time to resolution of CSL events;  
• 
Summarized incidence of albumin infusions and timing of infusions in relation to CLS 
onset;  
• 
Plots of liver function and albumin laboratory values over time for patients who 
experience CLS;  
• 
Comparison of demographic characteristics of patients who experience AESI of CLS to 
those who do not  
Additionally, analyses of capillary leak syndrome will be provided based on an FDA algorithm, 
found in Section 8.3.  
4.4.3.  
Laboratory Data  
Clinical laboratory values will be expressed in Système International (SI) units.  
The actual value and change from baseline (Day 1) to each on-study evaluation through cycle 6 
will be summarized for each clinical laboratory parameter, including hematology, clinical 
chemistry, coagulation, and urinalysis. In the event of repeat values, the last non-missing value 
per study day/time will be used.  
Shift tables of change in CTCAE grade of laboratory parameters from baseline to worst value 
and from baseline to last value on study will be presented. Both scheduled and unscheduled 
visits will be included in shift tables.  


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To assess for possible drug-induced liver injury (DILI) (FDA 2009), a figure plotting peak 
alanine aminotransferase (ALT) versus peak total bilirubin (both on a logarithmic scale × upper 
limit of normal [ULN]) will be produced similar to that recommended by Watkins et al 
(Watkins, et al. 2008) so that values within the normal reference range (<ULN) for ALT and 
total bilirubin are found in the left lower quadrant and Hy’s Law case candidates are in the 
upper right quadrant (ALT >3 × ULN and total bilirubin >2 × ULN). Patients with Gilbert’s 
syndrome or cholestasis are typically found in the upper left quadrant, and patients with ALT 
elevations without significant hepatic abnormality (ie, without increased total bilirubin) are 
found in the lower right quadrant. The peak total bilirubin value plotted will be the peak within 
± 7 days of the peak ALT value. If at least five patients are identified as potential Hy’s Law 
Cases, a summary table will be produced for the number and percentage of patients who have 
values of AST (>3 to ≤5 × ULN, >5 to ≤10 × ULN, >10 to ≤20 × ULN, >20 × ULN), ALT (>3 
to ≤5 × ULN, >5 to ≤10 × ULN, >10 to ≤20 × ULN, >20 × ULN), ALP (>1.5 × ULN), or TBL 
(>1.5 to ≤2 × ULN, >2 × ULN) after initiation of study drug. In this table, a patient may be 
counted only one time. For instance, a patient with a result of AST of 11 × ULN will be counted 
in the category of >10 to ≤20 × ULN.  
This plot will be repeated for peak aspartate aminotransferase (AST) by total bilirubin.  
An example of the scatterplot is provided in Figure 4-1.  
Figure 4-1:  
Hy’s Law Candidates Scatterplot  
  
  
Time to first onset of elevated AST and ALT will be analyzed using Kaplan-Meier analyses and 
be presented as figures.  
All laboratory data will be provided in by-patient data listings.  
A by-patient listing will also be presented for all laboratory values with CTCAE Grade ≥3.  


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4.4.4.  
Vital Signs and Physical Examination  
The actual value and change from baseline (Day 1) to each on-study evaluation and to the last 
on study evaluation will be summarized for vital signs.   
A summary table of the number and percent of patients with treatment-emergent potentially 
clinically significant (PCS) vital signs parameters will be tabulated based on the following 
criteria:  
Variable Name  
PCS – Low if:  
PCS – High if:  
Observed 
Value is:  
AND  
Decrease from 
Baseline is:  
Observed 
Value is:  
AND  
Increase from 
Baseline is:  
Systolic Blood Pressure   <90 mmHg  
  
≥20 mmHg  
>180 mmHg  
  
≥20 mmHg  
Diastolic Blood Pressure  <50 mmHg  
  
≥10 mmHg  
>105 mmHg  
  
≥10 mmHg  
Heart Rate   
<50 bpm  
  
≥15 bpm  
>120 bpm  
  
≥15 bpm  
PCS= potentially clinically significant.  
All tables summarizing vital sign measurements only include visits in which at least 10% of the 
analysis population had measurements. Vital sign measurements will be presented for each 
patient in a data listing.  
All physical examination findings and ECOG performance status findings will be presented in 
data listings.  
4.4.5.  
Electrocardiogram  
Electrocardiogram results will be summarized descriptively, including the number and 
percentage of patients with normal, abnormal, and clinically significant abnormal results at 
baseline and each study visit. Actual values and change from baseline will be summarized for 
QTc intervals; continuous summary statistics will be based on the mean of the triplicate ECG 
values, as appropriate. All tables summarizing ECG measurements only include visits in which 
at least 10% of the analysis population had measurements  
Based on 12-lead triplicate ECG results, the number and percentage of patients whose mean 
QTcF or QTcB value at any time point meets any of the following categories will be 
summarized:  
• 
>450 msec  
• 
>480 msec  
• 
>500 msec  
• 
increase from baseline >30 msec  
• 
increase from baseline >60 msec  
Electrocardiogram and echocardiogram/MUGA data for each patient will be provided in data 
listings.  


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4.4.6.  
Concomitant Medications and Subsequent Treatments  
Concomitant medications will be coded using the WHO Drug Dictionary. Results will be 
tabulated by anatomic therapeutic class (ATC) and preferred term.  
Concomitant medications will be tabulated for previously specified safety groups, where any 
medications that were not discontinued prior to the first dose of study drug will be included. If 
an end date is missing or the medication is ongoing at the time of first dose, the medication will 
be considered concomitant.  
The use of concomitant medications and subsequent treatment(s) will be included in by-patient 
data listings.  
4.4.7.  
Pre-Treatment Medications   
Pre-treatment medications will be coded using the WHO Drug Dictionary. Results will be 
tabulated by ATC and preferred term. In addition, the number and percent of patients who 
receive pre-treatment medication at least once will be summarized for previously specified 
safety groups.  
Pre-treatment medications will be included in by-patient data listings.  
4.5.  
Summary of Immunogenicity Parameters  
Immunogenicity parameters will be summarized for FL BPDCN, R/R BPDCN, all BPDCN, 
Stage 4 (lyophilized formulation) only, and all patients pooled across all doses and stages.    
Analyses will be conducted in accordance with the principles outlined in (Shankar, et al. 2014) 
and will include:  
• 
Incidence of patients with positive anti-drug antibodies, specific anti-hIL-3 antibodies, 
and neutralizing antibodies will be assessed by cycle uniquely through cycle 6 and 
cycles >6, collectively.  Incidence will be summarized by number and percent of patients 
with positive antibody results.   
• 
Mean fold increase from baseline and geometric mean titer are tabulated by scheduled 
assessments. Summary statistics will include mean, SD, median, min, and max.   
• 
Incidence of subjects with a ≥ 10 fold increase in anti-drug antibody titer and/or a ≥ 4 
fold increase in anti-hIL-3 antibody titer will be tabulated.   
• 
Complete response, objective response, and complete response rates will be tabulated 
with 95% clopper exact CIs for subjects with a ≥ 10 fold increase in anti-drug antibody 
titer and/or a ≥ 4 fold increase in anti-hIL-3 antibody titer.   
• 
Descriptive statistics will be provided for the count of AEs, AESIs, Immune-complex 
related AEs, serious AEs, and AEs leading to Discontinuation by antibody status and the 
fold increase populations previously described.   
Immunogenicity parameters will be included in by-patient data listings. 


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5.  
CHANGES TO PLANNED ANALYSES  
5.1.  
SAP Version 1.0 (28 April 2017)  
In the Study Protocol (Amendment 9), in Section 12.6.3 Duration of Response is defined as the 
time from CR to disease progression. In case a patient does not progress, the protocol definition 
specifies that censoring will occur on the last radiologic assessment while on study. In this SAP 
Section 4.3.2 (Duration of Response) and Section 4.3.4 (PFS), censoring will occur on the date 
of last disease assessment, including BM, skin, or radiologic assessments, as appropriate and in 
accordance with the patient-specific disease presentation.  
In the Study Protocol (Amendment 9), in Section 12.6.2 Bone Marrow Complete Response is 
defined as patients “who had either CR or PR with complete bone marrow response (reduction 
to <5% blast cells), as a proportion of all patients with marrow disease (≥5% blast cells) at 
baseline.” Per the response criteria; however complete BM response requires a reduction to ≤5% 
blast cells. This notation was corrected in the SAP Section 4.3.1.  
A footnote was added to the Response Criteria for BPDCN from Protocol (Amendment 9) to 
define marked clearance of skin disease and residual hyperpigmentation or abnormality 
identified on a biopsy (or no biopsy performed) as quantifiable changes to skin disease for 
identification of the achievement of CRc. (Section 8.2)  
5.2.  
Changes from SAP Version 1.0 (28 April 2017) to Version 2.0  
Changes from SAP Version 1.0 (28 April 2017) include:  
• 
Section 1.1.3: 
 
modification to the Study Protocol and SAP Version 1.0 definition to complete response 
from CR + CRc + CRi to include only CR + CRc. An assessment of rate and duration of 
CR + CRc + CRi was added as an exploratory analysis.    
  
In addition, the modification to the definition of CRc, including a quantifiable definition 
of “marked clearance” and “residual” were added to this SAP.  
• 
Section 2: The population definitions were updated to improve clarity on their 
implementation in the analysis of the patient data.  
• 
Section 3.5: Additional information was added to the Methods for Pooling Data to 
clarify the intent and implementation of analysis of the patient data.  
• 
Section 3.9: Subgroup analyses were updated to better describe the analyses to be 
performed.  The list of subgroups were modified to include only those relevant for 
analysis where at least 10% of patients fall within each group.  In addition, the efficacy 
subgroup analyses were removed since SAP Version 1.0 as the analyses will not be 
performed.  
• 
Section 3.14.3: The cutoff date for analysis is identified as 25 September 2017 to allow 
all surviving patients at least 6 months of follow-up.  
• 
Section 4: Corrections and clarification of efficacy and safety analyses were added to the 
document.    


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o Corrections were made to exploratory time to event endpoint descriptions and 
planned analysis methods, including the addition of TTP as an exploratory endpoint.    
o Time to event response endpoints of duration of CR, duration of BMCR, duration of 
OR, PFS, and RFS are censored on the latter of date of last treatment with 
tagraxofusp or date of last disease assessment prior to data cutoff. o In addition to 
other clarifications, the AESI section is updated for greater detail of the particular 
events of interest.  
o Additional specification of CLS outputs to be included in CSR.  
5.3.  
Changes from the SAP Version 2.0 (17 November 2017) to Version  
3.0  
Changes from SAP Version 2.0 (17 November 2017) include:  
• 
Section 1.1: The purpose of this document was updated for an updated report on the 
clinical efficacy and safety of tagraxofusp, emphasizing both the Stage 4 results that 
were not previously reported and the overall conclusions from the duration of the trial. 
Details are included in Section 3.13.3 and 3.13.4.  
• 
Section 1.2: Details on stages previous to Stage 4 were removed. Additional information 
on responses to be used in efficacy analyses were detailed in Section 1.2.5.1.  
• 
Section 2.1: The Per-Protocol Population was removed. Sensitivity analyses were also 
removed.  
• 
Section 3.5: Methods of pooling data were updated to emphasize Stage 4, including a 
pooling of Stages 3 and 4 (a permutation test described in Section 4.3.1, 4.3.2, and 
4.3.3).  
• 
Section 3.8: The efficacy endpoints were updated to emphasize stage 4 results and 
overall conclusions.  
• 
Section 3.9: Subgroup analyses for efficacy among subjects that bridged to SCT and Not 
Bridged to SCT, as well as by baseline disease site, were added.  
• 
Section 4.4.2.1: Analyses of CLS based on FDA algorithm were added.  
  
6.  
REFERENCES  
Adachi M, Maeda K, Takekawa M, Hinoda Y, Imai K, Sugiyama S, et al. High expression of 
CD56 (N-CAM) in a patient with cutaneous CD4-positive lymphoma. Am J Hematol. 
1994;47(4):278-82.  


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Statistical Analysis Plan, Protocol STML-401-0114 
19 April 2021, Final Version 3.0  
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Aoki T, Suzuki R, Kuwatsuka Y, Kako S, Fujimoto K, Taguchi J, et al. Long-term survival 
following autologous and allogeneic stem cell transplantation for blastic plasmacytoid dendritic 
cell neoplasm. Blood. 2015;125(23):3559-62.  
Assaf C, Gellrich S, Whittaker S, Robson A, Cerroni L, Massone C, et al. CD56-positive 
haematological neoplasms of the skin: a multicentre study of the Cutaneous Lymphoma Project 
Group of the European Organisation for Research and Treatment of Cancer. J Clin Pathol. 
2007;60(9):981-9.  
Bekkenk MW, Jansen PM, Meijer CJ, and Willemze R. CD56+ hematological neoplasms 
presenting in the skin: a retrospective analysis of 23 new cases and 130 cases from the literature. 
Ann Oncol. 2004;15(7):1097-108.  
Brody JP, Allen S, Schulman P, Sun T, Chan WC, Friedman HD, et al. Acute agranular 
CD4positive natural killer cell leukemia. Comprehensive clinicopathologic studies including 
virologic and in vitro culture with inducing agents. Cancer. 1995;75(10):2474-83.  
Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, et al. Revised 
recommendations of the International Working Group for Diagnosis, Standardization of 
Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in 
Acute Myeloid Leukemia. J Clin Oncol. 2003;21(24):4642-9.  
Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised 
response criteria for malignant lymphoma. J Clin Oncol. 2007;25(5):579-86.  
Dalle S, Beylot-Barry M, Bagot M, Lipsker D, Machet L, Joly P, et al. Blastic plasmacytoid 
dendritic cell neoplasm: is transplantation the treatment of choice? Br J Dermatol. 
2010;162(1):74-9.  
Facchetti F, Vermi W, Mason D, and Colonna M. The plasmacytoid monocyte/interferon 
producing cells. Virchows Arch. 2003;443(6):703-17.  
FDA. Guidance for Industry: Drug-Induced Liver Injury: Premarketing Clinical Evaluation. 
2009.  
Feuillard J, Jacob MC, Valensi F, Maynadie M, Gressin R, Chaperot L, et al. Clinical and 
biologic features of CD4(+)CD56(+) malignancies. Blood. 2002;99(5):1556-63.  
Herling M, and Jones D. CD4+/CD56+ hematodermic tumor: the features of an evolving entity 
and its relationship to dendritic cells. Am J Clin Pathol. 2007;127(5):687-700.  
Jacob MC, Chaperot L, Mossuz P, Feuillard J, Valensi F, Leroux D, et al. CD4+ CD56+ lineage 
negative malignancies: a new entity developed from malignant early plasmacytoid dendritic 
cells. Haematologica. 2003;88(8):941-55.  
Jordan CT, Guzman ML, and Noble M. Cancer stem cells. N Engl J Med. 2006;355(12):1253-
61.  
Jordan CT, Upchurch D, Szilvassy SJ, Guzman ML, Howard DS, Pettigrew AL, et al. The 
interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia 
stem cells. Leukemia. 2000;14(10):1777-84.  


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Kharfan-Dabaja MA, Lazarus HM, Nishihori T, Mahfouz RA, and Hamadani M. Diagnostic and 
therapeutic advances in blastic plasmacytoid dendritic cell neoplasm: a focus on hematopoietic 
cell transplantation. Biol Blood Marrow Transplant. 2013;19(7):1006-12.  
Leclerc M, Peffault de Latour R, Michallet M, Blaise D, Chevallier P, Rohrlich PS, et al. Can a 
reduced-intensity conditioning regimen cure blastic plasmacytoid dendritic cell neoplasm? 
Blood. 2017;129(9):1227-1230.  
National Cancer Institute. SEER Stat Fact Sheets: Acute Myeloid Leukemia. 2013, Vol. 2017: 
Surveillance, Epidemiology, and End Results (SEER) Program.  
Olsen EA, Whittaker S, Kim YH, Duvic M, Prince HM, Lessin SR, et al. Clinical end points and 
response criteria in mycosis fungoides and Sezary syndrome: a consensus statement of the  
International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma 
Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for 
Research and Treatment of Cancer. J Clin Oncol. 2011;29(18):2598-607.  
Pemmaraju N. Blastic plasmacytoid dendritic cell neoplasm. Clin Adv Hematol Oncol. 
2016;14(4):220-2.  
Pemmaraju NK, H.; Cortes, J.E.; Duvic, M.; Khoury, J.D.; Patel, K.; Daver, N.G.;  O'Brien,  
S.M.;  Pierce, S.; Garcia-Manero, G.; Jabbour, E; Jain, N.; Faderl, S.; Thomas, D.A.; Frankel,  
A.E.; Qazilbash, M.H.; Konopleva, M.; . 2015  
Blastic Plasmacytoid Dendritic Cell 
Neoplasm (BPDCN): A Large Single-Center Experience: Analysis of Clinical and Molecular 
Characteristics and Patient Outcomes. ASH, Orlando, FL, 2015.  
Pemmaraju NT, D.A.; Kantarjian, H.; Cortes, J.E.; Khoury, J.; Manning, J.T.; Medeiros, L.J.; 
O'Brien, S.M.; Daver, N.G.; Nazha, A.; Pierce, S.; Garcia-Manero, G.; Jabbour, E; Jain, N.; 
Qazilbash, M.H.; Faderl, S.; Frankel, A.E.; Konopleva, M. 2014  
Characteristics of patients 
with blastic plasmacytoid dendritic cell neoplasm (BPDCN): Male predominance, propensity for 
extramedullary involvement, and poor outcomes. ASCO Annual Meeting, 2014. Vol. 32:5s. J 
Clin Oncol.  
Pemmaraju NT, D.A.; Kantarjian, H.; O'Brien, S.M.; Daver, N.G.; Nazha, A.; Pierce, S.;  
Garcia-Manero, G.; Cortes, J.E.; Faderl, S. 2012  
Analysis of outcomes of patients (pts) with 
blastic plasmacytoid dendritic cell neoplasm (BPDCN). ASCO Annual Meeting, 2012. Vol. 30. 
J Clin Oncol.  
Petrella T, Bagot M, Willemze R, Beylot-Barry M, Vergier B, Delaunay M, et al. Blastic NKcell 
lymphomas (agranular CD4+CD56+ hematodermic neoplasms): a review. Am J Clin Pathol. 
2005;123(5):662-75.  
Petrella T, Dalac S, Maynadie M, Mugneret F, Thomine E, Courville P, et al. CD4+ CD56+ 
cutaneous neoplasms: a distinct hematological entity? Groupe Francais d'Etude des Lymphomes 
Cutanes (GFELC). Am J Surg Pathol. 1999;23(2):137-46.  
Poret E, et al. 2015  
How to Treat Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) 
Patients: Results on 86 Patients of the French BPDCN Network. American Society of 
Hematology, Orlando, FL, 2015.  


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19 April 2021, Final Version 3.0  
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Reichard KK, Burks EJ, Foucar MK, Wilson CS, Viswanatha DS, Hozier JC, et al. CD4(+) 
CD56(+) lineage-negative malignancies are rare tumors of plasmacytoid dendritic cells. Am J 
Surg Pathol. 2005;29(10):1274-83.  
Riaz W, Zhang L, Horna P, and Sokol L. Blastic plasmacytoid dendritic cell neoplasm: update 
on molecular biology, diagnosis, and therapy. Cancer Control. 2014;21(4):279-89.  
Roos-Weil D, Dietrich S, Boumendil A, Polge E, Bron D, Carreras E, et al. Stem cell 
transplantation can provide durable disease control in blastic plasmacytoid dendritic cell 
neoplasm: a retrospective study from the European Group for Blood and Marrow 
Transplantation. Blood. 2013;121(3):440-6.  
Shankar G, Arkin S, Cocea L, Devanarayan V, Kirshner S, Kromminga A, et al. Assessment and 
reporting of the clinical immunogenicity of therapeutic proteins and peptides-harmonized 
terminology and tactical recommendations. AAPS J. 2014;16(4):658-73.  
Shapiro R, Sangle, N., Keeney, M., Chin-Yee, I.H., Hsia, C.C., et al. Blastic Plasmacytoid 
Dendritic Cell Neoplasm: A Review of Diagnosis, Pathology, and Therapy. J Cell Sci Ther. 
2015;S8:008:2157-7013.  
Suzuki R, Nakamura S, Suzumiya J, Ichimura K, Ichikawa M, Ogata K, et al. Blastic natural 
killer cell lymphoma/leukemia (CD56-positive blastic tumor): prognostication and 
categorization according to anatomic sites of involvement. Cancer. 2005;104(5):1022-31.  
Tehranchi R, Woll PS, Anderson K, Buza-Vidas N, Mizukami T, Mead AJ, et al. Persistent 
malignant stem cells in del(5q) myelodysplasia in remission. N Engl J Med. 2010;363(11):1025-
37.  
Wang JP, Zhang L, Madera RF, Woda M, and Libraty DH. Plasmacytoid dendritic cell 
interferon-alpha production to R-848 stimulation is decreased in male infants. BMC Immunol. 
2012;13:35.  
Watkins PB, Seligman PJ, Pears JS, Avigan MI, and Senior JR. Using controlled clinical trials 
to learn more about acute drug-induced liver injury. Hepatology. 2008;48(5):1680-9.  
  
 


Stemline Therapeutics, Inc.  
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39  
7.  
STUDY FLOW CHARTS  
The following Study Flow Charts are from Protocol Amendment 8 and Amendment 9.  
  


Stemline Therapeutics, Inc.  
Statistical Analysis Plan, Protocol STML-401-0114 
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40 
Table 7-1:  
Study Events Schedule for Cycle 1 (Study Day -14 to Study Day 21): Stage 1 (All Pts) & Stage 2 (AML Pts: Arm 
A)  
Tests and Observations  
Study Day  
-14 to -4  
Cycle 1  
Study Day  
-1 to 0  
Study Days 1-5 (Up to Study  
Day 10 if Infusion(s) Held) 
tagraxofusp Treatment  
Study Day 
8±3(q) and 15±3 
Study Day 21±7  
Study Day 28±7, Then 
Every 7±3 Days  
Screening  
Pre- 
treatment  
Pre-Infusion  
Infusion  
End of Cycle  
Delayed End of Cycle for 
Toxicity Resolution  
Only if Required  
Informed consent form  
X  
  
  
  
  
  
  
Inclusion/exclusion criteria  
X  
  
  
  
  
  
  
Medical history including prior therapy, 
concomitant medications  
X  
  
  
  
  
  
  
Concomitant Medications  
  
X  
  
  
X  
X  
X  
ECOG performance status  
X  
  
  
  
  
X  
X  
Physical examination  
X  
X  
  
  
X  
X  
  
Pregnancy test (a)  
X  
  
  
  
  
  
  
Vital signs and weight(b)  
X  
X  
X  
X  
X  
X  
X  
12-lead ECG(c)  
X  
X  
X   
X (Infusions 1, 5)  
  
X  
X  
ECHO or MUGA scan(d)  
X  
  
  
  
  
  
  
Hematology(e)  
X  
X  
X  
  
X  
X  
X  
Serum electrolytes(f)  
X  
X  
X  
  
X  
X  
X  
Serum albumin(g)  
X  
X  
X  
  
X  
X  
X  
Serum chemistry(h)  
X  
X  
X  
  
X  
X  
X  
Coagulation parameters: PT/INR, 
aPTT  
X  
  
X  
  
X  
X  
X  
Urinalysis(i)   
X  
  
X (Infusion 1)  
  
X  
X  
X  
Tumor response assessment: Bone 
marrow  
aspiration ± biopsy(j)  
X  
  
  
  
  
X  
  


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Tumor response assessment: CT 
scan(k)  
X  
  
  
  
  
  
  
Tumor response assessment: Skin, 
including biopsies and/or 
photographs(l)  
X  
  
  
  
  
X  
  
Tumor response assessment: 
Peripheral blood  
  
  
  
  
  
X  
  
Translational assessment: Peripheral 
blood (m)  
  
  
X (Infusions 1, 5)  
  
X  
X  
  
Administration of premeds (n)  
  
  
X  
  
  
  
  
Tagraxofusp administration(o)  
  
  
  
X  
  
  
  
Tests and Observations  
Study Day  
-14 to -4  
Cycle 1  
 
 
Study Day  
-1 to 0  
Study Days 1-5 (Up to Study  
Day 10 if Infusion(s) Held) 
tagraxofusp Treatment  
Study Day 
8±3(q) and 15±3 
Study Day 
21±7  
Study Day 28±7, Then 
Every 7±3 Days  
Screening  
Pre- 
treatment  
Pre-Infusion  
Infusion  
End of Cycle  
Delayed End of Cycle for 
Toxicity Resolution  
Only if Required  
Pharmacokinetic sampling(p)   
  
  
X (Infusions 1, 5)  X (Infusions 1, 5)  
  
  
  
Immunogenicity sampling(q)   
  
  
X (Infusion 1)  
  
X (Day 15)  
X  
  
AE and SAE monitoring  
  
  
X  
X  
X  
X  
X  
(a) Urine or serum pregnancy test must be performed within 1 week prior to treatment in women of childbearing potential.  
(b) Vital signs should be performed after patient is sitting for 3-5 minutes. If during dosing period, vital signs should be taken immediately prior to infusion, immediately after 
completion of infusion, and 30, 60, and 240 minutes post-infusion.  
(c) All patients will have a 12-lead Electrocardiogram (ECG) performed at the screening visit and pre-treatment visit, as well as Day 21 (and Day 28 only if delayed end of cycle) 
of each cycle. During the days when patients are undergoing PK sampling (Cycle 1, infusions 1 and 5; Cycle 3, infusions 1 and 5), an ECG will be performed at 3 distinct 
time points (triplicates) within 5 minutes prior to each PK sample collection pre-infusion and at 30 and 60 minutes post-infusion (see (p) and Table 10 in the protocol).  
(d) Multigated Acquisition Scan (MUGA) or 2-D ECHO to quantify left ventricular ejection fraction (LVEF). Must be completed within 28 days prior to start of first cycle of 
study treatment.   
(e) To be collected prior to tagraxofusp infusion if during dosing period. Hematology includes White blood cell (WBC) count, differential white cell count, red blood cell count, 
hematocrit, hemoglobin and platelet count.  
(f) To be collected prior to tagraxofusp infusion if during dosing period. Electrolytes include sodium, potassium, bicarbonate, chloride, blood urea nitrogen (BUN), and 
creatinine.   


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42 
(g) To be collected prior to tagraxofusp infusion if during dosing period. Serum albumin may be a component of the chemistry panel (h). See protocol for administration of 
albumin if serum albumin decreases to <3.0 mg/dL during treatment days or in the immediate post-treatment period.  
(h) To be collected prior to tagraxofusp infusion if during dosing period. Serum electrolytes and chemistry: Sodium, potassium, bicarbonate, chloride, BUN, creatinine, glucose, 
alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), bilirubin (total, direct, and indirect), calcium, creatine 
phosphokinase (CPK), magnesium, lactate dehydrogenase (LDH), phosphate, total protein, uric acid  
(i) To be collected prior to tagraxofusp infusion if during dosing period. Urinalysis includes appearance, color, pH, specific gravity, ketones, leukocytes, protein, glucose, 
bilirubin, urobilinogen, and occult blood.  
(j) Morphology and differential WBC/blast count on aspirate. Baseline must be performed within 14 days prior to the first administration of tagraxofusp. Subsequent bone 
marrow aspirates (± biopsy) will be performed 21 (±7) days after the start of Cycles 1 and 2, and at the Investigator’s discretion thereafter until there is evidence of relapsed or 
progressive disease. If the Cycle 1 (Day 21 [±7]) bone marrow aspirate (±biopsy) is empty, hypocellular, or inadequate, a bone marrow examination should be repeated within 
7 (±7) days to document response. During Stage 2, AML patients (and BPDCN patients with evidence of bone marrow involvement prior to study treatment) will also have 
bone marrow evaluations following Cycles 4 and 6, and at the Investigator’s discretion prior to end of treatment and thereafter. Any additional bone marrow aspirate 
(±biopsy) remaining after the sample is aliquoted for tumor assessment will be collected for translational/correlative assessment. In general, the bone marrow aspirate will be 
prioritized for tumor assessment over translational/correlative assessment. However, submission of bone marrow aspirate material for translational/correlative assessment (5 
mL, larger when feasible) is required both for a pre-treatment (baseline) specimen, and at the end of Cycle 1. If CD123 flow cytometry or IHC stain was performed on the 
bone marrow aspirations (± biopsy), the results should be recorded in the eCRF.  
(k) BPDCN patients only. Baseline must be performed within 14 days prior to the first administration of tagraxofusp. Subsequent CT scans will be performed 21 (±3) days after 
the start of Cycle 2 and 4 and 21 (±7) days after the start of every 4th cycle thereafter until there is evidence of relapsed or progressive disease. Baseline CT scans should be 
full-body, whereas follow-up scans should document response of index lesions.  
(l) BPDCN patients only, with biopsies and/or photographs as indicated, for patients with skin involvement. Baseline must be performed within 14 days prior to the first 
administration of tagraxofusp. Subsequent skin assessments will be performed 21 (±3) days after the start of Cycles 1 and 2 and 21 (±7) days after the start of every 2nd cycle 
thereafter (Cycles 4, 6, etc.) until there is evidence of relapsed or progressive disease.  
(m) Cycle 1 and 3, and at end of treatment, Translational Assessment should be collected at Infusion 1 (Day 1), Infusion 5 (Day 5, 6, 7; if Infusion 5 does not occur by Day 8, 
please obtain this specimen on Day 8) and days 15, 21 (±3 days, but must occur prior to start of subsequent treatment cycle).  (n) Refer to protocol Section 7.5.3.1 – 
Premedication  
(o) Following treatment with premedication, tagraxofusp will be administered as a 15-minute infusion for the first 5 consecutive days of a 21-day cycle. Individual tagraxofusp 
infusions may be delayed to allow for toxicity resolution, all infusions should be completed within 10 days and fewer than 5 infusions are permitted in settings of incipient 
CLS or hepatotoxicity. Patients must be monitored for 4 hours post infusion.  
(p) Plasma samples (6 mL each) will be collected immediately prior to the start of the infusion of tagraxofusp, immediately after end of infusion (time recorded), then 15, 30, 45, 
60, 90, 120, 180, and 240 minutes after completion of the infusion during infusions 1 (ie, Study Day 1) and 5 (ie, Study Day 5) (see (c) and Table 10 in the protocol).  
(q) Blood samples (10 mL) will be collected for the detection of tagraxofusp reactive antibodies according on Day 1 (pre-infusion), Day 15, and Day 21 (if patient is to receive 
Cycle 2, can be Day 1, pre-infusion for Cycle 2). If infusions are held, please collect a sample within 3±3 days after the last tagraxofusp infusion(s) of the cycle.   


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43 
Table 7-2:  
Study Events Schedule for Cycles 2-6 and Subsequent Cycles: Stage 1 (All Pts) & Stage 2 (AML Pts: Arm A)  
Tests and Observations  
Cycle 2+  
End of 
Treatment  
Safety:  
Through  
30 Days  
After Last 
Infusion  
Survival:  
Every 90  
Days After  
Last Infusion  
Days 1-5 (Up to Day 10 if  
Infusion(s) Held)  
Tagraxofusp Treatment  
Day  
8±3(q) and  
15±3  
Day 
21±3  
Day 28±3, Then Every 
7±3 days  
Pre- 
Infusion  
Infusion  
End of Cycle  
Delayed End of Cycle 
for Toxicity Resolution  
Only if Required  
Medical history including prior therapy, 
concomitant medications  
  
  
  
  
  
  
  
  
Concomitant Medications  
  
  
X  
X  
X  
  
  
  
ECOG performance status  
  
  
  
X  
X  
X  
  
  
Physical examination  
  
  
X  
X  
  
X  
  
  
Vital signs and weight(a)  
X  
X  
X  
X  
X  
X  
  
  
12-lead ECG(b)  
X  
X (Cycle 3, 
Infusions 1, 5) 
  
X  
X  
  
  
  
Hematology(c)  
X  
  
X  
X  
X  
  
  
  
Serum electrolytes(d)  
X  
  
X  
X  
X  
  
  
  
Serum albumin(e)  
X  
  
X  
X  
X  
  
  
  
Serum chemistry(f)  
X  
  
X  
X  
X  
  
  
  
Coagulation parameters: PT/INR, 
aPTT  
X  
  
X  
X  
X  
  
  
  
Urinalysis(g)  
X  
(Infusion 1)  
  
X  
X  
X  
  
  
  
Tumor response assessment: Bone 
marrow aspiration ± biopsy(h)  
  
  
  
X (h)   
  
  
  
  
Tumor response assessment: CT 
scan(i)  
  
  
  
X   
  
  
  
  
Tumor response assessment: skin, 
including biopsies and/or 
photographs(j)  
  
  
  
X  
  
  
  
  


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Statistical Analysis Plan, Protocol STML-401-0114 
19 April 2021, Final Version 3.0  
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Tumor response assessment: 
peripheral blood  
  
  
  
X (k)  
  
  
  
  
Translational assessment: 
Peripheral blood (l)  
X  
(Infusions 1,5)  
  
X  
X  
  
X  
  
  
Administration of premeds (m)  
X  
  
  
  
  
  
  
  
Tagraxofusp administration(n)  
  
X  
  
  
  
  
  
  
Pharmacokinetic sampling(o)  
X (Cycle 3, 
Infusions 1, 5) 
X (Cycle 3, 
Infusions 1, 5) 
  
  
  
  
  
  
Immunogenicity sampling(p)  
X  
(Infusion 1)  
  
  
X  
  
  
  
  
Tests and Observations  
Cycle 2+  
End of 
Treatment  
Safety:  
Through  
30 Days  
After Last 
Infusion  
Survival:  
Every 90  
Days After  
Last Infusion  
Days 1-5 (Up to Day 10 if  
Infusion(s) Held)  
Tagraxofusp Treatment  
Day  
8±3(q) and  
15±3  
Day 
21±3  
Day 28±3, Then Every 
7±3 days  
Pre- 
Infusion  
Infusion  
End of Cycle  
Delayed End of Cycle 
for Toxicity Resolution  
Only if Required  
AE and SAE monitoring  
X  
X  
X  
X  
X  
  
X  
  
Long-term follow-up(q)  
  
  
  
  
  
  
X  
X  
(a) Vital signs should be performed after patient is sitting for 3-5 minutes. If during dosing period, vital signs should be taken immediately prior to infusion, immediately after 
completion of infusion, and 30, 60, and 240 minutes post-infusion.  
(b) All patients will have a 12-lead ECG performed at the screening visit and pre-treatment visit, as well as Day 21 (and Day 28 only if delayed end of cycle) of each cycle. 
During the days when patients are undergoing PK sampling (Cycle 1, infusions 1 and 5; Cycle 3, infusions 1 and 5), an ECG will be performed at 3 distinct time points 
(triplicates) within 5 minutes prior to each PK sample collection pre-infusion and at 30 and 60 minutes post-infusion (see footnote (n) and Table 10 in the protocol).  
(c) To be collected prior to tagraxofusp infusion if during dosing period. Hematology includes WBC count, differential white cell count, red blood cell count, hematocrit, 
hemoglobin and platelet count.  
(d) To be collected prior to tagraxofusp infusion if during dosing period. Electrolytes include sodium, potassium, bicarbonate, chloride, BUN, and creatinine.   
(e) To be collected prior to tagraxofusp infusion if during dosing period. Serum albumin may be a component of the chemistry panel (f). See protocol for administration of 
albumin if serum albumin decreases to <3.0 mg/dL during treatment days or in the immediate post-treatment period.  
(f) To be collected prior to tagraxofusp infusion if during dosing period. Serum electrolytes and chemistry: Sodium, potassium, bicarbonate, chloride, BUN, creatinine, glucose, 
ALT, ALP, AST, bilirubin (total, direct, and indirect), calcium, CPK, magnesium, LDH, phosphate, total protein, uric acid  
(g) To be collected prior to tagraxofusp infusion if during dosing period. Urinalysis includes appearance, color, pH, specific gravity, ketones, leukocytes, protein, glucose, 
bilirubin, urobilinogen, and occult blood.   
(h) Morphology and differential WBC/blast count on aspirate. Bone marrow aspirates (± biopsy) will be performed 21 (±7) days after the start of Cycle 2, and, in Stage 1, at the 
Investigator’s discretion prior to end of treatment and thereafter until there is evidence of relapsed or progressive disease. In Stage 1, submission of aspirate (5 mL or greater) 
for translational/correlative assessment at timepoints subsequent to Cycle 1 is strongly encouraged, whenever feasible. During Stage 2, AML patients (and BPDCN patients 
with evidence of bone marrow involvement prior to study treatment) will also have bone marrow evaluations following Cycles 4 and 6 and then every 3 months from Months 


Stemline Therapeutics, Inc.  
Statistical Analysis Plan, Protocol STML-401-0114 
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45 
6-12; every 6 months from 12 to 24 months; and every 12 months thereafter until there is evidence of relapsed or progressive disease. In Stage 2, any additional bone marrow 
aspirate (± biopsy) remaining after the sample is aliquoted for tumor assessment will be collected for translational/correlative assessment. The bone marrow aspirate will be 
prioritized for tumor assessment over translational/correlative assessment. If CD123 flow cytometry or IHC stain was performed on the bone marrow aspirations (± biopsy), 
the results should be recorded in the eCRF.  
(i) BPDCN patients only. Baseline must be performed within 14 days prior to the first administration of tagraxofusp. In Stage 1, subsequent CT scans will be performed 21 (±7) 
days after the start of Cycle 2 and 4 and 21 (±7) days after the start of every 4th cycle thereafter until there is evidence of relapsed or progressive disease. Baseline CT scans 
should be full-body, whereas follow-up scans should document response of index lesions.  
(j) BPDCN patients only, with biopsies and/or photographs as indicated, for patients with skin involvement. Baseline must be performed within 14 days prior to the first 
administration of tagraxofusp. Subsequent skin assessments will be performed 21 (±7) days after the start of Cycles 1 and 2 and 21 (±7) days after the start of every 2nd cycle 
thereafter (Cycles 4, 6, etc.) until evidence of relapsed or progressive disease. Quantification of disease burden via the mSWAT is required at the time of each skin 
assessment.  
(k) Patients with evidence of peripheral blasts at baseline will have peripheral blood samples collected 21 (±7) days after the start of Cycles 1 and 2 and 21 (±7) days after the 
start of every 2nd cycle thereafter (Cycles 4, 6, etc.) until there is evidence of relapsed or progressive disease.  
(l) Cycle 1 and 3, and at end of treatment, Translational Assessment should be collected at Infusion 1 (Day 1) and Infusion 5 (Day 5, 6, 7; if Infusion 5 does not occur by Day 8, 
please obtain this specimen on Day 8) and Days 15, 21 (±3 days, but must occur prior to start of subsequent treatment cycle). (m) Refer to protocol Section 7.5.3.1 – 
Premedication  
(n) Following treatment with premedication, tagraxofusp will be administered as a 15-minute infusion for the first 5 consecutive days of a 21-day cycle. Individual tagraxofusp 
infusions may be delayed to allow for toxicity resolution; all infusions should be completed within 10 days and fewer than 5 infusions are permitted in settings of incipient 
CLS or hepatotoxicity. Patients must be monitored for 4 hours post infusion.  
(o) Plasma samples (6 mL each) will be collected immediately prior to the start of the infusion of tagraxofusp, immediately after end of infusion (time recorded), then 15, 30, 45, 
60, 90, 120, 180, and 240 minutes after the start of the infusion during infusions 1 (ie, Day 1) and 5 (ie, Day 5) of Cycle 3 (see footnote (b) and Table 10 in the protocol).   
(p) Blood samples (10 mL) will be collected for the detection of tagraxofusp reactive antibodies according on Day 1 (pre-infusion), Day 15, and Day 21 (if patient is to receive 
additional cycles, can be Day 1, pre-infusion for next cycle). If infusions are held, please collect a sample within 3±3 days the last tagraxofusp infusion(s) of the cycle.  
(q) After the follow-up visit, patients will then be followed every 90 days for survival status. The survival follow-up may be by telephone contact. If the patient is in CR/PR at the 
time of discontinuation, disease assessments should continue to be performed as described in protocol Section 8.11 on an every 6-week basis (±1 week) through 6 months 
post-C1D1 and then on an every 90-day basis or until, in the judgment of the Investigator, there is evidence of relapsed or progressive disease.   
 


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Table 7-3:  
Study Events Schedule for Cycles 1 & 2 (Study Day -14 to Study Day 21): BPDCN (Arm B) Patients in Stage 2  
Tests and Observations  
Study Day  
-14 to -4  
Cycles 1 & 2  
Study Day  
-1 to 0  
Cycle Days 1-5 (Up to Study  
Day 10 if Infusion(s) Held) 
Tagraxofusp Treatment  
Study Day 
8±3(q) and 15±3 
Cycle Day 
21±7  
Cycle Day 28±7, Then 
Every 7±3 Days  
Screening  
Pre- 
treatment  
Pre-Infusion  
Infusion  
End of Cycle  
Delayed End of Cycle for 
Toxicity Resolution  
Only if Required  
Informed consent form  
X  
  
  
  
  
  
  
Inclusion/exclusion criteria  
X  
  
  
  
  
  
  
Medical history including prior therapy, 
concomitant medications  
X  
  
  
  
  
  
  
Concomitant Medications  
  
X  
  
  
X  
X  
X  
ECOG performance status  
X  
  
  
  
  
X  
X  
Physical examination  
X  
X  
  
  
X  
X  
  
Pregnancy test (a)  
X  
  
  
  
  
  
  
Vital signs and weight(b)  
X  
X  
X  
X  
X  
X  
X  
12-lead ECG(c)  
X  
X  
X   
X (Infusions 1, 5)  
  
X  
X  
ECHO or MUGA scan(d)  
X  
  
  
  
  
  
  
Hematology(e)  
X  
X  
X  
  
X  
X  
X  
Serum electrolytes(f)  
X  
X  
X  
  
X  
X  
X  
Serum albumin(g)  
X  
X  
X  
  
X  
X  
X  
Serum chemistry(h)  
X  
X  
X  
  
X  
X  
X  
Coagulation parameters: PT/INR, 
aPTT  
X  
  
X  
  
X  
X  
X  
Urinalysis(i)   
X  
  
X (Infusion 1)  
  
X  
X  
X  
Tumor response assessment: Bone 
marrow  
aspiration ± biopsy(j)  
X  
  
  
  
  
X  
  
Tumor response assessment: CT 
scan(k)  
X  
  
  
  
  
X (Cycle 2) (k)  
  


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Statistical Analysis Plan, Protocol STML-401-0114 
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Tumor response assessment: Skin, 
including biopsies and/or 
photographs(l)  
X  
  
  
  
  
X  
  
Tumor response assessment: 
Peripheral blood   
  
  
  
  
  
X  
  
Translational assessment: Peripheral 
blood (m)  
  
  
  
  
  
  
  
Administration of premeds (n)  
  
  
X  
  
  
  
  
Tagraxofusp administration(o)  
  
  
  
X  
  
  
  
Pharmacokinetic sampling(p)   
  
  
X (Infusions 1, 5)  X (Infusions 1, 5)  
  
  
  
Tests and Observations  
Study Day  
-14 to -4  
Cycles 1 & 2   
 
Study Day  
-1 to 0  
Cycle Days 1-5 (Up to Study  
Day 10 if Infusion(s) Held) 
Tagraxofusp Treatment  
Study Day 
8±3(q) and 15±3 
Cycle Day 21±7  
Cycle Day 28±7, Then 
Every 7±3 Days  
Screening  
Pre- 
treatment  
Pre-Infusion  
Infusion  
End of Cycle  
Delayed End of Cycle for 
Toxicity Resolution  
Only if Required  
Immunogenicity sampling(q)   
  
  
X (Infusion 1)  
  
X  
(C1D15 only)  
X  
  
Vision Assessment  
X  
  
  
  
  
  
  
AE and SAE monitoring  
  
  
X  
X  
X  
X  
X  
(a) Urine or serum pregnancy test must be performed within 1 week prior to treatment in women of childbearing potential.  
(b) Vital signs should be performed after patient is sitting for 3-5 minutes. If during dosing period, vital signs should be taken immediately prior to infusion, immediately after 
completion of infusion, and 30, 60, and 240 minutes post-infusion.  
(c) All patients will have a 12-lead ECG performed at the screening visit and pre-treatment visit, as well as Day 21 (and Day 28 only if delayed end of cycle) of each cycle. 
During the days when patients are undergoing PK sampling (Cycle 1, infusions 1 and 5; Cycle 3, infusions 1 and 5), an ECG will be performed at 3 distinct time points 
(triplicates) within 5 minutes prior to each PK sample collection pre-infusion and at 30 and 60 minutes post-infusion (see (p) and Table 10 in the protocol).  
(d) MUGA or 2-D ECHO to quantify LVEF. Must be completed within 28 days prior to start of first cycle of study treatment.   
(e) To be collected prior to tagraxofusp infusion if during dosing period. Hematology includes WBC count, differential white cell count, red blood cell count, hematocrit, 
hemoglobin and platelet count.  
(f) To be collected prior to tagraxofusp infusion if during dosing period. Electrolytes include sodium, potassium, bicarbonate, chloride, BUN, and creatinine.   
(g) To be collected prior to tagraxofusp infusion if during dosing period. Serum albumin may be a component of the chemistry panel (h). See protocol for administration of 
albumin if serum albumin decreases to <3.0 mg/dL during treatment days or in the immediate post-treatment period.  
(h) To be collected prior to tagraxofusp infusion if during dosing period. Serum electrolytes and chemistry: Sodium, potassium, bicarbonate, chloride, BUN, creatinine, glucose, 
ALT, albumin, ALP, AST, bilirubin (total, direct, and indirect), calcium, CPK, magnesium, LDH, phosphate, total protein, uric acid  


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(i) To be collected prior to initial tagraxofusp infusion of the cycle. Urinalysis includes appearance, color, pH, specific gravity, ketones, leukocytes, protein, glucose, bilirubin, 
urobilinogen, and occult blood.   
(j) Morphology and differential WBC/blast count on aspirate. Baseline must be performed within 14 days prior to the first administration of tagraxofusp. For BPDCN patients in 
Stage 2, subsequent bone marrow aspirates (± biopsy) will be performed 21 (±7) days after the start of Cycles 1 and 2. If the Cycle 1 (Day 21 [±7]) bone marrow aspirate (± 
biopsy) is empty, hypocellular, or inadequate, a bone marrow examination should be repeated within 7 (±7) days to document response. If CD123 flow cytometry stain was 
performed on the bone marrow aspirations (± biopsy), the results should be recorded in the eCRF. Submission of aspirate (5 mL or greater) for translational/correlative 
assessment is required for all patients with evidence of bone marrow involvement prior to study treatment at 1) pre-treatment baseline, and 2) end of Cycle 1. Any additional 
bone marrow (± biopsy) remaining after the sample is aliquoted for tumor assessment will be collected for exploratory translational/correlative assessments. The bone marrow 
aspirate will be prioritized for tumor assessment (by the Investigator) over translational/correlative assessments.  
(k) Baseline CT must be performed within 14 days prior to the first administration of tagraxofusp. For patients with baseline evidence of lymph node or visceral disease 
involvement, subsequent Stage 2 CT scans will be performed 21 (±7) days after the start of Cycles 2, 4 and 6, and 21 (±7) days after the start of every 4th cycle thereafter 
(approximately every 12 weeks) until there is evidence of relapsed or progressive disease. For patients with no baseline evidence of lymph node or visceral BPDCN 
involvement, subsequent scans should be performed at the end of Cycle 2 (±7 days; or at time of disease progression if PD occurs prior to end of Cycle 2), 21 (±7) days after 
the start of Cycle 6, and at Investigator’s discretion thereafter. Baseline CT scans should be full-body, whereas follow-up scans should document response of index lesions.  
(l) For patients with skin involvement. Baseline must be performed within 14 days prior to the first administration of tagraxofusp. Subsequent skin assessments will be performed 
21 (±7) days after the start of Cycles 1 and 2 and 21 (±7) days after the start of every 2nd cycle thereafter (Cycles 4, 6, etc.) until there is evidence of relapsed or progressive 
disease. Quantification of skin disease burden via the mSWAT instrument is required at the time of each skin assessment.   
(m) In Cycle 1 and 3, and at end of treatment, Translational Assessment should be collected at Infusion 1 (Day 1), Infusion 5 (Day 5, 6, 7; if Infusion 5 does not occur by Day 8, 
please obtain this specimen on Day 8) and days 15, 21 (±3 days, but must occur prior to start of subsequent treatment cycle).  (n) Refer to protocol section 7.5.3 – 
Premedication and Administration  
(o) Following treatment with premedication, tagraxofusp will be administered as a 15-minute infusion for the first 5 consecutive days of a 21-day cycle. Individual tagraxofusp 
infusions may be delayed to allow for toxicity resolution; all infusions should be completed within 10 days and fewer than 5 infusions are permitted in settings of incipient 
CLS or hepatotoxicity. Patient must be monitored for 4 hours post infusion.  
(p) Plasma samples (6 mL each) will be collected immediately prior to the start of the infusion of tagraxofusp, immediately after end of infusion (time recorded), then 15, 30, 45, 
60, 90, 120, 180, and 240 minutes after completion of the infusion during infusions 1 (ie, Study Day 1) and 5 (ie, Study Day 5) of Cycles 1 & 3 (see Table 10 in the protocol).   
(q) Blood samples (10 mL) will be collected for the detection of tagraxofusp reactive antibodies on Day 1 (pre-infusion), Day 15, and Day 21 (if patient is to receive Cycle 2, can 
be Day 1, pre-infusion for Cycle 2). If infusions are held, please collect a sample within 3±3 days after completion of the last tagraxofusp infusion of the cycle.  


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Table 7-4:  
Study Events Schedule for Cycles 3-6 and Subsequent Cycles: Stage 2 (BPDCN Patients)  
Tests and Observations  
Cycle 3+  
End of 
Treatment  
Safety:  
Through  
30 Days  
After Last 
Infusion  
Survival:  
Every 90  
Days After  
Last Infusion  
Days1-5 (Up to Day 10 if 
Infusion(s) Held)  
Tagraxofusp Treatment  
Day 8±3(q) 
and  
15±3(q)  
Day 
21±7  
Day 28±7, Then Every 
7±3 days  
Pre- 
Infusion  
Infusion  
End of Cycle  
Delayed End of Cycle 
for Toxicity Resolution  
Only if Required  
Medical history including prior therapy, 
concomitant medications   
  
  
  
  
  
  
  
  
Concomitant Medications  
  
  
Xr  
X  
X  
  
  
  
ECOG performance status  
  
  
  
X  
X  
X  
  
  
Physical examination  
  
  
  
X  
  
X  
  
  
Vital signs and weight(a)  
X  
X  
  
X  
X  
X  
  
  
12-lead ECG(b)  
X  
X (Cycle 3, 
Infusions 1, 5) 
  
X  
X  
  
  
  
Hematology(c)  
X  
  
Xr  
X  
X  
  
  
  
Serum electrolytes(d)  
X  
  
Xr  
X  
X  
  
  
  
Serum albumin(e)  
X  
  
Xr  
X  
X  
  
  
  
Serum chemistry(f)  
X  
  
Xr  
X  
X  
  
  
  
Coagulation parameters: PT/INR, 
aPTT  
X  
  
Xr  
X  
X  
  
  
  
Urinalysis(g)  
X (Infusion 1)  
  
Xr  
X  
X  
  
  
  
Tumor response assessment: Bone 
marrow aspiration ± biopsy(h)  
  
  
  
 X(i)  
  
  
  
  
Tumor response assessment: CT 
scan(i)  
  
  
  
X  
  
  
  
  
Tumor response assessment: skin, 
including biopsies and/or 
photographs(j)  
  
  
  
X  
  
  
  
  


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Tumor response assessment: 
peripheral blood  
  
  
  
X(k)  
  
  
  
  
Translational assessment: 
Peripheral blood (l)  
X(Infusions 1,5) 
  
  
X  
  
X  
  
  
Administration of premeds (m)  
X  
  
  
  
  
  
  
  
Tagraxofusp administration(n)  
  
X  
  
  
  
  
  
  
Pharmacokinetic sampling(o)  
X (Cycle 3, 
Infusions 1, 5) 
X (Cycle 3, 
Infusions 1, 5) 
  
  
  
  
  
  
Immunogenicity sampling(p)  
X (Infusion 1)  
  
  
X  
  
  
  
  
AE and SAE monitoring  
X  
X  
Xr  
X  
X  
  
X  
  
Long-term follow-up(q)  
  
  
  
  
  
  
X  
X  
(a) Vital signs should be performed after patient is sitting for 3-5 minutes. If during dosing period, vital signs should be taken immediately prior to infusion, immediately after 
completion of infusion, and 30, 60, and 240 minutes post-infusion.  
(b) All patients will have a 12-lead ECG performed at the screening visit and pre-treatment visit, as well as Day 21 (and Day 28 only if delayed end of cycle) of each cycle. 
During the days when patients are undergoing PK sampling (Cycle 1, infusions 1 and 5; Cycle 3, infusions 1 and 5), an ECG will be performed at 3 distinct time points 
(triplicates) within 5 minutes prior to each PK sample collection pre-infusion and at 30 and 60 minutes post-infusion (see (m) and Table 10 in the protocol).  
(c) To be collected prior to tagraxofusp infusion if during dosing period. Hematology includes WBC count, differential white cell count, red blood cell count, hematocrit, 
hemoglobin and platelet count.  
(d) To be collected prior to tagraxofusp infusion if during dosing period. Electrolytes include sodium, potassium, bicarbonate, chloride, BUN, and creatinine.   
(e) To be collected prior to tagraxofusp infusion if during dosing period. Serum albumin may be a component of the chemistry panel (f). See protocol for administration of 
albumin if serum albumin decreases to <3.0 mg/dL during treatment days or in the immediate post-treatment period.  
(f) To be collected prior to tagraxofusp infusion if during dosing period. Serum electrolytes and chemistry: Sodium, potassium, bicarbonate, chloride, BUN, creatinine, glucose, 
ALT, albumin, ALP, AST, bilirubin (total, direct, and indirect), calcium, CPK, magnesium, LDH, phosphate, total protein, uric acid  
(g) To be collected prior to initial tagraxofusp infusion of the cycle. Urinalysis includes appearance, color, pH, specific gravity, ketones, leukocytes, protein, glucose, bilirubin, 
urobilinogen, and occult blood.   
(h) Morphology and differential WBC/blast count on aspirate. In Stage 2, patients with evidence of bone marrow involvement prior to study will have bone marrow evaluations 
following Cycles 4 and 6 and then every 3 months from Months 6-12; every 6 months from 12 to 24 months; and every 12 months thereafter until there is evidence of 
relapsed or progressive disease. If CD123 flow cytometry stain was performed on the bone marrow aspirations (± biopsy), the results should be recorded in the eCRF. For 
patients with evidence bone marrow involvement at Baseline, any additional bone marrow (± biopsy) remaining after the sample is aliquoted for tumor assessment will be 
collected for exploratory translational/correlative assessments. The bone marrow aspirate will be prioritized for tumor assessment (by the Investigator) over 
translational/correlative assessments.  
(i) Baseline CT must be performed within 14 days prior to the first administration of tagraxofusp. For patients with baseline evidence of lymph node or visceral disease 
involvement, subsequent Stage 2 CT scans will be performed 21 (±7) days after the start of Cycles 1, 2, 4 and 6, and 21 (±7) days after the start of every 4th cycle thereafter 
(approximately every 12 weeks) until there is evidence of relapsed or progressive disease. For patients with no baseline evidence of lymph node or visceral BPDCN 
involvement, subsequent scans should be performed at the end of Cycle 2 (±7 days; or at time of disease progression if PD occurs prior to end of Cycle 2), 21 (±7) days after 
the start of Cycle 6, and at Investigator’s discretion thereafter. Baseline CT scans should be full-body, whereas follow-up scans should document response of index lesions.  


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Statistical Analysis Plan, Protocol STML-401-0114 
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51 
(j) For patients with skin involvement. Baseline must be performed within 14 days prior to the first administration of tagraxofusp. Subsequent skin assessments will be performed 
21 (±7) days after the start of Cycles 1 and 2 and 21 (±7) days after the start of every 2nd cycle thereafter (Cycles 4, 6, etc.) until there is evidence of relapsed or progressive 
disease. Quantification of skin disease burden via the mSWAT instrument is required at the time of each skin assessment.  
(k) Peripheral blood samples will be collected 21 (±7) days after the start of Cycles 1 and 2 and, for patients with evidence of peripheral blasts at baseline, 21 (±7) days after the 
start of every 2nd cycle thereafter (Cycles 4, 6, etc.) until there is evidence of relapsed or progressive disease.  
(l) In Cycle 1 and 3, and at end of treatment, Translational Assessment should be collected at Infusion 1 (Day 1) and Infusion 5 (Day 5, 6, 7; if Infusion 5 does not occur by Day 
8, please obtain this specimen on Day 8) and Days 15, 21 (±3 days, but must occur prior to start of subsequent treatment cycle). (m) Refer to protocol section 7.5.3 – 
Premedication and Administration  
(n) Following treatment with premedication, tagraxofusp will be administered as a 15-minute infusion for the first 5 consecutive days of a 21-day cycle. Individual tagraxofusp 
infusions may be delayed to allow for toxicity resolution; all infusions should be completed within 10 days and fewer than 5 infusions are permitted in settings of incipient 
CLS or hepatotoxicity. Patient must be monitored for 4 hours post infusion.  
(o) Plasma samples (6 mL each) will be collected immediately prior to the start of the infusion of tagraxofusp, immediately after end of infusion (time recorded), then 15, 30, 45, 
60, 90, 120, 180, and 240 minutes after the start of the infusion during infusions 1 (ie, Day 1) and 5 (ie, Day 5) of Cycles 1 & 3 (see Table 10 in the protocol).   
(p) Blood samples (10 mL) will be collected for the detection of tagraxofusp reactive antibodies on Day 1 (pre-infusion), Day 15, and Day 21 (if patient is to receive additional 
cycles, can be Day 1, pre-infusion for next cycle). If infusions are held, please collect a sample within 3±3 days after the last tagraxofusp infusion of the cycle.  
(q) After the follow-up visit, patients will then be followed every 90 days for survival status. The survival follow-up may be by telephone contact. If the patient is in CR/PR at the 
time of discontinuation, disease assessments should continue to be performed as described in protocol Section 8.12 on an every 6-week basis (±1 week) through 6 months 
post-C1D1 and then on an every 90-day basis or until, in the judgment of the Investigator, there is evidence of relapsed or progressive disease.   
(r) For Cycles 5 and beyond (Stage 2), the Day 8 and 15 concomitant medication and AE evaluations may be conducted via telephone and the laboratory evaluations may be 
performed at local laboratories for patients who live a considerable distance from the study center.  
  


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8.  
RESPONSE CRITERIA  
8.1. Tumor Response Criteria for Patients with AML  
Response  
Location  
Criteria  
Complete 
Remission (CR)  
Marrow  
• 
Normalization of blast percentage (≤5%)  
• 
No detectable Auer rods  
Peripheral Blood  
• 
Normalization neutrophil count (≥1,000/µL) and platelet count 
(≥100,000/µL)  
• 
Absence of leukemic blasts  
Extramedullary  
•  
No extramedullary disease (CNS or soft tissue)  
CR with 
incomplete blood  
count recovery  
(CRi)  
Marrow  
•  
Normalization of blast percentage (≤5%)  
Peripheral Blood  
• 
Incomplete recovery of neutrophil and/or platelet count  
• 
Absence of leukemic blasts  
Extramedullary  
•  
No extramedullary disease (CNS or soft tissue)  
Partial Remission 
(PR)  
Marrow  
•  
Decrease by ≥50% in blast percentage to  5 - 25% or to ≤5% with 
Auer rods present  
Peripheral Blood  •  
 
Stable Disease 
(SD)  
  
•  
Failure to achieve at least a PR, but no evidence of progression for 
at least 8 weeks  
Relapse after 
CR/CRi  
Marrow  
•  
Blast percentage >5% (if no peripheral blasts, then confirmation 
aspirate required ≥1 week later)  
Relapse after PR  
Marrow  
•  
 confirmation  
Progressive 
Disease (PD)  
Marrow  
•  
≥50% increase in blasts from baseline  
Peripheral Blood  
One or more of the following:  
• 
≥50% decrease from peak remission levels in platelets or 
granulocytes;  
• 
Reduction in hemoglobin concentration by at least 2 g/dL; 
•  
Transfusion dependence  
  
8.2. Tumor Response Criteria for Patients with BPDCN  
Response  
Location  
Criteria  
Complete 
Response (CR)  
Marrowb  
•  Normalization of blast percentage (≤5%) b  
Peripheral Blood  
•  
•  
Normalization of neutrophil count (≥1,000/µL) and platelet count  
(≥100,000/µL)  
Absence of leukemic blasts  


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Skina  
•  100% clearance of all skin lesions from baseline; no new lesions 
in patients without lesions at baselinea  
Nodal Masses  
•  Regression to normal size on CT  
Spleen, Liver  
•  Not palpable, nodules disappeared  
CR with 
incomplete blood  
count recovery  
(CRi)  
Marrowb  
•  Normalization of blast percentage (≤5%) b  
Peripheral Blood  •  
•  
Incomplete recovery of neutrophil and/or platelet count 
Absence of leukemic blasts  
Skina  
•  100% clearance of all skin lesions from baseline; no new lesions 
in patients without lesions at baselinea   
Nodal Masses  
•  Regression to normal size on CT  
Spleen, Liver  
•  Not palpable, nodules disappeared  
CR [clinical] with 
minimal residual 
skin abnormality  
(CRc)  
Marrowb  
•  Normalization of blast percentage (≤5%) b  
Peripheral Blood  
•  
•  
Normalization of neutrophil count (≥1,000/µL) and platelet count  
(≥100,000/µL)  
Absence of leukemic blasts  
Skina  
•  Marked clearance of all skin lesions from baseline; residual 
hyperpigmentation or abnormality with BPDCN identified on 
biopsy (or no biopsy performed) a, c  
Nodal Masses  
•  Regression to normal size on CT  
Spleen, Liver  
•  Not palpable, nodules disappeared  
Partial Response 
(PR)  
Marrowb  
•  Decrease by ≥50% in blast percentage to 5 − 25% b  
Peripheral Blood  •  Normalization of neutrophil count (≥1,000/µL) and platelet count  
(≥100,000/µL)  
Skina  
•  50% − <100% clearance of all skin lesions from baseline; no new 
lesions in patients without lesions at baselinea  
Nodal Masses  
•  ≥50% decrease in SPD of up to 6 largest dominant masses; no 
increase in size of other nodes  
Spleen, Liver  
•  ≥50% decrease in SPD of nodules (for single nodule in greatest 
transverse diameter); no increase in size of liver or spleen  
Stable Disease 
(SD)  
  
•  Failure to achieve at least a PR, but no evidence of progression for 
at least 8 weeks  
Relapse after 
CR/CRi/CRc  
Marrowb  
•  Blast percentage >5% (if no peripheral blasts, then confirmation 
aspirate required ≥1 week later) b  
Peripheral Blood  •  Presence of leukemic blasts  
Skina  
•  Increase in skin score greater than the sum of nadir plus 50% 
baseline scorea  
Nodal Masses  
•  Appearance of a new lesion(s) >1.5 cm in any axis, ≥50% increase 
from nadir in SPD of more than one node, or ≥50% increase from 
nadir in longest diameter of a previously identified node >1 cm in 
short axis  
Spleen, Liver  
•  >50% increase from nadir in the SPD of any previous lesions  
 
Marrowb  
•  
Blast percentage ≥25% (if no peripheral blasts, then confirmation 
aspirate required ≥1 week later) b  


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Skina  
•  
Increase in skin score greater than the sum of nadir plus 50% 
baseline scorea  
 
Relapse after PRd  
•  
Appearance of a new lesion(s) >1.5 cm in any axis, ≥50% increase  
 
Nodal Masses  from nadir in SPD of more than one node, or ≥50% increase from nadir in 
longest diameter of a previously identified node >1 cm in  
short axis  
 
Spleen, Liver  
•  
>50% increase from nadir in the SPD of any previous lesions  
Marrowb  
•  
≥50% increase in blasts from baseline (and blast percentage 
>5%)b One or more of the following: •  
≥50% decrease from peak 
remission levels in platelets or  
 
Peripheral Blood  
granulocytes;  
• 
Reduction in hemoglobin concentration by at least 2 g/dL;  
• 
Transfusion dependence  
 
Progressive  
One or more of the following:  
 
Disease (PD)d  
Skina  
•  ≥25% increase in skin disease from baselinea  
• 
Any new tumors in patients without tumors at baseline  
• 
Appearance of a new lesion(s) >1.5 cm in any axis, ≥50% increase  
 
Nodal Masses  
from nadir in SPD of more than one node, or ≥50% nadir in longest 
diameter of a previously identified node >1 cm in increase from  
short axis  
 
Spleen, Liver  
•  >50% increase from nadir in the SPD of any previous lesions  
Abbreviations: CT, computed tomography; SPD, sum of the product of the diameters.  
All parameters detailed above (including bone marrow, blood, skin [including mSWAT quantification], lymph 
nodes and viscera) are to be assessed both at baseline and stipulated subsequent timepoints.  Responses are 
determined via comparison to baseline values (or post-treatment nadir values as stipulated in the above table).   
a 
The percentage of clearance or increase in skin disease is calculated using the Modified Severity Weighted 
Assessment Tool (mSWAT), which is provided in protocol Section 16.3/Appendix C.  Detailed guidance and 
examples regarding the calculation of an mSWAT assessment based on the size and nature of a patient’s skin 
lesions are provided in a separate document.   
b 
In settings in which there is a change in the blast population on bone marrow evaluation by means of flow 
cytometry or other molecular methodology without a similar degree of change in the morphologic blast 
percentage, the morphologic percentage should be utilized to determine response/progression; however the 
findings from flow cytometry (or other molecular methodology) should be recorded as part of the study record.  c 
Marked clearance is defined as the resolution of ≥75% of a patient’s skin lesions from baseline.  Residual 
hyperpigmentation or abnormality identified on a biopsy (or no biopsy performed) is defined as residual skin 
abnormality, not indicative of active disease, that covers ≤10% of a patient’s skin overall.  d In settings in which 
there is preliminary but not conclusive evidence of disease progression (i.e., new skin lesions of indeterminate 
etiology, new lymph nodes ≤1.5cm, modest increase in bone marrow blast percentage subsequent to an initial 
marked reduction, appearance of new blast population on bone marrow evaluation by means of flow cytometry or 
other molecular methodology without increase in blast percentage consistent with PD), additional tagraxofusp 
cycles may be administered, provided that the Investigator documents that the evidence of potential disease 
progression is inconclusive and that the overall risk/benefit assessment favors additional investigational therapy.  
Additional tagraxofusp may also be administered in situations of mixed response BPDCN in which 
response/progression is not consistent between a given patient’s disease sites, provided that the Investigator 


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19 April 2021, Final Version 3.0  
55 
documents that the overall risk/benefit assessment favors additional investigational therapy.  In such situations, it 
is essential that relevant findings and assessments are documented, and that areas of potential disease progression 
are followed closely on subsequent assessments.  
  
  
8.3.  
Capillary Leak Syndrome FDA Algorithm  
Screen-positive subjects include those   
a. With Preferred Term “Capillary leak syndrome” as an adverse event, OR  
b. Those meeting 2 or more of the criteria in the table below with at least 2 criteria having a 
start date within 7 days of each other.   
Criteria  
Variable  
≥ 1 of these  
(Hypoalbuminemia)  
PT  
Lab result  
Albumin (any value ≤ 3 g/dL)  
  
≥ 1 of these  
(Edema)  
HLT  
Oedema  
PT  
Ascites  
PT  
Eyelid oedema  
PT  
Face oedema  
PT  
Fluid overload  
PT  
Fluid retention  
PT  
Generalized oedema  
PT  
Hypervolaemia  
PT  
Laryngeal oedema  
PT  
Oedema  
PT  
Oedema peripheral  
PT  
Periorbital oedema  
PT  
Peripheral swelling  
PT  
Swelling  
PT  
Swelling face  
PT  
Weight increased  
VS result  
Weight (any value > 5 kg from baseline)  
 
PT  
Hypotension  
PT  
Hypovolemia  
VS result  
Systolic Blood Pressure  (any 
value < 90 mmHg)    
Concomitant medication  Dopamine  
Concomitant medication  Ephedrine  
Concomitant medication  Epinephrine  
Concomitant medication  Norepinephrine  
Concomitant medication  Norepinephrine bitartrate  
Concomitant medication  Phenylephrine  


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56 
Concomitant medication  Vasopressin  
≥ 1 of these  
(CRS/IRR)  
PT  
Cytokine release syndrome  
PT  
Infusion related reaction  
(“Catch-all”)  
PT  
Cardiac arrest  
PT  
Cardiopulmonary failure  
PT  
Multi-organ failure  
PT  
Multiple organ dysfunction syndrome