Clinical trial NCT03894618
Conditions: Squamous Cell Carcinoma of the Head and Neck Melanoma Non Small Cell Lung Cancer Urothelial Carcinoma Gastric Adenocarcinoma Gastroesophageal Junction Adenocarcinoma Squamous Cell Carcinoma of the Anus Squamous Cell Carcinoma of the Cervix Squamous Cell Carcinoma of the Skin Renal Cell Carcinoma Hodgkin Lymphoma Diffuse Large B Cell Lymphoma Mismatch Repair Deficient or MSI-High Solid Tumors
Sponsor: Shattuck Labs, Inc.
Start date: 2019-03-26; Completion date: 2023-05-04
Enrollment: 49 participants; Allocation: NA; Intervention model: SEQUENTIAL

Brief summary:
This is a Phase 1 first in human, open label, multi-center, dose escalation and dose expansion study to evaluate the safety, tolerability, PK, anti-tumor activity and pharmacodynamic effects of SL-279252 in subjects with advanced solid tumors or lymphomas.

Detailed description:
This is a Phase 1 first in human, open label, multi-center, dose escalation and dose expansion study to evaluate the safety, tolerability, PK, anti-tumor activity and pharmacodynamic effects of SL-279252 in subjects with advanced solid tumors or lymphomas. The study design consists of Dose Escalation and Dose Expansion Cohorts. In the dose escalation phase of the study, subjects will be enrolled into sequential dose levels. During dose escalation, two possible schedules for administration of SL-279252 may be explored. The MTD or MAD may be determined for either schedule. Based on accumulating data from the dose escalation phase, including safety, PK, pharmacodynamic and anti-tumor activity, up to two dose expansion cohorts may be opened. The primary objective of the expansion phase is to further refine the safety and tolerability of SL-279252. The expansion cohorts will evaluate one or two doses of SL-279252 using one selected schedule. At the end of dose escalation and dose expansion, safety, PK, anti-tumor activity, and pharmacodynamic data will be reviewed to identify the RP2D.

Arms: arm 1: Intravenous administration; Two possible dosing schedules for SL-279252 may be evaluated
Interventions: intervention 1: SL-279252
Intervention descriptions: intervention 1: The investigational product (IP), SL-279252, is a first-in-class agonist redirected checkpoint (ARC) fusion protein (FP) consisting of the extracellular domains of human programmed cell death 1 (PD- 1) and OX40L, linked by a central Fc domain (PD1-Fc-OX40L).

Protocol documents:
Prot_000.pdf: 
CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
1 
 
 
 
 
 
Protocol Title: Phase 1 Dose Escalation and Dose Expansion Study of an Agonist 
Redirected Checkpoint Fusion Protein, SL-279252 (PD1-Fc-OX40L), in Subjects 
with Advanced Solid Tumors or Lymphomas 
Short Title: Phase 1 Study of SL-279252 (PD1-Fc-OX40L) in Subjects with Advanced Solid 
Tumors or Lymphomas   
Protocol Identifying Number: SL01-DEL-101 
Version Number: v07  
Compound Number: SL-279252 
Study Phase: Phase 1 
Investigational New Drug (IND) Sponsor: Shattuck Labs 
Legal Registered Address: 
Shattuck Labs, Inc. 
21 Parmer Way, Suite 200 
Durham, North Carolina 27709 
Regulatory Agency Identifier Number(s) 
IND: 137637 
EudraCT: 2019-000446-36 
NCT:03894618 
Approval Date: 12 July, 2021 
 
 
This document is the confidential property of Shattuck Labs. It contains proprietary information and 
is submitted to the clinical trial site for the sole purpose of reviewing and conduct of the named clinical 
trial. Reproduction, disclosure, or use of the submission or information contained therein in whole or 
part otherwise than for this purpose is prohibited unless Shattuck Labs provides prior written 
authorization for such reproduction, disclosure or use. 
 
 


CONFIDENTIAL 
 
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Compound: SL-279252 
 
Version no: 07  
2 
 
Shattuck Labs Document Number 
Date 
Version 
SL01-DEL-101_00 
05 November 2018 
Original 
SL01-DEL-101_01 
19 December 2018 
Amendment No. 1 
 
Rationale for Amendment 01 Changes 
The protocol is amended to address comments provided by the United States Food and Drug 
Administration to the original protocol submitted with the IND Application 
 
Summary of Changes 
 
1. The upper bound of the target DLT range was changed to 33%. 
2. The Dose Expansion cohorts may be opened to enroll subjects in parallel with the Dose 
Escalation cohorts. Clarified that only dose levels that have been cleared for safety 
(permitted to escalate per the Keyboard Design rules) with a minimum of 6 subjects 
treated at that dose level can be expanded. 
3. Since Grade 3 cytokine release syndrome (CRS) requires dose reduction and may 
result in discontinuation of investigational product (IP), the protocol was modified to 
include Grade ≥3 CRS as a DLT.  
4. Modified the protocol’s guidance for CRS to ensure subject safety:  
For any grade CRS 
a. Subjects will be admitted for close observation.  
For Grade 2 CRS 
b. All doses of IP are held until CRS has returned to Grade ≤1 for at least 3 days.  
c. Following a Grade 2 CRS event, the next two doses of SL-279252 must be 
administered in an inpatient setting.  
d. For continued treatment following a Grade 2 CRS event, subjects will be 
admitted to hospital for close observation until resolution of symptoms.  
For Grade 3 CRS 
e. All doses of study medication are held until symptoms have returned to grade 
≤1 for at least 3 days. If the decision is made to continue treatment following 
resolution, the dose of SL-279252 must be reduced one dose level and 
premedication with high dose steroids must be administered prior to the first 
dose following Grade 3 CRS event. The next two doses of SL-279252 must be 
administered with appropriate inpatient monitoring (e.g., observation for 24 
hours following infusion when receiving premedication).  
f. Any subject that experiences recurrence of Grade 3 CRS following re-treatment 
must be permanently discontinued from study treatment. 
 
 
 
 


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Version no: 07  
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Shattuck Labs Document Number 
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05 November 2018 
Original 
SL01-DEL-101_01 
19 December 2018 
Amendment No. 1 
5. The protocol was modified so that dose escalation between the second and third dose 
levels is a half-log increment (i.e., 0.0001 mg/kg, 0.001 mg/kg, 0.003 mg/kg, 0.01 
mg/kg, etc. instead of a log increment i.e., 0.0001 mg/kg, 0.001 mg/kg, 0.01 mg/kg, etc.) 
6. Modified dose escalation scheme such that dose level 9 corresponds to a dose of 3.0 
mg/kg of SL-279252 and dose level 10 corresponds to a dose of 6.0 mg/kg of SL-279252 
7. Modified ADA sampling schedule so that subjects who test positive for ADA while on 
study or within 7-30 days after receiving their last dose of SL-279252 will undergo 
periodic testing for ADA until levels return to baseline.  
 
Administrative Changes (28-March 2019): 
1. Added the EUDRACT and NCT numbers to the protocol title page and removed other 
as an option for adding another numeric identifier of the protocol. 
2. Corrected protocol number from SL01-DEL-01 to SL01-DEL-101 in the header of the  
summary of changes header. 
3. No content changes were made to the protocol.   
 
 
 
 


CONFIDENTIAL 
 
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Version no: 07  
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Shattuck Labs Document Number 
Date 
Version 
SL01-DEL-101_00 
19 December 2018 
Amendment No. 1 
SL01-DEL-101_01 
18 June 2019 
Amendment No. 2 
 
Rationale for Country-specific Amendment 02 for Belgium  
The protocol is amended to address comments provided by the Belgium Regulatory Authority 
to Amendment 01 of the protocol. 
 
Summary of Changes 
 
1. Removed the barrier method of contraception as an option for female subjects of child 
bearing potential. This method, of contraception does not meet criteria of <1% failure 
rate for preventing pregnancy.   
2. SL-279252 treatment may induce cytokines including IL-6 which can inhibit the activity 
of cytochrome P450 (CYP450) enzymes as described in the literature (Evers et al., 1013, 
Drug Metabolism and Disposition). A cautionary medications section was added to the 
protocol to address a potential drug-drug interaction of SL-279252 with concomitant 
medications that are CYP450 substrates.  SL-279252 may induce cytokine release and 
coincidentally increase blood levels of drugs that are CYP450 substrates.  
 
 
 
 


CONFIDENTIAL 
 
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Version no: 07  
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Shattuck Labs Document Number 
Date 
Version 
SL01-DEL-101_01 
19 December 2018 
Amendment No. 1 
SL01-DEL-101_03 
11 October 2019 
Amendment No. 3 
 
Rationale for Amendment 03   
The protocol is amended to include changes requested by the Belgium Regulatory Authority 
into the global protocol for consistency across the study. Amendment 02 was a country-specific 
amendment for Belgium. The summary of changes for Amendment 02 are provided in Appendix 
16.10. Additionally, Amendment 03 incorporates pharmacodynamic cohorts during Dose 
Escalation, in order to obtain additional pharmacodynamic data at a dose level that has 
previously completed evaluation for safety and has not exceeded the MTD.  Collection of 
additional blood samples for receptor occupancy and immunophenotyping has been added in 
Cycle 1 (receptor occupancy in dose expansion cohorts) and Cycle 2 (receptor occupancy and 
immunophenotyping in all subjects) to characterize pharmacodynamics at time points that will 
be helpful to inform the recommended phase 2 dose and schedule.  Minor changes to the study 
objectives and statistical plans are made to clarify planned analyses.  Editorial changes are 
included to remove unclear text or further clarify text (e.g., definitions of study populations, 
etc), and for consistency. Sample size estimates, objectives and endpoints, biomarker sample 
collection time points and other modifications are included to account for additional 
pharmacodynamic and other planned study assessments.   
 
Summary of Changes for Global Amendment 
1. Amendment 02 changes included for countries outside of Belgium 
2. Pharmacodynamic cohorts are now included for enrollment during dose escalation. 
3. Editorial changes to remove unclear text and to further clarify intent of study plans are 
provided throughout the document to statistical plans, definitions of study populations, etc). 
a) Time to tumor response added as an endpoint for assessment of antitumor activity,  
b) Minor response removed for subjects with lymphoma as part of the clinical benefit rate 
definition; 
c) iSD as part of clinical benefit rate defined as ≥16 weeks duration instead of ≥12 weeks  
d) Refined definitions of populations under study in statistical section 
e) Revised sample size estimates to accommodate the addition of pharmacodynamic 
cohorts for enrollment during dose escalation 
f) Clarification of MTD selection based on isotonic estimate  
4. Receptor occupancy samples will also be collected in dose expansion cohorts (no longer 
limited to collection in dose escalation cohorts). 
5. Additional time points for collection of biomarker samples (immunophenotyping and 
receptor occupancy) in cycle 2 on days 15 and 16 have been added that impact schedule of 
assessment and supplementary tables for dose escalation and dose expansion cohorts. 
 
 
 


CONFIDENTIAL 
 
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Version no: 07  
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Shattuck Labs Document Number 
Date 
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SL01-DEL-101_03 
11 October 2019 
Amendment No. 3 
SL01-DEL-101_04 
24 February 2020 
Amendment No. 4 
 
Rationale for Amendment 04   
Revised eligibility criteria and tumor types included for study participation. The summary of 
changes are provided in Appendix 16.12. 
 
 
 
 


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Version no: 07  
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Shattuck Labs Document Number 
Date 
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SL01-DEL-101_04 
24 February 2020 
Amendment No. 4 
SL01-DEL-101_05 
1 October 2020 
Amendment No. 5 
Rationale for Global Amendment 05   
The main purpose for this amendment is to revise eligibility criteria and tumor types included for study 
participation. The dosing day window for administration of SL-279252 was clarified in the Schedule of 
Assessment (SOA) tables. The dose escalation plan table was revised to include infusion time windows 
for administration of SL-279252.  In addition, predose, end of infusion (EOI) and 6 hour post EOI PK 
sample time points were added for collection on C4/D1 to confirm clearance and half-life parameters 
with repeat dosing of SL-279252. Language was added that clarifies protocol procedures to follow for 
assessment of AE severity and for recording and reporting AEs. Minor editorial text changes are also 
included with this amendment. 
 
The Summary of Changes for Global Amendment 05 is provided in Appendix 16.13 
 
 
 
 


CONFIDENTIAL 
 
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Compound: SL-279252 
 
Version no: 07  
8 
 
 
Shattuck Labs Document Number 
Date 
Version 
SL01-DEL-101_05 
1 October 2020 
Amendment No. 5 
SL01-DEL-101_06 
4 February 2021 
Amendment No. 6 
Rationale for Global Amendment 06   
The main purpose for this amendment is to revise exclusion criterion #2 to provide an exception for 
subjects with uveal melanoma, to clarify language about ad hoc samples to be collected if an infusion-
related or cytokine release adverse reaction occurs, and to clarify the DLT-evaluable population for 
subjects receiving SL-279252 therapy on Schedule 2.   
 
The Summary of Changes for Global Amendment 06 is provided in Appendix 16.14 
 
 
 
Shattuck Labs Document Number 
Date 
Version 
SL01-DEL-101_06 
4 February 2021 
Amendment No. 6 
SL01-DEL-101_07 
12 July 2021 
Amendment No. 7 
Rationale for Global Amendment 07   
The main purpose for this amendment is to institute the requirement that eligible subjects have tumors 
with PD-L1 expression ≥1%  according to tumor proportion score (TPS) or combined proportion score 
(CPS).  PD-L1 is a target of the PD1 portion of bifunctional fusion protein SL-279252.  Restricting 
enrollment to subjects whose tumors demonstrate expression of PD-L1 may improve the likelihood of 
subject benefit.  In addition, subjects with uveal or ocular melanoma are ineligible for participation.  
 
The description of the drug product is changed to remove reference to a 1 mL fill volume since a larger 
fill volume is planned to ease dose preparation.  Drug product fill volumes will be described in the Study 
Pharmacy Manual.  The length of time to thaw a vial is also removed since it is obvious when the frozen 
solution is completely thawed and the time will vary based on fill volume.  
 
Minor editorial changes were made to clarify study conduct procedures during dose escalation and 
requirements for collection of ad hoc labs if IRR and/or CRS occur. 
 
The Summary of Changes for Global Amendment 07 are provided in Appendix 16.15. 
 
 
 


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TABLE OF CONTENTS 
TABLE OF CONTENTS ................................................................................................................ 9 
LIST OF ABBREVIATIONS ....................................................................................................... 17 
STATEMENT OF COMPLIANCE .............................................................................................. 22 
KEY TRIAL CONTACTS ........................................................................................................... 23 
PROTOCOL SYNOPSIS ............................................................................................................. 24 
1. 
INTRODUCTION, BACKGROUND AND STUDY RATIONALE ................................... 34 
1.1 
Background Information ................................................................................................ 34 
1.2 
Investigational Product, SL-279252 ............................................................................... 36 
1.2.1 
Mechanism of Action .............................................................................................. 36 
1.2.2 
In Vitro Pharmacology ............................................................................................ 37 
1.2.3 
In Vivo Pharmacology ............................................................................................ 37 
1.2.4 
Toxicology .............................................................................................................. 37 
1.3 
Rationale......................................................................................................................... 41 
1.4 
Potential Risks and Benefits ........................................................................................... 42 
1.4.1 
Potential Risks ........................................................................................................ 42 
1.4.2 
Potential Benefits .................................................................................................... 43 
2. 
STUDY OBJECTIVES AND OUTCOME MEASURES ..................................................... 45 
3. 
STUDY DESIGN .................................................................................................................. 47 
3.1 
Description of Study Design .......................................................................................... 47 
3.1.1 
Sample Size ............................................................................................................. 48 
3.1.2 
Study Schema.......................................................................................................... 49 
3.2 
Dose Escalation .............................................................................................................. 49 
3.2.1 
Description .............................................................................................................. 49 
3.2.2 
Intrasubject Dose Escalation ................................................................................... 50 
3.2.3 
Justification for Starting Dose ................................................................................ 50 
3.2.4 
Starting Dose and Dose Escalation Plan ................................................................. 51 
3.2.5 
Criteria for Expanding a Single Subject Cohort in Schedule 1 .............................. 53 
3.2.6 
Definition of Dose-Limiting Toxicity ..................................................................... 53 
3.2.7 
Criteria for Decision to Transition from Schedule 1 to Schedule 2 ........................ 55 
3.3 
Dose Expansion .............................................................................................................. 55 
3.3.1 
Description .............................................................................................................. 55 


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3.3.2 
Selection of Recommended Phase 2 Dose and Schedule for SL-279252 ............... 56 
3.4 
Concomitant Medications, Treatments, and Procedures ................................................ 56 
3.4.1 
Tumor Lysis Syndrome Prevention and Treatment Recommendations ................. 56 
3.4.2 
Prohibited Medications/Treatments ........................................................................ 57 
3.4.3 
Medications to be used with Caution ...................................................................... 57 
3.5 
Toxicity Management Guidelines .................................................................................. 58 
3.5.1 
Management of Infusion-related Reactions ............................................................ 58 
Infusion or Hypersensitivity Reactions .............................................................................. 59 
Cytokine-release ................................................................................................................ 60 
3.5.2 
Management of irAEs ............................................................................................. 62 
irAEs - General .................................................................................................................. 62 
Skin Toxicity ...................................................................................................................... 62 
Gastrointestinal (GI) Toxicity ............................................................................................ 64 
Hepatotoxicity .................................................................................................................... 65 
Pulmonary Toxicity ........................................................................................................... 66 
Nephrotoxicity ................................................................................................................... 67 
Endocrine Toxicity............................................................................................................. 67 
Hypothyroidism ................................................................................................................. 68 
Hyperthyroidism ................................................................................................................ 68 
Hypophysitis ...................................................................................................................... 68 
Adrenal Insufficiency......................................................................................................... 68 
Diabetes Mellitus ............................................................................................................... 68 
Ocular Toxicity .................................................................................................................. 69 
Cardiotoxicity .................................................................................................................... 70 
Neurotoxicity ..................................................................................................................... 70 
Myasthenia Gravis ............................................................................................................. 71 
Guillain-Barre Syndrome ................................................................................................... 71 
Autoimmune Hemolytic Anemia ....................................................................................... 72 
Immune Thrombocytopenia ............................................................................................... 72 
Acquired Hemophilia ......................................................................................................... 73 
Musculoskeletal Toxicity ................................................................................................... 73 
3.5.3 
Management of Non-irAEs ..................................................................................... 74 


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3.6 
Discontinuation of Investigational Product .................................................................... 75 
3.7 
Criteria to Resume Treatment ........................................................................................ 75 
3.8 
Participant Discontinuation/Withdrawals from Study ................................................... 75 
3.9 
Lost to Follow-up ........................................................................................................... 75 
3.10 Premature Termination or Suspension of Study ............................................................ 76 
3.11 Duration of Treatment .................................................................................................... 76 
3.12 Duration of Follow-Up ................................................................................................... 77 
3.13 End-of Study Definition ................................................................................................. 77 
4. 
STUDY POPULATION ........................................................................................................ 77 
4.1 
Trial Participants ............................................................................................................ 77 
4.2 
Participant Inclusion Criteria ......................................................................................... 77 
4.3 
Participant Exclusion Criteria ........................................................................................ 80 
4.4 
Screen Failures ............................................................................................................... 81 
4.5 
Accrual Goal .................................................................................................................. 81 
5. 
INVESTIGATIONAL PRODUCT ....................................................................................... 82 
5.1 
Investigational Product Description ............................................................................... 82 
5.2 
Preparation/Handling/Storage of SL-279252 Investigational Product........................... 82 
5.2.1 
Preparation .............................................................................................................. 82 
5.2.2 
Handling .................................................................................................................. 83 
5.2.3 
Administration ........................................................................................................ 83 
5.2.4 
Storage .................................................................................................................... 83 
5.3 
Product Accountability ................................................................................................... 83 
5.4 
Dosing and Change in Weight ....................................................................................... 83 
5.5 
Physician Availability Required for Administration of SL-279252 .............................. 84 
5.6 
Monitoring Dose Administration ................................................................................... 84 
5.7 
Treatment of Investigational Product Overdose............................................................. 84 
6. 
STUDY ASSESSMENTS AND PROCEDURES ................................................................ 85 
6.1 
SOA Table: Schedule 1 Dose Escalation of SL-279252 ................................................ 86 
6.1.1 
Supplementary Tables for Schedule 1: PK, ADA, Cytokines / Dose Escalation ... 89 
6.1.2 
Correlative Sample Time points / Schedule 1 / Dose Escalation............................ 91 
6.2 
SOA Table: Schedule 2 Dose Escalation of SL-279252 ................................................ 92 
6.2.1 
Supplementary Tables for Schedule 2: PK, ADA, Cytokines / Dose Escalation ... 95 


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6.2.2 
Correlative Sample Time points / Schedule 2 / Dose Escalation............................ 97 
6.3 
SOA Table: Schedule 1 Dose Expansion Cohorts ......................................................... 98 
6.3.1 
Supplementary Tables for Schedule 1: PK, ADA, Cytokines / Dose Expansion . 101 
6.3.2 
Correlative Sample Time points / Schedule 1 / Dose Expansion ......................... 103 
6.4 
SOA Table: Schedule 2 Dose Expansion Cohorts ....................................................... 104 
6.4.1 
Supplementary Tables for Schedule 2: PK, ADA, Cytokines / Dose Expansion . 107 
6.4.2 
Correlative Sample Time points / Schedule 2 / Dose Expansion ......................... 109 
6.5 
Demographics, Medical History, Screening and Safety Assessments ......................... 110 
6.5.1 
Informed Consent.................................................................................................. 110 
6.5.2 
Eligibility Criteria ................................................................................................. 110 
6.5.3 
Subject Demographics .......................................................................................... 110 
6.5.4 
Medical History .................................................................................................... 110 
6.5.5 
Concomitant Medications ..................................................................................... 110 
6.6 
Safety Evaluations ........................................................................................................ 110 
6.6.1 
Physical Examination............................................................................................ 110 
6.6.2 
ECOG Performance Status ................................................................................... 110 
6.6.3 
Pulse Oximetry...................................................................................................... 110 
6.6.4 
Vital Signs ............................................................................................................. 110 
6.6.5 
Cardiac Assessments ............................................................................................. 111 
6.6.5.1 
Electrocardiograms ........................................................................................ 111 
6.6.5.2 
Echocardiogram ............................................................................................. 111 
6.6.6 
Clinical Safety and Other Laboratory Assessments .............................................. 111 
6.6.6.1 
Ad Hoc Labs for AEs of IRR and/or CRS ..................................................... 112 
6.6.6.2 
Pregnancy Testing ......................................................................................... 112 
6.7 
Pharmacokinetics ......................................................................................................... 112 
6.7.1 
Intensive PK Sampling in Dose Escalation (Schedule 1 or Schedule 2) .............. 112 
6.7.2 
Sparse PK Sampling in Dose Expansion (Schedule 1 or Schedule 2) .................. 113 
6.7.3 
Pharmacokinetic Endpoints .................................................................................. 113 
6.8 
Anti-drug Antibody Assessments ................................................................................ 113 
6.9 
Pharmacodynamic/Biomarker Assessments ................................................................ 114 
6.9.1 
Pharmacodynamic Assessments in Blood ............................................................ 114 
6.9.1.1 
Cytokine and Chemokine Analysis ............................................................... 114 


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6.9.1.2 
Peripheral Blood Mononuclear Cells for Receptor Occupancy .................... 114 
6.9.1.3 
PBMC for Immunophenotyping .................................................................... 114 
6.9.1.4 
Cell-free Nucleic Acids for Exome Sequencing and TMB ........................... 114 
6.9.2 
Pharmacodynamic Assessment of Tumor Tissue ................................................. 115 
6.9.2.1 
Fresh Tumor Biopsies .................................................................................... 115 
6.9.2.2 
Archival Tumor ............................................................................................. 116 
6.10 Assessment of Anti-tumor Activity.............................................................................. 117 
6.11 Unscheduled Visit ........................................................................................................ 117 
7. 
SAFETY ASSESSMENTS ................................................................................................. 117 
7.1 
Assessment of Severity ................................................................................................ 118 
7.2 
Definitions for Safety Parameters ................................................................................ 118 
7.2.1 
Events not Qualifying as AEs/SAEs ..................................................................... 119 
7.3 
Classification of an Adverse Event .............................................................................. 120 
7.3.1 
Assessment of Causality ....................................................................................... 120 
7.3.2 
Expectedness ......................................................................................................... 120 
7.4 
Timing for Event Assessment and Follow-up .............................................................. 121 
7.5 
Procedures for Recording and Reporting of Adverse Events ...................................... 121 
7.6 
Reporting of Pregnancy ................................................................................................ 122 
7.7 
Reporting of Overdose ................................................................................................. 122 
7.8 
Study Halting Rules ..................................................................................................... 122 
7.9 
Safety Oversight ........................................................................................................... 123 
8. 
ANTI-TUMOR ACTIVITY ASSESSMENTS ................................................................... 123 
8.1 
Disease Assessment for Solid Tumor Histologies ....................................................... 124 
8.1.1 
Assessment of Response by iRECIST – Solid Tumors ........................................ 124 
8.1.2 
Response and Stable Disease Duration ................................................................. 124 
8.2 
Disease Assessment for Lymphomas ........................................................................... 125 
8.2.1 
Assessment of Response by RECIL – Lymphomas ............................................. 125 
8.3 
Criteria for Treatment Beyond Initial Progression ....................................................... 125 
9. 
STATISTICAL CONSIDERATIONS ................................................................................ 126 
9.1 
Description of Statistical Methods ............................................................................... 126 
9.2 
Sample Size and Statistical Hypotheses ....................................................................... 126 
9.2.1 
Dose Escalation ..................................................................................................... 126 


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9.2.1.1 
Simulations for Schedule 1 (assuming 10 dose levels) ................................. 127 
9.2.1.2 
Simulations for Schedule 2 (assuming 4 dose levels) ................................... 131 
9.2.2 
Dose Expansion Cohorts ....................................................................................... 132 
9.3 
Populations for Analyses .............................................................................................. 133 
9.4 
Statistical Analyses ...................................................................................................... 133 
9.4.1 
Analysis of the Primary Outcome Measures ........................................................ 133 
9.4.1.1 
Dose Escalation ............................................................................................. 133 
9.4.1.2 
Dose Expansion ............................................................................................. 134 
9.4.2 
Analysis of the Secondary Outcome Measures .................................................... 134 
9.4.3 
Exploratory Analyses ............................................................................................ 135 
9.5 
Pharmacokinetic Analyses ........................................................................................... 135 
9.5.1 
Pharmacokinetic Populations ................................................................................ 135 
9.5.2 
Exploratory Exposure-Response Analyses ........................................................... 136 
9.6 
Anti-Drug Antibody Analysis ...................................................................................... 136 
10. CLINICAL MONITORING ................................................................................................ 136 
11. SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA AND DOCUMENTS ... 137 
11.1 Source Data .................................................................................................................. 137 
11.2 Access to Data .............................................................................................................. 137 
11.3 Data Recording and Record Keeping ........................................................................... 137 
12. QUALITY ASSURANCE PROCEDURES ........................................................................ 137 
13. ETHICS/PROTECTION OF HUMAN SUBJECTS ........................................................... 138 
13.1 Ethical Standard ........................................................................................................... 138 
13.2 Institutional Review Board/Institutional Ethics Committee ........................................ 138 
13.3 Informed Consent Process ............................................................................................ 138 
13.3.1 
Consent/Assent and Other Informational Documents Provided to Subjects ........ 138 
13.3.2 
Consent Procedures and Documentation .............................................................. 139 
13.4 Participant and Data Confidentiality ............................................................................ 139 
13.4.1 
Research Use of Stored Human Samples, Specimens, or Specimen Data ............ 140 
13.5 Future Use of Stored Specimens .................................................................................. 140 
14. DATA HANDLING AND RECORD KEEPING ............................................................... 140 
14.1 Communication and Data Dissemination Plan............................................................. 140 
14.1.1 
Periodic Data Summaries for Investigators and Regulatory Agencies ................. 141 


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14.2 Data Collection and Management Responsibilities ..................................................... 141 
14.3 Study Records Retention .............................................................................................. 141 
14.4 Protocol Deviations ...................................................................................................... 142 
14.5 Publications and Data Sharing Policy .......................................................................... 142 
15. LITERATURE REFERENCES .......................................................................................... 142 
16. APPENDICES ..................................................................................................................... 145 
16.1 ECOG Performance Status Criteria.............................................................................. 145 
16.2 Contraception Requirements ........................................................................................ 146 
16.2.1 
Pregnancy Status ................................................................................................... 147 
16.3 Keyboard Design .......................................................................................................... 148 
16.3.1 
Keyboard Design Decision Rules ......................................................................... 148 
16.3.1.1 
Dose Escalation – Schedule 1 ........................................................................ 149 
16.3.1.2 
Dose Escalation – Schedule 2 ........................................................................ 150 
16.3.1.3 
Keyboard Design Scenarios – Schedule 1 ..................................................... 151 
16.3.1.4 
Keyboard Design Scenarios – Schedule 2 ..................................................... 158 
16.4 Deauville Criteria ......................................................................................................... 159 
16.5 Cockcroft-Gault Formula for Creatinine Clearance ..................................................... 160 
16.6 RECIST 1.1 and iRECIST Criteria .............................................................................. 161 
16.6.1 
RECIST 1.1 Criteria.............................................................................................. 161 
16.6.2 
Evaluation of Response......................................................................................... 162 
16.6.3 
iRECIST 1.1 Criteria ............................................................................................ 163 
16.7 RECIL .......................................................................................................................... 166 
16.7.1 
Evaluation of Response......................................................................................... 166 
16.7.2 
Response Designations in Lymphoma Table ........................................................ 167 
16.8 Blood Requirements for Study ..................................................................................... 169 
16.9 Summary of Protocol Changes – Amendment 01 ........................................................ 171 
16.10 
Summary of Protocol Changes – Amendment 02 .................................................... 176 
16.11 
Summary of Protocol Changes – Amendment 03 .................................................... 177 
16.12 
Summary of Protocol Changes – Amendment 04 .................................................... 181 
16.13 
Summary of Protocol Changes – Amendment 05 .................................................... 184 
16.14 
Summary of Protocol Changes – Amendment 06 .................................................... 188 
16.15 
Summary of Protocol Changes – Amendment 07 .................................................... 190 


CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
16 
 
 
 
LIST OF TABLES 
Table 1: Broad Categories of Drugs/Targets that Enhance T-cell Activation .............................. 35 
Table 2: Non-human Primate Studies ........................................................................................... 38 
Table 3: Animal Deaths in GLP Study 2646-001 ......................................................................... 39 
Table 4: Study Objectives and Outcome Measures ...................................................................... 45 
Table 5: SL-279252 Dose Escalation Plan ................................................................................... 52 
Table 6: Schedule 1 Dose Escalation Serial PK, ADA, Cytokines (C1/D1 - 96 hrs post dose) ... 89 
Table 7: Schedule 1 Dose Escalation Serial PK, ADA, Cytokines (C1D15/D16 & C2D1/D2) ... 90 
Table 8: Schedule 1 Dose Escalation Serial PK, ADA (C3/D1 and Beyond) .............................. 90 
Table 9: Complement, Immunophenotyping, Receptor Occupancy Time Points ........................ 91 
Table 10: Schedule 2 Dose Escalation Serial PK, ADA, Cytokines (C1/D1 - 96 hrs post dose) . 95 
Table 11: Schedule 2 Dose Escalation Serial PK, ADA, Cytokines (C1D15/D16 & C2D1/D2). 96 
Table 12: Schedule 2 Dose Escalation Serial PK, ADA (C3D1 and Beyond) ............................. 96 
Table 13: Complement, Immunophenotyping, Receptor Occupancy Time Points ...................... 97 
Table 14: Schedule 1 Dose Expansion PK, ADA, Cytokines (C1/D1 - 24 hrs post EOI) .......... 101 
Table 15: Schedule 1 Dose Expansion PK, ADA, Cytokines (C1/D15 and Beyond) ................ 102 
Table 16: Complement, Immunophenotyping Sample Time Points ........................................... 103 
Table 17: Schedule 2 Dose Expansion PK, ADA, Cytokines (C1/D1 - 24 hrs post EOI) .......... 107 
Table 18: Schedule 2 Dose Expansion PK, ADA, Cytokines (C1/D15 and Beyond) ................ 108 
Table 19: Complement, Immunophenotyping Sample Time Points ........................................... 109 
Table 20: Serum SL-279252 PK Parameters .............................................................................. 113 
 
LIST OF FIGURES 
Figure 1: Mechanism of Action .................................................................................................... 36 
 
 
 


CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
17 
 
LIST OF ABBREVIATIONS 
Ab  
Antibody 
AchR 
Acetylcholine receptor 
ADA 
Anti-drug antibodies 
ADL 
Activities of daily living 
AE 
Adverse event 
ALC 
Absolute lymphocyte count 
ALT 
Alanine aminotransferase 
ANA 
Antinuclear antibody 
ANC 
Absolute neutrophil count 
ANCA 
Anti-neutrophil cytoplasmic antibodies 
APTT 
Activated partial thromboplastin time 
APC 
Antigen presenting cell 
AR 
Adverse reaction 
ARC 
Agonist redirected checkpoint 
AST 
Aspartate aminotransferase 
ATG 
Antithymocyte globulin 
AUC 
Area under the serum concentration time curve 
AUC0-last 
Area under the serum concentration time curve, time 0 to the last quantifiable 
concentration 
AUC0-inf 
Area under the serum concentration time curve from time 0 extrapolated to infinity 
AUC0-t 
Area under the serum concentration time curve, time 0 to time = t 
%AUCext 
Percentage of AUC0-inf due to extrapolation from Tlast to infinity 
AUCtau 
The area under the serum concentration time curve, over the dosing interval 
BAL 
Bronchoalveolar lavage 
β-hCG 
Beta- human chorionic gonadotropin 
BOR 
Best overall response 
BP 
Blood pressure 
BSA 
Body surface area 
BUN 
Blood urea nitrogen 
CBC 
Complete blood count 
CBR 
Clinical benefit rate 
CD 
Cluster of differentiation 
C 
Celsius 
C1D1 
Cycle 1, day 1 
cfNA 
Cell-free or circulating nucleic acids (note: tumor-associated)  
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
CIOMS 
Council for International Organizations of Medical Sciences 
CK 
Creatine kinase 
CK-MB 
Creatine kinase-muscle/brain 
CL 
Clearance 
Cm  
Centimeters 
Cmax 
Maximum observed concentration 
Cmin 
Minimum observed concentration 
CMP 
Clinical monitoring plan 
CNS 
Central nervous system 
CO2 
Bicarbonate 
CPS 
Combined proportion score 
CR 
Complete response 
CrCl 
Creatinine clearance 
CRF 
Case report form 
CRO 
Contract Research Organization 


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CRP 
C reactive protein 
CRS 
Cytokine release syndrome 
CSF 
Cerebrospinal fluid 
CT 
Computed tomography 
CTCAE 
Common terminology criteria for adverse event 
CTLA-4 
Cytotoxic T cell lymphocyte-associated antigen 4 
CV 
Coefficient of variation 
CYP450 
Cytochrome P450 
D1/D8/D15/D22 etc. 
Day 1/ Day 8/ Day 15/ Day 22 etc. 
dL 
Deciliter 
DL 
Dose level 
DLT(s) 
Dose-limiting toxicity(ies) 
DM 
Diabetes mellitus 
DMARD 
Disease- modifying antirheumatic drug  
DNA 
Deoxynucleic acid 
DOR 
Duration of response 
DRF 
Dose-range-finding 
EC50 
Half maximal effective concentration 
ECD 
Extracellular domain 
ECG 
Electrocardiogram 
ECHO 
Echocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic Case Report Form 
EOI 
End of infusion 
ESR 
Erythrocyte sedimentation rate 
FCBP 
Female of child bearing potential 
FDA 
Food and Drug Administration 
FDG-PET 
Fluorodeoxyglucose Positron Emission Tomography 
FFPE 
Formalin-fixed paraffin-embedded 
FP 
Fusion protein 
FSH 
Follicle stimulating hormone 
GBS 
Guillain-Barre Syndrome 
GCP 
Good Clinical Practice 
G-CSF 
Granulocyte colony stimulating factor 
GEJ 
Gastro-esophageal junction 
GI 
Gastrointestinal 
GITR 
Glucocorticoid-induced TNFR 
GLP 
Good Laboratory Practice 
GM-CSF 
Granulocyte macrophage colony stimulating factor 
H1/H2 
Histamine 1/ Histamine 2 
HBcAb 
Hepatitis B core antibody 
HBsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B virus 
HCV 
Hepatitis C virus 
Hgb 
Hemoglobin 
HIV 
Human immunodeficiency virus 
HL 
Hodgkin’s lymphoma 
HNSCC 
Head and neck squamous cell carcinoma 
HNSTD 
Highest non-severely toxic dose 
hr (time) 
Hour(s) 
HR 
Heart rate 
HSR(s) 
Hypersensitivity reaction(s) 
IB 
Investigator’s brochure 


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iBOR 
Immune response evaluation criteria in solid tumors best overall response 
ICF 
Informed consent 
ICH 
International Conference of Harmonisation 
iCPD 
Immune confirmed progression of disease 
iCR 
Immune complete response 
ICU 
Intensive care unit 
ID 
Identification 
IEC 
Institutional Ethics Committee 
IFNγ 
Interferon gamma 
IHC 
Immunohistochemistry 
IL 
Inteleukin 
IND 
Investigational new drug 
INR 
International normalized ratio 
IP 
Investigational product 
iPR 
Immune partial response 
irAE 
Immune-related adverse event 
IRB 
Institutional Review Board 
iRECIST 
Immune response evaluation criteria in solid tumors 
IRR(s) 
Infusion-related reaction(s) 
irSAE 
Immune-related serious adverse event 
iSD 
Immune stable disease 
ITIM 
Immunoreceptor tyrosine-based inhibition motif 
iUPD 
Immune unconfirmed progression of disease 
IV (i.v.) 
Intravenous 
IVIG 
Intravenous immunoglobulin 
Kd 
Receptor off-rate constant 
Kg 
Kilogram 
L 
Liter 
LAG-3 
Lymphocyte activation gene 3  
LDH 
Lactate dehydrogenase 
LLN 
Lower limit of normal 
LVEF 
Left ventricular ejection fraction 
m2 
Square meter 
mAb(s) 
Monoclonal antibody(ies) 
MABEL 
Minimum anticipated biological effect level  
MAD 
Maximum administered dose  
mg 
Milligrams 
mg/dL 
Milligrams per deciliter 
mg/kg 
Milligrams per kilogram 
Min 
Minutes 
mL 
milliliter 
mm 
millimeter 
MMF 
Mycophenolate mofetil 
Mmol 
Millimole 
MMRD 
Mismatch repair deficient 
MR 
Minor response 
MRI 
Magnetic resonance imaging  
MSI/ MSI-H 
Microsatellite instability / microsatellite instability high 
MTD 
Maximum tolerated dose  
NCI 
National Cancer Institute 
NE 
Not evaluable 
NHP 
Non-human primate 
Ng 
Nanogram 


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NIF/VC 
Negative inspiratory force / vital capacity 
NL(s) 
New lesion(s) 
NLNT 
New lesions non-target 
NLT 
New lesions target 
nM 
Nanomolar 
NSAIDS 
Non-steroidal anti-inflammatory drugs 
NSCLC 
Non-small cell lung cancer 
NYHA 
New York Heart Association 
ORR 
Objective response rate 
OX40 
TNFRSF4, also known as CD134 / OX40 receptor 
OX40L 
Ligand for OX40 receptor, also known as CD252 
PBMC 
Peripheral blood mononuclear cells 
PCR 
Polymerase chain reaction 
PD 
Progressive Disease 
PD-1 
Programmed cell death protein 1 
PD-L1 / PD-L2 
Programmed cell death ligand 1 / Programmed cell death ligand 2 
PFT 
Pulmonary function test 
PK 
Pharmacokinetic 
pM 
Picomolar 
PR 
Partial response 
PS 
Performance status 
PSPD 
Pseudo-progression of disease 
PT 
Prothrombin time 
PTU 
Propylthiouracil 
QID 
Quarter in die (4 times per day) 
QTc 
Corrected QT interval  
RBC 
Red blood cell 
RCC 
Renal cell cancer 
RECIL 
Response evaluation criteria in lymphoma 
RECIST 
Response evaluation criteria in solid tumors 
RNA 
Ribonucleic acid 
RP2D 
Recommended phase 2 dose 
RR 
Respiratory rate 
SAE 
Serious Adverse Event 
SAP 
Statistical analysis plan 
SCCA 
Squamous cell carcinoma of the anal canal 
scFv 
Single-chain variable fragment 
SD 
Stable disease 
SEB 
Staphylococcal enterotoxin B 
Skin-SCC 
Squamous cell carcinoma of the skin 
SL-279252 
PD1-Fc-OX40L agonist redirected checkpoint 
SLM 
Study Lab Manual 
SMC 
Safety Monitoring Committee 
SOA 
Schedule of Assessments 
SOI 
Start of infusion 
SOM 
Sum of measurements 
SPM 
Study Pharmacy Manual 
SRM 
Study Reference Manual 
SUSAR 
Suspected, unexpected serious adverse reaction 
T 
Temperature 
T3/T4 
Thyroxine 3/thyroxine 4 
t½ 
terminal elimination half-life 
TB 
Tuberculosis 


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TCR 
T cell receptor 
TFTs 
Thyroid function tests 
TGF 
Tissue growth factor  
TID 
Ter in die (3 times per day) 
TIGIT 
T-cell immunoglobulin and ITIM Domain 
TIM-3 
T cell immunoglobulin mucin 3 
TK 
Toxicokinetic  
Tlast 
Time of last observed quantifiable concentration 
TLS 
Tumor lysis syndrome 
Tmax 
Time of maximum observed concentration 
TMB 
Tumor mutational burden 
TMDD 
Target-mediated drug disposition 
TME 
Tumor microenvironment 
TNF-α 
Tumor necrosis factor alpha 
TNFR 
Tumor necrosis factor receptor 
TNFSF 
Tumor necrosis factor receptor superfamily 
TPO 
Thyroid peroxidase  
TPR 
Time point response 
TPS 
Tumor proportion score 
TSH 
Thyroid stimulating hormone 
TTR 
Time to response 
Txt 
Treatment 
µg 
Microgram 
ULN 
Upper limit of normal 
UP 
Unanticipated problems 
USPI 
United States Prescribing Information 
Vz  
Volume of distribution 
WBC 
White blood cell 
Wk 
Week 
λz 
Terminal elimination rate constant 
~ 
Approximately 
º 
Degree 
 
 
 


CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
22 
 
STATEMENT OF COMPLIANCE 
 
 
 
The trial will be conducted in accordance with the protocol and with the consensus ethical 
principles derived from international guidelines including the Declaration of Helsinki and Council 
for International Organizations of Medical Sciences (CIOMS) International Ethical Guidelines, 
International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines, and 
applicable Federal Regulations on the Protection of Human Subjects. The Principal Investigator 
will assure that no deviation from, or changes to the protocol will take place without prior 
agreement from the Sponsor and documented approval from the Institutional Review Board 
(IRB)/Institutional Ethics Committee (IEC), except where necessary to eliminate an immediate 
hazard(s) to the trial participants. All personnel involved in the conduct of this study have 
completed Human Subjects Protection Training. 
 
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments. 
 
Principal Investigator: 
 
 
________________________________       ___________________________________ 
Print/Type Name 
 
 
 
Signature 
 
Date: ______________ 
 
 
 




CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
24 
 
PROTOCOL SYNOPSIS 
Sponsor 
Shattuck Labs 
Product Name 
SL-279252 
Other Names 
PD1-Fc-OX40L recombinant fusion glycoprotein 
Protocol Title 
Phase 1 Dose Escalation and Dose Expansion 
Study of an Agonist Redirected Checkpoint Fusion 
Protein, SL-279252 (PD1-Fc-OX40L), in Subjects 
with Advanced Solid Tumors or Lymphomas 
Protocol Number 
SL01-DEL-101 
Clinical Phase 
Phase 1 
Planned Sample Size 
Approximately 78 to 93 subjects 
Planned Number of Sites & Countries 
8-10 clinical sites;  
United States, Canada, Belgium and Spain 
Recruitment Duration: 
24 months (2 years) 
Study Duration 
32 months (< 3 years) 
Background and Rationale 
The investigational product (IP), SL-279252, is a first-in-class agonist redirected checkpoint 
(ARC) fusion protein (FP) consisting of the extracellular domains of human programmed cell 
death 1 (PD- 1) and OX40L, linked by a central Fc domain (PD1-Fc-OX40L). The mechanism 
of action of SL-279252 is designed to intercept one of the key immunosuppressive pathways 
within the tumor microenvironment (TME): the PD-1 – programmed cell death 
ligand 1/programmed cell death-ligand 2 axis (PD-L1/PD-L2). SL-279252 can bind to PD-L1 
and PD-L2 expressed on tumor and antigen presenting cells, and replace that inhibitory signal 
with OX40L, resulting in an incoming T cell experiencing co-stimulation via engagement 
through its OX40 receptor instead of suppression through PD-1 interactions. Importantly, 
because the extracellular domains (ECDs) of PD-1 and OX40L are physically linked to one 
another and localized to the TME, tumor infiltrating T cells will receive co-stimulation at the 
same time they recognize a tumor antigen via the T cell receptor (TCR).  
 
SL-279252 is able to bind with high affinity to both targets simultaneously and stimulate anti-
tumor T cell activity. The PD-1 end of the fusion protein binds PD-L1 and PD-L2 with affinities 
of 2.08 and 1.76 nM, respectively, and the OX40L end binds OX40 with an affinity of 246 pM. 
The PD-1 domain efficiently outcompetes PD-L1 blocking antibodies for ligand binding, and 
the OX40L domain potently stimulates OX40-mediated nuclear factor kappa B signaling in a 
luciferase-based reporter assay. When activated human T cells were co-cultured with PD-L1 
positive human tumor cells, SL-279252 enhanced proliferation of T cells and production of 
interleukin (IL)-2, interferon-gamma (IFNγ) and tumor necrosis factor alpha (TNF-α), which 
led to efficient killing of tumor cells.  
 
SL-279252 was compared to sequence equivalents of nivolumab, pembrolizumab and 
tavolixizumab in several in vitro functional assays using human lymphocytes in the presence of 
Staphylococcal enterotoxin B (SEB): higher concentrations of cytokines were released with  
SL- 279252 than with the antibodies alone or in combination with one another.  The murine 
version of SL-279252 (mPD1-Fc-OX40L) was studied head-to-head with mouse PD-1/L1 and  
 


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Version no: 07  
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Background and Rationale (continued) 
OX40 antibodies both alone and in combination and led to improved tumor control and rejection 
rates as compared to the antibody combinations in multiple models.   
 
SL-279252 is a pharmacologically active molecule. In the non-human primate (NHP) studies, 
dose-dependent infusion-related reactions (IRRs) were the primary toxicity of concern. These 
adverse reactions were immune-mediated and multifactorial in etiology consistent with target-
mediated pharmacology of SL-279252 as well as immunogenicity (anti-drug antibodies (ADA), 
complement activation) related effects. Collectively, the effects at 40 and 80 mg/kg/dose were 
considered adverse and the effects at 10 mg/kg/dose were not considered adverse. The highest 
non-severely toxic dose (HNSTD) of SL-279252 was determined to be 10 mg/kg. 
 
The preclinical and nonclinical data collectively suggest that SL-279252 has unique 
immunological properties, with the potential for anti-tumor activity. This first-in-human, Phase 
1 trial will assess the safety, tolerability, PK, pharmacodynamics and anti-tumor activity of SL-
279252 in subjects with tumor types that have been documented to respond to anti-PD-1/PD-L1 
therapy. All subjects enrolled in this trial are required to have received or been intolerant to 
standard of care therapies. The majority of subjects will also have received PD-1/L1 and/or 
cytotoxic T cell lymphocyte-associated antigen 4 (CTLA-4) inhibitors and progressed.   
Study Objectives 
Primary Objectives 
Outcome Measures 
Dose Escalation:  
To evaluate the safety and tolerability and 
to identify the maximum-tolerated dose 
(MTD) or maximum administered dose 
(MAD) of SL-279252 in subjects with 
select locally advanced or metastatic 
malignancies 
(i.e., 
solid 
tumors 
or 
lymphomas)  
 
 
 
Dose Expansion: To further refine the 
safety and tolerability of SL-279252 in 
subjects with select locally advanced or 
metastatic select malignancies (i.e., solid 
tumors or lymphomas) 
 
Safety/tolerability outcomes include:  
Incidence of all adverse events (AEs) and 
immune-related adverse events (irAEs), serious 
adverse events (SAEs), fatal SAEs, dose limiting 
toxicity (DLT), AE and irAEs leading to 
discontinuation; changes in safety assessments 
(e.g., laboratory parameters, vital signs, etc.) per 
the 
National 
Cancer 
Institute 
Common 
Terminology Criteria for Adverse Events (NCI-
CTCAE – version [v]) 5.0). 
 
Dose Escalation: The MTD is defined based on 
the rate of DLTs and the MAD is the highest dose 
administered.  
Dose 
Expansion: 
Infusion-related 
reactions 
(IRRs) and discontinuation of SL-279252 will be 
closely monitored using sequential boundaries. 
Secondary Objectives 
Outcome Measures 
Dose Escalation and Dose Expansion:  
To select the dose and schedule i.e.,  
recommended Phase 2 dose (RP2D) for 
SL-279252 
Based on review of data collected during dose 
escalation and expansion, including safety, 
tolerability, pharmacokinetics (PK), anti-tumor 
activity outcomes, pharmacodynamic outcomes. 
 
 
 


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Secondary Objectives 
Outcome Measures 
Dose Escalation and Dose Expansion: 
To assess preliminary evidence of anti-
tumor activity of SL-279252   
 
 
 
 
 
 
Response assessment according to immune 
response evaluation criteria in solid tumors 
(iRECIST) for solid tumors or response evaluation 
criteria 
in 
lymphoma 
(RECIL) 
2017 
for 
lymphomas 
• Objective response rate (ORR; proportion of 
participants whose best overall response is a 
complete response [CR] or partial response 
[PR] evaluated via iRECIST, therefore referred 
to as iCR or iPR) 
• Clinical benefit rate (CBR; proportion of 
participants whose best overall response is an 
iCR, iPR or stable disease (iSD) of ≥16 
weeks);  
 
Dose Escalation and Dose Expansion:  
To evaluate immunogenicity to SL-
279252 during and after treatment 
• Number and proportion of participants with 
positive anti-drug-antibody (ADA) titer 
• ADA duration  
• Transient vs. Persistent ADA  
Dose Escalation and Dose Expansion 
Cohorts: To characterize the PK of SL-
279252 
 
 
 
 
 
 
 
 
• Maximum observed concentration (Cmax) 
and time at which the maximum 
concentration is observed (Tmax) and 
minimum observed concentration (Cmin) 
following single and multiple doses of SL-
279252 
• Area under the serum concentration-time 
curve (AUC)  
• Terminal elimination half-life (t½), Clearance 
(CL) and Volume of Distribution (Vz) 
 
Exploratory Objectives 
Outcome Measures 
Dose Escalation and Dose Expansion: 
To assess target engagement of PD-L1 
and OX40 on peripheral blood 
mononuclear cells (PBMCs) prior to, on-
treatment, and following SL-279252 
administration. 
Free/total receptor occupancy of OX40 and PD-L1 
in circulating CD45 positive cells by flow 
cytometry with further sub-gating into B and T cell 
subsets. 
 
 
 


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Exploratory Objectives 
Outcome Measures 
Dose Escalation and Dose Expansion 
Cohorts: To assess biomarkers in blood 
prior to, on-treatment, and following SL-
279252 administration. 
Pharmacodynamic biomarkers in blood: 
• Changes from baseline in plasma cytokine 
levels  
• Changes from baseline in cell counts and 
percentages of circulating immune cells 
• Complement activation by assessment of 
SC5b-9 terminal fragment 
 
Baseline biomarker: 
Cell-free tumor nucleic acid (cfNA) for tumor 
mutational 
burden 
(TMB) 
analysis 
[Dose 
Expansion ONLY]  
Dose Escalation and Dose Expansion 
To explore additional measures of anti-
tumor activity of SL-279252 
• Duration of response (DOR): time between 
first response (iCR or iPR, whichever is 
recorded 
first) 
and 
date 
of 
disease 
progression) 
• Time to response (TTR): time from the start 
of treatment with SL-279252 to the first 
objective tumor response (iCR or iPR, 
whichever is recorded first)  
• Progression free survival: time from first dose 
of SL-279252 to progression or death, 
whichever comes first 
• Overall survival: time from first dose of SL-
279252 to death 
 
Dose Escalation and Dose Expansion :  
To explore relationship between 
PK/pharmacodynamics and the 
relationship between PK and clinical 
activity including tumor growth kinetics  
PK/pharmacodynamics and clinical activity 
outcomes as described above 
Study Design 
This is a Phase 1 first in human, open label, multi-center, dose escalation and dose expansion 
study to evaluate the safety, tolerability, PK, anti-tumor activity and pharmacodynamic effects 
of SL-279252 in subjects with selected locally advanced or metastatic malignancies. The study 
design consists of Dose Escalation (Section 3.2) and Dose Expansion Cohorts (Section 3.3).  In 
the dose escalation phase of the study, subjects will be enrolled into sequential dose levels (DL) 
as outlined in Section 3.2.4 and Table 5. Enrollment into a DL cohort will follow the Keyboard 
Design outlined in the Appendix, Section 16.3 [Yan, 2017].  During dose escalation, two 
possible schedules (Schedule 1 and Schedule 2) for administration of SL-279252 may be 
explored as outlined in Section 3.2.4.  Schedule 1 will be evaluated first. A transition to 
Schedule 2 may be implemented for reasons outlined in Section 3.2.7.  If Schedule 2 is opened, 
the Sponsor may also elect to stop enrollment in Schedule 2 early (e.g., based on safety) and 


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resume enrollment in Schedule 1.  The MTD or MAD may be determined for either Schedule 1 
or Schedule 2. Alternatively, a less intensive dosing schedule may be instituted if safety and 
pharmacodynamic data on Schedule 1 support less frequent dosing of SL-279252 (e.g., one dose 
given every two weeks or every three weeks or every four weeks).   
 
Based on accumulating data from the dose escalation phase, including safety, PK, 
pharmacodynamic and anti-tumor activity, up to two dose expansion cohorts may be opened. 
The primary objective of the expansion phase is to further refine the safety and tolerability of 
SL-279252. One or two expansion cohorts will evaluate doses of SL-279252 using one  selected 
schedule. At the end of dose escalation and dose expansion, safety, PK, anti-tumor activity, and 
pharmacodynamic data will be reviewed to identify the RP2D. 
 
Treatment Schedule 
Two or more dosing schedules for SL-279252 may be evaluated: 
• 
Schedule 1: will determine the safety of administering SL-279252 on days 1, 8 and 15 
of the first 28-day cycle and then every 2 weeks thereafter on days 1 and 15 of each 28-
day cycle beginning with cycle 2. 
• 
Schedule 2: will determine the safety of weekly dosing of SL-279252 on days 1, 8, 15 
and 22 of each 28-day cycle. 
A less frequent dosing schedule (e.g., once every three weeks) may be investigated if safety 
data from Schedule 1 indicate this approach is most prudent   
Dose Escalation Scheme 
 
Dose Level 
Dose of SL-279252 (mg/kg)a,b,c,d 
Duration of Infusione 
Level 1 
0.0001 mg/kg 
5-30 minutes 
Level 2 
0.001 mg/kg 
5-30 minutes 
Level 3 
0.003 mg/kg 
5-30 minutes 
Level 4 
0.01 mg/kg 
30 minutes (+/- 10 minutes) 
Level 5 
0.03 mg/kg 
30 minutes (+/- 10 minutes) 
Level 6 
0.1 mg/kg 
30 minutes (+/- 10 minutes) 
Level 7 
0.3 mg/kg 
30 minutes (+/- 10 minutes) 
Level 8 
1.0 mg/kg 
1 hour (+/- 15 minutes) 
Level 9 
3.0 mg/kg 
1 hour (+/- 15 minutes) 
Level 10 
6.0 mg/kg 
1 hour (+/- 15 minutes)  
a) Dose escalation begins on Schedule 1: SL-279252 may be administered in the first cycle on days 1, 
8, and 15 of the first 28-day cycle and then once every 2 weeks on days 1 and 15 of each 28-day 
cycle beginning at cycle 2. 
b) Dose escalation on Schedule 2 may be tested: If Schedule 2 is opened, SL-279252 will be 
administered once weekly on days 1, 8, 15, and 22 of each 28-day cycle. The starting dose on 
schedule 2 will be at least one dose level below the current Schedule 1 dose level defined by the 
Keyboard design. If Schedule 2 is opened for enrollment, then enrollment on Schedule 1 will be 
halted. 


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c) Intermediate dose levels may be tested based on emerging safety data. The option to explore more 
than 10 dose levels on Schedule 1 or additional dose levels on Schedule 2 is also a possibility if safety 
allows. Escalations will not exceed half-log increments after dose level 2. 
d) The actual body weight in kg will be used for dose calculation in all subjects whose body weight is 
≤100 kg.  For subjects with body weight >100 kg, the dose to be administered should be the same as 
that calculated for a subject weighing 100 kg (See Sections 5.2.3 and 5.4 for details) 
e) Infusion time may change based on final drug volume needed for administration, safety and 
tolerability of the infusion for the subject, and/or observed safety findings during the study. Please 
refer to the Study Pharmacy Manual (SPM) for details. 
Definition of Dose Limiting Toxicity 
Dose limiting toxicities (DLTs) are defined in the bulleted points below.  Toxicities will be graded as per 
NCI CTCAE v5.  The determinate period for DLT is the first 21 days or 28 days of treatment on Schedule 
1 or Schedule 2, respectively. However, there is provision in the criteria below for toxicities that occur 
beyond this period to be considered in the definition of the RP2D. Note: Toxicities clearly related to 
disease progression or intercurrent illness are not considered DLTs.  Inflammatory reactions attributable 
to local anti-tumor responses (e.g., severe pain) are not considered DLTs. 
• 
Any Grade 4 irAE 
• 
Elevations in liver transaminases (aspartate aminotransferase [AST], alanine aminotransferase 
[ALT]) and/or total bilirubin: 
o In subjects who enroll with AST/ALT/total bilirubin ≤ upper limit of normal (ULN); AST or 
ALT elevation of >8 x ULN or total bilirubin > 5 x ULN 
o In subjects who enroll with AST/ALT/total bilirubin > ULN; AST or ALT elevation of >8 x 
baseline or total bilirubin > 5 x baseline 
o Evidence of Hy’s Law (AST or ALT > 3 x ULN [or baseline*] with concurrent increase in total 
bilirubin > 2 x ULN [or baseline*] without evidence of cholestasis or alternative explanation 
such as disease progression or viral hepatitis; *ULN or baseline dependent on value at enrollment 
as described above. 
• 
Any Grade 3 irAE that requires permanent discontinuation of SL-279252 
• 
Any other Grade 3 irAE with the following exceptions:  
o Grade 3 skin toxicity that downgrades to Grade 2 or less within 7 days with optimal supportive 
care 
o Grade 3 hypothyroidism, hyperthyroidism, or hyperglycemia that can be managed with treatment 
o Grade 3 diarrhea with no evidence of colitis that resolves within 72 hours with appropriate 
clinical management 
• 
The following Grade 2 irAEs: 
o Grade 2 ocular toxicity requiring systemic steroids 
o Grade 2 cardiotoxicity that requires permanent discontinuation of SL-279252 
o Grade 2 Guillain-Barre Syndrome 
• 
Any Grade 3 or greater non-irAE except for those listed below: 
o Grade 3 fatigue lasting ≤ 7 days 
o Grade 3 or 4 neutropenia not associated with fever that improves to Grade 2 within 7 days   
o Grade 3 or 4 lymphopenia 
o Grade 3 thrombocytopenia not associated with clinically significant bleeding and that does not 
require medical intervention 
o Grade 3 electrolyte abnormalities that are not associated with clinical signs/symptoms and are 
reversed with appropriate medical intervention 
o Grade 3 or 4 amylase and/or lipase abnormalities that are not associated with clinical 
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Definition of DLT (continued) 
o Grade 3 vomiting and/or Grade 3 nausea that resolves within 72 hours with appropriate clinical 
management 
• 
Other toxicities may be considered a DLT as determined by the investigator in conjunction with the 
Safety Monitoring Committee (SMC) 
A Grade ≥ 3 AE that occurs beyond the DLT period (21 days for schedule 1 or 28 days for schedule 2) 
or Grade 2 events that require continuous interruption of SL-279252 for more than 6 weeks or 
toxicities that result in subjects not receiving at least 66% of the scheduled dose during the DLT 
assessment period may be taken into consideration when assessing the totality of the data in 
determining evaluability for DLT and the RP2D.   
Eligibility Criteria 
Inclusion Criteria 
Participants are eligible to be included in the study only if all the following criteria apply. 
1. Subject has voluntarily agreed to participate by giving written informed consent in accordance with 
ICH/GCP guidelines and applicable local regulations. 
2. Subject has a histologically confirmed diagnosis of one of the following unresectable locally 
advanced or metastatic malignancies: melanoma, non-small cell lung cancer (squamous, adeno, or 
adeno-squamous), urothelial cancer, squamous cell carcinoma of the head and neck, squamous cell 
cervical cancer, gastric or gastro-esophageal junction adenocarcinoma, squamous cell carcinoma of 
the anal canal, squamous cell carcinoma of the skin, renal cell cancer, Hodgkin’s lymphoma, and 
microsatellite instability high (MSI-H) or mismatch repair deficient (MMRD) solid tumors excluding 
CNS malignancies. MSI and MMRD testing results as per institution is acceptable.    
• 
Head and neck cancers: Subjects must have primary tumor locations in the oropharynx, oral 
cavity, hypopharynx, or larynx. Primary tumor sites of nasopharynx,  maxillary sinus, paranasal, 
and unknown primary are excluded. 
• 
Non-small cell lung cancers: Subjects with a known EGFR sensitizing (activating) mutation or 
an ALK fusion are excluded.   
• 
Melanoma: Subjects with a diagnosis of uveal or ocular melanoma are excluded. 
3. Eligible subjects must have tumors expressing PD-L1  ≥1%  by tumor proportion score (TPS) or 
combined proportion score (CPS) as determined by a local laboratory. 
• 
This criteria does not apply to subjects with a diagnosis of melanoma, renal cell carcinoma, 
Hodgkin’s lymphoma and microsatellite instability high (MSI-H) or mismatch repair deficient 
(MMRD) solid tumors.   
4. Subject must have received, been intolerant to, or is ineligible for standard therapy (per local 
guidelines and approvals) or have a malignancy for which there is no approved therapy considered 
standard of care.  
5. Age 18 years and older.  
6. Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1. 
7. Has measurable disease by iRECIST (solid tumors) or RECIL 2017 (lymphoma). Refer to Appendix 
Sections 16.6 and 16.7 for details on criteria of measurable disease. 
8. Has life expectancy of greater than 12 weeks. 
 


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9. Laboratory values must meet the following criteria. 
Laboratory parameter                                 Threshold value 
• 
Absolute lymphocyte count (ALC) 
≥ 0.8 x 109/liter (L) 
• 
Absolute neutrophil count (ANC) 
≥ 1.5 x 109/L 
without growth factor support 
• 
Platelet count 
                                       ≥ 50 x 109/L 
• 
Hemoglobin (Hgb)                                   > 9.0 g/dL  
with no blood transfusions for at least 5 days prior to D1 of investigational product  
(IP; SL-279252) 
• 
Creatinine clearance (CrCl) 
             ≥ 30 milliliter (mL)/min (modified Cockcroft-Gault) 
• 
ALT/AST  
                                       ≤ 3 x ULN  
• 
Total bilirubin                                        ≤ 1.5 x ULN;  
subjects with isolated indirect hyperbilirubinemia are permitted if direct bilirubin ratio is <35% 
and total bilirubin is ≤ 3.0 x ULN 
• 
Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) ≥ lower limit of normal 
(LLN) per institutional threshold. If LLN is not defined for a given institution, then ejection 
fraction must be ≥50 %. 
  
10. Females of child bearing potential (FCBP) must have a negative serum or urine pregnancy test within 
72 hours of D1 of IP.  NOTE: FCBP unless they are surgically sterile (i.e., have undergone a complete 
hysterectomy, bilateral tubal ligation/occlusion, bilateral oophorectomy or bilateral salpingectomy), 
have a congenital or acquired condition that prevents childbearing or are naturally postmenopausal 
for at least 12 consecutive months (see Appendix Section 16.2 for additional details). Documentation 
of postmenopausal status must be provided.  FCBP should use an acceptable method of contraception 
(see Appendix Section 16.2) to avoid pregnancy during treatment and for 30 days (which exceeds 5 
half-lives) after the last dose of IP. FCBP must start using acceptable contraception at least 14 days 
prior to D1 of IP. 
11. Male subjects with female partners must have azoospermia from a prior vasectomy or underlying 
medical condition or agree to use an acceptable method of contraception during treatment and for 30 
days (which exceeds 5 half-lives) after last dose of SL-279252 (see Appendix Section 16.2). Male 
subjects of reproductive potential must start using acceptable contraception at least 14 days prior to 
D1 of treatment with SL-279252 as per Appendix Section 16.2.  
12. All AEs resulting from prior anti-cancer immunotherapy have resolved (NOTE: exceptions include 
alopecia, vitiligo, and endocrinopathies adequately treated with hormone replacement).  
• 
Subjects that were discontinued from prior PD-1/L1 therapy due to immune-related adverse 
events are not eligible 
13. Recovery from toxicities from prior anti-cancer treatments including surgery, radiotherapy, 
chemotherapy or any other anti-cancer therapy to baseline or ≤ Grade 1. (NOTE: Low-grade 
toxicities (e.g., alopecia, ≤ Grade 2 lymphopenia, ≤ Grade 2 hypomagnesemia, ≤ Grade 2 neuropathy) 
may be allowed at the discretion of the investigator if considered clinically insignificant. Please 
consult the Sponsor Medical Monitor to discuss these cases). 
Eligibility Criteria 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 


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1. Has received more than two prior checkpoint inhibitor containing treatment regimens (regimen 
refers to either monotherapy or combination immunotherapies) or has had prior treatment with an 
OX40 agonist.   
• Prior PD-1/L1 therapy is not required. 
2. Refractory to last PD-1/L1 inhibitor-based therapy which is defined as disease progression within 3 
months of treatment initiation. 
• Subjects must have had clinical benefit (stable disease or response) to last PD-1/L1 inhibitor-
based therapy for at least three months to be eligible.  
. 
3. Any anti-cancer therapy within the time intervals noted below prior to first dose (D1) of SL-
279252. 
 
Therapy 
Washout period 
Chemotherapy  
3 weeks 
Hormonal therapy 
3 weeks 
PD-1/L1 inhibitor and other immunotherapies not otherwise 
specified  
3 weeks  
Tumor vaccine  
4 weeks 
Cell-based therapy 
8 weeks 
Other mAbs or biologic therapies 
3 weeks 
Major surgery 
2 weeks 
Radiation (except palliative intent which does not require washout) 2 weeks  
 
4. Concurrent chemotherapy, immunotherapy, biologic or hormonal therapy is prohibited.  Concurrent 
use of hormones for non-cancer related conditions is acceptable.   
5. Use of corticosteroids or other immunosuppressive medication, current or within 14 days of D1 of 
IP with the following exceptions (i.e., the following are allowed during treatment with or within14 
days of D1 of IP): 
• Topical, intranasal, inhaled, ocular, intraarticular corticosteroids 
• Physiological doses of replacement steroid (e.g., for adrenal insufficiency) provided ≤ 10 
mg/day of prednisone or equivalent 
• Steroid premedication for hypersensitivity reactions (HSRs; e.g., reaction to IV contrast) 
6. Receipt of live attenuated vaccine within 28 days of D1 of IP. 
7. Active or documented history of autoimmune disease (autoimmune disease does not refer to irAEs; 
for irAEs see inclusion criteria #11).  Exceptions include Type I diabetes, vitiligo, alopecia areata or  
hypo/hyperthyroidism.  
8. Active pneumonitis (i.e. drug-induced, idiopathic pulmonary fibrosis, radiation-induced, etc.).   
9. Ongoing or active infection (e.g., no systemic antimicrobial therapy for treatment of infection within 
5 days of D1 of IP). 
10. Symptomatic peptic ulcer disease or gastritis, active diverticulitis, other serious gastrointestinal (GI) 
disease associated with diarrhea within 6 months of D1 of IP. 
11. Clinically significant or uncontrolled cardiac disease including any of the following: 
• Myocarditis 
• Unstable angina within 6 months from D1 of IP 
• Acute myocardial infarction within 6 months from D1 of IP  
• Uncontrolled hypertension 
• New York Heart Association (NYHA) Class II, III or IV congestive heart failure 


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• Clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular 
tachycardia, second- or third- degree atrioventricular block without a pacemaker, circulatory 
collapse requiring vasopressor or inotropic support, or arrhythmia requiring therapy) 
12.Untreated central nervous system (CNS) or leptomeningeal metastases. Subjects with treated CNS 
metastases must have completed definitive treatment (radiotherapy and/or surgery) > 2 weeks prior 
to D1 of IP and no longer require steroids.  
13.Women who are breast feeding. 
14. Psychiatric illness/social circumstances that would limit compliance with study requirements and 
substantially increase the risk of AEs or compromised ability to provide written informed consent. 
15. Another malignancy that requires active therapy and that in the opinion of the investigator and 
Sponsor would interfere with monitoring of radiologic assessments of response to IP.  
16. Has undergone allogeneic stem cell transplantation or organ transplantation. 
17. Known history or positive test for human immunodeficiency virus, or positive test for hepatitis B 
(positive for hepatitis B surface antigen [HBsAg]) or hepatitis C virus ([HCV]; if HCV antibody (Ab) 
test is positive check for HCV ribonucleic acid [RNA]).  
• (NOTE: Hepatitis B virus (HBV): Subjects who are hepatitis B core antibody [HBcAb] 
positive, but HBsAg negative are eligible for enrollment. HCV: Subjects who are HCV Ab 
positive, but HCV RNA negative are eligible for enrollment). 
Safety Oversight 
Study progress and safety will be reviewed throughout the conduct of the study.  Periodic safety 
reviews (once a month or more frequently if required) will be undertaken by the Safety 
Monitoring Committee (SMC) consisting of study investigators and Sponsor representatives. 
Available safety data for all subjects at the time of scheduled meetings will be reviewed and 
summarized. Based on the severity of the toxicities, indicators of potential anti-tumor activity, 
and other factors, a recommendation whether to modify the dose and/or study or continue 
enrollment will be made by the Sponsor collaboratively with input from the SMC. Regulatory 
authorities and IRBs/IECs will be notified of any decisions to halt the study or subject 
enrollment.  
Statistics 
Frequency tables will be used to describe safety and tolerability parameters such as: AEs, irAEs, 
SAEs, fatal SAEs and irAEs leading to discontinuation of SL-279252. During dose escalation, 
DLTs will be tabulated by dose level (within each schedule if applicable). Following the 
Keyboard design, the MTD will be estimated using isotonic regression (based on the DLTs 
observed in evaluable subjects) or the MAD will be reported if the DLT rate never reaches the 
target range of 25-33.3%. During dose expansion, continuous toxicity monitoring using 
sequential boundaries will be used to specifically monitor IRR and toxicities leading to 
discontinuation of SL-279252. 
 
 
 


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1. 
INTRODUCTION, BACKGROUND AND STUDY RATIONALE 
1.1 
Background Information 
The human immune system can prevent the initiation of cancer through constant immune 
surveillance or immunoediting, whereby nascent transformed cells are recognized by the immune 
system and eliminated, often preventing tumor outgrowth and metastasis [Schreiber, 2011; 
Muenst, 2016]. When cancer does arise, immunoediting results in an adaptive response within 
tumors, and the tumor microenvironment (TME), to co-opt endogenous immune suppressive 
pathways that provide an extrinsic survival advantage to the tumor cells through inhibition of the 
immune system. Thus, cancers avoid immune surveillance and destruction through multiple 
mechanisms including (but not limited to) downregulation of costimulatory signals required for 
lymphocyte activation, and upregulation of inhibitory signals essential for preventing 
autoimmunity, thereby circumventing the immune system’s ability to recognize tumor cells.  
Immune evasion is therefore an extrinsic hallmark of cancer, just as pro-survival or pro-growth 
mutations in tumor suppressor genes or oncogenes, respectively, are intrinsic hallmarks of cancer 
[Hanahan, 2011].  Advancements in our understanding of the mechanisms responsible for cancer 
immune evasion has led to the development of therapies that have shown promise in overcoming 
tumor-mediated immune suppression.   
In general, cancer immunotherapy encompasses a broad spectrum of approaches that either target 
tumor cells directly (e.g., monoclonal antibodies [mAbs], radioimmunotherapy, antibody drug 
conjugates, and immunotoxins/oncolytic viruses) or activate immune cells to kill cancer cells (e.g., 
vaccines, cellular therapies, checkpoint antagonists and stimulatory agonists) [Sathyanarayanan, 
2015].  Recent strategies in immunotherapy have focused on therapeutic interventions that 
modulate pathways governing T cell activation to overcome cancer immune evasion.  For example, 
checkpoint antagonists, or immune checkpoint inhibitors, are agents that block receptors or ligands 
involved in attenuating T cell activation. Stimulatory agonists are agents that engage co-
stimulatory pathways and immune receptors and lead to the activation and proliferation of T cells. 
Over the past decade, pharmaceutical research efforts have focused intently on developing 
immunotherapy drugs that either inhibit immune checkpoint molecules responsible for T cell 
anergy or stimulate tumor necrosis factor receptor (TNFR) pathways linked to T cell activation.   
The cytotoxic T cell lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 
protein 1 (PD-1) pathways are major negative regulators of T cell receptor (TCR) signaling.  These 
pathways are engaged by tumor cells to avoid immune surveillance by T cells. Targeted inhibitors 
of CTLA-4, PD-1 or PD-ligand (L)1 are immune checkpoint inhibitors that have demonstrated 
efficacy in many tumor types [Postow, 2015].  Moreover, since multiple inhibitory receptors and 
soluble factors are involved in T cell exhaustion in the TME apart from PD-1 and CTLA-4, such 
as T cell immunoglobulin mucin 3 (TIM-3), lymphocyte activation gene 3 (LAG-3) protein, and 
the T-cell immunoglobulin and immunoreceptor tyrosine-based inhibition motif (ITIM) domain 
(TIGIT) protein among others; a surge in pre-clinical/clinical development of these next 
generation-checkpoint inhibitors has occurred (Table 1) [Mahoney, 2015]. 
Agents that engage co-stimulatory pathways that lead to the proliferation and activation of T cells 
are also being evaluated in clinical trials.  Essentially, optimal T-cell activation requires two 


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signaling events that prime these cells for activation [Sturgill ER, 2017].  Signal 1 occurs when 
the TCR binds antigenic peptides presented by the major histocompatibility complex on the surface 
of antigen presenting cells (APC). Signal 2 involves the engagement of cluster of differentiation 
(CD)28 on the T cell with B7-1(CD80) and B7-2(CD86) receptors on APCs; together these signals 
constitute the minimal co-stimulatory signals necessary for T cell activation. In addition, co-
stimulatory signals via tumor necrosis factor receptors (TNFRs) are necessary to drive T cell 
differentiation/proliferation and potentiate the development of memory and effector subsets.  
TNFRs responsible for transducing the additional co-stimulatory signals needed for T cell 
activation include OX40 (CD134, tumor necrosis factor receptor superfamily [TNFRSF]4), 
glucocorticoid-induced TNFR (GITR, CD357, TNFRSF18), CD27 (TNFRSF7), and 4-1BB 
(CD137, TNFRSF9). The orchestration of these signaling events enables robust tumor killing 
activity by T cells in vivo.  To exploit this important co-stimulatory cascade, agonist mAbs or 
ligands targeting TNFRs are in various stages of preclinical and clinical development for cancer 
(Table 1).  
Table 1: Broad Categories of Drugs/Targets that Enhance T-cell Activation  
Immune Checkpoint Antagonist/Inhibitors 
Stimulatory Agonists 
Anti CTLA-4  
4-1BB (CD137, TNFRSF9) 
Anti PD-1/ L1 
OX40 (CD134, TNFRSF4) 
Anti-LAG-3 
GITR (CD357, TNFRSF18) 
Anti-TIM-3 
CD27 (TNFRSF7) 
Anti-TIGIT 
CD28 
[Mahoney, 2015; Sturgill ER, 2017; Rataj, 2018] 
Much excitement was generated when the first in class immune checkpoint inhibitors entered the 
clinic and elicited anti-tumor responses in patients with cancer [Postow, 2015]. Despite the initial 
success of PD-1/L1 and CTLA-4 inhibitors, clinical benefit as monotherapy occurs in a minority 
of patients (objectives responses in 10-45% with long term survival benefit in 20-30%). This has 
made the search for synergistic combinations or novel approaches an immediate priority. Along 
these lines, the first checkpoint-checkpoint combination of ipilimumab (CTLA-4 inhibitor) and 
nivolumab (PD-1 inhibitor) demonstrated improved response rates, progression free survival and 
overall survival compared to single agent therapy in late-stage melanoma albeit, with a high rate 
of severe toxicities [Larkin, 2015a; Larkin, 2015b; Boutros, 2016].  The use of other combination 
strategies pairing checkpoint inhibitors with stimulatory agonists are being explored in many 
ongoing clinical trials [Sturgill ER, 2017]. However, a critical issue is how best to combine and 
sequence these agents to elicit robust T cell responses against tumors.  
Although combination immunotherapy can improve efficacy, developing novel treatment 
strategies remains a formidable task given the complexity of the human immune system and the 
potential for toxicity which may result from such interventions [Andrews, 2015].  Moreover, as 
only a proportion of patients benefit from these therapies, there is a need for systematic biomarker-
driven approaches to identify patients most likely to respond to combination regimens targeting 
the immune system.   


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In an attempt to improve upon current paradigms, Shattuck Labs has developed a bifunctional 
fusion protein (FP) platform, capable of simultaneously blocking ‘checkpoints’ while activating 
TNFR co-stimulators. Shattuck’s Agonist Redirected Checkpoint (ARC) platform adjoins the 
extracellular domain (ECD) of a select type 1 membrane protein to the ECD of a select type 2 
membrane protein, via a central Fc domain. Using this approach, combination immunotherapy can 
be achieved by a single FP, having superior preclinical activity compared to the separate 
administration of two individual antibodies against identical targets. 
1.2 
Investigational Product, SL-279252  
The investigational product (IP), SL-279252, is a first-in-class ARC FP consisting of the ECDs of 
human PD-1 and OX40L, linked by a central Fc domain (PD1-Fc-OX40L). The preclinical data 
supporting the translational study of SL-279252 in human subjects with cancer is described in 
detail in the Investigator’s Brochure (IB) [SL2018IB001_01].  The mechanism of action, in vitro 
and in vivo pharmacology, toxicokinetics (TK), and the rationale for investigation are briefly 
summarized below.  
1.2.1 Mechanism of Action 
The mechanism of action of SL-279252 is designed to intercept one of the key immunosuppressive 
pathways within the TME: the PD-1 - PD-L1/PD-L2 axis. SL-279252 can bind to PD-L1 and PD-
L2 expressed on tumor and antigen-presenting cells, and replace that inhibitory signal with 
OX40L, resulting in an incoming T cell experiencing co-stimulation via engagement through its 
OX40 receptor (Figure 1) instead of suppression through PD-1 interactions. Importantly, because 
the ECDs of PD-1 and OX40L are physically linked to one another and localized to the TME, 
tumor infiltrating T cells will receive co-stimulation at the same time they recognize a tumor 
antigen via the TCR. 
 
  
Figure 1: Mechanism of Action 
(A) Tumor cell-expressed PD-L1 can bind to T cell-expressed PD-1 and (B) suppress activation. (C) SL-279252 can 
block this suppression while simultaneously providing T cell co-stimulation. 


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1.2.2 In Vitro Pharmacology 
The PD-1 end of SL-279252, binds PD-L1 and PD-L2 with affinities of 2.08 and 1.76 nanomolar 
(nM), respectively, and the OX40L end binds OX40 with an affinity of 246 picomolar (pM).  The 
PD1-Fc-OX40L ARC was also observed to have a considerably longer receptor off-rate constant 
(Kd) than control proteins (PD1-Fc and OX40L-Fc) when the dissociation from PD-L1 (18-fold 
longer), PD-L2 (13.4 fold longer) and OX40 (36-fold longer) was determined.  The PD-1 domain 
efficiently outcompetes PD-L1 blocking antibodies for ligand binding, and the OX40L domain 
potently stimulates OX40-mediated nuclear factor kappa B signaling in a luciferase-based reporter 
assay.  Furthermore, when activated human T cells were co-cultured with PD-L1 positive human 
tumor cells, SL-279252 enhanced proliferation of T cells and production of interleukin (IL)-2 ), 
interferon-gamma (IFNγ) and tumor necrosis factor alpha (TNF-α), which led to efficient killing 
of tumor cells.  
1.2.3 In Vivo Pharmacology 
The anti-tumor activity of the murine equivalent of SL-279252 (mPD1-Fc-OX40L) in established 
murine tumors was significantly superior to either PD-1 blocking, OX40 agonist, or combination 
antibody therapy. SL-279252 was shown to provide higher rates of tumor rejection and long-term 
immunity to tumor re-challenge than any of the antibody treatments in preclinical tumor models, 
including expansion of tumor antigen specific CD8 T cells. The SL-279252 drug product is a 
combination of trimers and hexamers resulting in highly potent signaling.  Thus, all agonist 
functions of SL-279252 are independent of Fc receptor cross-linking. Collectively, preclinical data 
demonstrate a highly potent FP platform, providing checkpoint blockade and TNFRSF co-
stimulation in a single molecule.   
1.2.4 Toxicology  
The cynomolgus macaque was selected for the toxicology studies due to the cross-reactivity of 
SL-279252 to the respective targets in this species.  The anatomical, physiological, and 
biochemical similarities to humans facilitate extrapolation of observed pharmacokinetic (PK) 
properties to human.  
Toxicology studies in non-human primates (NHP) (Table 2) were designed to evaluate the toxicity 
and identify the maximum tolerated dose (MTD) and TK of SL-279252 in cynomolgus monkeys 
following repeated weekly administrations (see the SL-279252 IB for further details).  Repeat dose 
studies consisted of a dose range finding (DRF) study (2
Table 2A) and a Good 
Laboratory Practice (GLP) toxicity study (
Table 2B). In both repeat dose studies, SL-
279252 was administered intravenous (IV), once weekly, for up to 5 weeks. The doses evaluated 
in DRF study 
 and GLP study 
 were 3, 10, 50, and 100 milligrams per kilogram 
(mg/kg), and 10, 40, and 80 mg/kg, respectively. The GLP study included a vehicle control group.  
The GLP toxicity study also sought to evaluate the reversibility, progression or delayed appearance 
of any observed changes following a four week recovery period. 
 
 


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Table 2: Non-human Primate Studies 
Table 2A  Group Assignments 
 
Group 
Number 
Dose Level 
(mg/kg/dose) 
Number of Animals 
Male 
Female 
 
1 
3 
1 
1 
2 
10 
1 
1 
3 
50 
1 
1 
4 
100 
1 
1 
 
Table 2B  Group Assignments 
 
Group 
Number 
Dose Level 
(mg/kg/dose) 
Number of Animals 
Male 
Female 
 
1 
Vehicle 
5 
5 
2 
10 
3 
3 
3 
40 
3 
3 
4 
80 
5 
5 
 
 
Across both studies, infusion-related reactions (IRRs) were the primary toxicity of concern.  IRRs 
appeared to be dose- and time-dependent and were observed in GLP study 
 at 40 and 80 
mg/kg doses in 4/6 and 9/10 animals, respectively. The IRR first occurred during or within 15 
minutes (min) of the start of infusion (SOI) of the third dose of SL-279252. The manifestations of 
these reactions (decreased activity, flaccid limbs, pale gums/face, constricted pupils, closed 
eyelids, salivation, skin cold to touch, increased respiratory rate) were similar across animals and 
ranged in severity from mild to severe.  
Deaths attributable to SL-279252 were noted in GLP study 
at the 40 mg/kg and 80 mg/kg 
doses in 1/6 and 6/10 animals, respectively. Deaths occurred at the 5th dose in the 40 mg/kg cohort 
and at the 3rd and 4th dose in the 80 mg/kg cohort (Table 3).  In DRF study 
, an IRR was 
observed after the 4th dose in 1 of 2 animals at the 100 mg/kg dose level.  The onset and 
presentation were consistent with IRRs observed in GLP study 
. 
Although severity and tissue distribution of histopathology findings were variable among affected 
animals, some consistency was noted in the type of findings and the organ/tissue distribution in 
the mid and higher dose group animals (≥40 mg/kg/dose) following repeat dose administration of 
SL-279252. These included vascular/sinusoidal leukocytosis, fibrin deposits mixed with 
predominant population of neutrophils, lymphocytes, and monocytes within vessels of lung, liver 
and/or kidney. Correlating laboratory findings were noted in affected animals. For the animals that 
died (Table 3), the cause of morbidity or euthanasia was due to leukocyte infiltration within the 
vascular lumina (vascular leukocytosis) as noted in the lungs, kidneys and liver sinusoids.  
 


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Table 3: Animal Deaths in GLP Study 
 
Dose 
(mg/kg) Sex Animal 
Study 
Day  
of  
Death 
Anti-
Drug 
Antibody 
Circumstances 
of Death 
Target Dose 
Received (%) 
Significant Pathology Findings 
40 
F 
3501 
29 
Positive 
Died after 
dosing 
Day 1: ~100%.  
Day 8: ~100%.   
Day 15: ~100%. 
Day 22: ~100% 
Day 29: ~30% 
Lung: vascular leukocytosis  
Liver: sinusoidal leukocytosis 
80 
M 
4002 
15 
Positive 
Died after 
dosing 
Day 1: ~100%    
Day 8: ~100%   
Day 15: ~40% 
Lung: hemorrhage and vascular 
leukocytosis 
80 
M 
4004 
15 
Positive 
Died after 
dosing 
Day 1: ~100%   
Day 8: ~100%   
Day 15: ~40% 
Lung: fibrin deposition and 
vascular leukocytosis 
80 
M 
4005 
15 
Positive 
Euthanized in 
extremis 
Day 1: ~100%    
Day 8: ~100%.   
Day 15: ~40% 
Liver: sinusoidal leukocytosis 
80 
F 
4502 
16 
Positive 
Euthanized in 
extremis 
Day 1: ~100%   
Day 8: ~100%.  
Day 15: ~60% 
Liver: sinusoidal leukocytosis  
Lung: hemorrhage, leukocytosis, 
fibrin deposition  
Kidney: hemorrhage, leukocytosis, 
fibrin deposition 
80 
M 
4003 
22 
Positive 
Died after 
dosing 
Day 1: ~100%.  
Day 8: ~100%.   
Day 15: ~40%.  
Day 22: ~10% 
Lung: fibrin deposition and 
vascular leukocytosis 
80 
F 
4503 
22 
Positive 
Euthanized in 
extremis 
Day 1: ~100%.  
Day 8: ~100%.  
Day 15: ~10%        
Day 22 - ~30% 
Liver: sinusoidal leukocytosis  
Lung: hemorrhage, leukocytosis, 
fibrin deposition  
Kidney: hemorrhage, leukocytosis, 
fibrin deposition 
 
All animals tested screened negative for anti-drug antibodies (ADA) prior to dosing, and all 
animals in the vehicle group remained negative for ADA throughout the study. In contrast, all 
treated animals except for one screened positive for ADA prior to receiving the 3rd dose. All treated 
animals were positive for ADA prior to the 4th dose. For the two animals that demonstrated 
consumptive coagulopathy and were euthanized in extremis following the 3rd dose or 4th dose, the 
ADA titer was observed to decrease following dosing, which may have been due to immune 
complex formation. Overall, infusion reactions were associated with the formation of an ADA 
response by the time the 3rd dose was administered; however, the ADA titer did not correlate with 
the occurrence of an infusion reaction. 
Cytokine levels were measured in both the 
 (Day 1, 29) and 
 (Day 1, 
8, 15, 29) studies . There was evidence of an SL-279252-related increase in multiple cytokines, 
primarily interleukin-1 receptor antagonist, IL-10, IL-6 and monocyte chemoattractant protein-1 
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1b. Cytokine effects tended to peak at 2 hours postdose with resolution in most cases by 24 hours 
postdose, although occasional increased cytokine levels were seen at the 80 mg/kg/dose at one or 
more predose intervals (Days 8, 15, or 29). The magnitude of cytokine increases tended to follow 
a dose response, and often became more pronounced following the 3rd dose at which point all but 
one animal had developed ADA. No discernable effects on IFN-γ, IL-2, IL-4, IL-17-α, or TNF-α 
were identified in any group. In general, the profile of cytokines elevated is consistent with a T 
helper 2-type immune response.  This profile could be consistent with OX40 activation in CD4+ 
T cells but interpretation is confounded by the presence of ADA. 
Complement activation was also measured in both the 
 (Day 22, 29) and 
 study (Day 1, 8, 15, 29). Complement analysis demonstrated evidence of dose-related and 
progressive SL-279252 related complement activation at all dose levels as indicated by increases 
in split products Bb, C3a, and/or SC5b-9. These effects tended to peak at 2 hours post-dose with 
resolution in most cases by 24 hours post-dose. The magnitude of the effects tended to follow a 
dose response. Effects were observed following the first dose in all animals, with vehicle and 
10 mg/kg dose groups showing mild elevation, while higher elevations were observed in the 
40 mg/kg and 80 mg/kg dose groups.  The magnitude of increase among complement endpoints 
tended to become more pronounced following the 3rd dose, with the effect also noted at the 10 
mg/kg dose level and persisting through the 24-hour post-dose interval.   
The bioanalytical assay measured only free, unbound SL-279525 and the TK results demonstrated 
targeted-mediated drug disposition (TMDD) following a single dose as there was a decrease in 
clearance (CL) and volume of distribution (Vz) with an increase in dose from 3 to 100 mg/kg. The 
apparent TMDD observed following the first dose was likely due to binding of SL-279252 to 
targeted receptors on the peripheral blood lymphocytes. The serum terminal phase half-life (t½) 
ranged from approximately 12 to 25 hours over doses ranging from 3 to 100 mg/kg for the 
combined DRF and GLP toxicology study. Interestingly, SL-279252 was detected on peripheral 
blood lymphocytes by flow cytometry up to 7 days post-infusion and by Day 15 was accompanied 
by expansion of OX40 positive lymphocytes and a consistent serum cytokine signature.  Based on 
the evidence of TMDD likely related to binding to receptors localized on peripheral blood 
lymphocytes, CL of SL-279252 may be affected by changes to lymphocyte count and/or receptor 
density. The TK profiles observed on Day 29 following weekly administration of SL-279252 were 
atypical with rapid clearance of free SL-279252.  By Day 29, all animals in the DRF and GLP 
toxicity study tested positive for ADA which likely explains the rapid clearance observed 
following administration on Day 29. 
Taken together the findings from the DRF 
 and GLP 
 studies were suggestive 
of expected target-mediated pharmacology as well as immunogenicity related effects which led to 
dose-dependent toxicity. The immune effects were considered to be multifactorial in etiology with 
potential contributions from cytokine increase, complement binding and ADA-mediated effects.  
Collectively, the effects at 40 and 80 mg/kg/dose were considered adverse and the effects at 10 
mg/kg/dose were not considered adverse. The highest non-severely toxic dose (HNSTD) was 
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1.3 
Rationale 
The preclinical data package provided in the IB [SL2018IB001_01] demonstrates that the tethering 
of these two signals using an ARC provides a mechanistic advantage over the separate 
administration of two antibodies that have different PK properties, distribute separately, and may 
compete for Fc receptor binding. We hypothesize that co-localization and co-stimulation is critical 
for combination immunotherapy and will result in superior clinical activity in comparison to the 
separate administration of two individual antibodies. In addition, SL-279252 has a strong 
specificity advantage over mAbs targeting a specific co-stimulatory ligand (i.e., PD-L1 inhibitors 
like atezolizumab, avelumab, and durvalumab), when multiple ligands exist for a given target and 
can all (at least partially) contribute to the overall immunosuppressive environment. For example, 
blocking only PD-L1 does not preclude an incoming T cell from becoming suppressed when its 
membrane bound PD-1 interacts with tumor expressed PD-L2.  SL-279252 binds to PD-L2 with 
similar affinity as it does to PD-L1 and is able to occupy/block both ligand binding sites.  
SL-279252 also overcomes several major functional limitations seen with existing bifunctional 
technologies (i.e., bispecific antibodies or linked single-chain variable fragment [scFv] molecules). 
The active unit of SL-279252 exists as a glycosylated multimer, thereby retaining high target 
avidity, and inducing OX40 receptor clustering and active signaling.  The TNF superfamily 
receptors (i.e., OX40, GITR, 4-1BB) require clustering on a cell membrane and coordinated 
binding of multiple receptors for signal activation. With bispecific antibodies or linked scFv 
molecules, one of the two target binding domains is replaced to bind a second molecule thus 
resulting in a loss of target avidity.  The monovalent binding interaction with each of these two 
targets is incapable of activating receptors that require clustering on a cell membrane. For this 
reason, there is not a current example of a bispecific antibody or linked scFv that is able to 
simultaneously block a checkpoint ligand while stimulating a TNF costimulatory receptor.  
This first-in-human Phase 1 study will evaluate the safety, tolerability, PK, anti-tumor and 
pharmacodynamic effects of SL-279252 to identify the dose and schedule i.e., recommended Phase 
2 dose (RP2D) for future development. The trial will enroll patients with tumor types that have 
demonstrated benefit from anti-PD1/L1 inhibitor therapy i.e., melanoma, non-small cell lung 
cancer (NSCLC), urothelial cancer, head and neck squamous cell carcinoma  (HNSCC), squamous 
cell cervical cancer, gastric or gastro-esophageal junction (GEJ) adenocarcinoma, squamous cell 
carcinoma of the anal canal (SCCA), squamous cell carcinoma of the skin (Skin-SCC), renal cell 
cancer (RCC), Hodgkin’s lymphoma (HL), and microsatellite instability high (MSI-H) or 
mismatch repair deficient (MMRD) solid tumors excluding central nervous system (CNS) 
malignancies. Given that SL-279252 likely requires binding of PD-L1 to mediate activity within 
the tumor, the study was amended to require eligible subjects to have tumors with PD-L1 
expression ≥1% by tumor proportion score (TPS) or combined proportion score (CPS) at baseline. 
Potential risks to subjects are addressed by safety guidelines and vigilant monitoring of participants 
as outlined in the protocol.  Potential safety concerns are based on preclinical safety toxicology 
findings in cynomolgus monkeys dosed with SL-279252 and other in vivo or in vitro studies of 
SL-279252 summarized in the IB, as well as established clinical management guidelines developed 
for immune checkpoint therapy inhibitors.  


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1.4 
Potential Risks and Benefits 
1.4.1 Potential Risks 
SL-279252 is a pharmacologically active molecule [SL2018IB001_01].  The risks (evaluation of 
safety and tolerability) and potential benefits (evaluation of anti-tumor activity) of SL-279252 in 
humans will be assessed for the first time in this Phase 1 clinical trial.  In the absence of data in 
humans, an assessment of potential safety risks is based on (1) the results of nonclinical studies 
with SL-279252 (e.g., NHP studies); and (2) the immune-related adverse event (irAE) profile of 
other immune checkpoint inhibitors and costimulatory molecules.   
Based on a thorough review of the totality of the NHP data (including laboratory studies, cytokine 
and complement data, TK and immunogenicity studies, anatomical pathology), the underlying 
etiology of the SL-279252-related effects is most likely due to a combination of both the 
pharmacologic activity of the molecule and to immunologic reactions to SL-279252 
administration. The following are potential contributory factors to these reactions: (1) high levels 
of cytokine release; (2) increase in pre-dose lymphocytes; (3) development of ADA; and/or (4) 
complement activation.   
Implications for the first-in-human clinical trial [SL2018IB001_01]: 
1) The data indicate a potential risk for cytokine release syndrome (CRS) in humans. The IRRs 
that were noted in the NHP studies were potentially cytokine-mediated as they demonstrated 
dose- and time-dependence. In contrast, antibody-mediated type 1 or type 3 hypersensitivity 
reactions (HSRs) would not be expected to demonstrate dose-dependence. Furthermore, CRS 
is to be expected given the mechanism of action of SL-279252.  The steps taken to minimize 
the risks include: low starting dose, decreased dose frequency in comparison to the dosing 
schedule for the NHP studies for the first schedule to be evaluated (i.e., Schedule 1), 
administration in an outpatient oncology clinic or inpatient setting, management guidelines 
(e.g., rescue treatments, prophylaxis), extended monitoring in a hospital setting and/or hospital 
admission when indicated. The steps taken to minimize the risks are outlined in the Toxicity 
Management Guidelines section of the protocol (Section 3.5).  
 
2) Immunogenicity Risk: SL-279252 is considered to have a low risk of immunogenicity in 
humans. To evaluate the risk of immunogenicity in humans, the following 2 in vitro studies 
were performed: (1) Antitope/Abzena in silico analysis showed that the SL-279252 construct 
did not contain any identifiable T cell epitopes; and (2) EpiScreen™ time course T cell assay 
assessed the probability for SL-279252 to induce CD4+ T cell responses. No proliferation or 
cytokine release was observed in this assay with peripheral blood mononuclear cells (PBMCs) 
from 50 healthy donors.  Subjects in the clinical trial will, nevertheless, be monitored starting 
at baseline and serially for ADA. In the event of a positive ADA response, antibody titer will 
be measured, and antibody isotype will be characterized. A guideline for monitoring and 
management of HSRs is included in the protocol (Section 3.5.1). 
 
3) Toxicity secondary to complement activation: Complement activation secondary to treatment 
with SL-279252 could potentially result in toxicity. In the NHP studies, SL-279252 caused 
complement activation in vivo, as measured by CH50, C3a, Bb and SC5b9 assays. The 
cynomolgus monkey is a sensitive species for complement activation [Shen, 2014]. Thus, in 


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vitro assays were performed to determine whether SL-279252 directly activated human and/or 
cynomolgus complement proteins. The magnitude of complement activation observed in vitro 
appears to be increased in cynomolgus monkey serum as compared to human serum. It was 
noted that SL-279252 activated human and cynomolgus complement proteins in vitro at 
concentrations above 15.3 µg/mL. Based on toxicokinetic simulations, less than 1% of subjects 
will have a serum concentration of SL-279252 exceeding 15.3 microgram/milliliter (µg/mL) 
at human doses below 0.3 mg/kg. Patients in the clinical trial will be monitored for complement 
activation at all dose levels.   
 
As with other checkpoint inhibitors and costimulatory molecules, irAEs resulting from a 
breakdown of self-tolerance are anticipated with SL-279252. As experience using these therapies 
has grown, the list of toxicities has increased, and the types of AEs observed span essentially every 
organ class.  Extensive knowledge in managing these toxicities has developed over the years and 
led to the publication of consensus guidelines in peer reviewed journals [Haanen, 2017; Puzanov, 
2017; Brahmer, 2018].  Similarly, robust management guidelines are available for managing CRS 
in the context of treatment with adoptive T-cell therapies, bispecific antibodies, and agonist 
antibodies.  Moreover, clinical trial sites familiar with these therapeutic agents have developed 
institutional guidelines to ensure effective management of these toxicities. Monitoring and 
management of irAE follow these consensus guidelines in this first in human study. 
In summary, this Phase 1 study has taken the following precautions to minimize the potential for 
adverse outcome: (1) the study is being conducted at centers that have extensive experience with 
this class of agents and the management of associated toxicities; (2) the starting dose of SL-279252 
is estimated based on minimum anticipated biological effect level (MABEL) and is 100,000x 
lower than the HNSTD observed in the NHP studies (Section 3.2.3). Therefore, the starting dose 
is expected to be lower than doses associated with adverse events (AEs) in humans; (3) staggered 
enrollment between dose cohorts and within cohorts allows for the monitoring of acute toxicities 
in one subject before treating another; (4) administration  of SL-279252 in an outpatient oncology 
treatment center/hospital allows for close monitoring of subjects for AEs and for timely action; (5) 
guidelines for management of AEs based on established guidelines [Haanen, 2017; Puzanov, 2017; 
Rosello, 2017; Brahmer, 2018; Porter, 2018] are provided in the clinical trial protocol (Section 
3.5); (6) a Safety Monitoring Committee (SMC) will meet monthly and on an ad hoc basis to 
review emerging toxicities, and assess the impact of these toxicities on study conduct. 
1.4.2 Potential Benefits 
The clinical benefits of SL-279252 are unknown: no clinical trials in human subjects have been 
conducted to date. SL-279252 targets both the PD-1/L1 and the OX40/OX40L axes.  Mabs 
targeting each of these axes have been extensively evaluated in clinical trials [Marin-Acevedo, 
2018].   
PD-1/L1 inhibitors (pembrolizumab, nivolumab, atezolizumab, durvalumab, and avelumab) have 
demonstrated a favorable benefit:risk profile in clinical trials and gained regulatory approval in an 
expanding array of indications. HL harbors genetic alterations in the chromosome 9p24.1 
amplicon, resulting in overexpression of the PD-1 ligands, PD-L1 and PD-L2 [Roemer, 2016]. 
This makes HL unique among all tumors. The overall response rates in patients with 


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relapsed/refractory HL were 87% and 65%, with nivolumab and pembrolizumab, respectively 
[Ansell, 2015; Armand, 2016].  In other tumor types depending on the indication, clinical 
responses have been less impressive (reported in 10-45% of patients) [Larkin, 2015b; Carbone, 
2017; Grywalska, 2018].  The most mature survival outcome results for checkpoint inhibitors are 
in advanced melanoma.  A pooled analysis of 12 clinical trials of ipilimumab in patients with 
advanced melanoma with follow-up to 10 years revealed a plateau at 21% in the survival curve 
beginning around year 3 [Schadendorf, 2015].  In a survival follow-up of patients who received 
nivolumab in advanced melanoma, the 60-month overall survival rate was 34% with a plateau 
occurring at approximately (~) 48 months [Hodi, 2016]. In a quest to improve on such results, PD-
1 inhibitors have been combined with other agents including checkpoint inhibitors, costimulatory 
agents, vaccines, chemotherapeutic agents, targeted therapies and radiation. Along these lines, the 
first checkpoint-checkpoint combination of ipilimumab (CTLA-4 inhibitor) and nivolumab (PD-1 
inhibitor) was approved for late-stage melanoma based on a significant improvement in 
progression free survival compared to ipilimumab [Larkin, 2015a].   
Despite promising preclinical results of anti-tumor activity with OX40 agonists, early clinical trials 
of these agents as monotherapy have been underwhelming.  Combination immunotherapy trials 
with PD-1 inhibitors and anti-OX40 antibodies are ongoing but results are pending. However, the 
data from the preclinical studies for this combination has been conflicting.  In vivo experiments in 
mice have demonstrated that simultaneous addition of anti–PD-1 to anti-OX40 antibodies negates 
the antitumor effects of the anti-OX40 antibody [Messenheimer, 2017; Shrimali, 2017]. In 
contrast, sequential combination of anti-OX40 antibody followed by anti-PD-1 antibody (but not 
the reverse order) resulted in significant increases in therapeutic efficacy [Messenheimer, 2017]. 
These results suggest that in some cases the sequencing of agents must be carefully considered due 
to competition for Fc receptor binding [Gao, 2017]. The synchronized blockade of immune 
suppression and costimulation of T cells is more difficult to achieve if separate antibodies are 
administered, as opposed to a single agent designed to engage both targets simultaneously 
[SL2018IB001_01]. This hurdle could be overcome by an immunotherapeutic such as SL-279252. 
The ECDs of PD-1 and OX40L are physically linked to one another and localized to the TME.  
Tumor infiltrating T cells will receive costimulation at the same time that they recognize a tumor 
antigen via the T cell receptor. 
This first in human, Phase 1 trial will assess the safety, tolerability, PK, pharmacodynamics and 
anti-tumor activity of SL-279252 in patients with tumor types that have been documented to 
respond to anti-PD1/L1 therapy. All patients enrolled in this trial are required to have received or 
been intolerant to standard of care therapies. The majority of subjects will also have received 
PD1/L1 and/or CTLA-4 inhibitors and progressed.   
 
 








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is opened for enrollment, then enrollment on Schedule 1 will be halted. If Schedule 2 is opened, 
the Sponsor may also elect to stop enrollment in Schedule 2 early (e.g., based on safety) and resume 
enrollment in Schedule 1.  The MTD or MAD may be determined for either Schedule 1 or 
Schedule 2. Alternatively, a less intensive dosing schedule may be instituted if safety and 
pharmacodynamic data on Schedule 1 support less frequent dosing of SL-279252.  
Pharmacodynamic Cohorts in Dose Escalation: The Sponsor, in consultation with the SMC, 
may elect to open a pharmacodynamic cohort in order to obtain additional pharmacodynamic data 
from a total of approximately 6 additional subjects at one or more dose levels that have previously 
completed evaluation for safety and has not exceeded the MTD. Subjects enrolled in the 
pharmacodynamic cohort will not inform dose escalation decisions but the pharmacodynamic 
information gathered from these additional subjects may inform selection of doses for further 
evaluation in dose expansion. As a result, the maximum planned sample size estimate in dose 
escalation may increase by approximately 6 subjects  and the overall total planned sample size 
estimates would increase accordingly. Subjects in the pharmacodynamic cohort will be followed 
per the Dose Escalation Schedule of Assessment (SOA) tables provided in Sections 6.1 (schedule 
1) and 6.2 (schedule 2). 
Based on accumulating data from the dose escalation phase, including safety, PK, 
pharmacodynamic and anti-tumor activity, up to two Dose Expansion cohorts may be opened. 
NOTE: Only one schedule will be evaluated in the expansion phase. The primary objective of the 
expansion phase is to further refine the safety and tolerability of SL-279252. The expansion 
cohorts will also provide additional pharmacodynamic data and a preliminary estimate of anti-
tumor activity. At the end of dose escalation and dose expansion, safety, PK, anti-tumor activity, 
and pharmacodynamic data will be reviewed to identify a RP2D (Section 3.3.2).   
3.1.1 Sample Size 
If only Schedule 1 is evaluated, the maximum planned sample size is 42 for dose escalation. If 
Schedule 1 and 2 are both fully evaluated in dose escalation, the maximum planned sample size is 
57. If pharmacodynamic cohorts are opened in dose escalation, the maximum sample size is 48 if 
schedule 1 is fully evaluated or 63 if Schedule 1 and 2 are fully evaluated. The sample size in each 
Expansion Cohort is ~15 subjects (see Section 3.3 for details).  Overall, the total sample size 
estimate for this study is ~ 78 subjects assuming only Schedule 1 is evaluated and 
pharmacodynamic cohorts are opened and ~93 subjects if both Schedule 1 and 2 are fully evaluated 
and pharmacodynamic cohorts are opened. See Sections 9.2.1 and 9.2.2 for more details. 
 
 


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3.1.2 Study Schema 
 
Safety evaluation of SL-279252 will begin on Schedule 1. Dose escalation will proceed as described in Section 3.2.4 
and Table 5. Initially, cohort size may be limited to 1 subject for enrollment until ≥ Grade 2 toxicity or DLT (see 
Section 3.2.5 for criteria to expand single subject cohort size and Section 3.2.6 for DLT definitions) is observed or 
DL 6 is reached; any of these scenarios trigger enrollment of ≥ 3 subjects in dose cohorts from that point forward. 
Enrollment into a DL will proceed based on the Keyboard Design outlined in the Appendix Section 16.3.  Schedule 2 
will be tested if investigation of a more frequent dosing schedule is considered necessary (Section 3.2.7). The starting 
dose on Schedule 2 will be at least 1 DL below the current safe Schedule 1 DL defined by the Keyboard design 
(denoted as DL X-1 in the schema above). An MTD or MAD may be identified on either Schedule 1 or Schedule 2. 
Up to 2 doses may be selected for further evaluation in dose expansion cohorts and up to 15 subjects may enroll per 
cohort. Only dose levels that have been cleared for safety (permitted to escalate per the Keyboard Design rules) with 
a minimum of 6 subjects treated at that dose level will be expanded. The Dose Expansion cohorts may be opened to 
enroll subjects in parallel with the Dose Escalation cohorts.    Fresh tumor biopsies (obtained prior to C1D1, during 
C1D16 to C1D23, and at progression) are requested of subjects in Dose Escalation or Expansion cohorts who have 
tumor accessible to biopsy. In addition, blood will be obtained for serial assessment of PK and relevant biomarkers 
during dose escalation and dose expansion. A pharmacodynamic cohort may also be explored during dose escalation 
as described in Section 3.1.  A RP2D will be selected for further evaluation at the end of the study based on the totality 
of the data.   
Abbreviations for Schema: D and d = Day; DL = dose level; MAD = maximum administered dose; MTD = maximum 
tolerated dose; PD = pharmacodynamic; PK = pharmacokinetics; q = every; RP2D = recommended phase 2 dose 
 
3.2 
Dose Escalation 
3.2.1 Description 
Dose escalation will proceed as described below.  Enrollment will be based on the Keyboard 
Design outlined in the Appendix Section 16.3 [Yan, 2017].  During dose escalation, two possible 


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schedules for administration of SL-279252 may be explored. The first schedule (Schedule 1) will 
determine the safety of administering SL-279252 on days 1, 8 and 15 of the first 28-day cycle and 
then every 2 weeks thereafter on days 1 and 15 of each 28-day cycle beginning with cycle 2. The 
second schedule (Schedule 2) will explore the safety of weekly dosing of SL-279252 on days 1, 8, 
15 and 22 of each 28-day cycle.  The DLT assessment period will end 7 days after the last dose 
administered in the first cycle. Therefore, DLTs will be assessed over 21 days for Schedule 1 and 
over 28 days for Schedule 2. DLTs are defined in Section 3.2.6.  
Enrollment on Schedule 2 may be instituted if safety and pharmacodynamic data support 
exploration of more frequent dosing based on defined inadequate evidence of pharmacodynamic 
activity on Schedule 1 (see Section 3.2.7). The starting dose on Schedule 2 will be at least 1 DL 
below the current safe Schedule 1 DL defined by the Keyboard design. Doses beyond the 
maximum dose stated in the protocol may be explored if the MTD has not been reached. In 
summary, an MTD or MAD may be determined on Schedule 1 or Schedule 2 depending on how 
the study evolves. Alternatively, a less intensive dosing schedule may be instituted if safety and 
pharmacodynamic data on Schedule 1 support less frequent dosing of SL-279252 (e.g., one dose 
given every two weeks or every three weeks or every four weeks).   
Blood will be collected prior to, during, and following SL-279252 administration for serial 
assessment of PK (Section 6.7.1) and relevant biomarkers (e.g., cytokines, complement, receptor 
occupancy, etc.) during dose escalation (Section 6.9.1). Tumor tissue (archival tissue and fresh 
tumor biopsies predose, on-treatment and at progression) will be requested of subjects as described 
in Section 6.9.2.  
3.2.2 Intrasubject Dose Escalation  
For subjects enrolled in Dose Escalation cohorts, intra-subject dose escalations may be considered 
on a case-by-case basis, provided that the subject completed at least 2 cycles at the originally 
assigned dose, has tolerated treatment well, and did not experience Grade 3 or higher toxicity. A 
subject’s dose may be increased to that of the current DL that has been evaluated for safety and 
has not exceeded the MTD. Approval for intra-subject dose escalation must be obtained from the 
Sponsor Medical Monitor.  Dose-escalation decisions will be documented on a Dose 
Escalation/De-escalation Decision Form (see the Study Reference Manual; SRM). 
3.2.3 Justification for Starting Dose  
The starting dose of 0.0001 mg/kg SL-279252 for this first in human study was derived using 
available nonclinical pharmacology, toxicology, PK and pharmacodynamic data from NHP studies 
in the cynomolgus species. The starting dose was selected based on MABEL principles. 
In cynomolgus monkeys administered IV doses of 0.03 and 0.3 mg/kg over 30 minutes (n=2 for 
each DL) resulted in median Cmax values of 564 and 7464 nanogram (ng)/mL, respectively, which 
are approximately 738- and 56-fold below the Cmax observed in monkeys for the HNSTD dose 
of 10 mg/kg (416,000 ng/mL).  Assuming linear kinetics from the 0.03 mg/kg dose in cynomolgus 
monkeys (Cmax 564 ng/mL and AUC0-infinity [inf]  304 ng*h/mL), a 0.0001 mg/kg dose of SL-
279252 would achieve an estimated Cmax of 1.88 and AUC0-inf of 1.01 ng*h/mL which is 


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approximately 200,000- and 700,000-fold lower than the Cmax and AUC0-inf observed for the 
HNSTD dose of 10 mg/kg (Cmax 416,000 ng/mL; AUC0-inf  726,000 ng*h/mL). 
However, because non-linear kinetics were observed for SL-279252 following single dose IV 
infusion in cynomolgus monkeys, a PK model was developed to capture the PK in monkeys 
adequately and to facilitate human exposure predictions. The PK model for serum SL-279252 
concentrations following a single dose was developed using a two-compartment model with 
Michaelis-Menten clearance and allometric scaling by body weight on clearance and volume 
parameters. After accounting for body weight, there were no other important covariates in the 
model. The model tended to over-predict Cmax for the lowest doses (0.03 and 0.3 mg/kg) in 
monkeys by 1.2- to 2.1-fold, thus, the model was deemed a conservative model for simulating 
human exposure.  
Simulated human serum SL-279252 concentrations suggest that a starting dose of 0.0001 mg/kg 
results in median (95% confidence interval [CI]) Cmax of 3.73 (2.83, 4.92) ng/mL and is 111,500-
fold lower than the median Cmax following administration of the HNSTD dose (416,000 ng/mL). 
Simulated concentrations for the 0.0001 mg/kg dose are almost 10-fold below the Staphylococcal 
Enterotoxin B (SEB) Activity Assay half maximal effective concentration (EC50; geometric mean 
and 95% CI of 34.0 [21.3 – 54.4] ng/mL) MABEL. While simulations of a 0.0001 mg/kg dose 
result in concentrations that are comparable to the SEB Assay EC20 (5.3 [2.69, 10.4] ng/mL), the 
SEB Assay is known to be a sensitive assay and given the in vivo data, it is likely a single dose of 
0.0001 mg/kg will result in minimal to no biologic activity. Simulation of SL-279252 
concentrations following multiple doses were not possible with the available data.  
Justification for Schedule: A weekly dosing schedule for 5 consecutive weeks was implemented 
in the NHP studies.  Toxicity was dose-dependent (only at the higher doses) and occurred at the 
third and subsequent doses.  In the clinical trial, the initial dosing schedule (Schedule 1) 
incorporates administration of SL-279252 on Day 1, 8, 15, and then every 2 weeks thereafter. The 
Day 8 dose was retained as no toxicity was observed at this time point, minimal pharmacodynamic 
effects were noted, and this dose may have contributed to the pharmacodynamic effect on day 15. 
In NHPs, multiple factors may have contributed to the onset of reactions at Day 15 including ADA, 
complement activation, increase in lymphocytes and cytokine elevations.  It is unknown if these 
contributing factors would be observed in humans at the doses studied.  Therefore, dosing on Day 
1, 8, 15 was considered acceptable.  The 2-week treatment free interval beyond Day 15 may allow 
for pharmacodynamic effects to subside between subsequent doses and to mitigate toxicity. A less 
intensive dosing schedule may be instituted if safety and pharmacodynamic data on Schedule 1 
support less frequent dosing of SL-279252 (e.g., one dose given every two weeks or every 3 weeks 
or every 4 weeks).   
3.2.4 Starting Dose and Dose Escalation Plan  
Enrollment of subjects at each DL proceeds based on the Keyboard design outlined in the 
Appendix Section 16.3. Dose escalation will begin on Schedule 1 at the starting dose of 0.0001 
mg/kg as outlined in Table 5 below; intermediate DLs not shown may be explored based on 
emerging data (e.g., safety). As it is likely that the dose of 0.0001 mg/kg will result in minimal to 
no biologic activity, escalations for the first two DLs will proceed in log increments. Beyond DL2, 


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escalations will not exceed half-log increments. Doses beyond the maximum dose stated in the 
protocol may be explored if the MTD has not been reached.  An MTD or MAD may be determined 
on Schedule 1 or Schedule 2 and up to 10 or more dose levels may be explored if safety allows. 
Table 5: SL-279252 Dose Escalation Plan  
Dose Level 
Dose of SL-279252 (mg/kg)a,b,c,d 
Duration of Infusione 
Level 1 
0.0001 mg/kg 
5-30 minutes 
Level 2 
0.001 mg/kg 
5-30 minutes 
Level 3 
0.003 mg/kg 
5-30 minutes 
Level 4 
0.01 mg/kg 
30 minutes (+/- 10 minutes) 
Level 5 
0.03 mg/kg 
30 minutes (+/- 10 minutes) 
Level 6 
0.1 mg/kg 
30 minutes (+/- 10 minutes) 
Level 7 
0.3 mg/kg 
30 minutes (+/- 10 minutes) 
Level 8 
1.0 mg/kg 
1 hour (+/- 15 minutes) 
Level 9 
3.0 mg/kg 
1 hour (+/- 15 minutes) 
Level 10 
6.0 mg/kg 
1 hour (+/- 15 minutes) 
a) Dose escalation begins on Schedule 1: SL-279252 may be administered in the first cycle on days 1, 8, and 
15 of the first 28-day cycle and then once every 2 weeks on days 1 and 15 of each 28-day cycle beginning at 
cycle 2. 
b) Dose escalation on Schedule 2 may be tested: If Schedule 2 is opened, SL-279252 may be administered 
once weekly on days 1, 8, 15, and 22 of each 28-day cycle. The starting dose on schedule 2 will be at least 
one dose level below the current Schedule 1 dose level defined by the Keyboard design. If Schedule 2 is 
opened for enrollment, then enrollment on Schedule 1 will be halted. 
c) Intermediate dose levels may be tested based on emerging safety data. The option to explore more than 10 
dose levels on Schedule 1 or additional dose levels on Schedule 2 is also a possibility if safety allows. 
Escalations will not exceed half-log increments after dose level 2. 
d) The actual body weight in kg will be used for dose calculation in all subjects whose body weight is ≤100 kg.  
For subjects with body weight >100 kg, the dose to be administered should be the same as that calculated for 
a subject weighing 100 kg (See Sections 5.2.3 and 5.4 for details) 
e) Infusion time may change based on final drug volume needed for administration, safety and tolerability of the 
infusion for the subject, and/or observed safety findings during the study. Please refer to the Study Pharmacy 
Manual (SPM) for details.  
Evaluation of Schedule 1: Initially, and as outlined in Section 16.3.1, cohort size in Schedule 1 
may be limited to 1 subject for enrollment until one of the following occurs: a ≥ Grade 2 toxicity 
or DLT is observed (see Sections 3.2.5 and 3.2.6 for definitions ) or DL 6 is reached; any of these 
scenarios will trigger enrollment of ≥ 3 subjects in dose level cohorts from that point forward. 
Multiple-subject cohorts will incorporate a minimum 3-day stagger between dosing the first and 
second subject at the same dose level, although this requirement may change based on emerging 
safety data as determined by the SMC. The incidence of DLT will be assessed over a period of 21 
days during the first cycle of therapy (DLTs are defined in Section 3.2.6) on Schedule 1.   
Evaluation of Schedule 2: If safety and pharmacodynamic data from Schedule 1 (see Section 
3.2.7 for criteria needed to transition to Schedule 2) support exploration of more frequent dosing, 
then cohort enrollment on Schedule 2 will be instituted in lieu of Schedule 1. During dosing on 
Schedule 2, SL-279252 will be administered once weekly (D1, D8, D15, and D22) every 28 days.  
The starting dose on Schedule 2 will be at least 1 DL lower than the current safe Schedule 1 DL 
defined by the Keyboard design. Dose escalation (or de-escalation) may then proceed based on a 


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DL previously evaluated on Schedule 1 as shown in Table 5. For example, if 0.1 mg/kg (DL 6) is 
the current DL being evaluated on Schedule 1, then the starting dose on Schedule 2 will be 
0.03 mg/kg (DL 5) or lower.  
A minimum of 3 subjects will be evaluated in each DL during dose escalation on Schedule 2. A 
minimum 3-day stagger between dosing the first and second subject at the same DL is required, 
although this mandate may change based on emerging safety data. The incidence of DLT will be 
assessed over a period of 28 days during the first cycle of therapy (DLTs are defined in Section 
3.2.6) on Schedule 2.  
Evaluation of a Less Frequent Dosing Schedule: If safety and pharmacodynamic data from 
Schedule 1 support exploration of a less intensive dosing schedule, then cohort enrollment on this 
as yet to be identified schedule will be instituted in lieu of Schedule 1. For example, SL-279252 
may be administered once every two weeks in every cycle including the first cycle or once every 
21 or 28 days.  The starting dose on this less intensive schedule would be instituted at the current 
Schedule 1 dose level defined by the Keyboard design or a lower dose level based on emerging 
safety data. 
3.2.5 Criteria for Expanding a Single Subject Cohort in Schedule 1 
Dose escalation on Schedule 1 allows enrollment of a single subject (minimum of one subject per 
DL) into dose levels 1 to 5 unless a Grade ≥ 2 toxicity or DLT (Section 3.2.6) is observed over the 
21-day DLT assessment period with the exceptions listed below.  A qualifying event of Grade ≥ 2 
toxicity or DLT will trigger a switch to enrollment of ≥ 3 subjects for DLT assessment in that 
specific dose level and each DL thereafter.  
Toxicity exceptions that will not trigger a switch to enrollment of ≥ 3 subjects: 
• 
Grade 2 fatigue 
• 
Grade 2 nausea and vomiting controllable with anti-emetics within 72 hours 
• 
Vitiligo and alopecia of any Grade 
• 
Grade 2 IRR that can be managed with premedication and/or change in infusion duration 
• 
Grade 2 hematologic abnormalities not associated with clinical signs/symptoms 
• 
Grade 2 electrolyte abnormalities that are not associated with clinical signs/symptoms 
• 
Grade 2 amylase and lipase without evidence of clinical symptoms of pancreatitis 
• 
Toxicities related to disease progression or intercurrent illness, inflammatory reactions 
related to local tumor response such as severe pain 
3.2.6 Definition of Dose-Limiting Toxicity 
DLTs are defined in the bulleted points below.  Toxicities will be graded as per NCI CTCAE v5.  
The determinate period for DLT is the first 21 days or 28 days of treatment on Schedule 1 or 
Schedule 2, respectively. However, there is provision in the criteria below for toxicities that occur 
beyond this period to be considered in the definition of a DLT and the RP2D.  Note: Toxicities 
clearly related to disease progression or intercurrent illness are not considered DLTs.  
Inflammatory reactions attributable to local anti-tumor responses (e.g., severe pain) are not 
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• Any Grade 4 irAE 
• Elevations in liver transaminases (aspartate aminotransferase [AST], alanine aminotransferase 
[ALT]) and/or total bilirubin: 
o In subjects who enroll with AST/ALT/total bilirubin ≤ upper limit of normal (ULN); 
AST or ALT elevation of >8 x ULN or total bilirubin > 5 x ULN 
o In subjects who enroll with AST/ALT/total bilirubin > ULN; AST or ALT elevation of 
>8 x baseline or total bilirubin > 5 x baseline 
o Evidence of Hy’s Law (AST or ALT > 3 x ULN [or baseline*] with concurrent increase 
in total bilirubin > 2 x ULN [or baseline*] without evidence of cholestasis or alternative 
explanation such as disease progression or viral hepatitis; *ULN or baseline dependent 
on value at enrollment as described above. 
• Any Grade 3 irAE that requires permanent discontinuation of SL-279252 
• Any other Grade 3 irAE with the following exceptions:  
o Grade 3 skin toxicity that downgrades to Grade 2 or less within 7 days with optimal 
supportive care 
o Grade 3 hypothyroidism, hyperthyroidism, or hyperglycemia that can be managed with 
treatment 
o Grade 3 diarrhea with no evidence of colitis that resolves within 72 hours with 
appropriate clinical management 
• The following Grade 2 irAEs: 
o Grade 2 ocular toxicity requiring systemic steroids 
o Grade 2 cardiotoxicity that requires permanent discontinuation of SL-279252 
o Grade 2 Guillain-Barre Syndrome 
• Any Grade 3 or greater non-irAE except for those listed below: 
o Grade 3 fatigue lasting ≤ 7 days 
o Grade 3 or 4 neutropenia not associated with fever that improves to Grade 2 within 7 
days.   
o Grade 3 or 4 lymphopenia 
o Grade 3 thrombocytopenia not associated with clinically significant bleeding and does 
not require medical intervention 
o Grade 3 electrolyte abnormalities that are not associated with clinical signs/symptoms 
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o Grade 3 or 4 amylase and/or lipase abnormalities that are not associated with clinical 
signs/symptoms or finding on imaging consistent with pancreatitis 
o Grade 3 vomiting and/or Grade 3 nausea that resolves within 72 hours with appropriate 
clinical management 
• Other toxicities may be considered a DLT as determined by the investigator in conjunction 
with the SMC. 
A Grade ≥ 3 AE that occurs beyond the DLT period (21 days for schedule 1 or 28 days for schedule 
2) or Grade 2 events that require continuous interruption of SL-279252 for more than 6 weeks or 
toxicities that result in subjects not receiving at least 66% of the scheduled dose during the DLT 
assessment period may be taken into consideration when assessing the totality of the data in 
determining evaluability for DLT and the RP2D.   
3.2.7 Criteria for Decision to Transition from Schedule 1 to Schedule 2 
If Schedule 1 is safe and tolerable, and pharmacodynamic effects are not present or detectable, this 
may suggest that a more frequent dosing schedule is warranted. In this event an alternative dosing 
schedule (Schedule 2) will be explored in lieu of Schedule 1.  During dose escalation subjects will 
be monitored for pharmacodynamic effects pre- and post-dose. Dynamic changes that are 
anticipated following administration of pharmacologically active doses of SL-279252 include: 
• Evidence of increasing target density on PBMCs following repeated dosing  
• Increase in lymphocyte count 
• Increase in cytokines 
• Appearance of activation markers (e.g., Human Leukocyte Antigen D Related, CD25, etc.) 
on the surface of CD4 lymphocytes in the peripheral blood 
The anticipated timing of pharmacodynamic effects based on NHP studies is at cycle 1, day 15 
(C1D15) and beyond, although these effects may be observed as early as C1D1 and C1D8.    
3.3 
Dose Expansion  
3.3.1 Description  
Based on accumulating data from the dose escalation phase, including safety, PK, 
pharmacodynamic and anti-tumor activity, up to two Dose Expansion Cohorts may be opened for 
enrollment. The primary objective for the Dose Expansion Cohorts is to further refine the safety 
and tolerability of SL-279252. Safety will be carefully monitored, and sequential boundaries will 
be used to monitor for IRRs and discontinuation of SL-279252 due to toxicity based on Pocock 
stopping rules [Ivanova, 2005] as outlined in Section 9.2.2. The expansion cohorts could 
potentially begin enrollment prior to the end of dose escalation. Only dose levels that have been 
cleared for safety (permitted to escalate per the Keyboard Design rules) with a minimum of 6 
subjects treated at that dose level will be expanded. Up to 15 subjects will be evaluated in each 


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Expansion Cohort at a selected dose. One or two doses of SL-279252 (on the same schedule, i.e., 
only one schedule will be evaluated in the expansion phase) may be expanded.   
Secondary objectives for the dose expansion cohorts include a preliminary estimate of anti-tumor 
activity as measured by ORR and CBR. In addition, exploratory pharmacodynamic objectives will 
be further examined in the Dose Expansion Cohorts. Blood will be collected prior to and following 
SL-279252 administration for assessment of PK (sparse sampling; Section 6.7.2) and relevant 
biomarkers (e.g., cytokines, complement, immunophenotyping, etc.) during dose expansion 
(Section 6.9.1). Tumor tissue (archival tissue and fresh tumor biopsies predose,  on-treatment and 
at progression) will be requested of subjects in Expansion Cohorts as described in Section 6.9.2. 
Cell-free or circulating-free tumor nucleic acid (cfNA; see Section 6.9.1.4) and archival tumor 
tissue (Section 6.9.2.2) will be obtained for retrospective assessment of tumor mutational burden 
(TMB).   
3.3.2 Selection of Recommended Phase 2 Dose and Schedule for SL-279252  
If an MTD is not observed, the MAD would then be the highest dose administered as specified in 
the protocol. Selection of the dose and schedule for further study will therefore be based upon 
safety, tolerability, PK, anti-tumor activity, and pharmacodynamic markers consistent with the 
mechanism of action of SL-279252. Exploratory PK/pharmacodynamic modeling will be 
performed.  Based on the totality of the data, from the Dose Escalation and Dose Expansion 
Cohorts, a RP2D will be selected.   
3.4 
Concomitant Medications, Treatments, and Procedures 
Investigators may prescribe concomitant medications or treatments deemed necessary to provide 
supportive care except for prohibited medications (see Section 3.4.2).  Best supportive care should 
be provided when necessary for all subjects (including antibiotics, bisphosphonates, receptor 
activator of nuclear factor kappa B ligand (RANKL) inhibitors, nutritional support, correction of 
metabolic disorders, optimal symptom control, and pain management including palliative 
radiotherapy) after consultation with the Sponsor Medical Monitor. 
Use of inhaled, topical, intranasal corticosteroids or local steroid injections (e.g., intra-articular 
injection) is permitted. Temporary use of corticosteroids (e.g., prior to computed tomography [CT] 
to prevent contrast allergies) is acceptable after consultation with the Sponsor Medical 
Monitor. Use of immunosuppressive medication for the management of SL-279252-related AEs 
(e.g., prophylaxis in subjects who experience IRRs/CRS, treatment of immune-related toxicities) 
is permitted. 
3.4.1 Tumor Lysis Syndrome Prevention and Treatment Recommendations 
Hematologic malignancies are associated with a higher risk of tumor lysis syndrome (TLS). 
Although TLS has been reported with solid tumors, its occurrence is rare.  The incidence of TLS 
with immune checkpoint inhibitors and costimulatory molecules is not well characterized.  TLS 
was recently reported in a subject with bladder cancer following treatment with atezolizumab 
[Brunnhoelzl, 2017]. Guidance for identifying subjects at risk and for management of TLS is 
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• The risk factors for developing acute TLS after initiation of chemotherapy include uric acid 
level (>8 mg/deciliter [dL] or 25% increase from baseline), high tumor burden, high lactate 
dehydrogenase (i.e., LDH ≥2 x ULN), hypercalcemia, elevated creatinine (>1.6 mg/dL), 
leukocytosis (>50x109/liter [L]), and rapidly proliferating drug sensitive neoplasms 
[Rampello, 2006; Tufan, 2006].   
       
• All subjects with elevated uric acid (>8 mg/dL, or >476 millimole [mmol]/L) should 
receive prophylaxis with allopurinol or rasburicase, and hydration per standard of care. 
Blood chemistries should be monitored as indicated. If the constellation of clinical and/or 
laboratory signs indicate a possibility of developing TLS, subjects should be hospitalized 
with frequent monitoring of clinical signs and clinical chemistries and treated accordingly.  
IV hydration should be continued, as needed, in subsequent cycles and subjects should be 
monitored for fluid overload during this period.   
 
Treatment of TLS should be instituted when appropriate according to institutional guidelines. 
3.4.2 Prohibited Medications/Treatments 
Subjects must be instructed not to take any medications, including over-the-counter products 
without first consulting with the investigator.  The following medications are prohibited during the 
study: 
• Any investigational anti-cancer therapy not described in this protocol 
• Any concurrent chemotherapy, radiotherapy (except palliative radiotherapy after 
consultation with the Sponsor Medical Monitor), hormonal therapy for anti-cancer intent, 
immunotherapy, or biologic therapy for cancer treatment   
• Concurrent granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage 
colony stimulating factor (GM-CSF)  
• Immunosuppressive medications for primary prophylaxis against IRRs are not permitted. 
Subjects who require immunosuppressive medications (e.g., corticosteroids) for 
management of irAEs or IRRs/CRS should be managed per Toxicity Management 
Guidelines in Section 3.5. 
• Live attenuated vaccines during the study through 30 days after the last dose of SL-279252 
 
3.4.3 Medications to be used with Caution 
SL-279252 is a therapeutic protein that may induce the transient release of cytokines including IL-
6 which in turn, may inhibit the activity of cytochrome P450 (CYP450) enzymes including 
CYP3A4 activity [Evers, 2013].  Although not tested clinically, a drug-drug interaction may occur 
with the coadministration of medications that are CYP450 substrates. Drugs metabolized by 
CYP450 enzymes may have reduced clearance or an increase in half-life or peak plasma 
concentration and should be used with caution. There may be an increased risk of side effects for 
drugs that are CYP450 substrates. Where possible consider substitutions for these medicinal 
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A complete list of drugs that are CYP450 substrates including CYP3A4 substrates is available at: 
https://drug-interactions.medicine.iu.edu/Main-Table.aspx (Flockhart Table). 
3.5 
Toxicity Management Guidelines  
All AEs should be assessed using NCI-CTCAE v5.0 criteria. NOTE: Hereafter in this Section, 
SL-279252 may be referred to as SL-279252 or as IP. Please see sections 5.5 Physician 
Availability Required for Administration of SL-279252 and 5.6 Monitoring Dose Administration. 
NOTE: Dose reductions of SL-279252 are not permitted except in the event of rechallenge after 
Grade 3 CRS as noted in the guideline below.  
3.5.1 Management of Infusion-related Reactions 
The data from the NHP studies indicate a potential risk for IRRs including CRS in humans dosed 
with SL-279252. The IRRs that were noted in cynomolgus monkeys were potentially cytokine-
mediated as they a) demonstrated dose dependence and b) the severity of clinical symptoms 
correlated with cytokine level increases in the peripheral blood. It is important to note that the 
reactions that were noted in monkeys occurred during or immediately after SL-279252 infusion. 
Given the mechanism of action of SL-279252 (T cells become activated as they recognize tumor 
antigen), rapid onset of IRRs would be expected but the possibility of delayed reactions cannot be 
excluded. It is unlikely that SL-279252 infusion reactions are antibody-mediated type I or type 3, 
allergic HSRs as these reactions would not be expected to demonstrate dose dependence.  
Differentiating between IRRs that are due to either the common non-allergic HSRs (e.g., CRS) or 
the rarer allergic HSRs can be challenging due to overlapping clinical manifestations. There are 
no specific clinical features (including symptoms and timing of reaction) that can absolutely 
distinguish between these two entities.  
General guidance is provided below for IRRs secondary to both allergic and non-allergic HSRs 
e.g., CRS. These guidelines are not meant to be prescriptive. Established institutional guidelines 
should be followed where appropriate.  
At the resolution of the event, the entirety of the data including clinical symptoms, response to 
treatment and laboratory studies should be re-evaluated to determine the final etiology of the event. 
For purposes of standardized reporting, utilize terms based on best medical judgement of the 
AE/SAE and the definition found in NCI-CTCAE v5.0 for IRR, allergic reaction, anaphylaxis, and 
CRS. 
Primary prophylaxis against IRRs is not permitted to avoid obscuring a potential safety signal and 
to enable an assessment of whether pre-medications should be required for all subjects.  However, 
as noted in the guidance below, secondary prophylaxis (i.e., prevention of IRRs following an initial 
episode) is appropriate and permitted at the discretion of the investigator.  
NOTE: In the event of any Grade IRR (including CRS), subjects will be admitted for closer 
observation until resolution of symptoms.


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Adverse Event 
General Guidance for Infusion-related Reactions (IRRs) [Rosello, 2017; Porter, 2018] 
 
Infusion or 
Hypersensitivity 
Reactions 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Acute reactions to the IV administration of biologic agents is not uncommon. Reactions are either allergic reactions to foreign proteins 
or non-immune reactions. The term HSR is used to describe objectively reproducible signs or symptoms initiated by exposure to a 
defined stimulus at dose tolerated by a normal person. Allergy is HSR initiated by specific immunological mechanisms.  Anaphylaxis is 
a severe, life threatening HSR.  CRS consists of a non-allergic, cytokine mediated HSR.  Differentiation between the common non-
allergic HRS reactions and the rarer allergic HSR reactions can be challenging due to overlapping clinical manifestations. Fever, chills, 
rigors, headache, arthralgias, back pain, abdominal pain, nausea, vomiting, diarrhea, dyspnea, flushing, pruritus, and changes in heart 
rate and blood pressure are manifestations of common acute infusion reactions. Proinflammatory cytokines such as TNF-α and IL-6 
may play a role in these reactions. Symptoms more suggestive of allergic HSR include generalized pruritus, urticaria, wheezing, 
frequent coughing, and anaphylactic symptoms. Subjects must be monitored for signs and symptoms of IRRs with prompt institution of 
treatment.   
Severity 
Management 
Grade 1 
• 
Infusion interruption not indicated 
• 
Admit to hospital for close observation until resolution of symptoms. 
• 
Consider pre-medication (antipyretics, histamine (H)1 and H2 anti-histamines) for subsequent infusions per 
investigator/institutional guidelines 
Grade 2 
• 
Temporarily interrupt IP, or decrease the rate of the infusion by 50%, until resolution of the event.  
• 
Begin IV infusion of normal saline and treat with antipyretics, histamine 1 and 2 (H1 and H2) anti-
histamines.  Corticosteroids and/or bronchodilator therapy may also be administered as appropriate. 
Monitor subject until resolution of symptoms. 
• 
If the infusion is interrupted, then restart the infusion at no more than 50% of the rate at which the reaction 
symptoms occurred 
• 
If no further symptoms are experienced, infusion rate may be escalated at intervals and increments as 
clinically appropriate  
• 
If symptoms recur, then no further investigational product (IP) will be administered at this visit. 
• 
Admit to hospital for close observation until resolution of symptoms. 
• 
The following prophylactic pre-medications are recommended for future infusions: antipyretics, anti-
histamines with/without corticosteroids per institutional guidelines  
Grade 3  
• 
Immediately discontinue infusion.   
• 
Begin IV infusion of normal saline and treat with epinephrine, bronchodilators, diphenhydramine, ranitidine, 
corticosteroids, oxygen, fluids, vasopressors etc.as indicate and per institutional guidelines. Epinephrine is 
the drug of choice in an anaphylactic reaction and its administration should not be delayed. 
• 
Admit to hospital for close observation until resolution of symptoms. 
• 
Rechallenge should not be attempted in cases of true anaphylaxis. In other cases, once subject has 
completely recovered, carefully consider if it is safe for the subject to receive IP at the next scheduled dose 
with pre-medication (e.g., corticosteroids, anti-histamines, antipyretics) and slow infusion (≤ 50% of the rate 
at which the reaction occurred). If no further symptoms, rate may be escalated at intervals and increments 
as clinically appropriate. If symptoms recur, permanently discontinue IP  
Grade 4 
• 
Permanently discontinue IP 
• 
Manage severe IRRs per institutional standards (e.g., epinephrine, diphenhydramine, ranitidine, 
corticosteroids, bronchodilators, oxygen, fluids etc.).  Epinephrine is the drug of choice in an anaphylactic 
reaction and its administration should not be delayed  
• 
Admit to hospital for close observation until resolution of symptoms. 


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Adverse Event 
General Guidance for Cytokine Release Syndrome (CRS)  [Rosello, 2017; Porter, 2018] 
 
 
 
 
 
 
 
 
 
Cytokine-release  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CRS is a non-antigen specific, systemic inflammatory response that occurs as result of high-level immune activation with concomitant 
elevations of cytokines (e.g., IL-6, IL-10, TNF-α, IL-2, IFNɣ). Clinical features of the syndrome include (but are not confined to) fever, 
flu-like symptoms, rash, nausea, vomiting, diarrhea, hypotension, tachypnea, transaminitis, hypofibrinogenemia, elevation in D-dimer, 
hyperbilirubinemia, azotemia, neurologic manifestations.  The syndrome can progress to life-threatening capillary leak, hypoxic 
respiratory failure, vasodilatory shock and end-organ dysfunction. NOTE: CRS may have a similar presentation to a type 1 HSR and 
may be clinically indistinguishable.  
Severity 
(symptoms) 
Management of CRS 
Grade 1 
 
• Decrease the rate of the infusion by 50%, until resolution of the event 
• Maintain IV access. Symptomatic treatment with antipyretics, antiemetics, analgesics, H1/H2 antihistamines 
as needed; monitor fluid balance; assess for infection. Regularly evaluate for signs of further deterioration 
• Admit to hospital for close observation until resolution of symptoms. 
• For subsequent infusions, consider pre-medication (e.g., antipyretics, anti-histamines) per institutional 
guidelines 
Grade 2 
 
• Interrupt IP and do not-restart until symptoms are returned to grade ≤1 for at least 3 days. Once symptoms 
have resolved, administer dose per next scheduled time point. 
• Start IV infusion with normal saline. Administer oxygen if needed. Treat with antipyretics, H1/H2 antagonists 
(diphenhydramine 50 mg IV plus ranitidine 50 mg IV), and/or methylprednisolone 1-2 mg/kg or equivalent 
dose of corticosteroid every 6 hours and manage per institutional guidelines. Closely monitor cardiac and 
other organ functions. 
• Admit to hospital for close observation until resolution of symptoms. 
• The next two subsequent infusions of SL-279252 (after an event of grade 2 CRS) must be administered in an 
inpatient setting for prolonged observation  (e.g., 24 hours). 
• For subsequent infusions, start infusion at 50% rate at which the symptoms occurred and titrate to tolerance. 
Consider pre-medication with dexamethasone 20 mg, antipyretics, H1/H2 anti-histamines, and manage per 
institutional guidelines. 
• Subjects with extensive comorbidities or those of older age should be treated as for Grade 3.  Subjects with 
worsening symptoms should be treated as for Grade 3 
Grade 3 
• Interrupt IP and do not-restart until symptoms are returned to grade ≤1 for at least 3 days. Once symptoms 
have resolved, administer dose per next scheduled timepoint. 
• Admit to hospital for close observation until resolution of symptoms. 
• For Grade 3 CRS, may consider rechallenge at the next lower dose level after consultation with medical 
monitor.  
• After a Grade 3 CRS event, subjects must be premedicated with high dose steroids prior to the next infusion 
of SL-279252.  
• If there is no evidence of CRS with the infusion at the reduced dose level, premedication with high dose 
steroids may be omitted for subsequent infusions.  
• The two subsequent infusions of SL-279252 after an event of grade 3 CRS should be administered in an 
inpatient setting for prolonged observation (e.g., 24 hours). 
• Any patient that experiences recurrence of Grade 3 CRS following re-treatment must be permanently 
discontinued from study treatment. 
 (Continued on next page) 


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Cytokine-release 
(continued from 
previous page) 
Severity 
(symptoms) 
Management of CRS 
Grade 3  
(continued) 
 
• Monitor for organ dysfunction: admit to the intensive care or equivalent for close monitoring and management. 
• Treat hypotension with IV fluid for blood pressure support and/or pressers.  Administer oxygen for treatment of 
hypoxia. Cryoprecipitate or fresh frozen plasma may be required for coagulopathy. Manage per institutional 
guidelines. 
• Administer tocilizumab at a dose of 8 mg/kg. If clinical improvement does not occur within 24 hours, administer 
a second dose of tocilizumab.  
• Second-line therapies:  
• Methylprednisolone 2 mg/kg/day IV tapered over several days. For subjects with severe neurologic 
symptoms, consider using dexamethasone due to more efficient penetration of the blood-brain barrier.   
• Anti-TNF-α mAbs (infliximab) or soluble TNF-α receptor (etanercept), or IL-1R-based inhibitors 
(anakinra). 
Grade 4 
• For Grade 4 CRS, permanently discontinue IP 
• Admit to hospital for close observation until resolution of symptoms. 
• Monitor for organ dysfunction: admit to the intensive care or equivalent for close monitoring and management  
• Treat hypotension with IV fluid for blood pressure support and/or pressers.  Administer oxygen for treatment of 
hypoxia. Cryoprecipitate or fresh frozen plasma may be required for coagulopathy. Manage per institutional 
guidelines. 
• Administer tocilizumab at a dose of 8 mg/kg. If clinical improvement does not occur within 24 hours, administer 
a second dose of tocilizumab.  
• Second-line therapies:  
• Methylprednisolone 2 mg/kg/day IV tapered over several days. For subjects with severe neurologic 
symptoms, consider using dexamethasone due to more efficient penetration of the blood-brain barrier.   
• Anti-TNF-α mAbs (infliximab) or soluble TNF-α receptor (etanercept), or IL-1R-based inhibitors 
(anakinra). 
 
 


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3.5.2 Management of irAEs 
Adverse Event 
General Guidance for Management of Immune-related Adverse Events (irAEs) [Haanen, 2017; 
Puzanov, 2017; Brahmer, 2018] 
 
irAEs - General 
 
 
Guidelines for management of irAEs across body systems are outlined in this section.  These guidelines are not meant to be 
prescriptive. Established institutional guidelines should be followed where appropriate. Severity of irAE are categorized according to 
NCI CTCAEv5. Limitations of classification and grading by CTCAEv5 for specific irAEs may be encountered.  Based on the severity of 
the irAE, the IP may either be continued, held or permanently discontinued.  Management relies heavily on corticosteroids and other 
immunomodulatory agents.  Generally, the decision on IP and institution of immunosuppressive therapy (corticosteroid therapy) can be 
approached as noted below.  However, treatment should be individualized depending on the subject’s medical history, the nature and 
severity of the AE, co-morbidities, and ability to tolerate corticosteroids.  When starting corticosteroid therapy, consider initiating proton 
pump inhibitors for gastrointestinal (GI) toxicity prophylaxis.  Once toxicity has improved to ≤ Grade 1 AE, start tapering corticosteroid 
therapy over a 4 to 6-week period. Add pneumocystis pneumonia prophylaxis (cotrimoxazole or inhaled pentamidine if cotrimoxazole 
allergy) if more than 3 weeks of immunosuppression expected (>30 mg prednisone or equivalent).  Consider calcium & vitamin D 
supplementation as per local guidelines. 
Severity  
Management 
Grade 1 
• IP is continued, and treatment with corticosteroids is usually not indicated 
Grade 2 
 
• Depending on the nature of the AE, corticosteroids may be indicated.  
• Start with oral prednisone 0.5-1 mg/kg/day. IP is generally held during corticosteroid therapy and until irAE has 
resolved to ≤ Grade 1 and corticosteroids have been tapered to ≤ prednisone 10 mg/day (or equivalent) or 
discontinued. 
• If IV therapy is required, use methylprednisolone 0.5 – 1 mg/kg/day.  If no improvement in symptoms, the dose 
may be increased to 2 mg/kg/day.   
Grade 3 
• Hold IP.  
• Start prednisone 1-2 mg/kg/day (or equivalent dose of methylprednisolone).   
• If no improvement, consider adding alternative immune suppressant therapy. 
Grade 4 
• Permanently discontinue IP and start IV methylprednisolone 1-2 mg/kg/day.   
• If no improvement, consider adding alternative immunosuppressant. 
Adverse Event 
General Guidance for Skin Toxicity  
 
 
 
 
 
 
 
Skin Toxicity 
 
 
Monitor for signs and symptoms of dermatitis (rash and pruritus). Exclude other causes (e.g., infection, drug, another systemic disease 
or unrelated primary skin disorder).  IP must be discontinued if there is any bullous formation (any grade), or if Severe Cutaneous 
Adverse Reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, 
drug reaction with eosinophilia and systemic symptoms) are present. Severity may be based on affected body surface area (BSA), 
tolerability, morbidity, and duration.   
Severity 
(symptoms)  
Management 
Grade 1 
(Skin rash <10% 
BSA, with or 
without symptoms) 
• Continue IP.  
• Topical emollients and/or mild-moderate potency topical corticosteroids +/- oral or topical antihistamines for 
pruritus. 
• Counsel subject to avoid skin irritants and sun exposure.   
 
 


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Skin Toxicity 
(continued from 
previous page) 
Severity 
(symptoms) 
Management 
Grade 2 
(Rash covers 10% - 
30% of BSA with or 
without symptoms; 
limiting instrumental 
activities of daily 
living (ADL) 
• Continue IP. 
• Treat with moderate-to-high potency topical corticosteroid twice daily and supportive management as above.  
• If no resolution, interrupt IP until AE has reverted to Grade 1.  
• Consider initiating systemic steroid as for Grade 3. 
• Consider dermatology referral and skin biopsy.    
Grade 3 
(Rash covering 
>30% BSA with or 
without symptoms; 
limiting self-care 
ADL, or Grade 2 
with substantial 
symptoms)  
• Hold IP.  
• Consider hospitalization; consult dermatology; monitor extent of rash; consider punch biopsy and clinical 
photography.   
• Rule-out systemic hypersensitivity. Treat with high potency topical corticosteroids, topical emollients, and oral 
antihistamines.  
• Initiate oral (or IV) steroids: prednisone 0.5-1 mg/kg/day (or equivalent), tapering over 2-4 weeks. 
• Consult dermatology to determine appropriateness of resuming IP once the dermatitis has resolved to Grade 1 
and the dose of prednisone is ≤ 10 mg/day (or equivalent). 
Severity (symptoms)  
Management 
Grade 4 
(Skin sloughing >30% 
BSA with symptoms 
e.g., erythema, 
purpura, epidermal 
detachment) 
• Permanently discontinue IP.  
• Seek urgent dermatology consult; admit to hospital; consider punch biopsy and clinical photography. 
• Treat with methylprednisolone 1 – 2 mg/kg/day (or equivalent) with slow taper when the toxicity resolves. 
 
NOTE: Grade 4 maculopapular rash/dermatitis is not included in CTCAEv5. 
 
 


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Adverse Event 
General Guidance for Gastrointestinal (GI) Toxicity 
 
 
 
 
 
 
 
 
Gastrointestinal 
(GI) Toxicity 
 
 
 
 
 
 
 
 
 
 
 
 
 
• Counsel subjects to inform their physician if they experience symptoms that may be related to diarrhea/enterocolitis (e.g., abdominal 
pain, cramping, increased frequency of bowel movements over baseline, blood in stool, peritoneal signs, fever, ileus).   
• Rule out alternative etiologies (e.g., infection, disease progression). Stool microscopy for leukocytes/ova/parasites, calprotectin, 
lactoferrin, culture, viral polymerase chain reaction (PCR), Clostridium difficile toxin and cryptospordia.   
• Sigmoidoscopy/colonoscopy (+/- biopsy) is recommended in subjects with severe diarrhea (Grade 3 or 4) or persistent Grade 2 
diarrhea. Subjects with Grade 1 or 2 diarrhea with dehydration, fever, tachycardia or hematochezia would be managed as per Grade 
3 or 4. Steroids should be considered in the absence of clear alternative etiology, even for low grade events, to prevent potential 
progression to higher grade event.  
• Use analgesics carefully; they may mask symptoms of perforation and peritonitis. Use antidiarrheal agents with caution (avoid in 
patients with obstruction, colonic dilation, fever, abdominal tenderness, infectious colitis, moderate to severe inflammation of the 
colon). 
Severity (symptoms) 
Management 
Diarrhea 
Enterocolitis 
Grade 1 
(< 4 liquid stools per 
day over baseline, 
mild increase in 
ostomy output 
compared to 
baseline) 
Grade 1 
(Asymptomatic; 
clinical or 
diagnostic 
observations 
only; 
intervention not 
indicated) 
• Continue IP. 
• Monitor closely for worsening symptoms.  
• If symptoms persist, start routine work-up. 
• Institute symptomatic management: hydration, electrolyte replacement, dietary changes 
(bland diet advisable, avoid high fiber/lactose diet) and antidiarrheal medication (exercise 
caution as above).  
• Obtain gastroenterology consult for prolonged Grade 1 cases. 
Grade 2 
(4-6 stools per day 
over baseline, 
moderate increase 
in ostomy output 
compared to 
baseline) 
Grade 
2(Abdominal 
pain; mucus or 
blood in stool) 
• Hold IP. 
• Outpatient management, if appropriate; work-up as above for Grade 1. Symptomatic 
management. If diarrhea only, observe for 2-3 days, and if no improvement, start 
prednisone 0.5 – 1 mg/kg/day or equivalent.  
• If diarrhea and colitis, start prednisone 1 mg/kg/day (or equivalent dose of 
methylprednisolone).  If no improvement, increase to 2 mg/kg/day. 
• If subject improves, taper corticosteroids.  
• Consider resuming IP when symptoms improved to ≤Grade 1 and corticosteroid is tapered 
to ≤10 mg/day prednisone or equivalent. 
Severity (symptoms) 
Management 
Diarrhea 
Diarrhea 
Grade 3 
(≥7 stools per day 
over baseline; 
hospitalization 
indicated; severe 
increase in ostomy 
output compared to 
baseline; limiting 
self-care ADL) 
Grade 3 
(Severe or 
persistent 
abdominal pain; 
fever, ileus, 
peritoneal signs; 
medical 
intervention 
indicated) 
• Hold IP 
• Consider hospitalization; obtain gastroenterology consult, blood and stool work-up, 
imaging, endoscopy. 
• Start methylprednisolone 1–2 mg/kg/day immediately.  
• If refractory or no improvement on IV corticosteroids, consider infliximab 5 mg/kg which can 
be repeated after 2 weeks if needed.  
• Consider resuming IP when corticosteroid is tapered to ≤10 mg/day prednisone or 
equivalent and subject recovers to ≤Grade 1.   
 
 


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GI Toxicity 
(continued from 
previous page) 
 
Severity  
Management 
Grade 4 
(Life threatening consequences; urgent 
intervention indicated) 
• Permanently discontinue IP. 
• Hospitalize; gastroenterology consult; work-up as above. 
• Start methylprednisolone 1-2 mg/kg/day or equivalent until symptoms improve to Grade 1, 
then taper.  If refractory to steroids, consider infliximab 5 mg/kg (if no perforation, sepsis, 
tuberculosis (TB), hepatitis, New York Heart Association [NYHA] III/IV congestive heart 
failure), can repeat 2 weeks later. Other treatment options include mycophenolate mofetil 
(MMF) or tacrolimus. 
Adverse Event 
General Guidance for Hepatotoxicity 
 
 
Hepatotoxicity 
 
 
 
 
 
 
 
 
 
 
 
 
Monitor signs, symptoms and laboratory evidence of liver dysfunction.  Evaluate alternative etiologies: review medications for 
hepatotoxic drugs and alcohol history; perform liver screen: hepatitis A, B, C serology, hepatitis E PCR, antinuclear antibody 
(ANA)/smooth muscle antibody/liver kidney microsomal antibodies /soluble liver antibody/liver-pancreas antigen/liver cytosol iatrogene 
antibodies, iron studies; consider imaging for metastases/thrombosis.  Guidelines are based on elevations in ALT, AST and bilirubin per 
CTCAEv5. Discontinue IP for Hy’s law as follows: in subjects who enroll with AST/ALT/total bilirubin≤ ULN who experience concomitant 
AST or ALT > 3 x ULN and total bilirubin > 2 x ULN; or in subjects who enroll with AST/ALT/total bilirubin > ULN who experience 
concomitant AST or ALT > 3 x baseline and total bilirubin > 2 x baseline. 
Severity 
Management 
Grade 1 
• Continue IP with close monitoring. 
• Monitor liver function at least weekly; if liver function is stable, reduce frequency of blood tests. 
Grade 2 
• Hold IP.  
• Assessments as above; monitor liver function ~every 3 days; liver biopsy is optional.  
• If persistent or rising liver chemistries, or significant clinical symptoms, start oral prednisone 0.5-1 mg/kg/day 
(or equivalent of methylprednisolone) with 4-week taper. 
• Resume IP when toxicity ≤ G1 and corticosteroid taper to ≤ 10 mg/day prednisone or equivalent. 
Grade 3 or 4 
• Grade 3: hold IP; permanently discontinue IP for liver function test abnormality that meets following criteria in 
subjects who enroll with AST/ALT/total bilirubin ≤ ULN:  AST or ALT > 8 x ULN or total bilirubin > 5 x ULN; 
permanently discontinue IP for liver function test abnormality that meets following criteria in subjects who enroll 
with AST/ALT/total bilirubin > ULN:  AST or ALT > 8 x baseline or total bilirubin > 5 x baseline.  Other Grade 3 
laboratory abnormalities: re-challenge may be considered only after consultation with hepatologist. 
• Grade 4: permanently discontinue. 
• Consider hospitalization; obtain hepatology consult; assessments as above; monitor liver function daily; 
consider liver biopsy.  
• Immediately start methylprednisolone 1-2 mg/kg (start with 2 mg/kg for Grade 4) or equivalent. 
• If refractory after 3 days, consider MMF.  
• Avoid the use of infliximab in immune mediated hepatitis. 
 
 


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Pulmonary 
Toxicity 
 
 
 
General Guidance for Pulmonary Toxicity 
Monitor subjects for signs and symptoms of pneumonitis or interstitial lung disease (new onset or worsening shortness of breath or 
cough). Initial work-up may include clinical evaluation, chest X-ray, pulse oximetry (resting and exertion), laboratory work-up, screen for 
viral, opportunistic or bacterial infections depending on the clinical context. High resolution computed tomography (CT) scan +/- 
bronchoscopy and bronchoalveolar lavage (BAL). 
Severity 
Management 
Grade 1 
• Consider holding IP as clinically appropriate and during diagnostic work-up.   
• Monitor every 2 – 3 days for clinical symptoms, pulse oximetry (resting and exertion) and laboratory work-up as 
clinically indicated.  
• Consider pulmonary and infectious disease consult. 
• May resume IP with radiographic evidence of improvement or resolution.  If no improvement, should treat as 
Grade 2. 
• Monitor patients weekly with history, physician examination, pulse oximetry, and chest X-ray if required. 
Grade 2 
• Hold IP until resolution to baseline.  
• If Grade 2 toxicity improves to baseline, then consider re-challenge if symptoms and imaging abnormalities 
resolve and corticosteroids ≤10 mg/day prednisone or equivalent. 
• Monitor symptoms daily and consider hospitalization.   
• Institute work-up – high resolution CT +/- bronchoscopy and BAL pending clinical status, repeat chest X-ray 
weekly and baseline bloods, pulmonary function tests (PFTs) including transfer factor for carbon monoxide. 
Obtain pulmonary and infectious disease consult. 
• Start antibiotics if suspicion of infection (fever, C reactive protein (CRP), neutrophil counts).  
• If no evidence of infection or no improvement with antibiotics after 48 hours, add in oral prednisone 1 mg/kg/day.  
• If no improvement after 48 hours of oral prednisone, manage as per Grade 3 or 4. 
• Once improved to baseline, wean steroids over at least 6 weeks, titrate to symptoms. 
 
Grade 3 or 4 
• Permanently discontinue IP. 
• Promptly initiate methylprednisolone 2 to 4 mg/kg/day or equivalent. 
• Hospitalize; provide supportive care (oxygen, etc.); obtain baseline tests as above including high resolution CT 
and respiratory review +/- bronchoscopy and BAL pending appearances. Obtain pulmonary and infectious 
disease consult.  
• Initiate empiric antibiotics.   
• If no improvement or worsening after 48 hours, add infliximab at 5 mg/kg, or MMF (if concurrent hepatotoxicity).  
• Continue with IV steroids and wean as clinically indicated.   
• Once improved to baseline, wean steroids over at least 8 weeks. 
 
 
 


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Adverse Event General Guidance for Nephrotoxicity 
Nephrotoxicity 
Monitor serum creatinine and urea prior to every dose. Stop nephrotoxic drugs (including over the counter medications), rule out 
infection, urinary tract obstruction and correcting hypovolemia. Withhold IP in the event of significant renal dysfunction; consider the use 
of systemic corticosteroids therapy (0.5–2 mg/kg methylprednisolone or equivalent) – dose and schedule should be individualized and 
based on grade. Taper corticosteroids when creatinine improves to Grade 1. In the event of severe renal dysfunction, a nephrologist 
should be consulted. Reflex renal biopsy should be discouraged until steroid treatment has been attempted. Toxicity grading is based on 
increase in creatinine level as per CTCAEv5. 
Severity 
Management 
Grade 1 
• Initiate work-up and monitor closely.  
• Alternatively, consider temporarily holding IP, pending consideration of potential alternative etiologies and 
baseline renal function. 
Grade 2 
• Hold IP; consider resuming when creatinine decreased to ≤ Grade 1 and steroids have been tapered.  
• Discontinue IP for persistent or recurrent elevation. 
• For persistent creatinine elevation with no other identifiable causes, start prednisone 0.5-1 mg/kg/day or 
equivalent. 
Grade 3 
• Hold IP.  
• Start prednisone 1-2 mg/kg/day or equivalent. 
• Consider resuming treatment if Grade 3 resolves and cause of event is confirmed. 
• Discontinue IP permanently for persistent or recurrent elevation of serum creatinine and urea. 
Grade 4 
• Permanently discontinue IP. Start methylprednisolone 1-2 mg/kg/day or equivalent. 
Adverse Event 
General Guidance for Endocrine Toxicity 
Endocrine 
Toxicity 
• Monitor subject for signs and symptoms of endocrinopathies. Non-specific symptoms include headache, fatigue, behavior changes, 
changed mental status, vertigo, abdominal pain, unusual bowel habits, hypotension and weakness.  Severe mass effect symptoms 
(severe headache, any visual disturbances) or severe hypoadrenalism (hypotension, severe electrolyte disturbances) are observed 
with hypophysitis (observed with anti-CTLA4 therapy; very rare with PD-1/L1 inhibitor therapy. Perform magnetic resonance imaging 
(MRI) to visualize the pituitary gland and rule out any alternative etiology (e.g., disease progression including brain metastases, 
infection).   
• Consult endocrinologist. 
Evaluate thyroid function (thyroid stimulating hormone [TSH], free thyroxine [T]3, free T4) and other relevant endocrine labs (e.g., 
blood glucose, cortisol, sex hormones) depending on suspected endocrinopathy.  Falling TSH across 2 measurements with normal or 
lowered T4 may also suggest pituitary dysfunction and weekly cortisol measurements (9 am cortisol) should be performed.  Iodine 
from CT scans may impact thyroid function tests (TFTs).  If a subject has an AE that is thought to be possibly of autoimmune nature 
(e.g., thyroiditis, pancreatitis, hypophysitis, diabetes insipidus), the investigator should send a blood sample for appropriate 
autoimmune antibody testing (e.g., anti-thyroid antibodies for thyroid dysfunction, C-peptide and antibodies against glutamic acid 
decarboxylase and islet cell antibodies should be measured to distinguish between type 1 and 2 diabetes mellitus [DM]).   
 
 
 


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Adverse Event Endocrine Toxicity 
Hypothyroidism 
Severity 
Management 
Grade 1 or 2 
• Continue IP 
Grade 3 or 4 
• Hold IP for ≥ Grade 3 and consider restarting when symptoms under control. 
• Check anti-TSH receptor antibodies, anti-thyroid peroxidase (TPO) antibody, nuclear medicine thyroid uptake 
scan. 
• Propranolol or atenolol for symptoms; consider thionamide (carbimazole, methimazole, propylthiouracil 
[PTU]) if anti-TSH receptor antibody positive. 
• Consider hospitalization and initiate prednisone 0.5–2 mg/kg or equivalent, with gradual taper for painful 
thyroiditis, severe symptoms or thyroid storm. 
• Introduce thyroid replacement if patient develops hypothyroidism. 
Hyperthyroidism 
(differential 
diagnosis includes 
thyroiditis, Grave’s 
disease) 
Grade 1 or 2 
• Continue IP 
Grade 3 or 4 
• Hold IP for ≥ Grade 3 and consider restarting when symptoms under control. 
• Check anti-TSH receptor antibodies, anti-TPO antibody, nuclear medicine thyroid uptake scan. 
• Propranolol or atenolol for symptoms; consider thionamide (carbimazole, methimazole, PTU) if anti-TSH 
receptor antibody positive. 
• Consider hospitalization and initiate prednisone 0.5–2 mg/kg or equivalent, with gradual taper for painful 
thyroiditis, severe symptoms or thyroid storm. 
• Introduce thyroid replacement if patient develops hypothyroidism. 
Hypophysitis 
Grade 1 
• Continue IP. 
Grade 2 or greater 
• Hold IP for any ≥ Grade 2.   
• Treatment consisting of hormone replacement therapy for adrenal insufficiency, central hypothyroidism, 
central hypogonadism should be instituted immediately.  
• For life threatening symptoms (e.g., adrenal crisis, severe headache, visual field defect): hospitalize and treat 
with prednisone 1 mg/kg/day or equivalent or higher doses of methylprednisolone, followed by gradual taper. 
Manage adrenal crisis per standard guidelines. Replace thyroid hormone after corticosteroids have been 
initiated. 
Adrenal 
Insufficiency 
Grade 1 
• Continue IP. 
Grade 2 or greater 
• Hold until subject is stabilized on replacement hormone therapy prednisone or hydrocortisone as per standard 
practice.  
• May require mineralocorticoid replacement. Titrate as symptoms dictate.   
• With Grade 2-4, administer stress dose corticosteroids at presentation with gradual taper down to 
maintenance. 
Diabetes Mellitus 
(Type 1 or Type 2)  
Note 
Clinical Signs 
Management 
Even subjects with 
Type 2 Diabetes 
mellitus (DM) may 
develop     
ketoacidosis, an 
infrequent event 
DM with diabetic 
ketoacidosis 
• 
Hold IP; hospitalize and initiate treatment per standard guidelines. 
• 
Once the subject has been regulated with insulin substitution, consider restarting IP 
DM without 
ketoacidosis 
• 
Hold IP for hyperglycemia ≥ Grade 3 
• 
Once the subject has been regulated with insulin substitution, consider restarting IP 
 


CONFIDENTIAL 
 
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Version no: 07  
69 
 
Adverse Event General Guidance for Ocular Toxicity 
Ocular Toxicity 
Counsel all subjects to inform their healthcare provider immediately if they experience ocular symptoms. Evaluate under guidance of 
ophthalmology. Ocular irAEs are many times seen in the context of other organ irAEs. High level of clinical suspicion as symptoms may 
not always be associated with severity. Treatment depends on severity, with topical corticosteroids in the case of episcleritis and 
anterior uveitis, and systemic corticosteroids in the case of severe ocular inflammation and orbital inflammation.  Intravitreal anti-
vascular endothelial growth is indicated for choroidal neovascularization.  Unlike anterior uveitis, posterior uveitis can be asymptomatic 
but nonetheless, proceed to visual loss.    
Severity (symptoms) 
Management 
Uveitis/Iritis 
Episcleritis 
Grade 1 
(Asymptomatic 
anterior uveitis with 
trace cells) 
Grade 1 
(No change in 
vision from 
baseline) 
• Continue IP 
• Ophthalmology referral within 1 week. 
• Start lubrication drops (artificial tears). 
Grade 2 
(Anterior uveitis with 
1+ or 2+ cells; 
medical intervention 
required) 
Grade 2 
(Symptomatic; 
moderate 
decrease in 
visual acuity; 
limiting 
instrumental 
ADL) 
• Hold IP 
• Urgent ophthalmology referral; coordinate treatment with ophthalmologist (topical 
steroids, cycloplegic agents, systemic corticosteroids). 
• May resume IP after returned to ≤ Grade 1 and off systemic steroids indicated for ocular 
side effects, or once corticosteroids for other concurrent irAE are reduced to ≤10mg/day 
prednisone or equivalent.   
Continued topical/ocular steroids are permitted when resuming therapy to manage and 
minimize local toxicity. 
 
Grade 3 
(Anterior uveitis with 
≥3+ cells; posterior or 
pan-uveitis) 
Grade 3 
(Symptomatic 
with marked 
decrease in 
visual acuity; 
limiting self-care 
ADL) 
• Permanently discontinue IP  
• Urgent ophthalmology referral. 
• Systemic corticosteroids and intravitreal/periocular corticosteroids/topical steroid 
treatment as recommended by ophthalmologist with cycloplegic agents. 
• Consider infliximab or other TNF-α blockers in cases that are severe and refractory to 
standard treatment. 
Grade 4  
(Best corrected visual 
acuity of 20/200 or 
worse) 
Grade 4 
(Best corrected 
visual acuity of 
20/200 or worse) 
• Permanently discontinue IP  
• Emergent ophthalmology referral. 
• Systemic corticosteroids (prednisone 1-2 mg/kg or equivalent dose of 
methylprednisolone) and intravitreal/periocular corticosteroids/topical steroid treatment as 
recommended by ophthalmologist with cycloplegic agents. 
• Consider infliximab or other TNF-α blockers in cases that are severe and refractory to 
standard treatment. 
Blepharitis 
• There is no formal grading system for blepharitis. Treat with warm compresses and 
lubrication drops.  
• Continue therapy unless persistent and serious. 
 
 
 


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Adverse Event 
General Guidance for Cardiotoxicity 
Cardiotoxicity 
 
 
Early consultation with a cardiologist is recommended. Obtain baseline electrocardiogram (ECG).  All grades warrant work-up: ECG, 
creatine kinase (CK), creatine kinase – muscle/brain (CK-MB), troponin, brain natriuretic peptide, echocardiogram (ECHO), chest X-ray; 
additional testing as guided by cardiologist. High dose corticosteroids should be instituted rapidly if immune-mediated cardiotoxicity is 
suspected.  Escalation to other immunosuppressive drugs, such as infliximab, MMF, antithymocyte globulin (ATG) may be necessary if 
symptoms do not promptly respond to steroids. 
Severity 
Management 
Grade 1 
• Hold IP 
• Initiate diagnostic work-up; resume IP if symptoms resolve; permanently discontinue IP if AE worsens or does 
not improve. 
Grade 2 or greater 
• Permanently discontinue IP 
• Treat with high-dose corticosteroids (1-2 mg/kg prednisone) until improved to ≤ Grade 1 with gradual taper. 
• Manage cardiac symptoms according to American College of Cardiology /American Heart Association 
guidelines and with guidance from cardiology. 
• Immediate transfer to cardiac care unit should be considered for subjects with elevated troponin or conduction 
abnormalities. 
• In subjects without an immediate response to high-dose corticosteroids, consider early institution of cardiac 
transplant rejection doses of corticosteroids (methylprednisolone 1 g/day) and the addition of other 
immunosuppressive agents (MMF, infliximab, ATG).   
Adverse Event 
General Guidance for Neurotoxicity 
Neurotoxicity 
 
 
 
Monitor for symptoms of confusion, altered behavior, headaches, seizures, short term memory loss, depressed level of consciousness, 
focal weakness, speech abnormality etc. Neurology consultation. Work-up to include, brain MRI w/wo contrast, lumbar puncture for 
cerebrospinal (CSF) analysis, electroencephalogram to evaluate for subclinical seizures, blood tests (complete blood count [CBC], 
comprehensive metabolic panel, erythrocyte sedimentation rate [ESR], CRP, anti-neutrophil cytoplasmic antibodies [ANCA], TFTs, 
treponema pallidum immobilization and thyroglobulin). 
Severity 
Management 
Grade 1 
• 
Hold IP 
• 
Initiate diagnostic work-up; consider permanent discontinuation of IP if AE worsens or does not improve. 
Grade 2  
• 
Hold IP  
• 
Start methylprednisolone 0.5-1.0 mg/kg/day (or equivalent) once infection has been excluded.  
• 
Consider permanent discontinuation of IP if AE worsens or does not improve.  
Severity 
Management 
Grade 3 
• 
Permanently discontinue IP  
• 
Start methylprednisolone 1-2 mg/kg/day (or equivalent) and prophylactic antibiotics.  
• 
Consider plasmapheresis if no improvement or symptoms worsen after 3 days. 
Grade 4 
• 
Permanently discontinue IP  
• 
Start methylprednisolone 1-2 mg/kg/day (or equivalent) and prophylactic antibiotics. 
• 
Consider plasmapheresis if no improvement or symptoms worsen after 3 days. 
• 
Contact intensive care unit 
 
 
 


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Version no: 07  
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General Guidance for Myasthenia Gravis 
 
 
 
 
Myasthenia 
Gravis 
 
 
 
Neurological consultation. All grades warrant work up and intervention given potential for progressive myasthenia gravis to lead to 
respiratory compromise. Check acetylcholine receptor (AchR) and anti-striated muscle antibodies in blood.  If AchR antibodies are 
negative, consider muscle specific kinase and lipoprotein-related 4 antibodies in blood. Monitor PFTs with negative inspiratory force 
and vital capacity (NIF/VC).  Consider magnetic resonance imaging (MRI) brain to rule out central nervous system (CNS) involvement 
by malignancy or alternate diagnosis. Check creatine phosphokinase, aldolase, ESR, CRP for possible concurrent myositis.  Rule out 
concomitant myocarditis.   
Severity 
Management 
Grade 1 
• 
Continue IP 
• 
Consider permanent discontinuation if AE worsens or does not improve. 
Grade 2 
• 
Hold IP;  
• 
Discontinue permanently if AE worsens or does not improve; may resume only if symptoms resolve.  
• 
Pyridostigmine starting at 30 mg oral 3 times per day (TID) and gradually increase to maximum of 120 mg 
oral 4 times per day (QID) as tolerated and based on symptoms.  
• 
Administer prednisone 1-1.5 mg/kg/day orally and wean based on symptom improvement. 
Grade 3 or 4 
• 
Permanently discontinue IP 
• 
Hospitalize, may need intensive care unit (ICU)-level monitoring.  
• 
Frequent pulmonary function assessment and daily neuro review. 
• 
Treat with methylprednisolone 1-2 mg/kg/day and IV immunoglobulin (IVIG) (0.4 gm/kg/day x 5 days) or 
plasmapheresis x 5 days. 
Guillain-Barre 
Syndrome 
 
General Guidance for Guillain-Barre Syndrome (GBS) 
Neurological consultation. All grades warrant work up and intervention given potential to lead to respiratory compromise. Obtain MRI 
spine w/wo contrast to rule out compressive lesion; perform lumbar puncture for CSF analysis; check serum antibody tests for GBS 
variants (GQ1b for Miller Fisher variant); PFTs (NIF/VC), and electrodiagnostic studies to evaluate polyneuropathy. 
Severity 
Management 
Grade 1 
• 
Continue IP; Consider permanent discontinuation of IP if AE worsens or does not improve 
Grade 2 or higher 
• 
Discontinue IP. 
• 
Admit to inpatient unit with capability for rapid transfer to ICU-level monitoring. Frequent neuro review and 
pulmonary function assessment.  
• 
Non-opioid management of neuropathic pain. 
• 
Start IVIG (0.4 gm/kg/day x 5 days for a total dose of 2 gm/kg) or plasmapheresis.  Corticosteroids are 
usually not recommended for idiopathic GBS, however, in immunotherapy-related forms, a trial is 
reasonable (methylprednisolone 2 – 4 mg/kg/day followed by slow taper).  
• 
Pulse steroid dosing may also be considered along with IVIG or plasmapheresis.   
 
 
 


CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
72 
 
Adverse Event 
General Guidance for Hematologic Toxicity 
Autoimmune 
Hemolytic Anemia 
 
Although rare, hematologic irAEs have been described (case reports of hemolytic anemia, red cell aplasia, neutropenia, 
thrombocytopenia, myelodysplasia, and hemophilia A) with intracerebral pathogenicity index.  A hematologic irAE needs to be 
distinguished from transient changes in laboratory values that can occur during initiation of an immune response (e.g., 
lymphocytosis, eosinophilia, neutrophilia, monocytosis can be observed following treatment). Development of persistent or 
progressive cytopenias should prompt evaluation of potential causes. In cases where an obvious cause cannot be identified, an 
autoimmune cause should be considered and investigated accordingly. Since the CTCAE definition of thrombocytopenia describes 
absolute platelet levels rather than a change in cell number, it is not a reliable tool for evaluating potentially life-threatening 
cytopenias.   
Severity 
Management 
Grade 1 
• 
Continue IP with close clinical follow-up and laboratory evaluation 
Grade 2 
• 
Hold IP; consider permanent discontinuation.  
• 
Prednisone 0.5-1 mg/kg/day or equivalent. 
Grade 3 
• 
Permanently discontinue IP.  
• 
Prednisone 1-2 mg/kg/day or equivalents (oral or IV depending on symptoms and speed of development). 
• 
Hematology consult; consider hospitalization, transfusion per existing guidelines (minimum number of units to 
relieve symptoms of anemia or to return subject to safe Hgb range), folic acid supplementation. 
Grade 4 
• 
Permanently discontinue IP. 
• 
Prednisone 1-2 mg/kg/day; if no improvement on or if worsening on corticosteroids or severe symptoms on 
presentation, initiate other immunosuppressive drugs, such as rituximab, IVIG, cyclosporine, infliximab, MMF, 
ATG. 
• 
Hospitalize; hematology consult; transfuse per existing guidelines. 
Immune 
Thrombocytopenia 
Severity 
Management 
Grade 1 
• 
Continue IP with close clinical follow-up and laboratory evaluation. 
Grade 2 
• 
Hold IP until AE has reverted to Grade 1.  
• 
Administer oral prednisone 1 mg/kg per day (dosage range, 0.5 – 2 mg/kg per day) for 2-4 weeks after which 
time this medication should be gradually tapered to lowest effective dose.  
• 
IVIG may be used in conjunction with corticosteroids if a more rapid increase in platelet count is required. 
Grade 3 or 4 
• 
Hold IP until AE has reverted to Grade 1. Hematology consult. 
• 
Prednisone 1-2 mg/kg/day or equivalent.   
• 
IVIG 1 g/kg may be used with corticosteroids when a more rapid increase in platelet count is required.  This 
dosage may be repeated if necessary.  
• 
If treatment with corticosteroids and/or IVIG has been unsuccessful, subsequent treatment may include 
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Acquired 
Hemophilia 
Severity 
Management 
Grade 1 
• 
Hold IP and discuss resumption only after considering the risk and benefits. 
• 
Administer prednisone 0.5 – 1 mg/kg/day. 
• 
Transfusion support as required. 
• 
Hematology consult. 
Grade 2 
• 
Hold IP and discuss resumption only after considering the risk and benefits. 
• 
Hematology consult.  
• 
Administer factor replacement (choice based on presence or absence of inhibitor) 
• 
Administer prednisone 1 mg/kg/day +/- rituximab (dose 375 mg/square meter [m2] weekly x 4 weeks) and/or 
cyclophosphamide 1-2 mg/kg/day. 
• 
Transfusion support as required. 
Grade 3 or 4 
• 
Permanently discontinue IP. 
• 
Hospitalize; hematology consult; transfusion support as required.   
• 
Administer factor replacement (choice based on Bethesda units’ level of inhibitor); bypassing agents may be 
used. 
• 
Prednisone 1-2 mg/kg/day (oral or IV depending on symptoms) +/- rituximab (dose 375 mg/m2 weekly x 4 
weeks) and/or cyclophosphamide 1-2 mg/kg/day. If worsening or no improvement add cyclosporine, or 
immunosuppression/immunoadsorption. 
Adverse Event 
General Guidance for Musculoskeletal Toxicity 
 
 
 
Musculoskeletal 
Toxicity  
 
 
 
 
 
 
 
 
Complete rheumatologic history and examination. Obtain CK and CK-MB. Consider autoimmune blood panel including ANA, 
rheumatoid factor, anti-cyclic citrullinated peptide, ESR and CRP.  If symptoms are suggestive of reactive arthritis or affect the spine, 
consider HLA-B27 testing.  Prior to initiation of immunosuppressive medications, consider obtaining muscle biopsy and other 
relevant tests (e.g., electromyography). Consider ultrasound and/or MRI of affected joints if clinically indicated. Consider early 
referral to rheumatologist. 
Severity 
Management 
Grade 1 
• 
Continue IP  
• 
Initiate analgesia with acetaminophen and/or nonsteroidal anti-inflammatory drugs (NSAIDS) 
Grade 2 
• 
Hold IP; 
• 
Resume when symptoms are controlled and prednisone ≤ 10mg/day 
• 
Escalate analgesia and consider higher doses of NSAIDs as needed. Consult rheumatologist. 
• 
If inadequate control, initiate prednisone 10-20 mg/day or equivalent, slow taper according to response.  If no 
improvement after initial 4-6 weeks, treat as Grade 3.  If unable to lower corticosteroid dose to below 10 mg/d 
after 3 months, consider disease- modifying antirheumatic drug (DMARD). Consider intra-articular steroid 
injections for large joints. 
 
 
 


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Musculoskeletal 
Toxicity 
(continued from previous page) 
Severity 
Management 
Grade 3 
• 
Hold IP temporarily;  
• 
May resume in consultation with rheumatology, if recover to ≤G1.   
• 
Initiate oral prednisone 0.5-1 mg/kg.  If failure to improve after 4 weeks or worsening in 
meantime, consider synthetic (methotrexate, leflunomide) or biologic (anti-cytokine 
therapy such as TNF-α or IL6 receptor inhibitors) DMARD. 
• 
Test for viral hepatitis B, C and latent/active TB test prior to DMARD treatment 
Grade 4 
• 
Permanently discontinue IP 
 
 
 
3.5.3 Management of Non-irAEs 
Severity  
Dose Modification 
Toxicity Management 
Any Grade 
Note: Dose modifications are not required for AEs not deemed to be related to SL-279252 
(i.e., events due to underlying disease) or for laboratory abnormalities not deemed to be 
clinically significant. 
• Treat accordingly, as per institutional 
standard 
Grade 1 
No dose modifications  
• Treat accordingly, as per institutional 
standard 
Grade 2 
Consider holding SL-279252 until resolution to ≤Grade 1 or baseline. 
 
• Treat accordingly, as per institutional 
standard 
 
Grade 3 
Hold SL-279252 until resolution to ≤Grade 1 or baseline. 
 
For AEs that downgrade to ≤Grade 2 within 7 days or resolve to ≤Grade 1 or baseline within 
14 days, resume SL-279252 administration. Otherwise, discontinue SL-279252. 
(Note: For Grade 3 labs, decision to hold should be based on accompanying clinical 
signs/symptoms, the Investigator’s clinical judgment, and consultation with the Sponsor). 
 
• Treat accordingly, as per institutional 
standard 
 
Grade 4  
Discontinue SL-279252  
 
(Note: For Grade 4 labs, decision to discontinue should be based on accompanying clinical 
signs/symptoms, the Investigator’s clinical judgment, and consultation with the Sponsor). 
 
• Treat accordingly, as per institutional 
standard 
 
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3.6 
Discontinuation of Investigational Product 
SL-279252 should be discontinued by the investigator when a participant meets one of the 
conditions requiring discontinuation outlined in Section 3.5.  The investigator may, however, elect 
to discontinue SL-279252 for an AE, laboratory abnormality, or intercurrent illness which, in the 
judgment of the investigator, presents substantial clinical risk to the subject with continued dosing 
of the IP. If SL-279252 is permanently discontinued for reasons other than progressive disease or 
withdrawal of consent, the participant will remain in the study to be evaluated for disease 
progression, and survival.  See the SOA in Section 6  for data to be collected at the time of 
discontinuation of SL-279252.   
3.7 
Criteria to Resume Treatment 
A participant may resume IP per the guidance outlined in Section 3.5.  If the criteria to resume 
treatment are met, the subject should restart treatment at the next scheduled time point per protocol.    
3.8 
Participant Discontinuation/Withdrawals from Study 
• A participant may withdraw from the study at any time at his/her own request; or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance, or administrative reasons. This is expected to be uncommon. 
• At the time of discontinuing from the study, an early discontinuation visit should be 
conducted, as shown in the SOA in Section 6. See SOA for data to be collected at the time 
of study discontinuation and follow-up and for any further evaluations that need to be 
completed. The participant will be permanently discontinued both from the IP and from 
the study at that time.  Every effort must be made to continue follow-up of participants for 
protocol-specified safety follow-up procedures to capture AEs, SAEs, and unanticipated 
problems (UPs). 
• If the participant withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
• If a participant withdraws from the study, he/she may request destruction of any samples 
taken and not tested, and the investigator must document this in the site study records. 
3.9 
Lost to Follow-up 
• A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
 
• The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
 
o The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to and/or 
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o Before a participant is deemed lost to follow up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter sent to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record. 
 
o Should the participant continue to be unreachable, he/she will be considered as lost 
to follow up and withdrawn from the study. 
3.10 
Premature Termination or Suspension of Study 
The Sponsor reserves the right to close the study site or terminate the study at any time for any 
reason. Written notification, documenting the reason for study suspension or termination, will be 
provided by the Sponsor to investigators, the Food and Drug Administration (FDA), Health 
Canada, European Medicines Agency and other regulatory authorities. If the study is prematurely 
terminated or suspended, the investigator will promptly inform the Institutional Review 
Board/Institutional Ethics Board (IRB/IEC) and will provide the reason(s) for the termination or 
suspension.  Study sites will be closed upon study completion. A study site is considered closed 
when all required documents and study supplies have been collected or destroyed and a study-site 
closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or investigator may include but are not 
limited to: 
• 
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the Sponsor's procedures, or GCP guidelines 
• 
Inadequate recruitment of participants by the investigator 
• 
Discontinuation of further development of the IP 
• 
Determination of unexpected, significant, or unacceptable risk to participants  
3.11 
Duration of Treatment 
In the absence of treatment delays due to AE(s), treatment may continue until one of the following 
criteria applies: 
• 
Disease progression per iRECIST or RECIL 2017; NOTE: See Section 8.3 for 
 
criteria allowing for continuing treatment past initial progression. 
• 
Death 
• 
Intercurrent illness that prevents further administration of treatment 
• 
Unacceptable AE(s) 
• 
Participant decides to withdraw from the study 
• 
General or specific changes in the participant's condition render the participant 
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• 
Pregnancy 
• 
Termination of the study by Sponsor 
All women of childbearing potential should be instructed to contact the investigator immediately 
if they suspect they might be pregnant (e.g., missed or late menstrual period) at any time during 
study participation.  The investigator should immediately notify PrimeVigilance upon knowledge 
of pregnancy (Section 7.6). 
The investigator may consider discontinuing IP after agreement with the Sponsor if a subject has 
achieved maximal clinical benefit (a durable CR or PR or SD of >6 months).  The subject will be 
followed until confirmed disease progression as per protocol. Subject may be eligible for treatment 
past progression if they meet criteria as outlined in Section 8.3.   
Impact of ADA on clinical efficacy (non-response or loss of response to the IP) and safety (product 
specific immunogenicity risk) will be evaluated and reported on an on-going basis once a validated 
ADA assay becomes available.  If a subject develops ADA, the Sponsor and investigator may take 
into consideration these factors in assessing the duration of the therapy.   
3.12 
Duration of Follow-Up 
Safety follow-up is at least 90 days after the last dose of SL-279252 (Section 6).  Subjects who are 
withdrawn from study for unacceptable AE(s) will be followed until resolution or stabilization of 
the AE.  Participants who permanently discontinue IP for reasons other than progression will 
continue with disease assessments until progression (per iRECIST or RECIL) or start of another 
anti-cancer therapy.  Participants who discontinue IP for any reason other than withdrawal of 
consent will be followed for survival.   
3.13 
End-of Study Definition 
The end-of-study is defined as the point of final data capture (the point at which all required data 
has been collected to answer the research questions in the protocol).  At least 3 months of follow 
up from the last subject enrolled is required.   
4. 
STUDY POPULATION  
4.1 
Trial Participants 
Participants with advanced stage solid tumors or lymphomas of the histologic types described 
below may be considered for enrollment in the study if they meet all the eligibility criteria stated 
in Sections 4.2 and 4.3.  Prospective approval of protocol deviations to recruitment and enrollment 
criteria, also known as protocol waivers or exemptions, is not permitted.   
4.2 
Participant Inclusion Criteria 
Participants are eligible to be included in the study only if all the following criteria apply. 
1. Subject has voluntarily agreed to participate by giving written informed consent in 
accordance with ICH/GCP guidelines and applicable local regulations. 
 




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Platelet count 
≥ 50 x 109/L 
Hemoglobin (Hgb) 
> 9.0 g/dL with no blood transfusions for at least 5 days prior 
to D1 of IP. 
Creatinine clearance (CrCl) 
≥ 30 milliliter (mL)/min (using modified Cockcroft-Gault 
formula; Appendix Section 16.5) 
ALT/AST  
≤ 3 x ULN  
Total bilirubin 
≤ 1.5 x ULN; subjects with isolated indirect 
hyperbilirubinemia are permitted if direct bilirubin ratio is 
<35% and total bilirubin is ≤ 3.0 x ULN 
Left ventricular ejection 
fraction (LVEF) by ECHO  
≥ Lower limit of normal (LLN) per institutional threshold 
If LLN is not defined for a given institution, then ejection 
fraction must be ≥50 % 
10. Females of child bearing potential (FCBP) must have a negative serum or urine pregnancy 
test within 72 hours of D1 of IP.  NOTE: FCBP unless they are surgically sterile (i.e., have 
undergone a complete hysterectomy, bilateral tubal ligation/occlusion, bilateral 
oophorectomy or bilateral salpingectomy), have a congenital or acquired condition that 
prevents childbearing or are naturally postmenopausal for at least 12 consecutive months 
(see Appendix Section 16.2 for additional details). Documentation of postmenopausal 
status must be provided.  FCBP should use an acceptable method of contraception (see 
Appendix Section 16.2) to avoid pregnancy during treatment and for 30 days (which 
exceeds 5 half-lives) after the last dose of IP. FCBP must start using acceptable 
contraception at least 14 days prior to D1 of IP. 
11. Male subjects with female partners must have azoospermia from a prior vasectomy or 
underlying medical condition or agree to use an acceptable method of contraception during 
treatment and for 30 days (which exceeds 5 half-lives) after last dose of SL-279252 (see 
Appendix 16.2). Male subjects of reproductive potential must start using acceptable 
contraception at least 14 days prior to D1 of treatment with SL-279252 as per Appendix 
Section 16.2.  
12. All AEs resulting from prior anti-cancer immunotherapy have resolved (NOTE: 
exceptions include alopecia, vitiligo, and endocrinopathies adequately treated with 
hormone replacement).  
• 
Subjects that were discontinued from prior PD-1/L1 therapy due to immune-related adverse 
events are not eligible 
13. Recovery from toxicities from prior anti-cancer treatments including surgery, radiotherapy, 
chemotherapy or any other anti-cancer therapy to baseline or ≤ Grade 1. (NOTE: Low-
grade toxicities (e.g., alopecia, ≤ Grade 2 lymphopenia, ≤ Grade 2 hypomagnesemia, ≤ 
Grade 2 neuropathy) may be allowed at the discretion of the investigator if considered 
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4.3 
Participant Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. Has received more than two prior checkpoint inhibitor containing treatment regimens 
(regimen refers to either monotherapy or combination immunotherapies) or has had prior 
treatment with an OX40 agonist.   
• 
Prior PD-1/L1therapy is not required. 
2. Refractory to last PD-1/L1 inhibitor-based therapy which is defined as disease progression 
within 3 months of treatment initiation.  
• 
Subjects must have had clinical benefit (stable disease or response) to last PD-1/L1 
inhibitor-based therapy for at least three months to be eligible.  
3. Any anti-cancer therapy within the time intervals noted below prior to first dose (D1) of 
SL-279252. 
Therapy 
Washout period 
Chemotherapy  
3 weeks 
Hormonal therapy 
3 weeks 
PD-1/L1 inhibitor and other immunotherapies not otherwise specified  
3 weeks  
Tumor vaccine  
4 weeks 
Cell-based therapy 
8 weeks 
Other mAbs or biologic therapies 
3 weeks 
Major surgery 
2 weeks 
Radiation (except palliative intent which does not require washout) 
2 weeks  
 
4. Concurrent chemotherapy, immunotherapy, biologic or hormonal therapy is prohibited.  
Concurrent use of hormones for non-cancer related conditions is acceptable.   
5. Use of corticosteroids or other immunosuppressive medication, current or within 14 days 
of D1 of SL-279252 treatment with the following exceptions (i.e., the following are 
allowed with or within 14 days of D1 of IP): 
• 
Topical, intranasal, inhaled, ocular, intraarticular corticosteroids 
• 
Physiological doses of replacement steroid (e.g., for adrenal insufficiency) not to 
exceed 10 mg/day of prednisone or equivalent 
• 
Steroid premedication for HSRs (e.g., reaction to IV contrast) 
 
6. Receipt of live attenuated vaccine within 28 days of D1 of IP. 
7. Active or documented history of autoimmune disease (autoimmune disease does not refer 
to irAEs; for irAEs see inclusion criteria #11).  Exceptions include Type I diabetes, vitiligo, 
alopecia areata or  hypo/hyperthyroidism.  
8. Active pneumonitis (i.e. drug-induced, idiopathic pulmonary fibrosis, radiation-induced, 
etc.).   
9. Ongoing or active infection (e.g., no systemic antimicrobial therapy for treatment of 
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10. Symptomatic peptic ulcer disease or gastritis, active diverticulitis, other serious GI disease 
associated with diarrhea within 6 months of D1 of IP. 
11. Clinically significant or uncontrolled cardiac disease including any of the following: 
• 
Myocarditis 
• 
Unstable angina within 6 months from D1 of IP 
• 
Acute myocardial infarction within 6 months from D1 of IP  
• 
Uncontrolled hypertension 
• 
NYHA Class II, III or IV congestive heart failure 
• 
Clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained 
ventricular tachycardia, second- or third- degree atrioventricular block without a 
pacemaker, circulatory collapse requiring vasopressor or inotropic support, or 
arrhythmia requiring therapy) 
12. Untreated CNS or leptomeningeal metastases. Subjects with treated CNS metastases must 
have completed definitive treatment (radiotherapy and/or surgery) > 2 weeks prior to D1 
of IP and no longer require steroids.  
13. Women who are breast feeding. 
14. Psychiatric illness/social circumstances that would limit compliance with study 
requirements and substantially increase the risk of AEs or compromised ability to provide 
written informed consent. 
15. Another malignancy that requires active therapy and that in the opinion of the investigator 
and Sponsor would interfere with monitoring of radiologic assessments of response to IP.  
16. Has undergone allogeneic stem cell transplantation or organ transplantation. 
17. Known history or positive test for human immunodeficiency virus, or positive test for 
hepatitis B (positive for hepatitis B surface antigen [HBsAg]) or hepatitis C virus ([HCV]; 
if HCV antibody (Ab) test is positive check for HCV ribonucleic acid [RNA]).  
• (NOTE: Hepatitis B virus (HBV): Subjects who are hepatitis B core antibody [HBcAb] 
positive, but HBsAg negative are eligible for enrollment. HCV: Subjects who are HCV Ab 
positive, but HCV RNA negative are eligible for enrollment). 
4.4 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study but are not 
subsequently entered in the study.  A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials publishing requirements and to respond to queries from regulatory authorities.  
Minimal information includes demography, screen failure details, eligibility criteria, and any AEs 
or SAEs. 
4.5 
Accrual Goal  
The total sample size expected to complete this study is approximately 78-93 subjects (see Section 
9.2.1).  Approximately 8-10 clinical sites may participate in SL01-DEL-101. Overall, the study 
may be completed within approximately 32 months (< 3 years). 


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5. 
INVESTIGATIONAL PRODUCT 
5.1 
Investigational Product Description 
Investigational Product Name: 
SL-279252  
Formulation description: 
Solution containing 20 mg/mL SL-279252  
Dosage form: 
Supplied as frozen liquid.  Recommended storage condition 
is -85 degrees Celsius (°C) to -65°C and store protected 
from light.  
Unit dose strength(s)/Dose Level(s): 
20 mg/mL; in a glass vial (Refer to Section 3.2.4 for dose 
levels). Refer to the Study Pharmacy Manual (SPM) for 
further description of drug product.   
Physical Description: 
SL-279252 solution for infusion is a slightly yellow liquid  
Route/ 
Administration/ Duration: 
Delivered as IV solution via a syringe or IV infusion pump. 
See the Study Pharmacy Manual (SPM) for additional 
details. Duration of infusion depends on the dose. See Table 
5: SL-279252 Dose Escalation Plan in Section 3.2.4 of the 
protocol.  
Dosing instructions: 
Determine the number of vials needed based on the 
assigned dose level (in mg/kg) and the subject’s weight (in 
kg). See the SPM for instructions on IP preparation and 
information on compatible administration materials.  Doses 
of SL-279252 are to be administered as an IV infusion via 
an infusion or syringe pump that can ensure precision to at 
least 0.1 mL/min. Delivery of the prescribed dose within 
+/- 5% is acceptable. 
Secondary Packaging/Quantity/Label 
type 
One Vial of SL-279252/Open Label will be supplied in a 
carton. See SPM for details. 
Manufacturer/ Source of Procurement: 
Manufactured for Shattuck Labs 
 
SL-279252 will be provided to sites by the Sponsor.  The contents of the label will be in accordance 
with all applicable regulatory requirements.  
5.2 
Preparation/Handling/Storage of SL-279252 Investigational Product 
5.2.1 Preparation 
Standard aseptic technique is acceptable. DO NOT USE a filter for drug preparation.  
SL-279252 solution for infusion, 20 mg/mL is supplied as a frozen liquid.  Before use, thaw each 
vial of SL-279252 for infusion (20 mg/mL) overnight under refrigerated conditions protected from 
light or at room temperature until completely thawed to a clear solution.  Following thawing, gently 
swirl the vial to ensure uniformity.  SL-279252 should be diluted in sterile normal saline (0.9%).  
The dosing solution of SL-279252 can be held up to 24 hours under refrigerated conditions or 
4 hours at room temperature (diluted drug product in bag or syringe) from a stability perspective; 
but should be used as soon as possible as the product does not contain an antimicrobial 
preservative. See the SPM for details. 


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5.2.2 Handling 
Under normal conditions of handling and administration, IP is not expected to pose significant 
safety risks to site staff.  A Safety Data Sheet (describing the occupational hazards and 
recommended handling precautions) will be provided to site staff if required by local laws or will 
otherwise be available from the Sponsor upon request. 
In the case of unintentional occupational exposure notify the Sponsor and consult the SPM. 
Refer to the SPM for detailed procedures for the disposal and/or return of unused IP. 
5.2.3 Administration 
Doses of SL-279252 are to be administered as an IV infusion via an infusion pump or syringe 
pump that can ensure precision to at least 0.1 mL/min for the infusion rate at lower doses.  
Infusion rate: The duration of infusion stipulated for each dose is outlined in Table 5: SL-279252 
Dose Escalation Plan in Section 3.2.4.  
NOTE: A physician must be present at the site or immediately available to respond to emergencies 
during all administrations of IP.  A fully functional resuscitation facility must be available.  IP 
must not be administered via IV push or bolus but as an IV infusion using an infusion or syringe 
pump.  
5.2.4 Storage 
SL-279252 must be stored in a secure area under the appropriate physical conditions for the 
product.  Access to and administration of SL-279252 drug product will be limited to the 
investigator and authorized site staff.  SL-279252 must be dispensed or administered only to 
subjects enrolled in the study and in accordance with the protocol.   
SL-279252 drug product vials are to be stored frozen at a temperature range of -85°C to -65°C.  
Maintenance of a temperature log is required. The drug product should be stored protected from 
light. 
The expiry date, where required, is stated on the product label.   
5.3 
Product Accountability 
In accordance with local regulatory requirements, the investigator or designated site staff must 
document the amount of IP dispensed and/or administered to study subjects, relevant dates, 
dilution amounts, SL-279252 lot or batch numbers as on the label, and the amount received from 
the Sponsor, when applicable.  Product accountability records must be maintained throughout the 
course of the study.  Refer to the SPM for further detailed instructions on product accountability. 
5.4 
Dosing and Change in Weight 
The actual body weight in kg will be used for dose calculation in all subjects whose body weight** 
is ≤100 kg.  For subjects with body weight >100 kg, the dose to be administered should be the 
same as that calculated for a subject weighing 100 kg.  The subject should be dosed according to 


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their C1D1 weight throughout the study (mg/kg) if there is no significant change in their weight 
from the weight recorded at the C1D1 visit.  A change in weight (i.e., increase or decrease) of the 
subject by 10% OR greater will require re-calculation of dose (mg/kg).  
**Subject weight should be rounded to a whole number prior to calculating the dose to be 
administered (e.g., 72.5 kg should be rounded up to 73 kg, 72.4 kg should be rounded down to 
72 kg). 
5.5 
Physician Availability Required for Administration of SL-279252 
SL-279252 has a risk for inducing CRS and IRRs. A physician must be present on site or 
immediately available to respond to emergencies every time a subject is administered SL-
279252.  Fully functional resuscitation facilities must be available and close in proximity to the 
infusion room.  Prompt recognition of AEs and immediate medical attention is essential.  
5.6 
Monitoring Dose Administration  
SL-279252 must be administered in an outpatient oncology treatment center or inpatient unit to 
enable close monitoring of subjects and proactive management of AEs. As SL-279252 contains 
only human protein sequences, the chance for SL-279252 to be immunogenic and induce allergic 
HSRs should be low.  However, as with any biologic therapy, infusion or allergic HSRs are 
possible.  Based on the pre-clinical toxicology studies, is anticipated that subjects could also be at 
risk to develop CRS.  Therefore, appropriate drugs and medical equipment to treat acute HSRs and 
monitoring and management of CRS must be immediately available, and study personnel must be 
trained to recognize and treat these toxicities.  Subjects will be monitored prior to, during, and 
after infusion of SL-279252.  Vital signs will be measured as outlined in the Schedule of 
Assessments (SOA) in Section 6 and as needed.  In the event of any Grade IRR (including CRS), 
subjects will be admitted for closer observation until resolution of symptoms. 
5.7 
Treatment of Investigational Product Overdose 
In the event of an overdose (defined as administration of a dose and/or schedule greater than the 
dose and/or schedule that had been studied to date) of SL-279252, the investigator should: 
• Contact the Sponsor immediately 
• 
Closely monitor the subject for AEs/SAEs and laboratory abnormalities for at least 2 
weeks following the infusion. The appropriate AE management guideline should be 
followed (Section 3.5). The pharmacologic effect (e.g., expansion of lymphocytes) 
could persist even after the IP is no longer detectable in the serum.  Subject should 
have recovered from toxicities that occurred because of the excess dose before the next 
scheduled dose is administered. 
 
• Obtain a serum sample for PK analysis within 24 hours of the event if requested by 
the Sponsor (determined on a case-by-case basis) 
• Document the quantity of the excess dose as well as the duration of the overdosing in 
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• If a SAE related to overdose of the IP occurs, it should be documented and reported 
accordingly (Section 7.5) 
Decisions regarding dose interruptions for overdose of IP will be made by the investigator in 
consultation with the Sponsor Medical Monitor based on the clinical evaluation of the subject. 
6. 
STUDY ASSESSMENTS AND PROCEDURES  
• Study procedures and their timing are summarized in the Schedule of Assessments 
(SOA). Protocol waivers or exemptions are not allowed. 
• Assessments throughout the study are calendar based starting from the first day of 
dosing (day 1) in the first treatment period. Dose interruptions should not alter the 
assessment schedule for any subsequent treatment period. 
• Adherence to the study design requirements, including those specified in the SOA, is 
essential and required for study conduct. 
• All screening evaluations must be completed and reviewed to confirm that potential 
subjects meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all subjects screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
• Procedures conducted as part of the participant’s routine clinical management (e.g., 
blood count) and obtained before signing of the informed consent (ICF) may be utilized 
for screening or baseline purposes provided the procedures met the protocol-specified 
criteria and were performed within the time-frame defined in the SOA. 
• Immediate safety concerns should be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the subject should continue or discontinue SL-
279252. 
• Blood volumes for correlative studies of PK, ADA, cytokines, immunophenotyping, 
receptor occupancy, cfNA and other laboratory tests are provided in the Study 
Laboratory Manual (SLM)  
 
Please consult the SLM for details and blood volumes required. Estimates of 
blood requirements for the study are provided in Appendix Section 16.8. 
 


CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
86 
6.1 
SOA Table: Schedule 1 Dose Escalation of SL-279252  
Dosing Schedule 1 
 
D1, D8, D15 in cycle 1 over 28 days, thereafter every 2 weeks (D1, D15) over 28 days 
 
Post 
Txtr 
 
 
 
Follow ups 
Cycle Length = 28 days 
 
Cycle 1 
Cycle 2 
Cycle 3 
≥ Cycle 4 
Procedures/Assessmentsb 
Screena 
D1 
 
 
 
D8 
D15 
 
D22 
D1 
D2 
D15 
D16 
D1 
D15 
D1 
D15 
Study Days 
Days 
 -21 to -1 
1 
2 
3, 4 
5 
8 
15 
16 
22 
29 
30 
43 
44 
57 
71 
85 
etc. 
99 
etc. 
w/in 
30 d 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteriac 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics & medical 
history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cancer treatment history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
X 
 
 
 
X 
X 
 
 
X 
 
 
 
X 
 
X 
 
X 
 
Pulse oximetryd 
X 
Xd1 
Xd
2 
Xd2 
Xd2 
Xd1 
Xd1 
Xd2 
X 
Xd1 
Xd2 
Xd3 
 
Xd3 
Xd3 
Xd3 
Xd3 
X 
 
Vital signsd 
X 
Xd1 
Xd
2 
X d2 
Xd2 
Xd1 
Xd1 
Xd2 
X 
Xd1 
Xd2 
Xd3 
 
Xd3 
Xd3 
Xd3 
Xd3 
X 
 
Height  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
 
 
 
 
X 
 
 
X 
 
X 
 
X 
X 
X 
X 
X 
 
ECOG performance status 
X 
X 
 
 
 
X 
X 
 
 
X 
 
 
 
X 
 
X 
 
X 
 
Pregnancy teste 
X 
Every 8 weeks 
X 
Every 8 weeks 
X 
 
Hematology profilef 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Chemistry profilef 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Ferritin 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Coagulation profileg 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
Thyroid testh 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
X 
 
Xh 
 
X 
 
Antiviral testing (HBV/HCV)i 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cardiac:12-Lead ECG/ECHOj 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tumor imagingk 
X 
 
Every 8 weeks through week 24 (see footnote k) 
X 
(see footnote k)  
X 
X 
PK/immunogenicity/ 
cytokine sample(s) in dose 
escalation cohortsL 
 
X 
X 
X 
X 
 
X 
X 
 
X 
X 
 
 
X 
 
X 
 
X 
 
Complementm 
 
X 
X 
 
 
 
X 
X 
 
X 
X 
 
 
 
 
 
 
 
 
Immunophenotypingm 
 
X 
X 
 
X 
X 
X 
X 
 
X 
X 
X 
X 
 
 
 
 
 
 
Receptor Occupancym 
 
X 
X 
 
 
 
X 
X 
 
X 
X 
X 
X 
 
 
 
 
 
 
SL-279252 administrationn 
 
X 
 
 
 
X 
X 
 
 
X 
 
X 
 
X 
X 
X 
X 
 
 
Concomitant medications 
X 
X 
Continuous Monitoring 
X 
 
AEs/SAEso 
X 
X 
Continuous Monitoring: Collect Ad hoc sample of clinical safety labs if IRR or CRS event occurs as 
outlined in Section 6.6.6.1 
X 
 
Archival tumor tissuep 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
87 
Dosing Schedule 1 
 
D1, D8, D15 in cycle 1 over 28 days, thereafter every 2 weeks (D1, D15) over 28 days 
 
Post 
Txtr 
 
 
 
Follow ups 
Cycle Length = 28 days 
 
Cycle 1 
Cycle 2 
Cycle 3 
≥ Cycle 4 
Procedures/Assessmentsb 
Screena 
D1 
 
 
 
D8 
D15 
 
D22 
D1 
D2 
D15 
D16 
D1 
D15 
D1 
D15 
Study Days 
Days 
 -21 to -1 
1 
2 
3, 4 
5 
8 
15 
16 
22 
29 
30 
43 
44 
57 
71 
85 
etc. 
99 
etc. 
w/in 
30 d 
Tumor Biopsyq 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Survival  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Abbreviations: Txt = Treatment; w/in = within; C = Cycle; D = Day 
a. 
Screening:  Screening Period extends from Day -21 to Day -1.  The following screening assessments must be performed within 72 hours of the first dose of SL-
279252: hematology profile, chemistry profile, coagulation profile, pregnancy test. Baseline CT or positron emission tomography (PET)/CT or MRI tumor 
assessments are required for all subjects within 28 days prior to enrollment. Subjects will be enrolled based on local PD-L1 tumor testing results. Any PD-L1 
tumor testing results prior to enrollment are acceptable.  
b. Assessment Window: A physical exam, weight and ECOG performance status obtained for a subject within 24 hours prior to dosing on Cycle 1, Day 1 is 
acceptable.With the exception of Screening  asessments and unless otherwise specified, assessments performed at ≤ 3-week intervals will have a +/- 3-day window 
and assessments performed at > 3-week intervals will have a +/- 1-week window. Assessments throughout the study are calendar based starting from the first day 
of dosing (day 1) in the first treatment period. Dose interruptions should not alter the assessment schedule for any subsequent treatment period. 
c. 
Inclusion/Exclusion criteria: Subjects must meet eligibility criteria prior to first dose of SL-279252 on C1D1. 
d. Vital Signs: Blood pressure (BP), heart rate (HR), temperature (T) and respiratory rate (RR) must be measured after the subject has been sitting for at least five 
minutes (min). Pulse oximetry will be collected to coincide with vital sign time points noted below. 
1) Collect vital signs/pulse oximetry during Cycle 1 on D1, D8, D15 and C2D1: Predose (within 30 min of starting the infusion) and 15 min (± 5 min), 
0.5 hour [hr] (± 5 min), 1 hr (±10 min), 1.5 hr (± 10 min) 2 hr (± 10 min), 4 hr (± 10 min) , and 6 hr (± 10 min) after SOI. 
2) Vital signs/pulse oximetry should be taken once prior to scheduled PK samples on C1D2, C1D3, C1D4, C1D5, C1D16 and C2D2 
3) Collect vital signs/pulse oximetry on dosing days ≥ C2D15: Predose (within 30 min of starting the infusion) and at the end of infusion [EOI] (± 2 min)  
e. 
Pregnancy Test:  A serum pregnancy test (beta-human chorionic gonadotropin [β-hCG]) or urine pregnancy test must be performed at screening for all FCBP 
within 72 hrs of starting SL-279252. Repeat this test every 8 weeks during SL-279252. Contraception should be continued for at least 30 days after the last dose 
of SL-279252. 
f. 
Clinical Laboratory Tests (Hematology/Clinical Chemistry): Clinical laboratory tests will be performed at local laboratories according to the laboratory’s 
normal procedures.  See Section 6.6.6 for list of laboratory test required. 
g. Coagulation Tests: prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen, d-dimer (Cycles 1 
and 2 only) 
h. Thyroid Function Test: TSH, and free T4 tests will be performed at screening, C2D1, C3D1, C4D1 and then every 8 weeks. 
i. 
Antiviral Testing: Please see exclusion criterion 17 in Section 4.3.  


CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
88 
j. 
Cardiac Assessments (obtain within 28 days of first dose): 1) Electrocardiagram (ECG):  12-lead ECG reading must be performed at screening to serve as 
baseline for comparison with ECG obtained for safety reason. 2) ECHO: An ECHO must be performed at screening for comparison with ECHO obtained for 
safety reason. 
k. Tumor Assessment: Tumor assessments are required for all subjects within 28 days prior to enrollment. Baseline and on-treatment tumor assessments for solid 
tumors by iRECIST should include CT with contrast of chest, abdomen, and pelvis and other known sites of disease at each time point. Bone scan and positron 
emission tomography (PET)/CT should be performed only if clinically indicated.  Baseline and on-treatment tumor assessment for lymphoma by RECIL 2017 
should be done using CT scan with contrast and PET/CT of neck, chest, abdomen, and pelvis and other known sites of disease at each time point. Please refer to 
Section 8 for requirements regarding disease assessment. Tumor assessments must be performed at screening and at the following intervals until disease 
progression is confirmed: approximately every 8 weeks through week 24 (e.g., C3D1, C5D1, C7D1), every 12 weeks up to year 2 (prior to cycles 10, 13, 16, 19, 
22, 25, 28 and 31), and then every 6 months (prior to cycles 37, cycle 43, etc.) up to conclusion of the study.  Confirmatory scans should be performed at least 4 
weeks (>28 days), but no longer than 8 weeks after initial documentation of an objective response. Subjects who discontinue study treatment for reasons other 
than disease progression (e.g., AE or withdrawal of consent) will be monitored for radiologic response until start of another anti-cancer therapy, or disease 
progression, withdrawal of consent or death.  
l. 
PK/immunogenicity (i.e., ADA) and cytokine sampling (Dose Escalation Cohorts): PK, ADA, and cytokine time points for collection of samples are outlined 
in supplementary tables in Section 6.1.1. (Table 6, Table 7 and Table 8). Blood volumes required are provided in the SLM. PK, ADA, cytokine samples should 
not be collected from infusion port for drug delivery i.e., recommend having a separate line in the opposite arm for sample collection. If subject has positive ADA 
test on D1 of cycle 13, then follow up predose samples for PK/ADA should be collected every ~90 days on D1 of subsequent treatment cycles until ADA resolves 
to baseline. If ADA positivity is detected within 7-30 days after the last dose of SL-279252, then follow up testing for PK/ADA should be performed at monthly 
intervals until ADA resolves to baseline. 
m. Correlative laboratory studies:  Refer to supplementary Table 9 for details in Section 6.1.2 plus see the SLM for amount of blood needed. 
• 
Complement  
• 
Immunophenotyping and Receptor Occupancy 
n. SL-279252 Administration: SL-279252 should be administered on D1, D8, and D15 according to the prescribed dosing schedule without deviation in cycle 1 to 
align with the safety DLT assessment and sample (PK, ADA, etc.) collection schedules. Beginning on cycle 2, day 1, a window of +/- 1 day is allowed for 
scheduled dosing days for drug administration. 
o. AE Monitoring: Subjects will be followed continuously for AEs during the study and for 90 days after the last dose of IP. After a subject is discontinued from 
SL-279252 due to progressive disease or for other reasons, any ongoing AE should be followed until resolution (or return to baseline) and documented in the 
eCRF. If another anti-cancer agent is started, only SAEs and AEs that occur prior to starting the new anticancer therapy should be recorded.  In the event of a 
continuing SAE or a non-serious AE, the subject will be asked to return for follow-up until the SAE or AE has resolved or is deemed to be continuing indefinitely. 
AEs will be characterized per NCI-CTCAE criteria v5.0 and events recorded in the eCRF.  
• 
Ad hoc blood samples for clinical safety labs should be collected for AE related to IRR and/or CRS events as noted in Section 6.6.6.1 and the SLM. 
p. Archival tumor tissue (from most recent biopsy): Provide formalin-fixed-paraffin-embedded (FFPE) tissue on slides (recommended minimum of 10 slides) or 
a block of formalin-fixed paraffin embedded (FFPE) tissue (the latter is preferred). Refer to Section 6.9.2.2 and the SLM for details.  
 
q. Tumor Biopsy: Paired biopsies (pre- and on-treatment) obtained in subjects who have tumor accessible to core-needle biopsy.  The on-treatment biopsy should 
be obtained during the first cycle on or between D16-D23. On-treatment biopsies of responding or progressing lesions may be obtained for further characterization 
of the changes in the TME. Please refer to Section 6.9.2.1 and SLM for details regarding biopsy. 






CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
91 
 
 
6.1.2 Correlative Sample Time points / Schedule 1 / Dose Escalation  
Table 9: Complement, Immunophenotyping, Receptor Occupancy Time Points 
Dose Escalation 
C1/D1 
& 
C2/D1 
C1/D2 
& 
C2/D2 
C1/D5 
C1/D8 
C1/D15  
&  
C2/D15 
C1/D16  
& 
C2/D16 
Schedule 1 
Predose 
(-90 to -30 min) 
1 hr 
post  
EOI 
(±10 min) 
2 hr 
post  
EOI 
(±10 min) 
24 h 
post  
EOI 
(±2 hr) 
96 h 
post  
EOI 
(±2 hr) 
Predose 
(-90 to -30 
min) 
Predose 
(-90 to -30 min) 
1 hr 
post EOI 
(±10 min) 
2 hr 
post EOI 
(±10 min) 
24 h 
post EOI 
(±2 hr) 
Complement (SC5b-9)1  
X 
X 
 
X 
 
 
X  
(C1D15 only) 
X 
(C1D15 only) 
 
X 
(C1D16 only) 
Immunophenotyping1 
X 
 
 
X 
X 
X 
X 
 
 
X 
Receptor Occupancy1  
 
X 
 
 
 
X 
1. 
Refer to SLM for details. Complement is NOT collected on C2D15 or C2D16. 
 
 


CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
92 
6.2 
SOA Table: Schedule 2 Dose Escalation of SL-279252  
Dosing Schedule 2 
 
Once weekly (D1, D8, D15, D22)  X 4 every 28 days  
Post 
Txtr 
 
Follow
Ups 
Cycle Length = 28 days         
 
Cycle 1 
Cycle 2 
≥ Cycle 3 
Procedures/ Assessmentsb 
Screena 
D1 
 
 
 
D8 
D15 
 
D22 
D1 
D2 
D8 
D 
15 
D 
16 
D22 
D1 
D8 
D 
15 
D22 
Study Days 
Days 
 -21 to -1 
1 
2 
3, 4 
5 
8 
15 
16 
22 
29 
30 
36 
43 
44 
50 
57 
etc
. 
64 
etc. 
71 
etc. 
78 
etc. 
w/in 
30 d 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteriac 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics & medical 
history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cancer treatment history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
X 
 
 
 
X 
X 
 
X 
X 
 
 
 
 
 
X 
 
 
 
X 
 
Pulse oximetryd 
X 
Xd1 
Xd2 
Xd2 
Xd2 
Xd1 
Xd1 
Xd2 
Xd1 
Xd1 
Xd2 
Xd1 
Xd3 
 
Xd3 
Xd
3 
Xd3 
Xd3 
Xd3 
X 
 
Vital signsd 
X 
Xd1 
Xd2 
X d2 
Xd2 
Xd1 
Xd1 
Xd2 
Xd1 
Xd1 
Xd2 
Xd1 
Xd3 
 
Xd3 
Xd
3 
Xd3 
Xd3 
Xd3 
X 
 
Height  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
X 
 
X 
 
ECOG performance status 
X 
X 
 
 
 
X 
X 
 
X 
X 
 
 
 
 
 
X 
 
 
 
X 
 
Pregnancy teste 
X 
Every 8 weeks 
X 
Every 8 weeks 
X 
 
Hematology profilef 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Chemistry profilef 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Ferritin 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Coagulation profileg 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
Thyroid testh 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
Xh 
 
 
 
X 
 
Antiviral testing 
(HBV/HCV)i 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cardiac:12-Lead 
ECG/ECHOj 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tumor imagingk 
X 
Every 8 weeks through week 24 (see footnote k) 
X 
(see footnote k) 
X 
X 
PK/immunogenicity/ 
cytokine sample(s) in dose 
escalation cohortsL 
 
X 
X 
X 
X 
 
X 
X 
 
X 
X 
 
 
 
 
X 
 
 
 
X 
 
Complementm 
 
X 
X 
 
 
 
X 
X 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
Immunophenotypingm 
 
X 
X 
 
X 
X 
X 
X 
 
X 
X 
 
X 
X 
 
 
 
 
 
 
 
Receptor Occupancym 
 
X 
X 
 
 
 
X 
X 
 
X 
X 
 
X 
X 
 
 
 
 
 
 
 
SL-279252 administrationn 
 
X 
 
 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
X 
X 
X 
 
 
Concomitant meds 
X 
X 
Continuous monitoring 
X 
 
AEs/SAEso 
X 
X 
Continuous monitoring: Collect Ad hoc sample if IRR or CRS event occurs as outlined in  
Section 6.6.6.1 and SLM 
X 
 


CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
93 
Dosing Schedule 2 
 
Once weekly (D1, D8, D15, D22)  X 4 every 28 days  
Post 
Txtr 
 
Follow
Ups 
Cycle Length = 28 days         
 
Cycle 1 
Cycle 2 
≥ Cycle 3 
Procedures/ Assessmentsb 
Screena 
D1 
 
 
 
D8 
D15 
 
D22 
D1 
D2 
D8 
D 
15 
D 
16 
D22 
D1 
D8 
D 
15 
D22 
Study Days 
Days 
 -21 to -1 
1 
2 
3, 4 
5 
8 
15 
16 
22 
29 
30 
36 
43 
44 
50 
57 
etc
. 
64 
etc. 
71 
etc. 
78 
etc. 
w/in 
30 d 
Archival tumor tissuep 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tumor biopsyq 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Survival  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Abbreviations: Txt = Treatment; w/in = within; C = Cycle; D = Day 
a. 
Screening: Screening Period extends from Day -21 to Day -1.  The following screening assessments must be performed within 72 hours of the first dose of SL-
279252: hematology profile, chemistry profile, coagulation profile, pregnancy test. Baseline CT or PET/CT or MRI tumor assessments are required for all subjects 
within 28 days prior to enrollment. Subjects will be enrolled based on local PD-L1 tumor testing results. Any PD-L1 tumor testing results prior to enrollment are 
acceptable. 
b. Assessment Window: A physical exam, weight and ECOG performance status obtained for a subject within 24 hours prior to dosing on Cycle 1, Day 1 is 
acceptable. With the exception of Screening assessments and unless otherwise specified, assessments performed at ≤ 3-week intervals will have a +/- 3-day window 
and assessments performed at > 3-week intervals will have a +/- 1-week window. Assessments throughout the study are calendar based starting from the first day 
of dosing (day 1) in the first treatment period. Dose interruptions should not alter the assessment schedule for any subsequent treatment period. 
c. 
Inclusion/Exclusion criteria: Subjects must meet eligibility criteria prior to first dose of SL-279252 on C1/D1. 
d. Vital Signs: Blood pressure (BP), heart rate (HR), temperature (T) and respiratory rate (RR) must be measured after the subject has been sitting for at least five 
minutes (min). Pulse oximetry will be collected to coincide with vital sign time points noted below. 
1) Collect vital signs/pulse oximetry during Cycle 1 on D1, D8, D15, D22 and Cycle 2 D1 and D8: Predose (within 30 min of starting the infusion) and 
15 min (± 5 min), 0.5 hour [hr] (± 5 min), 1 hr (±10 min), 1.5 hr (± 10 min) 2 hr (± 10 min), 4 hr (± 10 min) , and 6 hr (± 10 min) after SOI. 
2) Vital signs/pulse oximetry should be taken once prior to scheduled PK samples on C1D2, C1D3, C1D4, C1D5, C1D16 and C2D2 
3) Collect vital signs/pulse oximetry on dosing days ≥ C2D15: Predose (within 30 min of starting the infusion) and at the end of infusion [EOI] (± 2 min)  
e. 
Pregnancy Test:  A serum pregnancy test (β-hCG) or urine pregnancy test must be performed at screening for all FCBP within 72 hrs of starting SL-279252. 
Repeat this test every 8 weeks during SL-279252. Contraception should be continued for at least 30 days after the last dose of SL-279252. 
f. 
Clinical Laboratory Tests (Hematology/Clinical Chemistry): Clinical laboratory tests will be performed at local laboratories according to the laboratory’s 
normal procedures.  See Section 6.6.6 for list of laboratory tests required.  
g. Coagulation Tests:  PT, INR, APTT, fibrinogen, d-dimer (the latter test Cycles 1 and 2 only) 
h. Thyroid Function Test: TSH, and free T4 tests will be performed at screening, C2D1, C3D1, C4D1 and then every 8 weeks.  
i. 
Antiviral Testing: Please see exclusion criterion 17 in Section 4.3.  


CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
94 
j. 
Cardiac Assessments (obtain within 28 days of first dose): 1) ECG:  12-lead ECG reading must be performed at screening to serve as baseline for comparison 
with ECG obtained for safety reason. 2) ECHO: An ECHO must be obtained at screening to serve as baseline for comparison with ECHO 
k. Tumor Assessment: Tumor assessments are required for all subjects within 28 days prior to enrollment. Baseline and on-treatment tumor assessments for solid 
tumors by iRECIST should include CT with contrast of chest, abdomen, and pelvis and other known sites of disease at each time point. Bone scan and positron 
emission tomography (PET)/CT should be performed only if clinically indicated.  Baseline and on-treatment tumor assessment for lymphoma by RECIL 2017 
should be done using CT scan with contrast and PET/CT of neck, chest, abdomen, and pelvis and other known sites of disease at each time point. Please refer to 
Section 8 for requirements regarding disease assessment. Tumor assessments must be performed at screening and at the following intervals until disease progression 
is confirmed: approximately every 8 weeks through week 24 (e.g.,C3D1, C5D1, C7D1), every 12 weeks up to year 2 (prior to cycles 10, 13, 16, 19, 22, 25, 28 and 
31), and then every 6 months (prior to cycles 37, cycle 43, etc.) up to conclusion of the study. Confirmatory scans should be performed at least 4 weeks (>28 days), 
but no longer than 8 weeks after initial documentation of an objective response. Subjects who discontinue study treatment for reasons other than disease progression 
(e.g., AE or withdrawal of consent) will be monitored for radiologic response until start of another anti-cancer therapy, or disease progression, withdrawal of 
consent or death.    
l. 
PK/immunogenicity (i.e., ADA) and cytokine sampling (Dose Escalation Cohorts): PK, ADA, and cytokine time points for collection are outlined in 
supplementary tables for PK in Section 6.2.1 (Table 10, Table 11 and Table 12) plus the SLM. PK, ADA, cytokine samples should not be collected from infusion 
port for drug delivery. Recommendation is to use a separate line in the opposite arm for sample collection. If subject has positive ADA test on D1 of cycle 13, then 
follow up predose samples for PK/ADA should be collected every ~90 days on D1 of subsequent treatment cycles until ADA resolves to baseline. If ADA positivity 
is detected within 7-30 days after the last dose of SL-279252, then follow up testing for PK/ADA should be performed at monthly intervals until ADA resolves to 
baseline. 
m. Correlative laboratory studies:  Refer to supplementary Table 13 for details in Section 6.2.2 plus SLM 
• 
Complement  
• 
Immunophenotyping and receptor occupancy  
 
n. SL-279252 Administration: SL-279252 should be administered on D1, D8, D15, and D22 according to the prescribed dosing schedule without deviation in 
cycle 1 to align with the safety DLT assessment and sample (PK, ADA, etc.) collection schedules. Beginning on cycle 2, day 1, a window of +/- 1 day is allowed 
for scheduled dosing days for drug administration. 
o. Adverse Event (AE) Monitoring: Subjects will be followed continuously for AEs during the study and for 90 days after the last dose of IP. After a subject is 
discontinued from SL-279252 due to progressive disease or for other reasons, any ongoing AE should be followed until resolution (or return to baseline) and 
documented in the eCRF. If another anti-cancer agent is started, only SAEs and AEs that occur prior to starting the new anticancer therapy should be recorded.  In 
the event of a continuing SAE or a non-serious AE, the subject will be asked to return for follow-up until the SAE or AE has resolved or is deemed to be continuing 
indefinitely.  AEs will be characterized per NCI-CTCAE criteria v5.0 and events recorded in the eCRF.  
• 
Ad hoc blood samples for clinical safety labs should be collected for AE related to IRR and/or CRS events as noted in Section 6.6.6.1 and the SLM. 
p. Archival tumor tissue (from most recent biopsy): Provide formalin-fixed-paraffin-embedded (FFPE) tissue on slides (recommended minimum of 10 slides) or 
a block of FFPE tissue (the latter is preferred). Refer to Section 6.9.2.2 and the SLM for details.  
q. Tumor Biopsy: Paired biopsies (pre- and on-treatment) obtained in subjects who have tumor accessible to core-needle biopsy.   The on-treatment biopsy should 
be obtained during the first cycle on or between D16-D23. On-treatment biopsies of responding or progressing lesions may be obtained for further characterization 
of the changes in the TME. Please refer to Section 6.9.2.1 and SLM for details regarding biopsy. 
r. 
Post-Treatment: A Post-Treatment visit will be conducted within 30 days (±3 days) after the last dose of SL-279252, or prior to the start of a new therapy, or at 
the end of study, or if the subject's participation is terminated early.  See AE monitoring footnote above.   






CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
97 
6.2.2 Correlative Sample Time points / Schedule 2 / Dose Escalation 
Table 13: Complement, Immunophenotyping, Receptor Occupancy Time Points 
Dose Escalation 
C1/D1 
& 
C2/D1 
C1/D2 
& 
C2/D2 
C1/D5 
C1/D8 
C1/D15  
&  
C2/D15 
C1/D16  
& 
C2/D16 
Schedule 2 
Predose 
(-90 to -30 min) 
1 hr 
post  
EOI 
(±10 min) 
2 hr 
post  
EOI 
(±10 min) 
24 h 
post  
EOI 
(±2 hr) 
96 h 
post  
EOI 
(±2 hr) 
Predose 
(-90 to -30 min) 
Predose 
(-90 to -30 min) 
1 hr 
post EOI 
(±10 min) 
2 hr 
post EOI 
(±10 min) 
24 h 
post EOI 
(±2 hr) 
Complement (SC5b-9)1  
X 
X 
 
X 
 
 
X 
(C1D15 only) 
X 
(C1D15 only) 
 
X 
(C1D16 only) 
Immunophenotyping1 
X 
 
 
X 
X 
X 
X 
 
 
X 
Receptor Occupancy1  
 
X 
 
 
 
X 
1. 
Refer to SLM for details. Complement is NOT collected on C2D15 or C2D16. 
 
 


CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
98 
6.3 
SOA Table: Schedule 1 Dose Expansion Cohorts   
Dosing Schedule 1 
 
D1, D8, D15 in cycle 1 over 28 days, thereafter every 2 weeks (D1, D15) over 28 days 
Post 
Txtt 
 
Follow 
Upu 
Cycle Length = 28 days                
 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
≥ Cycle 5 
Procedures/Assessmentsb 
Screena 
D1 
D2 
D8 
D15 
D16 
D22 
D1 
D2 
D15 
D16s 
D1 
D15 
D1 
D15 
D1 
D15 
Study Days 
Days 
 -21 to -1 
1 
2 
8 
15 
 
16 
 
22 
29 
30 
43 
57 
71 
85 
etc. 
99 
etc. 
113 
etc. 
127 
etc. 
w/in 
30 d 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteriac 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics & medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cancer treatment history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
X 
 
X 
X 
 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
Pulse oximetryd 
X 
Xd1 
 
Xd1 
Xd1 
 
 
Xd2 
 
Xd2 
X d2 
Xd2 
Xd2 
Xd2 
Xd2 
Xd2 
X 
 
Vital signsd 
X 
Xd1 
 
Xd1 
Xd1 
 
 
Xd2 
 
Xd2 
Xd2 
Xd2 
Xd2 
Xd2 
Xd2 
Xd2 
X 
 
Height  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
 
 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
ECOG performance status 
X 
X 
 
X 
X 
 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
Pregnancy teste 
X 
Every 8 weeks 
X 
Every 8 weeks 
X 
 
Hematology profilef 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Chemistry profilef 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Ferritin 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Coagulation profileg 
X 
X 
X 
 
X 
X 
 
X 
X 
 
 
 
 
 
 
 
 
 
Thyroid testh 
X 
 
 
 
 
 
 
X 
 
 
X 
 
X 
 
Xh 
 
X 
 
Antiviral testing (HBV/HCV)i 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cardiac:12-Lead ECG/ECHOj 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tumor imagingk 
X 
Every 8 weeks through week 24 (see footnote k) 
X 
(see footnote k) 
X 
 
X 
X 
PK/immunogenicity/ 
cytokine sample(s) in Expansion  
cohortsL 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
 
X 
 
 
 
X 
 
Complementm 
 
X 
X 
 
X 
X 
 
X 
X 
 
 
 
 
 
 
 
 
 
Immunophenotypingm 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
 
 
 
 
 
 
 
Receptor Occupancym 
 
X 
X 
 
X 
X 
 
X 
X 
X 
 
 
 
 
 
 
 
 
Cell-free nucleic acid (cfNA)n 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SL-279252 administrationo 
 
X 
 
X 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
 
Concomitant medications 
X 
X 
Continuous monitoring 
X 
 
AEs/SAEsp 
X 
X 
Continuous monitoring: Collect Ad hoc sample if IRR or CRS event occurs as outlined in  
Section 6.6.6.1 and SLM 
X 
 
Archival tumor tissueq 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tumor biopsyr 
X 
 
 
 
 
X  
 
 
 
 
 
 
 
 
 
 
 
Survival  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Abbreviations: Txt = Treatment; w/in=within; C = Cycle; D = Day 


CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
99 
a. 
Screening:  Screening Period extends from Day -21 to Day -1.  The following screening assessments must be performed within 72 hours of the first dose of SL-
279252: hematology profile, chemistry profile, coagulation profile, pregnancy test. Baseline CT or PET/CT or MRI tumor assessments are required for all subjects 
within 28 days prior to enrollment.  Subjects will be enrolled based on local PD-L1 tumor testing results. Any PD-L1 tumor testing results prior to enrollment are 
acceptable. 
b. Assessment Window: A physical exam, weight and ECOG performance status obtained for a subject within 24 hours prior to dosing on Cycle 1, Day 1 is 
acceptable. With the exception of Screening assessements and unless otherwise specified, assessments performed at ≤ 3-week intervals will have a +/- 3-day 
window and assessments performed at > 3-week intervals will have a +/- 1-week window. Assessments throughout the study are calendar based starting from the 
first day of dosing (day 1) in the first treatment period. Dose interruptions should not alter the assessment schedule for any subsequent treatment period. 
c. 
Inclusion/Exclusion criteria: Subjects must meet eligibility criteria prior to first dose of SL-279252 on C1/D1. 
d. Vital Signs: BP, HR, T and respiratory rate (RR) must be measured after the subject has been sitting for at least five min. Pulse oximetry will be collected to 
coincide with vital sign time points noted below. 
1) Collect vital signs during Cycle 1 on Day 1, D8, D15: Predose (within 30 min of starting the infusion) and 15 min (± 5 min), 0.5 hr (± 5 min), 1 hr (±10 
min), 1.5 hr (± 10 min) and 2 hr (± 10 min) after SOI. 
2) Collect vital signs on dosing days (Cycles ≥ 2, Days 1 and 15): Predose (within 30 minutes of starting the infusion) and at the EOI (± 2 min)  
e. 
Pregnancy Test:  A serum pregnancy test (β-hCG) or urine pregnancy test must be performed at screening for all FCBP within 72 hrs of starting SL-279252. 
Repeat this test every 8 weeks during SL-279252. Contraception should be continued for at least 30 days after the last dose of SL-279252. 
f. 
Clinical Laboratory Tests (Hematology/Clinical Chemistry): Clinical laboratory tests will be performed at local laboratories according to the laboratory’s 
normal procedures.  See Section 6.6.6 for list of laboratory tests required. 
g. Coagulation Tests:  PT, INR, APTT, fibrinogen, d-dimer (the latter test at screening and then as needed for clinical assessment) 
h. Thyroid Function Test: TSH, and free T4 tests will be performed at screening, C2D1, C3D1, C4D1 and then every 8 weeks.   
i. 
Antiviral Testing:  Please see exclusion criterion 17 in Section 4.3.  
j. 
Cardiac Assessments (obtain within 28 days of first dose): 1) ECG:  12-lead ECG reading must be performed at screening to serve as baseline for comparison 
with ECG obtained for safety reason. 2) ECHO: An ECHO must be performed at screening to serve as baseline for comparison with ECHO obtained for safety 
reason. 
k. Tumor Assessment: Tumor assessments are required for all subjects within 28 days prior to enrollment. Baseline and on-treatment tumor assessments for solid 
tumors by iRECIST should include CT with contrast of chest, abdomen, and pelvis and other known sites of disease at each time point. Bone scan and positron 
emission tomography (PET)/CT should be performed only if clinically indicated.  Baseline and on-treatment tumor assessment for lymphoma by RECIL 2017 
should be done using CT scan with contrast and PET/CT of neck, chest, abdomen, and pelvis and other known sites of disease at each time point. Please refer to 
Section 8 for requirements regarding disease assessment.  Tumor assessments must be performed at screening and at the following intervals until disease progression 
is confirmed: approximately every 8 weeks through week 24 (e.g., C3D1, C5D1, C7D1), every 12 weeks up to year 2 (prior to cycles 10, 13, 16, 19, 22, 25, 28 and 
31), and then every 6 months (prior to cycles 37, cycle 43, etc.) up to conclusion of the study. Confirmatory scans should be performed at least 4 weeks (>28 days), 
but no longer than 8 weeks after initial documentation of an objective response. Subjects who discontinue study treatment for reasons other than disease progression 
(e.g., AE or withdrawal of consent) will be monitored for radiologic response until start of another anti-cancer therapy, or disease progression, withdrawal of 
consent or death.  
l. 
Sparse PK, immunogenicity (i.e., ADA) and cytokine sampling (Dose Expansion Cohorts): PK/ADA/cytokines time points for collection are outlined in 
supplementary PK tables in Section 6.3.1 (Table 14 and Table 15). Blood volumes required are provided in the SLM.  PK, ADA, cytokine samples should not 


CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
100 
be collected from infusion port for drug delivery i.e., recommendation is to use a separate line in the opposite arm for sample collection. If subject has 
positive ADA test on D1 of cycle 13, then follow up predose samples for PK/ADA should be collected every ~90 days on D1 of subsequent treatment cycles until 
ADA resolves to baseline. If ADA positivity is detected within 7-30 days after the last dose of SL-279252, then follow up testing for PK/ADA should be performed 
at monthly intervals until ADA resolves to baseline. 
m. Correlative laboratory studies:  Refer to supplementary Table 16 for details in Section 6.3.2 plus the SLM. 
• 
Complement  
• 
Immunophenotyping and receptor occupancy 
 
n. cfNA: Collect blood prior to dosing into 2 separate cfNA Streck tubes and invert to mix thoroughly as described in SLM. 
o. SL-279252 Administration: SL-279252 should be administered on D1, D8, and D15 according to the prescribed dosing schedule without deviation in cycle 1 to 
align with the safety assessment and sample (PK, ADA, etc.) collection schedules. Beginning on cycle 2, day 1, a window of +/- 1 day is allowed for scheduled 
dosing days for drug administration. 
p. AE Monitoring: Subjects will be followed continuously for AEs during the study and for 90 days after the last dose of IP. After a subject is discontinued from SL-
279252 due to progressive disease or for other reasons, any ongoing AE should be followed until resolution (or return to baseline) and documented in the eCRF. If 
another anti-cancer agent is started, only SAEs and AEs that occur prior to starting the new anticancer therapy should be recorded.  In the event of a continuing 
SAE or a non-serious AE, the subject will be asked to return for follow-up until the SAE or AE has resolved or is deemed to be continuing indefinitely. AEs will 
be characterized per NCI-CTCAE criteria v5.0 and events recorded in the eCRF.  
• 
Ad hoc blood samples for clinical safety labs should be collected for AE related to IRR and/or CRS events as noted in Section 6.6.6.1 and SLM. 
 
q. Archival tumor tissue (from most recent biopsy): Provide formalin-fixed-paraffin-embedded (FFPE) tissue on slides (recommended minimum of 10 slides) or 
a block of FFPE tissue (the latter is preferred). Refer to Section 6.9.2.2 and the SLM for details.  
r. 
Tumor Biopsy: Paired biopsies (pre- and on-treatment) obtained in subjects who have tumor accessible to core-needle biopsy.  .  The on-treatment biopsy should 
be obtained during the first cycle on or between D16-D23. On-treatment biopsies of responding or progressing lesions may be obtained for further characterization 
of the changes in the TME. Please refer to Section 6.9.2.1 and SLM for details regarding biopsy. 
s. 
Cycle 2 Days 15 and 16: Collect biomarker samples outlined in Table 16 in Section 6.3.2. Refer to the SLM for details. 
t. 
Post-Treatment: A Post-Treatment visit will be conducted within 30 days (±3 days) after the last dose of SL-279252, or prior to the start of a new therapy, or at 
the end of study, or if the subject's participation is terminated early.  See AE monitoring footnote above.      
u. Follow-Up: All subjects will be contacted after discontinuing study therapy to collect survival status. Subjects should be contacted every 3 months (+/- 14 days) 
until death, withdrawal of consent or subject is lost to follow-up. Contact may include clinic visit, telephone contact, email or mail to document survival status. 
 
 
 






CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
103 
6.3.2 Correlative Sample Time points / Schedule 1 / Dose Expansion  
Table 16: Complement, Immunophenotyping Sample Time Points 
Dose Expansion 
Cohorts 
C1/D1 
& 
C2/D1 
C1/D2 
& 
C2/D2 
C1/D5 
C1/D8 
C1/D15  
&  
C2/D15 
C1/D16  
& 
C2/D16 
Schedule 1 
Predose 
(-90 to -30 min) 
1 hr 
post  
EOI 
(±10 min) 
2 hr 
post  
EOI 
(±10 min) 
24 h 
post  
EOI 
(±2 hr) 
96 h 
post  
EOI 
(±2 hr) 
Predose 
(-90 to -30 min) 
Predose 
(-90 to -30 min) 
1 hr 
post EOI 
(±10 min) 
2 hr 
post EOI 
(±10 min) 
24 h 
post EOI 
(±2 hr) 
Complement (SC5b-9)1  
X 
X 
 
X 
 
 
X 
(C1D15 only) 
X 
(C1D15 only) 
 
X 
(C1D16 only) 
Immunophenotyping1 
X 
 
 
X 
X 
X 
X 
 
 
X 
Receptor Occupancy1  
 
X 
 
 
 
X 
1. 1. Refer to SLM for details. Complement is NOT collected on C2D15 or C2D16. 
 


CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
104 
6.4 
SOA Table: Schedule 2 Dose Expansion Cohorts  
Dosing Schedule 2 
 
Once weekly (D1, D8, D15, D22)  X 4 every 28 days  
Post 
Txts 
Follow 
Upt 
Cycle Length = 28 days 
 
Cycle 1 
Cycle 2 
Cycle 3 
≥ Cycle 4 
Procedures/ Assessmentsb 
Screena 
D1 
D2 
D8 
D15 
D16 
D22 
D1 
D2 
D8 
D15 
D16 
D22 
D1 
D8 
D15 
D22 
D1/ 
D15 
D8/ 
D22 
Study Days 
Days 
-21 to -
1 
1 
2 
8 
15 
 
16 
 
22 
29 
30 
36 
43 
44 
50 
57 
etc. 
64 
etc. 
71 
etc. 
78 
etc. 
85 
etc. 
99 
etc. 
w/in 
30 d 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteriac 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics & medical 
history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cancer treatment history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
X 
 
X 
X 
 
X 
X 
 
 
 
 
 
X 
 
 
 
X 
D1 
only 
 
X 
 
Pulse oximetryd 
X 
Xd1 
 
Xd
1 
Xd1 
 
Xd1 
Xd2 
 
 
Xd2 
 
 
Xd2 
 
Xd2 
 
Xd2 
 
X 
 
Vital signsd 
X 
Xd1 
 
Xd
1 
Xd1 
 
Xd1 
Xd2 
 
 
Xd2 
 
 
Xd2 
 
Xd2 
 
Xd2 
 
X 
 
Height  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
ECOG performance status 
X 
X 
 
X 
X 
 
X 
X 
 
 
 
 
 
X 
 
 
 
X 
D1 
only 
 
X 
 
Pregnancy teste 
X 
Every 8 weeks 
X 
Every 8 weeks 
X 
 
Hematology profilef 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
 
Chemistry profilef 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
 
Ferritin 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Coagulation profileg 
X 
X 
X 
 
X 
X 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Thyroid testh 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
Xh 
 
X 
 
Antiviral testing 
(HBV/HCV)i 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cardiac:12-Lead 
ECG/ECHOj 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tumor imagingk 
X 
Every 8 weeks through week 24 (see footnote k) 
X 
(see footnote k) 
X 
X 
Sparse PK/ 
immunogenicity/cytokine 
samples in Expansion  
cohortsL  
 
X 
X 
 
X 
X 
 
X 
X 
 
 
 
 
X 
 
 
 
X 
 
X 
 
Complementm 
 
X 
X 
 
X 
X 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Immunophenotypingm 
 
X 
X 
X 
X 
X 
 
X 
X 
 
X 
X 
 
 
 
 
 
 
 
 
 


CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
105 
Dosing Schedule 2 
 
Once weekly (D1, D8, D15, D22)  X 4 every 28 days  
Post 
Txts 
Follow 
Upt 
Cycle Length = 28 days 
 
Cycle 1 
Cycle 2 
Cycle 3 
≥ Cycle 4 
Procedures/ Assessmentsb 
Screena 
D1 
D2 
D8 
D15 
D16 
D22 
D1 
D2 
D8 
D15 
D16 
D22 
D1 
D8 
D15 
D22 
D1/ 
D15 
D8/ 
D22 
Study Days 
Days 
-21 to -
1 
1 
2 
8 
15 
 
16 
 
22 
29 
30 
36 
43 
44 
50 
57 
etc. 
64 
etc. 
71 
etc. 
78 
etc. 
85 
etc. 
99 
etc. 
w/in 
30 d 
Receptor Occupancym 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
 
 
 
 
 
 
 
 
Cell-free nucleic acid 
(cfNA)n 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SL-279252 administrationo 
 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
 
Concomitant medications 
X 
X 
Continuous monitoring 
X 
 
AEs/SAEsp 
X 
X 
Continuous monitoring: Collect Ad hoc sample if IRR or CRS event occurs as outlined in  
Section 6.6.6.1 and SLM 
X 
 
Archival tumor tissueq 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tumor biopsyr 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Survival  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Abbreviations: Txt = Treatment; w/in=within; C = Cycle; D = Day 
a. 
Screening:  Screening Period extends from Day -21 to Day -1.  The following screening assessments must be performed within 72 hours of the first dose of SL-
279252: hematology profile, chemistry profile, coagulation profile, pregnancy test. Baseline CT or PET/CT or MRI tumor assessments are required for all subjects 
within 28 days prior to enrollment.  Subjects will be enrolled based on local PD-L1 tumor testing results. Any PD-L1 tumor testing results prior to enrollment are 
acceptable. 
b. Assessment Window: A physical exam, weight and ECOG performance status obtained for a subject within 24 hours prior to dosing on Cycle 1, Day 1 is 
acceptable. With exception of Screening assessments and unless otherwise specified, assessments performed at ≤ 3-week intervals will have a +/- 3-day window 
and assessments performed at > 3-week intervals will have a +/- 1-week window. Assessments throughout the study are calendar based starting from the first day 
of dosing (day 1) in the first treatment period. Dose interruptions should not alter the assessment schedule for any subsequent treatment period. 
c. 
Inclusion/Exclusion criteria: Subjects must meet eligibility criteria prior to first dose of SL-279252 on C1/D1. 
d. Vital Signs: BP, HR, T and RR must be measured after the subject has been sitting for at least five minutes. Pulse oximetry will be collected to coincide with vital 
sign time points noted below. 
1) Collect vital signs during Cycle 1 on Day 1, D8, D15, D22: Predose (within 30 min of starting the infusion) and 15 min (± 5 min), 0.5 hr (± 5 min), 1 hr 
(±10 min), 1.5 hr (± 10 min) and 2 hr (± 10 min) after SOI. 
2) Collect vital signs on dosing days (Cycles ≥ 2, Days 1 and 15): Predose (within 30 minutes of starting the infusion) and at the EOI (± 2 min)  
e. 
Pregnancy Test:  A serum pregnancy test (β-hCG) or urine pregnancy test must be performed at screening for all females who are of childbearing potential within 
72 hrs of starting SL-279252. Repeat this test every 8 weeks during SL-279252. Contraception should be continued for at least 30 days after the last dose of SL-
279252. 
f. 
Clinical Laboratory Tests (Hematology/Clinical Chemistry): Clinical laboratory tests will be performed at local laboratories according to the laboratory’s 
normal procedures.  See Section 6.6.6 for list of laboratory tests required. 


CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
106 
g. Coagulation Tests:  PT, INR, APTT, fibrinogen, d-dimer (the latter test at screening and then as needed for clinical assessment) 
h. Thyroid Function Test: TSH, and free T4 tests will be performed at screening, C2D1, C3D1, C4D1 and then every 8 weeks.  
i. 
Antiviral Testing: Please see exclusion criterion 17 in Section 4.3.  
j. 
Cardiac Assessments (obtain within 28 days of first dose): 1) ECG: 12-lead ECG reading must be performed at screening to serve as baseline for comparison 
with ECG obtained for safety reason. 2) ECHO: An ECHO must be performed at screening to serve as baseline for comparison with ECHO obtained for safety 
reason. 
k. 
Tumor Assessment: Tumor assessments are required for all subjects within 28 days prior to enrollment. Baseline and on-treatment tumor assessments for solid 
tumors by iRECIST should include CT with contrast of chest, abdomen, and pelvis and other known sites of disease at each time point. Bone scan and positron 
emission tomography (PET)/CT should be performed only if clinically indicated.  Baseline and on-treatment tumor assessment for lymphoma by RECIL 2017 
should be done using CT scan with contrast and PET/CT of neck, chest, abdomen, and pelvis and other known sites of disease at each time point. Please refer to 
Section 8 for requirements regarding disease assessment.  Tumor assessments must be performed at screening and at the following intervals until disease progression 
is confirmed: approximately every 8 weeks through Week 24 (e.g., C3D1, C5D1, C7D1), every 12 weeks up to year 2 (prior to cycles 10, 13, 16, 19, 22, 25, 28 
and 31), and then every 6 months (prior to cycles 37, cycle 43, etc.) up to conclusion of the study. Confirmatory scans should be performed at least 4 weeks (>28 
days), but no longer than 8 weeks after initial documentation of an objective response. Subjects who discontinue study treatment for reasons other than disease 
progression (e.g., AE or withdrawal of consent) will be monitored for radiologic response until start of another anti-cancer therapy, or disease progression, 
withdrawal of consent or death.  
l. 
Sparse PK and immunogenicity (i.e., ADA) and cytokine sampling (Dose Expansion Cohorts): PK, ADA, and cytokine time points for collection are outlined 
in supplementary PK tables in Section 6.4.1 (Table 17 and Table 18).  Blood volumes required are provided in the SLM.  PK, ADA, cytokine samples should 
not be collected from infusion port for drug delivery i.e., recommendation is to use a separate line in the opposite arm for sample collection. If subject has positive 
ADA test on D1 of cycle 13, then follow up predose samples for PK/ADA should be collected every ~90 days on D1 of subsequent treatment cycles until ADA 
resolves to baseline. If ADA positivity is detected within 7-30 days after the last dose of SL-279252, then follow up testing for PK/ADA should be performed at 
monthly intervals until ADA resolves to baseline. 
m. Correlative laboratory studies:  Refer to supplementary Table 19 for details in Section 6.4.2 plus the SLM. 
• 
Complement 
• 
Immunophenotyping and receptor occupancy 
n. cfNA: Collect blood into 2 separate cfNA Streck tubes and invert to mix thoroughly as described in SLM. 
o. SL-279252 Administration: SL-279252 should be administered on D1, D8, D15, and D22 according to the prescribed dosing schedule without deviation in 
cycle 1 to align with the safety assessment and sample (PK, ADA, etc.) collection schedules. Beginning on cycle 2, day 1, a window of +/- 1 day is allowed for 
scheduled dosing days for drug administration. 
p. AE Monitoring: Subjects will be followed continuously for AEs during the study and for 90 days after the last dose of IP. After a subject is discontinued from SL-
279252 due to progressive disease or for other reasons, any ongoing AE should be followed until resolution (or return to baseline) and documented in the eCRF. If 
another anti-cancer agent is started, only SAEs and AEs that occur prior to starting the new anticancer therapy  should be recorded.  In the event of a continuing 
SAE or a non-serious AE, the subject will be asked to return for follow-up until the SAE or AE has resolved or is deemed to be continuing indefinitely. AEs will 
be characterized per NCI-CTCAE criteria v5.0 and events recorded in the eCRF.  
• 
Ad hoc blood samples for clinical safety labs should be collected for AE related to IRR and/or CRS events as noted in Section 6.6.6.1. 
q. Archival tumor tissue (from most recent biopsy): Provide FFPE tissue on slides (recommend a minimum of 10 slides) or a block of FFPE tissue (the latter is 
preferred). Refer to Section 6.9.2.2 and the SLM for details.  






CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
109 
 
6.4.2 Correlative Sample Time points / Schedule 2 / Dose Expansion  
Table 19: Complement, Immunophenotyping Sample Time Points 
Dose Expansion 
Cohorts 
C1/D1 
& 
C2/D1 
C1/D2 
& 
C2/D2 
C1/D5 
C1/D8 
C1/D15  
&  
C2/D15 
C1/D16  
& 
C2/D16 
Schedule 2 
Predose 
(-90 to -30 min) 
1 hr 
post  
EOI 
(±10 min) 
2 hr 
post  
EOI 
(±10 min) 
24 h 
post  
EOI 
(±2 hr) 
96 h 
post  
EOI 
(±2 hr) 
Predose 
(-90 to -30 min) 
Predose 
(-90 to -30 min) 
1 hr 
post EOI 
(±10 min) 
2 hr 
post EOI 
(±10 min) 
24 h 
post EOI 
(±2 hr) 
Complement (SC5b-9)1  
X 
X 
 
X 
 
 
X 
(C1D15 only) 
X 
(C1D15 only) 
 
X 
(C1D16 only) 
Immunophenotyping1 
X 
 
 
X 
X 
X 
X 
 
 
X 
Receptor Occupancy1  
 
X 
 
 
 
X 
1. Refer to SLM for details. Complement is NOT collected on C2D15 or C2D16. 
 
 
 


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6.5 
Demographics, Medical History, Screening and Safety Assessments 
6.5.1 Informed Consent 
The participant must personally sign and date the latest approved version of the Informed Consent 
form before any trial specific procedures are performed and prior to starting treatment with SL-
279252.  Refer to Section 13.3. 
6.5.2 Eligibility Criteria  
Subjects must meet all the eligibility criteria outlined in the protocol to be eligible for participation.   
6.5.3 Subject Demographics 
The age, sex, race, and ethnicity of each subject will be recorded during Screening. 
6.5.4 Medical History 
A complete medical history will be taken during the Screening period. The history will include the 
background and progress of the participant’s malignancy and a description of prior therapies 
received to treat the disease under study and the response to these therapies. Documenting the 
response to prior PD-1/L1 inhibitor therapies is relevant to the inclusion criteria. 
6.5.5 Concomitant Medications 
Concomitant medications and procedures will be recorded during the Screening period and 
throughout the study as specified in the SOA. 
6.6 
Safety Evaluations 
6.6.1 Physical Examination 
A complete physical examination should be performed at screening and at the post-treatment visit 
by a qualified physician or their designee.  The exam will include, at a minimum, assessments of 
the head and neck, eyes, ears, nose throat, skin, thyroid, cardiovascular, respiratory, 
gastrointestinal and neurological systems, lymph nodes and extremities. Height (at screening) and 
weight will also be measured and recorded.  Investigators should pay special attention to clinical 
signs related to previous serious illnesses. Physical exams should be performed per standard of 
care during the on-treatment period. 
6.6.2 ECOG Performance Status 
Participant’s performance status will be assessed using the ECOG performance status tool (see 
Appendix Section 16.1). 
6.6.3 Pulse Oximetry 
Oxygen saturation will be measured with a pulse oximeter at room air without supplementation. 
6.6.4 Vital Signs 
Vital signs will be assessed in a semi-supine position at rest and will include temperature (T), 
systolic and diastolic blood pressure (BP), heart rate (HR), and respiratory rate (RR). BP and RR 
measurements should be preceded by at least 5 min of rest for the participant in a quiet setting 
without distractions. Refer to footnote “d” in the SOA for details on when to collect vital signs. 


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6.6.5 Cardiac Assessments 
6.6.5.1 
Electrocardiograms 
A single 12-lead ECG will be obtained as outlined in the SOA using an ECG machine that 
automatically calculates HR and measures PR, QRS, QT, and corrected QTc (QTc) intervals.  
ECGs should be performed as clinically indicated during the conduct of the study.  Any treatment 
emergent abnormalities of clinical consequence should be reported as AEs.  
6.6.5.2 
Echocardiogram 
An ECHO will be obtained as outlined in the SOA to assess left ventricular ejection fraction. 
ECHOs should be performed as clinically indicated during the conduct of the study. Any treatment 
emergent abnormalities of clinical consequence should be reported as AEs. 
6.6.6 Clinical Safety and Other Laboratory Assessments 
Refer to the SOA for the timing and frequency. 
Clinical Safety Labs 
Hematology 
Clinical Chemistry  
Hemoglobin (Hgb) 
Blood urea nitrogen (BUN) 
Magnesium 
Hematocrit 
Creatinine 
Phosphorus 
Platelet Count 
Glucose 
Total Protein 
Red Blood Cell (RBC) Count  
Sodium 
Albumin 
White Blood Cell (WBC) Count  
Potassium 
Lactate dehydrogenase 
Automated WBC Differential 
Calcium 
Bicarbonate (CO2) 
Neutrophils 
C reactive protein (CRP) 
Ferritin (C1D1 only) 
Lymphocytes 
Liver Panel 
Monocytes 
Total and direct bilirubin 
Aspartate aminotransferase (AST) 
Eosinophils 
Alanine aminotransferase (ALT) 
Alkaline phosphatase 
Basophils 
 
 
Coagulation  
Thyroid 
Serum/Urine Pregnancy Test 
Prothrombin time (PT) and International- 
normalized ratio (INR) 
Thyroid stimulating hormone (TSH) 
Free thyroxine 4 (T4) 
β-human chorionic gonadotropin 
(β-hCG) 
Activated partial thromboplastin time (aPTT) 
 
 
Fibrinogen 
 
 
D-Dimer 
 
 
Immunogenicity Testa 
Complement 
Antiviral Testing 
Anti-drug antibodies (ADA) 
SC5b-9 test 
 
Hepatitis B: HBsAg / HBV core Ab 
Hepatitis C: HCV Ab / HCV RNA viral 
load 
Additional Laboratory Testsa 
cfNA (Dose Expansion Cohorts only) 
 
Cytokines and Chemokines Panela 
Including but not limited to GM-CSF, G-CSF, tissue growth factor (TGF)-alpha, IFN-gamma, etc. See SLM for details 
 
Flow Cytometry Panelsa 
Receptor Occupancy Panel  
Immunophenotyping Panel 
Memory Panel and Treg Panel: See SLM for details 
a) Refer to the SLM for details for sample collection, handling, storage and shipment instructions.  


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6.6.6.1 
 Ad Hoc Labs for AEs of IRR and/or CRS 
Ad hoc labs should be collected as noted if IRR and/or CRS occur. The samples to be collected 
are provided below. 
CBC and differential 
Complement (SC5b-9) 
CRP 
Ferritin 
PK, ADA 
Flow Cytometry 
• Cytokines and Chemokines Panel 
• Immunophenotyping Panel 
a) Refer to the SLM for sample collection, handling, storage and shipment instructions.  PK will be measured with each 
corresponding ADA sample. 
b) Specific biomarker, PK, ADA, and clinical samples will be collected as soon as possible if AE related to CRS and/or IRR to 
SL-279252 occurs.  
All protocol-required laboratory assessments must be conducted in accordance with the 
SLM.  
6.6.6.2 
Pregnancy Testing 
All FCBP subjects must have a negative pregnancy test (serum or urine) at Screening. A separate 
assessment is required if a negative Screening pregnancy test is obtained more than 72 hours before 
the first dose of SL-279252. Subjects with a positive pregnancy test must be excluded from the 
study. Subjects with a negative pregnancy test result must agree to use an effective contraception 
method as described in Appendix Section 16.2.  
 
In the rare event that β-hCG is elevated as a tumor marker, please see guidance in Appendix 
Section 16.2.1. 
 
6.7 
Pharmacokinetics 
6.7.1 Intensive PK Sampling in Dose Escalation (Schedule 1 or Schedule 2) 
Intensive serial PK samples will be collected for all subjects enrolled in dose escalation cohorts. 
In the first cycle starting on Day 1, samples will be collected pre-dose, at the EOI, and 0.5, 1, 1.5, 
2, 3, 4, 6, 8 and 24 hours post EOI. Additional PK samples will be collected at 48, 72, and 96 hours 
post EOI. Actual dose administration and PK sampling times will be documented in the subject’s 
medical record. Sample collection out to 96 hours post EOI may be truncated during dose finding 
based on emerging data (e.g., lower doses may require collection of PKs only through the 48-hour 
time point following the first infusion). Subsequently, pre-dose, EOI, 2-hour, 6-hour and 24-hour 
post EOI samples will be obtained on C1D15/D16 and C2D1/D2. On C3/D1 and C4/D1, a pre-
dose, EOI, and 6-hour post EOI sample will be collected. Beyond cycle 4, only pre-dose samples 
will be collected for ADA and PK analyses on D1 of C7, C10, C13 and C25.  A final PK/ADA 
sample should be collected within 7 – 30 days after permanently stopping treatment with SL-
279252. 
Refer to supplementary tables provided in Sections 6.1.1 and 6.2.1 for details. 


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6.7.2 Sparse PK Sampling in Dose Expansion (Schedule 1 or Schedule 2) 
Sparse PK samples will be collected for all subjects enrolled in Expansion Cohorts. Actual dose 
administration and PK sampling times will be documented in the subject’s medical record. A 
sample will be collected pre-dose, at the EOI and then 2 and 6 hours after the infusion on C1/D1. 
A 24-hour post EOI sample will be collected on Day 2 of the first cycle (C1/D2). Subsequently, 
pre-dose, EOI, 2-hour, 6-hour, and 24-hour post EOI samples will be obtained on C1D15/D16 and 
C2D1/D2. A predose, EOI and 6-hour post EOI sample will be collected on C3/D1 and cycle 4/D1. 
Beyond cycle 4, only pre-dose samples will be collected for ADA and PK analyses on D1 of C7, 
C10, C13 and C25. A final PK/ADA sample should be collected within 7 – 30 days after 
permanently stopping treatment with SL-79252. 
Refer to supplementary tables provided in Sections 6.3.1 and 6.4.1. for details. 
6.7.3 Pharmacokinetic Endpoints  
The Pharmacokinetics of SL-279252 will be described using the PK parameters listed in Table 
20. 
Table 20: Serum SL-279252 PK Parameters 
Cmax 
Maximum observed concentration 
Tmax 
Time of maximum observed concentration 
AUC0-last 
The area under the serum concentration time curve, from time 0 to the last 
quantifiable concentration, calculated by a combination of linear and 
logarithmic trapezoidal methods (Linear up/log down method). 
AUC0-t 
The area under the serum concentration time curve, from time 0 to time=t, 
calculated by a combination of linear and logarithmic trapezoidal methods 
(Linear up/log down method). 
AUC0-inf 
Area under the serum concentration time curve from time 0 extrapolated to 
infinity, calculated as AUClast + Clast/terminal elimination rate constant (λz). 
Reliability of AUC0-inf values is contingent on the percent of the total area 
obtained by extrapolation: 
AUC0-inf values with <20% of the total area coming from Clast/λz are 
considered acceptable.   
Any exceptions to the above procedures will be clearly documented/justified 
in the PK report. 
AUCtau 
The area under the serum concentration time curve, over the dosing interval 
following doses > first dose, calculated by a combination of linear and 
logarithmic trapezoidal methods (Linear up/log down method). 
%AUCext 
Percentage of AUC0-inf due to extrapolation from Tlast to infinity 
t½ 
Terminal elimination half-life, estimated using the equation [ln(2)/λz] 
CL 
Clearance; calculated as Dose/AUC0-inf 
Vz 
Volume of distribution; calculated as Dose/(λz * AUC0-inf) 
6.8 
Anti-drug Antibody Assessments 
Pre-dose blood samples will be collected from all subjects enrolled in the study (Dose Escalation 
and Dose Expansion Cohorts) for determination of ADA prior to the first dose, on C1D15, and on 


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the first day of cycles 2, 3, 4, 7, 10, 13 and 25 and within 7-30 days of the last dose of SL-279252. 
The following endpoints will be calculated for each subject: 
• ADA titer and status (positive, negative, inconclusive) at each timepoint 
• ADA onset 
• ADA duration 
• Persistent vs. transient ADA  
6.9 
Pharmacodynamic/Biomarker Assessments 
Blood samples and tumor tissue (where available) will be collected from all subjects in this study 
for pharmacodynamic/biomarker research as specified in the SOA for the appropriate dosing 
schedule (Schedule 1 or Schedule 2). Below is an overview of the Pharmacodynamic/Biomarker 
plan, the sample requirements, supporting analytics, and intended goal of performing the proposed 
assays. A separate SLM detailing the preparation, storage, and shipping requirements for blood or 
fresh and archival tumor tissue collection during the study will be provided. 
6.9.1 Pharmacodynamic Assessments in Blood 
6.9.1.1 
Cytokine and Chemokine Analysis  
The levels of serum proteins such as cytokines and chemokines will be measured as noted in 
Section 6.6.6.  Levels of serum cytokines/chemokines may provide context to AEs observed in 
subjects following infusion of SL-279252 and may act as pharmacodynamic markers of activity. 
Serum cytokines will be measured for SL-279252 in dose escalation and dose expansion cohorts. 
6.9.1.2 
Peripheral Blood Mononuclear Cells for Receptor Occupancy 
Receptor occupancy of SL-279252 on PD-L1 and OX40 will be measured by flow cytometry. This 
analysis will provide evidence that SL-279252 is engaging its expected targets and allow receptor 
occupancy (free and total) to be calculated and assessed across dose groups. Samples for receptor 
occupancy will be collected during dose escalation and dose expansion.  
6.9.1.3 
PBMC for Immunophenotyping  
Protein expression of phenotypic markers, proliferation markers, and activation markers will be 
assessed by flow cytometry. The composition of T cells in the peripheral blood may provide 
insights into the mechanism of action of SL-279252 and serve as biomarkers for immune response. 
Samples for immunophenotyping will be collected during dose escalation and in dose expansion. 
6.9.1.4 
Cell-free Nucleic Acids for Exome Sequencing and TMB 
Cell-free nucleic acids (cfNA)  samples will only be collected in subjects in Dose Expansion 
Cohorts. These samples may be utilized for exome sequencing and TMB analyses. Assessing 
mutations (including point, insertions/deletions, etc.) in the coding sequence of nucleic acids 
isolated from  nucleic acids shed by tumor cells into the peripheral blood or in the actual tumor 
environment will allow for evaluation of the mutational load, which can be correlated with subject 
response. Additionally, exome sequencing can provide insights into other genetic 


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pathways/mechanisms associated with either response or resistance to SL-279252 (e.g., mutations 
in antigen presentation).   
6.9.2 Pharmacodynamic Assessment of Tumor Tissue 
6.9.2.1 
Fresh Tumor Biopsies 
The efficacy of cancer immunotherapy is conditioned by the infiltration of tumors by activated 
tumor-specific T cells. The activity of these T cells will be affected by the immunosuppressive 
environment in the tumor (e.g., T-regulatory cells, and suppressive myeloid cells such as myeloid-
derived suppressor cells and M2 macrophages). Therefore, the direct evaluation of the “immune 
landscape” inside the tumor is of great value for understanding the mechanism of action of SL-
279252 and optimizing cancer immunotherapy. Immunohistochemistry (IHC) analyses and exome 
sequencing will be performed on the fresh tumor samples. The immune infiltrate of the tumor will 
be assessed by visualizing and assessing the phenotype of cells in the tumor micro-environment 
by IHC.  Additionally, the spatial distribution and redistribution upon treatment of immune cells 
within the TME has also been found to be linked to the response to immunotherapies and can be 
evaluated by these procedures. The immune profile of the tumor could be used to predict clinical 
response or validate the mechanism of the immune response to SL-279252. Exome sequencing 
analysis will be used to detect mutations in genes associated with mechanisms of resistance (e.g., 
defects in antigen presentation) or response.  Additional DNA/RNA analyses may be performed. 
For these reasons, core needle biopsies are highly recommended in subjects with tumors accessible 
for biopsy enrolled in the Dose Escalation or Expansion Cohorts. Three cores at each biopsy time 
point should be obtained for research studies (see SLM for details).  
Paired biopsies are requested at Screening/Baseline (to evaluate the immune status of the tumor 
before SL-279252 treatment), and at Week 3 in the first treatment cycle at any time between Days 
16-23, (at the expected time of an immune response to SL-279252 therapy).  If the baseline biopsy 
is non-evaluable, the Sponsor will inform the investigator that the follow-up on-treatment biopsy 
can be omitted. The time interval for the second biopsy may be changed by the Sponsor if 
pharmacodynamic data from the Dose Escalation indicates a different time point would be more 
suitable. 
It is strongly recommended that the biopsies are obtained from non-target and measurable lesions. 
If such a lesion is not present, a biopsy may be obtained from a target lesion that is 2 centimeters 
(cm) or more. The same lesion should be biopsied at both Screening and subsequent time points, 
and measurement of the lesion that is biopsied should be documented. Where possible, lymph node 
biopsies should be avoided (except for lymphoma subjects) as reliable measure of tumor 
infiltrating lymphocytes (or their activation) in a background of (non-tumor) lymphoid tissue is 
challenging. 
If feasible, biopsy material should be collected after disease progression has been confirmed and 
documented, ideally on lesions that have progressed. 
Priority for fresh biopsy tissue analysis based on tissue availability is IHC (including central 
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DNA and/or RNA analyses. Samples collected on treatment or at the time of progression will be 
compared with baseline results. 
Biopsy Collection Safety Considerations and Procedure 
Three tissue cores per subject should be obtained at time points noted in the SOA.  Further details 
are provided in the SLM.  
Only percutaneous biopsies will be performed on subjects with solid tumors. Mediastinal, open 
surgical or laparoscopic, gastrointestinal, peritoneal or bronchial endoscopic biopsies are permitted 
ONLY when obtained incidentally to a clinically necessary procedure and not for the sole purpose 
of the clinical trial.  No laparoscopic, or endoscopic or open surgical procedure will be performed 
solely to obtain a biopsy for this protocol.  However, excisional biopsy or endoscopic biopsy is 
allowed if medically-indicated and can be used for analysis.  Biopsies will be sent for analyses as 
defined in the protocol.   
Contraindications to percutaneous biopsy: 
• 
Significant coagulopathy or anticoagulation treatment that cannot be adequately 
corrected.  
• 
Severely compromised cardiopulmonary function or hemodynamic instability. 
• 
Lack of a safe pathway to the lesion.  
• 
Inability of the subject to cooperate with, or to be positioned for, the procedure. 
 
If a site is deemed appropriate for biopsy with minimal risk (no more than 2% risk of serious 
complication requiring hospitalization) to the participant by agreement between the investigators 
and Interventional Radiology, an attempt at biopsy should be made.  
The use of imaging to facilitate biopsies will be decided by members of the Interventional 
Radiology team at the clinical site and may include ultrasound, CT scan, or MRI.  Should CT scan 
be needed for biopsy, the number of scans for each procedure will be limited to the minimum 
number needed to safely obtain a biopsy.  Tumor biopsies and local anesthesia will be performed 
only if they are of low risk (<2% major complication rate) to the participant as determined by the 
investigators and Interventional Radiologist. 
6.9.2.2 
Archival Tumor  
TMB analysis may be performed on archival tumor tissue. Archival tumor tissue (1 block preferred 
or a minimum of 10 unstained slides of FFPE tissue; see SLM for details) that is representative of 
current disease status (e.g., metastatic disease) is requested in Dose Escalation and Dose Expansion 
Cohorts. If an inadequate amount of archived tissue is available, the subject may still participate 
in the study if they meet eligibility criteria for the study. Archival tissue may be accepted as a pre-
treatment specimen in lieu of a fresh biopsy if the subject has not undergone treatment since time 
of specimen collection and if the sample was collected via core needle biopsy.  
Priority for archival tissue analysis based on tissue availability is IHC > TMB* > additional DNA 
and/or RNA analyses. Samples collected on treatment or at the time of progression will be 
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*NOTE: Preferred source for TMB analysis is cfNA; however, if cfNA is inadequate for analysis 
the archived tumor tissue will be used. 
6.10 
Assessment of Anti-tumor Activity 
Anti-tumor activity will be assessed in solid tumors according to iRECIST, and in lymphoma 
according to RECIL 2017. Treatment beyond progression is permitted provided the subject meets 
protocol specified criteria (see Section 8.3).  Imaging studies including CT scan, FDG-PET or MRI 
for disease assessment will be performed at baseline and at the following intervals until disease 
progression is confirmed: every 8 weeks through week 24, and every 12 weeks thereafter until 
year 2, and every 6 months until study conclusion. Refer to Section 8 for additional details. All 
subjects will be followed up for survival unless they withdraw consent. 
6.11 
Unscheduled Visit  
In the event of an unscheduled visit, the subject should undergo safety screening to include a 
physical exam, vital signs (HR, BP, T, and RR) and pulse oximetry.  Clinical hematology and 
chemistry labs may be collected if considered necessary for subject assessment. The reason for the 
unscheduled visit should be documented in the eCRF. If the subject is experiencing an AE, they 
should be referred to the appropriate medical service for proper follow up of the AE(s). All AEs 
or SAEs reported by the subject or observed by the investigator should be documented and 
reported; this includes relevant medical information gathered during the unscheduled visit related 
to clinical assessment of AEs or SAEs (Section 7.5). 
7. 
SAFETY ASSESSMENTS  
Subjects will be followed continuously for AEs starting when a subject has signed the ICF, 
throughout the course of treatment and for 90 days after the last dose of IP. After a subject is 
discontinued from SL-279252 due to progressive disease or for other reasons, any ongoing AEs 
should be followed until resolution (or return to baseline) and documented in the eCRF. If another 
anti-cancer agent is started within 90 days after the last dose of SL-279252, only SAEs and AEs 
that occur prior to starting the new anticancer therapy should be recorded. All observed or 
volunteered AEs (serious or non-serious) and abnormal laboratory test findings, if applicable, 
whether suspected to have a causal relationship to the SL-279252 or not will be recorded in the 
subject medical record and in the eCRF.  AEs will be graded according to NCI-CTCAE v5.0.  For 
all AEs, sufficient information will be pursued and/or obtained to permit an adequate 
determination of seriousness and outcome of the event (i.e., whether it should be classified as a 
SAE or not) and an assessment of the causal relationship between the AE and SL-279252.  AEs 
will be followed until resolution (or return to baseline) or stabilization.  Refer to Section 7.5 for 
documentation and reporting of AEs. 
 
 


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7.1 
Assessment of Severity  
The descriptions and grading scales found in the revised NCI-CTCAE version 5.0 will be utilized 
for AE reporting.  A copy of these criteria can be downloaded from the website: 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm. 
• Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated 
• Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age 
appropriate instrumental ADL* 
• Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
ADL** 
• Grade 4: Life-threatening consequences; urgent intervention indicated 
• Grade 5: Death related to AE 
 
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, 
etc. 
** Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not 
bedridden. 
 
For AEs not included in the NCI-CTCAE v5.0 grading system, the following guidelines will be 
used to describe severity. 
• Mild – Events require minimal or no treatment and do not interfere with the subject’s daily 
activities.  
• Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning.  
• Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events may be potentially life-threatening or 
incapacitating. 
NOTE: A distinction should be drawn between serious and severe AEs. Severity is an estimate or 
measure of the intensity of an AE, while the criteria for serious AEs are indications of adverse 
subject outcomes for regulatory reporting purposes. A severe AE need not necessarily be 
considered serious and a serious AE need not be considered severe. 
7.2 
Definitions for Safety Parameters 
Event 
Definition 
Adverse Event (AE) 
The AE observation period starts at the time of signing informed consent and includes 
baseline or washout periods, even if no study treatment has been administered.  
AE is any untoward medical occurrence in a subject to whom the IP has been 
administered, regardless of whether the event is considered related to that product. An 
AE is also an undesirable medical condition due to a study-related procedure.  
Adverse Reaction (AR) 
AR is an untoward and unintended response in a subject to an IP. A causal relationship 
between a trial medication and an AE is at least a reasonable possibility, i.e. the 
relationship cannot be ruled out. 
Serious Adverse  
An AE or suspected AR that is considered "serious" if, in the view of either the 
investigator or Sponsor, it results in any of the following outcomes:  


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Event 
Definition 
Event (SAE) or Serious 
Adverse Reaction 
(SAR) 
• Death (Note: death is an outcome not an event) 
• A life-threatening AE (an event in which the subject was at risk of death at the time 
of the event; it does not refer to an event which hypothetically might have caused 
death if it were more severe) 
• Inpatient hospitalization or prolongation of existing hospitalization 
• A persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions 
• A congenital anomaly/birth defect.  
• Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the participant and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse. 
Laboratory test(s) that 
meet definition of an 
AE or SAE: 
 
• 
Any laboratory test result that meets the definition of an AE or SAE or requires 
holding or discontinuation of SL-279252, or requires corrective therapy, must be 
documented appropriately. 
• 
Ad hoc labs should be collected as noted in Section 6.6.6.1 above if AEs of IRR 
and/or CRS occur. 
The investigator must review the laboratory report, document this review, and record 
any clinically relevant changes occurring during the study in the subject’s medical 
record and recorded in the AE section of the eCRF.  The laboratory reports must be filed 
with the source documents. Clinically significant abnormal laboratory findings are those 
which are not associated with the underlying disease, unless judged by the investigator 
to be more severe than expected for the participant's condition. 
All laboratory tests with clinically significant abnormal values during participation in 
the study should be repeated until the values return to normal or baseline or are no longer 
considered clinically significant by the investigator. 
If such values do not return to normal/baseline within a period judged reasonable by the 
investigator, the etiology should be identified, and the Sponsor notified.  
If laboratory values from non-protocol specified laboratory assessments performed at 
the institution’s local laboratory require a change in subject management or are 
considered clinically significant by the investigator (e.g., AE, SAE or dose 
interruption), then the results must be recorded in the eCRF.  
Unexpected Adverse 
Reaction 
An adverse reaction (causality related Adverse Event), the nature, severity or outcome 
of which is not consistent with the reference safety information section of the product 
IB. Product reference safety information is contained in the current Guidance for 
Investigators in Section  6.0 of the Investigator’s Brochure provided to the Investigator 
by the Sponsor. 
Suspected Unexpected 
Serious Adverse 
Reaction (SUSAR) 
Suspected Adverse Reaction (causality related AE) that is serious and unexpected. 
 
7.2.1 Events not Qualifying as AEs/SAEs 
The following are not considered to be AEs or SAEs: 
• Medical or surgical procedures (e.g., endoscopy, appendectomy). The condition that leads 
to the procedure is considered the AE. 


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• Elective procedures, planned hospitalizations, and procedures for treatment of conditions 
noted in the patient’s medical history (present prior to signing the ICF) that have not 
worsened are not considered AEs.  
• Situations where an untoward medical occurrence did not occur (i.e., admission to hospital 
for social circumstances). 
• Anticipated day-to-day fluctuations of pre-existing medical conditions that were present at 
start of study. These conditions are considered part of the patient’s medical history and 
must be adequately documented on the appropriate page of the CRF. 
• Clear progression of disease under study should not be reported as an AE or SAE (unless 
the investigator considers the progression of underlying neoplasia to be atypical in its 
nature, presentation or severity from the normal course of the disease in a particular 
patient). Findings that are clearly consistent with the expected progression of the 
underlying cancer should not be reported as an adverse event, and hospitalizations due to 
the progression of cancer do not necessarily qualify for an SAE. 
• In the case where the medical condition is known when the participant enters the trial, only 
worsening (increased frequency or intensity of the episodes or attacks) will be documented 
as an AE. If the disease is detected during the trial, and if repeated episodes enable 
diagnosis of a chronic disease, the episodes will be grouped together in the CRF, and the 
diagnosis will be clearly described. 
• Laboratory abnormalities: An isolated, out-of-range laboratory result in the absence of 
any associated, clinical finding may or may not be considered an AE; the Investigator’s 
evaluation should be based on a consideration of the overall clinical context. 
 
7.3 
Classification of an Adverse Event 
7.3.1 Assessment of Causality  
The clinician’s assessment of an AE's relationship to IP is part of the documentation process, but 
it is not a factor in determining what is or is not reported in the study. If there is any doubt as to 
whether a clinical observation is an AE, the event should be reported. All AEs must have their 
relationship to IP assessed. In a clinical trial, the IP must always be suspect. To help assess 
causality, the following guidelines are used.  
Related – The AE is known to occur with the IP, there is a reasonable possibility that the IP caused 
the AE, or there is a temporal relationship between the IP and event. Reasonable possibility means 
that there is evidence to suggest a causal relationship between the IP and the AE.   
Not Related – There is not a reasonable possibility that the administration of IP caused the event, 
there is no temporal relationship between IP and event onset, or an alternate etiology has been 
established.   
7.3.2 Expectedness 
The Sponsor will be responsible for determining whether an AE is expected or unexpected.  
• Unexpected - An AE will be considered unexpected if the nature, severity, or frequency 
of the event is not consistent with the safety information section 6.0 (Guidance for 


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Investigators) of the IB [SL2018IB001_01] for the IP.  "Unexpected," as used in this 
definition, also refers to AEs or ARs that are mentioned in the IB as occurring with a class 
of drugs or as anticipated from the pharmacological properties of the drug not specifically 
mentioned as occurring with the IP under investigation.   
• Expected - AEs that are common and known to occur for the IP being studied.  
Expectedness refers to the awareness of AEs previously observed, not on what might be 
anticipated from the properties of the IP. 
7.4 
 Timing for Event Assessment and Follow-up 
All AEs occurring while on study must be documented appropriately regardless of relationship. 
All AEs will be followed to adequate resolution.  The occurrence of an AE or SAE may come to 
the attention of study personnel during study visits and interviews of a study subject presenting for 
medical care, or upon review by a study monitor.  
Any medical condition that is present at the time that the subject is screened will be considered as 
baseline and not reported as an AE. However, if the pre-existing condition deteriorates at any time 
after the subject signs the main study ICF, it will be recorded as an AE. Unanticipated problems 
will be recorded in the data collection system throughout the study.  
The highest grade in severity for each AE will be documented. AEs characterized as intermittent 
require documentation of onset and duration of each episode.  
 
7.5 
Procedures for Recording and Reporting of Adverse Events  
Event 
Reporting Procedures 
Adverse Event 
Subjects will be followed continuously for AEs during the study and for 90 days after the last 
dose of IP. After a subject is discontinued from SL-279252 due to progressive disease or for 
other reasons, any ongoing AE should be followed until resolution (or return to baseline) and 
documented in the eCRF, regardless of whether the event(s) is attributed to trial medication. If 
another anti-cancer agent is started, only SAEs and AEs that occur prior to starting the new 
anticancer therapy should be recorded. The following information will be recorded: description, 
date of onset and end date, severity, assessment of relatedness to trial medication, and action 
taken.  Follow-up information should be provided as necessary.  AEs will be followed either 
until resolution, or the event is considered stable. 
 
It will be left to the Investigator’s clinical judgment to decide whether an AE is of sufficient 
severity to require the subject’s removal from treatment.  A subject may also voluntarily 
withdraw from treatment due to what he or she perceives as an intolerable AE.  If either of these 
occurs, the subject must undergo an end of trial assessment and be given appropriate care under 
medical supervision until symptoms cease, or the condition becomes stable. 
 
Serious 
Adverse Event 
 
 
 
 
 
 
 
 
Serious  
The study clinician will complete a SAE Form within the following timelines:  
• 
All deaths and immediately life-threatening events, whether related or unrelated, will 
be recorded on the SAE Form and submitted to the study Sponsor or designee within 
24 hours of site awareness.  
• 
Other SAEs regardless of relationship, will be submitted to the study Sponsor or 
designee within 24 hours of site awareness.  
 
All SAEs will be followed until satisfactory resolution or until the site investigator deems the 
event to be chronic or the adherence to be stable. Other supporting documentation of the event 




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recommendations. The study Sponsor will inform the regulatory authorities (i.e., FDA, European 
Medicines Agency , Health Canada, etc.) of the temporary halt and the disposition of the study. 
7.9 
Safety Oversight 
An SMC will be implemented in this study and will consist of investigators and Sponsor 
representatives. SMC meetings will be conducted monthly (or more frequently if required) during 
dose escalation provided subjects have been enrolled and data are available to be reviewed.  The 
SMC will operate in accordance with the SMC charter which will define roles and accountabilities 
and the process for safety review.   
Throughout the conduct of the study, safety data will be reviewed for each subject on an ongoing 
basis. Additionally, periodic safety reviews will be undertaken by the SMC. Based on the severity 
of the DLTs, indicators of potential anti-tumor activity, and other factors, a recommendation on 
whether to modify the dose and/or study design; or continue enrollment will be made by the 
Sponsor collaboratively with input from the SMC. Regulatory authorities and IRBs/IECs will be 
notified of any decisions to prematurely halt the study or subject enrollment. (See section 14.1 for 
details on safety meetings). 
A safety governance board will also be formed. The remit of this board will be to conduct periodic 
safety reviews across all trials conducted by the Sponsor including protocol SL01-DEL-101. The 
safety governance board will be comprised of two physicians with pertinent expertise who are not 
involved in the design, conduct or analysis of SL01-DEL-101. The safety governance board will 
operate in accordance with a charter which will define roles and accountabilities and the process 
for their safety review.  
8. 
ANTI-TUMOR ACTIVITY ASSESSMENTS 
Although the clinical benefit of SL-279252 has not yet been established, the intent of offering this 
IP is to provide a possible therapeutic benefit, and thus the participant will be carefully monitored 
for tumor response and symptom relief in addition to safety and tolerability.  
For the purposes of this study, participants should be evaluated for response as outlined in the 
SOA. Confirmatory scans should be performed at least 4 weeks (>28 days), but no longer than 8 
weeks after initial documentation of an objective response.  All participants who receive at least 3 
doses of SL-279252 and had the first disease assessment at the 8-week time point will be 
considered evaluable for response.   
 
Assessments must be performed on a calendar schedule and should not be affected by dose 
interruptions or delays. Refer to the SOA (Section 6) for the schedule of disease assessments. More 
frequent disease assessments may be performed at the discretion of the investigator. For subjects 
whose disease may be followed by well-characterized tumor markers, disease assessments should 
include results of tumor marker assessments. If study treatment is withdrawn for reasons other than 
disease progression, radiographic disease assessments should continue as per the SOA until 
documented disease progression, the start of new anti-cancer therapy, withdrawal of consent or 
death. See Sections 8.3 for criteria for continuing treatment past disease progression. 
 


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8.1 
Disease Assessment for Solid Tumor Histologies 
For solid tumor histologies, response and progression will be evaluated in this study using the 
international criteria proposed by the RECIST working group for use in trials testing 
immunotherapies (iRECIST) [Seymour, 2017].   
The iRECIST guidelines are based on principles used in RECIST 1.1 [Eisenhauer, 2009].  The 
responses assigned using iRECIST have a prefix of “i” (i.e., immune) to differentiate from 
responses assigned using RECIST 1.1. e.g. iCR, iPR, iSD, iUPD (unconfirmed progressive 
disease), iCPD (confirmed progressive disease).  The major change for iRECIST is the concept of 
resetting the bar if RECIST 1.1 progression is followed at the next assessment by tumor shrinkage.  
iRECIST defines progression based on RECIST 1.1 principles; however, progression requires 
confirmation.   The RECIST 1.1 guidelines and iRECIST guidelines are included in this document 
for this reason (Section 16.6).   
Screening and on-treatment disease assessments will include imaging of the chest, abdomen and 
pelvis (e.g., computed tomography (CT), magnetic resonance imaging (MRI), bone scan, PET/CT 
and/or plain radiographs). CT scan with contrast of the chest, abdomen and pelvis is the preferred 
method to measure lesions selected for response assessment and should be performed at screening 
and on-treatment.  PET/CT scan cannot be substituted for lesion measurements. For subjects with 
known brain metastases, MRI of the brain with contrast should be performed at screening and on-
treatment to assess for response or progression. Bone scans and PET/CT scans should be 
performed at screening and on-treatment as clinically indicated. 
Screening/baseline CT or MRI tumor assessments are required for all subjects within 28 days prior 
to enrollment. All post-baseline assessments require imaging of disease sites identified by baseline 
scans. The method used to document screening disease status should be used consistently 
throughout the study to facilitate comparison of scan results.  
If a CT scan with contrast is contraindicated (i.e., hypersensitivity reaction to contrast agent), MRI 
may be used as an alternative method of baseline disease assessment, except for chest CT scan. If 
a chest CT scan with contrast is contraindicated, a chest CT scan without contrast should be 
performed.  
8.1.1 Assessment of Response by iRECIST – Solid Tumors 
Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the 
shortest diameter in the case of malignant lymph nodes are used in the iRECIST criteria. Please 
see Appendix Section 16.6 for detailed information regarding iRECIST methodology and criteria.  
 
8.1.2 Response and Stable Disease Duration  
Response duration will be measured from the time measurement criteria for iCR/iPR (whichever 
is first recorded) are first met until the first date that recurrent or progressive disease is objectively 
documented, taking as reference the smallest measurements recorded on study (including 
baseline). Stable disease (SD) duration will be measured from the time of start of treatment until 


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the criteria for progression are met, taking as reference the smallest sum on study (including 
baseline).  
8.2 
Disease Assessment for Lymphomas  
International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017) 
will be used for assessment of tumor response in participants with lymphoma [Younes, 2017].   
Screening/baseline and on-treatment disease assessments will include both CT scan with contrast 
of the neck, chest, abdomen and pelvis and FDG-PET scan. CT scan with contrast of the neck, 
chest, abdomen and pelvis is the preferred method to measure lesions selected for response 
assessment. For subjects with known brain metastases, MRI of the brain with contrast should be 
performed at screening and on-treatment to assess for response or progression. Other imaging 
including MRI, bone scan, and/or plain radiographs will be performed as clinically indicated.  
Screening/baseline MRI, CT or PET/CT tumor assessments are required for all subjects within 28 
days prior to enrollment. All post-baseline assessments require imaging of disease sites identified 
by baseline scans. The method used to document screening disease status should be used 
consistently throughout the study to facilitate comparison of scan results.  
If a CT scan with contrast is contraindicated (i.e., hypersensitivity reaction to contrast agent), MRI 
may be used as an alternative method of baseline disease assessment, except for chest CT scan. If 
a chest CT scan with contrast is contraindicated, a chest CT scan without contrast should be 
performed.  
8.2.1 Assessment of Response by RECIL – Lymphomas 
In participants with disseminated disease, a maximum of three target lesions should be selected 
and used to estimate tumor response.  Please see Appendix Section 16.7 for detailed information 
regarding RECIL methodology and criteria. 
8.3 
Criteria for Treatment Beyond Initial Progression 
Subjects will be permitted to continue IP beyond initial progressive disease provided the subject 
does not have clinical symptoms of progression, is tolerating IP, and is gaining clinical benefit as 
assessed by the investigator.  The subject must be made aware of the potential benefits and risks 
of continuing the IP in the setting of progressive disease by providing a separate written informed 
consent.   
The subject may continue to be treated until one of the following criteria is met: 
• Confirmed progressive disease (defined in Appendix Section 16.6.3 for solid tumors and 
Appendix Section 16.7.1 for lymphomas) 
• Meets any of the criteria for discontinuation of IP  (see Section 3.6) 
• Develops clinical symptoms or signs such that the benefit-risk ratio of continuing therapy 
is no longer justified 
• Experiences rapid progressive disease with risk to vital organs or critical anatomical sites 
requiring urgent medical intervention  
• Decline in ECOG PS 


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9. 
STATISTICAL CONSIDERATIONS 
9.1 
Description of Statistical Methods 
The study has 2 parts: dose escalation and dose expansion. During dose escalation, the primary 
objective is to evaluate the safety and tolerability of SL-279252 and to identify the MTD or MAD 
of SL-279252 in participants with locally advanced or metastatic select malignancies. Schedule 1 
will be evaluated first, with dose escalation following the Keyboard design with a target DLT rate 
of 30% (acceptable range of 25-33.3%). Ten DLs are planned with a planned maximum sample 
size of 42 subjects. Single subject cohorts may  initially be enrolled until the subject in a single 
subject cohort experiences a qualifying ≥ Grade 2 toxicity (see Sections 3.2.5 and 3.2.6) or a DLT 
OR DL 6 is reached. Subsequently, cohorts of at least 3 subjects will be enrolled. The full dose 
escalation rules are outlined in Appendix Section 16.3. The Sponsor, in consultation with the SMC, 
may decide to stop enrollment in Schedule 1 early (e.g., based on safety, pharmacodynamics) and 
begin enrollment in Schedule 2 (see Section 3.2.7). If Schedule 2 is opened, dose escalation will 
also follow the Keyboard design with the same target DLT rate of 30%. We anticipate that 4 DLs 
will be evaluated in Schedule 2 with a planned maximum sample size of 15 subjects. All cohorts 
will enroll at least 3 subjects in Schedule 2 (see full dose escalation rules in Appendix Section 
16.3). NOTE: If Schedule 2 is opened, the Sponsor may also elect to stop enrollment in schedule 
2 early (e.g., based on safety) and resume enrollment in Schedule 1. If both schedules are 
evaluated, the MTD or MAD may be determined for each schedule (denoted MTD1/MAD1 and 
MTD2/MAD2). The MTD(s) will be determined using isotonic regression based on DLTs 
observed during dose escalation (see Section 9.2.1). A MAD will be reported if a schedule is fully 
evaluated, but the DLT rate never reaches the target range of 25-33.3%.  
During the dose escalation additional subjects (approximately 6) may be enrolled into a 
pharmacodynamic cohort to obtain additional pharmacodynamic data at select dose levels that 
have previously completed evaluation for safety and not exceeded the MTD.   
After dose escalation, up to 2 expansion cohorts (n=up to 15 subjects each) may be enrolled to 
further explore up to 2 different doses. The Sponsor, in consultation with the SMC, will determine 
the dose(s) and schedule to be evaluated during dose expansion based on the totality of data in the 
dose escalation cohorts. The primary objective during dose expansion is to further characterize the 
safety of SL-279252. Special attention will be paid to IRRs and toxicities that require 
discontinuation of SL-279252. See Section 9.2.2 for details on the continuous toxicity monitoring 
that will be implemented across the expansion cohorts. The tumor types for dose expansion will 
be determined after review of data collected during dose escalation. The RP2D will be determined 
after review of data collected during both dose escalation and dose expansion and will take safety 
(including delayed toxicities that do not occur during the DLT period), pharmacodynamics, PK, 
and efficacy into account. The RP2D will not exceed the MTD.  
9.2 
Sample Size and Statistical Hypotheses 
9.2.1 Dose Escalation 
The planned sample size for the dose escalation part of the study is 63 subjects. For Schedule 1, 
the maximum planned sample size for dose escalation will be 42 subjects, and for Schedule 2, the 


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maximum planned sample size for dose escalation will be 15 subjects. The planned number of 
subjects to obtain additional pharmacodynamic data at select dose levels is approximately 6 
subjects.  
These sample sizes for dose escalation were chosen based on simulation results demonstrating 
good operating characteristics (see tables below) with these sample sizes using the Keyboard 
design (see dose escalation rules in Appendix Section 16.3). NOTE: The maximum planned 
sample sizes may be revised if additional DLs are evaluated or if more subjects (i.e., subjects 
available for dosing beyond the number required in a cohort) are enrolled than anticipated. The 
Sponsor, in consultation with the SMC, may also elect to add subjects if additional safety data are 
needed to select a dose and schedule for the expansion cohorts.  Six (6) subjects must be treated at 
a dose level to confirm safety and tolerability before a dose can be used in an expansion cohort. 
All simulation results are based on 5000 simulations and assume the following: 
• The target DLT rate is 30% (acceptable range of 25-33.3%) 
• Dose escalation will stop early if 12 subjects are enrolled at the same DL (See Scenarios 1 
and 3 in Appendix Section 16.3) 
• If there is more than a 95% chance that the current dose is above the MTD, that dose and 
higher doses will be eliminated from the trial to prevent exposing future subjects to overly 
toxic doses 
9.2.1.1 
Simulations for Schedule 1 (assuming 10 dose levels) 
The first set of simulations assume the following: 
• 
Subjects are enrolled in cohorts of 3 (i.e., dose escalation decisions are made after the 3 subjects in a cohort 
are evaluated) 
• 
Maximum sample size = 42 
 
 












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9.3 
Populations for Analyses 
For the analysis, the following populations are defined: 
Population 
Description 
Enrolled 
All subjects who sign the main study ICF.  
Screen Failures 
A subject who signs the informed consent but has not received any 
dose of SL-279252  
All Treated 
All subjects who receive at least one dose of SL-279252. Safety data 
will be evaluated based on this population. 
DLT Evaluable  
All subjects in the All Treated population who receive at least 2 
doses of SL-279252 for Schedule 1 or at least 3 doses for Schedule 
2, complete the safety follow up through DLT evaluation period or 
experience any DLT during the DLT evaluation period. The DLT 
evaluation period is defined as the first 21 days or 28 days of 
treatment on Schedule 1 or Schedule 2, respectively. Evaluable 
subjects will be used to guide dose escalation and to determine the 
MTD or MAD. 
Evaluable for Efficacy  
A subject who received at least 3 doses of SL-279252 and had at 
least one post-baseline disease assessment or had progressed or died 
before the first post-baseline disease assessment. . 
Pharmacokinetic 
All subjects in the All Treated population who received at least one 
dose of SL-279252 and have at least one evaluable post-dose sample 
collected. The PK population will be used for PK analysis. 
Pharmacodynamic 
All subjects in the All Treated population for whom sufficient 
samples are available for the analysis. The pharmacodynamic 
population will be used for the pharmacodynamic data analysis. 
9.4 
Statistical Analyses 
The statistical analysis plan (SAP) will be developed and finalized before database lock and will 
describe the participant populations to be included in the analyses, and procedures for accounting 
for missing, unused, and spurious data. This section is a summary of the planned statistical analyses 
of the primary and secondary outcome measures. The planned statistical analyses for 
pharmacokinetic and specific pharmacodynamic markers that will be utilized in dose selection will 
also be summarized.  Other biomarker exploratory analyses will be described in the SAP finalized 
before database lock. 
9.4.1 Analysis of the Primary Outcome Measures 
9.4.1.1 
Dose Escalation 
During dose escalation, DLTs will be tabulated for evaluable subjects by dose level within each 
schedule. For single subject cohorts, qualifying ≥ Grade 2 toxicities that trigger a change to at least 
3 subject cohorts will also be tabulated. Frequency tables will be used to describe safety and 
tolerability parameters such as: AEs, irAEs, SAEs, fatal SAEs and irAEs leading to discontinuation 
of SL-279252. Tables will be presented for the whole population, and within each dose level 
separately. Changes in safety assessments (e.g., laboratory parameters, etc.) will also be 
summarized using descriptive statistics. These will also be presented for the whole population, and 


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within each dose level separately. Graphs may also be presented where appropriate. The All 
Treated population will be used for these analyses. 
The MAD will be reported, or the MTD will be estimated using isotonic regression (based on the 
DLTs observed in evaluable subjects). A MAD will be reported if a schedule is fully evaluated, 
but the DLT rate never reaches the target range of 25-33.3%.  Otherwise, an MTD will be reported.  
Isotonic regression is a way to estimate the MTD under the assumption that toxicity increases with 
dose. Specifically, the MTD is selected as the dose for which the isotonic estimate of the DLT rate 
is closest to the target DLT rate of 0.3. If there are ties, we select the highest dose level when the 
isotonic estimate is lower than the target DLT rate; and we select the lowest dose level when the 
isotonic estimate is greater than the target DLT rate. When using isotonic regression, the first step 
is to identify the doses where the dose-toxicity monotonicity assumption is violated. The DLT 
estimate is then adjusted for the violators such that the final estimate of the DLT rate increases 
with the dose. The target DLT rate is then used to select the MTD. For example, suppose that when 
the trial is completed, the observed DLT rates [# subjects who experienced DLT]/[# evaluable 
subjects] at five dose levels are (0/3, 1/3, 0/3, 4/15, 2/4). In this example the observed DLT rate at 
Dose Level 2 (i.e., 1/3=33%) is higher than the observed DLT rate at Dose Level 3 (i.e., 0/3=0%). 
To adjust for this violation, the DLT estimates are replaced with their average, i.e., 
(1/3+0/3)/2=1/6, resulting in the isotonic regression DLT estimates (0/3, 1/6, 1/6, 4/15, 2/4) = (0%, 
16.7%, 16.7%, 26.7%, 50%), which monotonically increases with the dose level. Based on this 
isotonic estimate, assuming that the trial goal is to find the dose with the DLT rate of 30%, Dose 
Level 4 will be selected as the MTD. If there are no violators of the dose-toxicity monotonicity 
assumption, isotonic regression directly uses the observed DLT rates as the final estimates for 
MTD selection. The Evaluable for Dose Escalation population will be used for these analyses. 
NOTE: for subjects who undergo intra-subject dose escalation, only DLTs that occur during the 
DLT period on the subject’s initial dose will be used for MTD determination.  
9.4.1.2 
Dose Expansion  
During dose expansion, frequency tables will be used to describe safety and tolerability parameters 
such as: AEs, irAEs, SAEs, fatal SAEs and irAEs leading to discontinuation of SL-279252. 
Summaries will be presented within each cohort separately. Changes in safety assessments (e.g., 
laboratory parameters etc.) will also be summarized using descriptive statistics. These will also be 
presented within each cohort separately. Graphs may also be presented where appropriate. The All 
Treated population will be used for these analyses. 
Continuous toxicity monitoring will be used to specifically monitor IRRs and toxicities leading to 
discontinuation of SL-279252 as described in Section 9.2.2. 
9.4.2 Analysis of the Secondary Outcome Measures 
ORR and CBR will be estimated and reported along with exact 95% confidence intervals.  Efficacy 
will be evaluated within each expansion cohort separately. Efficacy will be summarized by dose 
level during dose escalation and will be summarized across dose levels and across the study as a 
whole as appropriate. iRECIST will be the disease assessment tool for solid tumors and RECIL 
2017 will be the disease assessment tool for lymphoma.  


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The RP2D will be selected after review of all the data collected during dose escalation and 
expansion and will take safety (including delayed toxicities that do not occur during the DLT 
period), pharmacodynamics and efficacy into account. The RP2D will not exceed the MTD or 
MAD. 
9.4.3 Exploratory Analyses 
Descriptive statistics will be used to summarize changes from baseline in plasma cytokine levels, 
cell counts and percentages of circulating immune cells. Complement activation by assessment of 
SC5b-9 terminal fragment and immune cell activation state will also be evaluated. During dose 
escalation and expansion, receptor occupancy (free and total) of SL-279252 on PD-L1 and OX40 
will be measured by flow cytometry and will be assessed within each dose level separately. During 
dose expansion, cfNA samples will be evaluated for analysis for TMB and exome sequencing.  
Associations between biomarkers and efficacy outcomes may be explored as appropriate. 
If paired biopsies are collected in subjects from the dose escalation or expansion cohorts, they will 
be evaluated for changes in the TME pre-and post-treatment. Additional details will be provided 
in the SAP. 
Each subject will be followed for progression-free survival and overall survival, and this 
information will be presented graphically using swimmer plots or Kaplan-Meier plots. If 
appropriate, TTR, DOR, progression-free survival and overall survival may also be summarized 
using the Kaplan-Meier method, with medians reported along with 95% confidence intervals. 
9.5 
Pharmacokinetic Analyses 
9.5.1 Pharmacokinetic Populations 
The PK population is defined as all subjects in the All Treated population who received at least 
one dose of SL-279252 and have at least one evaluable post-dose PK sample collected.  
All PK analyses and reporting will be performed according to applicable Standard Operating 
Procedures and protocol specifications. Programming of tables, figures, and listings will be 
performed using R version 3.4.0 or later (R Foundation for Statistical Computing, Vienna, 
Austria). PK parameters will be calculated using Phoenix® WinNonlin® 6.3 or later software 
(
) using actual sampling times. If actual sampling times are not 
available, nominal sampling times will be used.   
Individual serum concentrations will be listed by nominal times. Summaries of serum 
concentration data will include data for all subjects who receive at least one dose of SL-279252 
and have at least one evaluable serum sample. Table summaries of serum concentrations will be 
displayed versus nominal times. Figures of individual subject drug concentrations versus actual 
sampling times will be presented on linear and semi-logarithmic scales by dose and schedule, as 
appropriate. Figures of summarized drug concentrations versus nominal sampling times will be 
presented on linear and semi-logarithmic scales by dose, as appropriate. PK parameters for SL-
279252 will be calculated as described in Table 20. Additional parameters may be calculated as 
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PK parameters will be calculated using non-compartmental methods for subjects with sufficient 
data to estimate the parameters. PK parameters will be listed for each individual subject and 
summarized by cohort, dose and schedule, as appropriate. The following descriptive statistics will 
be provided: n (number of subjects with non-missing data), arithmetic mean (mean), standard 
deviation, standard error, arithmetic coefficient of variation (CV%), median, minimum, and 
maximum.  Geometric mean (geomean), geometric mean CV%, lower 95% confidence interval 
around the geometric mean (95% confidence interval lower geomean), and upper 95% confidence 
interval around the geometric mean (95% confidence interval upper geomean) will be calculated.  
Tmax and Tlast will be presented as median, minimum and maximum. 
9.5.2 Exploratory Exposure-Response Analyses 
Exploratory exposure-response and exposure-safety relationships may be performed by various 
methods that may include population PK/pharmacodynamic analysis.  Exposure-response analysis 
may be explored by evaluating potential relationships between exposure and efficacy and/or safety 
parameters such as incidence of ADA and AEs, receptor occupancy, cytokines, lymphocytes, and 
response rates. 
9.6 
Anti-Drug Antibody Analysis 
Individual subject ADA titer and status (positive, negative, inconclusive) vs. nominal time will be 
reported and summarized by dose level during dose escalation and during dose expansion.  Onset 
and duration of ADA by subject, characterization of subjects as having a persistent or transient 
ADA response will also be summarized by dose level during dose escalation and dose expansion.  
ADA isotype may be reported, if supported by the data. Descriptive statistics, including 95% 
confidence intervals where appropriate, will be reported for each endpoint.  
10. 
CLINICAL MONITORING 
 
Clinical site monitoring is conducted to ensure that the rights and well-being of human subjects 
are protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct 
of the trial complies with the currently approved protocol/amendment(s), with GCP, and with 
applicable regulatory requirement(s).  
• Monitoring for this study will be performed by Sponsor or its designees  
• Details of clinical site monitoring are documented in a Clinical Monitoring Plan (CMP). 
The CMP describes in detail who will conduct the monitoring, at what frequency 
monitoring will be done, at what level of detail monitoring will be performed, and the 
distribution of monitoring reports.  
• Independent audits will be conducted by the Sponsor or designee of the Sponsor to ensure 
GCP and monitoring practices are performed consistently across all participating sites and 
that monitors are following the CMP.  


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11. 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA AND DOCUMENTS 
11.1 
Source Data 
Source documents are where data are first recorded, and from which subjects’ eCRF data are 
obtained. These include, but are not limited to, hospital records (from which medical history and 
previous and concurrent medication may be summarised into the eCRF), clinical and office charts, 
laboratory and pharmacy records, diaries, microfiches, radiographs, and correspondence. 
11.2 
Access to Data 
The study monitor, other authorized representatives of the Sponsor, representatives of the IRB/IEC 
or regulatory authorities may inspect all documents and records required to be maintained by the 
investigator, including but not limited to, medical records (office, clinic, or hospital) and pharmacy 
records for the participants in this study. The clinical study site will permit access to such records 
to permit trial-related monitoring, audits and inspections.  
The study subject’s contact information will be securely stored at each clinical site for internal 
use during the study. At the end of the study, all records will continue to be kept in a secure 
location for as long a period as dictated by local IRB/IEC and Institutional regulations.  
Study subject research data, which is for purposes of statistical analysis and scientific reporting, 
will be transmitted to and stored by the Sponsor. This will not include the subject’s contact or 
identifying information. Rather, individual subject’s and their research data will be identified by 
a unique study identification number. The study data entry and study management systems used 
by clinical sites and by Sponsor research staff will be secured and password protected. At the 
end of the study, all study databases will be de-identified and archived by the Sponsor.  
11.3 
Data Recording and Record Keeping 
All trial data will be entered on electronic data entry systems that are validated and are maintained 
in accordance with Standard Operating Procedures. 
The subjects will be identified by a unique trial specific number and/or code in any database.  The 
name and any other identifying detail will NOT be included in any trial data electronic file. 
12. 
QUALITY ASSURANCE PROCEDURES 
The trial will be conducted in accordance with the current approved protocol, GCP, relevant 
regulations and standard operating procedures. 
Regular monitoring will be performed according to GCP. Data will be evaluated for compliance 
with the protocol, GCP, and accuracy in relation to source documents. Following written standard 
operating procedures, the monitors will verify that the conduct of the clinical trial and data 
generated, are documented and reported in compliance with the protocol, GCP and the applicable 
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13. 
ETHICS/PROTECTION OF HUMAN SUBJECTS 
13.1 
Ethical Standard 
The investigator will ensure that this study is conducted in full conformity with Regulations for 
the Protection of Human Subjects of Research codified in 45 Code of Federal Regulations (CFR) 
Part 46, 21 CFR Part 50, 21 CFR Part 56, and/or the ICH E6 or in compliance with the Declaration 
of Helsinki, CIOMS, International Ethical Guidelines for Biomedical Research Involving Human 
Subjects (2002), or ethical policy statement specific to the country, whichever provides the most 
protection to human subjects. 
13.2 
Institutional Review Board/Institutional Ethics Committee 
The protocol, informed consent form(s), recruitment materials, and all subject materials will be 
submitted to the IRB/IEC for review and approval. Approval of both the protocol and the consent 
form must be obtained before any subject is screened and enrolled. Any amendment to the protocol 
will require review and approval by the IRB/IEC before the changes are implemented to the study. 
All changes to the consent form will be IRB/IEC approved; a determination will be made regarding 
whether previously consented subjects need to be re-consented. 
13.3 
Informed Consent Process 
13.3.1 Consent/Assent and Other Informational Documents Provided to Subjects 
The investigator or his/her representative will explain the nature of the study to the subject or 
his/her legally authorized representative and answer all questions regarding the study. Subjects 
will be required to sign and date a study consent form prior to any study-related procedures are 
performed if they meet eligibility requirements of the protocol and wish to participate in the trial. 
If applicable, it will be provided in a certified translation of the local language.  
• Subjects must be informed that their participation is voluntary. Subjects  or their legally 
authorized representative [defined as an individual or judicial or other body authorized 
under applicable law to consent on behalf of a prospective subject to the subject's 
participation in the procedure(s) involved in the research] will be required to sign a 
statement of informed consent that meets the requirements of 21 CFR 50, local regulations, 
ICH guidelines, Health Insurance Portability and Accountability Act requirements, where 
applicable, and the IRB/IEC or study center. 
• The medical record must include a statement that written informed consent was obtained 
before the subject was enrolled in the study and the date the written consent was obtained. 
The authorized person obtaining the informed consent must also sign the ICF. 
• Subjects must be re-consented to the most current version of the ICF(s) during their 
participation in the study. 
• A copy of the ICF(s) must be provided to the subject or the subject’s legally authorized 
representative. 
• Subjects who are rescreened are required to sign a new ICF. 
The ICF will contain a separate section for optional exploratory research. The investigator or 
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Subjects will be informed that they are free to refuse to participate and may withdraw their consent 
at any time and for any reason during the study period. Subjects who decline to participate in this 
optional research will not provide this separate signature. 
13.3.2 Consent Procedures and Documentation 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. Extensive discussion of risks 
and possible benefits of participation will be provided to the participants and their families. 
Consent forms will be IRB/IEC approved and the participant and/or the legally authorized 
representative will be asked to read and review the document. The investigator and/or his/her 
authorized designee will explain the research study to the participant and answer any questions 
that may arise. All participants will receive a verbal explanation in terms suited to their 
comprehension of the purposes, procedures, and potential risks of the study and of their rights as 
research participants. Participants will have the opportunity to carefully review the written consent 
form and ask questions prior to signing. The participants should have the opportunity to discuss 
the study with their surrogates or think about it prior to agreeing to participate. The participant will 
sign and date the informed consent document prior to any procedures being done specifically for 
the study. The participants may withdraw consent at any time throughout the course of the trial. A 
copy of the informed consent document will be given to the participants for their records. The 
rights and welfare of the participants will be protected by emphasizing to them that the quality of 
their medical care will not be adversely affected if they decline to participate in this study. 
13.4 
Participant and Data Confidentiality  
Participant confidentiality is strictly held in trust by the participating investigators, their staff, and 
the Sponsor(s) and their agents. This confidentiality is extended to cover testing of biological 
samples in addition to the clinical information relating to participants. Therefore, the study 
protocol, study documentation, data, and all other study-related information generated will be held 
in strict confidence. No information concerning the study, or the data will be released to any 
unauthorized third party without prior written approval of the Sponsor.   
The study monitor, auditors, other authorized representatives of the Sponsor including the contract 
research organization (CRO), if applicable, representatives of the IRB/IEC or the Sponsor 
supplying study product, the Federal government or its designee and applicable regulatory 
authorities will be granted direct access to the study participants’ original medical records 
(including but not limited to office, clinic, hospital, or pharmacy records), all documents required 
to be maintained by the investigator, for verification of clinical trial procedures and/or data, 
without violating the confidentiality of the participants, to the extent permitted by the law and 
regulations.   
All documents will be stored safely in a secure location to protect confidentiality. On all trial-
specific documents, other than the signed consent, the participant will be referred to by the trial 
participant identification number/code, not by name. At the end of the study, all records will 
continue to be kept in a secure location for as long a period as dictated by local IRB/IEC and 
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Study participant research data, which is for purposes of statistical analysis and scientific reporting, 
will be transmitted to and stored a Sponsor location. This will not include the participant’s contact 
or identifying information. Rather, individual participants and their research data will be identified 
by a unique study identification number. The study data entry and study management systems used 
by research staff at the clinical sites and by authorized representatives of the Sponsor will be 
secured and password protected. At the end of the study, all study databases will be de-identified 
and archived at a Sponsor location. 
13.4.1 Research Use of Stored Human Samples, Specimens, or Specimen Data  
• Intended Use: Samples and data collected under this protocol may be used to study the effects 
of the investigational drug on how one’s immune system reacts and how the body responds to 
this type of treatment in treating different types of cancers.  
• Storage: Access to stored samples will be limited to specified study personnel/vendor 
personnel. Samples will be identified by unique subject identification (ID) codes. Samples and 
data will be stored using subject ID assigned by the Sponsor and investigators.   
13.5 
Future Use of Stored Specimens 
Specimens collected for this study will be analysed and stored at the Sponsor Data Repository or 
Sponsor-approved vendor.  
During the conduct of the study, an individual subject can choose to withdraw consent to have 
biological specimens stored for future research. However, withdrawal of consent related to bio-
sample storage, will not be possible after the study is completed.  
14. 
DATA HANDLING AND RECORD KEEPING 
14.1 
Communication and Data Dissemination Plan 
During the study while subjects are receiving treatment with SL-279252, SMC meetings will be 
held to review relevant data with the investigators or delegates.  These meetings will be held once 
a month (or more frequently if required) during dose escalation to share safety data and 
communicate results of ongoing analyses. Available safety, PK, pharmacodynamic, and clinical 
outcome data for all subjects at the time of the scheduled SMC Meeting will be reviewed and 
summarized.  Attendees of SMC meetings will include but not be limited to clinical investigators 
(or designees), the Sponsor Medical Monitor and Statistician.  
The Sponsor will remain in constant contact with the clinical sites during the enrollment period to 
ensure that cohort enrollment during the dose escalation or dose expansion phases of this study are 
completed as per protocol.  Investigators will be informed about available openings for enrollment 
on the trial and will be asked to pre-screen subjects to determine their potential for eligibility to 
avoid over-enrollment. Enrollment will be offered to all sites and slots filled based on the Keyboard 
Design method.   
Dose escalation decisions will be made based on the DLTs observed at the current dose level with 
guidance provided by the Keyboard design as stated in the study protocol.  All dose escalation and 
dose expansion or safety decisions will be documented in writing with copies maintained at each 
site and the Trial Master File at the CRO.  


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14.1.1 Periodic Data Summaries for Investigators and Regulatory Agencies 
In addition to standard regulatory reporting requirements for serious AEs and annual reporting, the 
Sponsor will provide the following data summaries to Investigators and Regulatory Agencies: 
• 
During the conduct of the study, a summary of safety (SAE and AEs) will be provided 
every 6 months beginning with the date of the first subject enrolled.   
At the end of the dose escalation and dose expansion, an outline of the key findings, including 
overall safety (SAEs, AEs), tolerability, PK, pharmacodynamic activity and anti-tumor activity; 
and the justification for the dose and schedule to take forward to Phase 2 (RP2D). 
14.2 
Data Collection and Management Responsibilities 
An eCRF will be used to record all subject data specified by this protocol. The eCRF must be 
completed by designated and trained study personnel.  The eCRF will be electronically signed by 
the Principal Investigator or a Sub-investigator listed on the Form FDA 1572.  Data collection is 
the responsibility of the clinical trial staff at the site under the supervision of the site investigator. 
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported.  All source documents should be completed in a neat, legible manner to ensure 
accurate interpretation of data.  Source documents may include but are not limited to, study 
progress notes, e-mail correspondence, computer printouts, laboratory data, and drug 
accountability records.    
Data reported in the eCRF derived from source documents should be consistent with the source 
documents or the discrepancies should be explained and captured in a progress note and 
maintained in the subject’s official electronic study record.  
Clinical data (including but not limited to AEs, concomitant medications, and expected ARs data) 
and clinical laboratory data will be entered into the study database, a 21 CFR Part 11-compliant 
data capture system provided by the Sponsor. The data system includes password protection and 
internal quality checks, such as automatic range checks, to identify data that appear inconsistent, 
incomplete, or inaccurate. Clinical data will be entered into an electronic data capture system 
directly from the source documents.  
Study data will be entered into eCRFs at the study site.  Prior to database lock, programmed 
computer edit checks and manual checks will be performed to check for discrepancies and 
reasonableness of the data.  All issues resulting from the computer-generated checks are to be 
resolved as quickly as possible with clarification from study sites. 
14.3 
Study Records Retention 
The Sponsor follows US regulations and ICH guidelines in its retention policy. 
US IND regulations (21CFR 312.62c) require that records and documents pertaining to the conduct 
of this study and the distribution of investigational drug(s) including eCRFs, consent forms, 
laboratory test results, and medication inventory records be kept on file by the Principal 
Investigator for 2 years following the date a marketing application is approved for the drug for the 
indication for which it is being studied.  If no application is to be filed or if the application is not 


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approved for such indication, these records must be kept until 2 years after the investigation has 
been discontinued and regulatory authorities (i.e., FDA, Health Canada, European Medicines 
Agency, etc.) have been notified.  ICH guidelines indicate that study documents should be retained 
until at least 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 IP. If there is a country 
or institutional policy that specific records and documents be retained for a longer period than 
described above, the applicable sites must comply with those policies in addition to US and ICH 
policies.   
No study records should be destroyed without prior authorization from The Sponsor, the written 
consent of the Sponsor, if applicable. It is the responsibility of the Sponsor to inform the 
investigator when these documents no longer need to be retained. 
14.4 
Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol or GCP requirements.  
The noncompliance may be either on the part of the subject, the investigator, or the study site staff.  
As a result of deviations, corrective actions are to be developed by the site and implemented 
promptly.  
 
It is the responsibility of the site to use continuous vigilance to identify and report deviations by 
completing the Sponsor Protocol Deviation Form to the Sponsor Medical Monitor or designee as 
soon as protocol deviation is identified.  A completed copy of the Sponsor Protocol Deviation 
Form will be maintained in the regulatory file. All deviations must be addressed in study source 
documents, reported to Sponsor. Protocol deviations must be sent to the local IRB/IEC per their 
guidelines. The site Principal Investigator is responsible for ensuring all study staff understands 
the local IRB/IEC reporting guidelines and adhere to all related requirements and documentation. 
Further details about the handling of protocol deviations will be included in the study reference 
manual. 
14.5 
Publications and Data Sharing Policy 
The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a coordinating 
investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with the International Committee 
of Medical Journal Editors authorship requirements. 
15. 
LITERATURE REFERENCES 
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2015;8:9. 
Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory 
Hodgkin's lymphoma. N Engl J Med 2015;372:311-9. 


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Armand P, Shipp MA, Ribrag V, et al. Programmed Death-1 Blockade With Pembrolizumab in Patients 
With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure. J Clin Oncol 2016;34:3733-9. 
Boutros C, Tarhini A, Routier E, et al. Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and 
in combination. Nat Rev Clin Oncol 2016;13:473-86. 
Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of Immune-Related Adverse Events in Patients 
Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical 
Practice Guideline. J Clin Oncol 2018;36:1714-68. 
Brunnhoelzl D, Weed M, Trepet R, Wang J. Tumor Lysis Syndrome Following a Single Atezolizumab 
Infusion for Metastatic Urothelial Carcinoma Involving Both Upper and Lower Tract. Archives in Cancer 
Research 2017;05. 
Carbone DP, Reck M, Paz-Ares L, et al. First-Line Nivolumab in Stage IV or Recurrent Non–Small-Cell 
Lung Cancer. N Engl J Med 2017;376:2415-26. 
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised 
RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47. 
Evers R, Dallas S, Dickmann LJ, et al. Critical review of preclinical approaches to investigate cytochrome 
p450-mediated therapeutic protein drug-drug interactions and recommendations for best practices: a white 
paper. Drug Metab Dispos 2013;41:1598-609. 
Gao C, Engelhardt, J., Dito, G., Glick, S., Raymond, M., Gaudreau, M-C., et al. Optimizing anti-Ox40 
mediated immunotherapy: preclinical exploration of the relationship between antitumor activity and isotype 
choice, ligand blocking capacity, dose and schedule.  SITC Annual Meeting. National Harbor, MD: 
Conference Proceedings for the Society for Immunotherapy in Cancer; 2017:445-6 (Abstract P373). 
Grywalska E, Pasiarski M, Gozdz S, Rolinski J. Immune-checkpoint inhibitors for combating T-cell 
dysfunction in cancer. Onco Targets Ther 2018;11:6505-24. 
Haanen J, Carbonnel F, Robert C, et al. Management of toxicities from immunotherapy: ESMO Clinical 
Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017;28:iv119-iv42. 
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646-74. 
Hodi FS, Kluger H., Sznol. M, Carvajal, R., et al. Durable, long-term survival in previously treated patients 
with advanced (MEL) who received nivolumab (NIVO) monotherapy in a phase I trial. In: Proceedings of 
the 107th Annual Meeting of the American Association for Cancer Research; Apr 16-20; New Orleans, 
LA.; 2016:76(14 Suppl):Abstract nr CT001. 
Ivanova A, Qaqish BF, Schell MJ. Continuous toxicity monitoring in phase II trials in oncology. Biometrics 
2005;61:540-5. 
Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined Nivolumab and Ipilimumab or Monotherapy in 
Untreated Melanoma. N Engl J Med 2015a;373:23-34. 
Larkin J, Hodi FS, Wolchok JD. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated 
Melanoma. N Engl J Med 2015b;373:1270-1. 
Mahoney KM, Rennert PD, Freeman GJ. Combination cancer immunotherapy and new immunomodulatory 
targets. Nat Rev Drug Discov 2015;14:561-84. 
Marin-Acevedo JA, Dholaria B, Soyano AE, Knutson KL, Chumsri S, Lou Y. Next generation of immune 
checkpoint therapy in cancer: new developments and challenges. J Hematol Oncol 2018;11:39. 
Messenheimer DJ, Jensen SM, Afentoulis ME, et al. Timing of PD-1 Blockade Is Critical to Effective 
Combination Immunotherapy with Anti-OX40. Clin Cancer Res 2017;23:6165-77. 


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Muenst S, Laubli H, Soysal SD, Zippelius A, Tzankov A, Hoeller S. The immune system and cancer evasion 
strategies: therapeutic concepts. J Intern Med 2016;279:541-62. 
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the CAR T cell therapy tisagenlecleucel. J Hematol Oncol 2018;11:35. 
Postow MA, Callahan MK, Wolchok JD. Immune Checkpoint Blockade in Cancer Therapy. J Clin Oncol 
2015;33:1974-82. 
Puzanov I, Diab A, Abdallah K, et al. Managing toxicities associated with immune checkpoint inhibitors: 
consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management 
Working Group. J Immunother Cancer 2017;5:95. 
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2006;3:438-47. 
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Adoptive T Cell Therapy in Models of Pancreatic Cancer and Non-hodgkin Lymphoma. Front Immunol 
2018;9:1955. 
Roemer MG, Advani RH, Ligon AH, et al. PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin 
Lymphoma and Predict Outcome. J Clin Oncol 2016;34:2690-7. 
Rosello S, Blasco I, Garcia Fabregat L, Cervantes A, Jordan K. Management of infusion reactions to 
systemic anticancer therapy: ESMO Clinical Practice Guidelines. Ann Oncol 2017;28:iv100-iv18. 
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Schadendorf D, Hodi FS, Robert C, et al. Pooled Analysis of Long-Term Survival Data From Phase II and 
Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma. J Clin Oncol 2015;33:1889-94. 
Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity's roles in cancer 
suppression and promotion. Science 2011;331:1565-70. 
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Pharmacol Exp Ther 2014;351:709-17. 
Shrimali RK, Ahmad S, Verma V, et al. Concurrent PD-1 Blockade Negates the Effects of OX40 Agonist 
Antibody in Combination Immunotherapy through Inducing T-cell Apoptosis. Cancer Immunol Res 
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2018. 
Sturgill ER RW. TNFR Agonist: A Review of Current Biologics Targeting OX40, 4-1BB, CD27, and 
GITR. AJHO 2017;13:4-15. 
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with diffuse large B cell lymphoma and Richter syndrome. Ann Hematol 2006;85:183-4. 
Yan F, Mandrekar SJ, Yuan Y. Keyboard: A Novel Bayesian Toxicity Probability Interval Design for Phase 
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in lymphoma (RECIL 2017). Ann Oncol 2017;28:1436-47. 


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16. 
APPENDICES 
 
16.1 
ECOG Performance Status Criteria 
Grade 
Description 
0 
Normal activity. Fully active, able to carry on all pre-disease performance without restriction 
1 
Symptoms but ambulatory. Restricted in physically strenuous activity, but ambulatory and 
able to carry out work of a light or sedentary nature (e.g., light housework, office work) 
2 
In bed < 50% of the time. 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 
In bed > 50% of the time. Capable of only limited self-care, confined to bed or chair more 
than 50% of waking hours. 
4 
100% bedridden. Completely disabled. Cannot carry on any self-care. Totally confined to 
bed or chair. 
5 
Dead. 
Source: Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET et al. Toxicity and response criteria 
of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5 (6):649-55. 
 
 
 


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16.2 
Contraception Requirements 
Females or males of reproductive potential must agree to avoid becoming pregnant or avoid 
impregnating a partner, respectively. Female or males of reproductive potential are required to use 
adequate methods of birth control from the time of screening (i.e., at least 14 days prior to D1 of 
SL-279252) through at least 30 days after the last dose of SL-279252.  
  
Definition of Female of Childbearing Potential: 
A female subject who is not sterile due to surgery (i.e., from bilateral tubal ligation/occlusion, 
bilateral oophorectomy, bilateral salpingectomy or complete hysterectomy) or who does not have 
a congenital or acquired condition that prevents childbearing or who is not naturally post-
menopausal for at least 12 consecutive months.  
  
Definition of Female of Non-Reproductive Potential: 
Female subjects will be considered of non-reproductive potential if they:  
 
1. 
Are post-menopausal if defined as amenorrhoeic for 12 consecutive months without an 
alternative medical cause. In women < 45 years of age a high follicle stimulating hormone 
(FSH) level in the postmenopausal range may be used to confirm a postmenopausal state 
in women not using hormonal contraception or hormonal replacement therapy. In the 
absence of 12 consecutive months of amenorrhea, a single FSH measurement is 
insufficient; 
OR 
2. 
Have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or 
bilateral tubal ligation/occlusion, at least 6 weeks prior to screening; 
OR 
3. 
Have a congenital or acquired condition that prevents childbearing. 
 
Definition of Male of Non-Reproductive Potential: 
Male subjects will be considered of non-reproductive potential if they have azoospermia (whether 
due to having had a vasectomy or due to an underlying medical condition).   
 
Highly Effective Methods of Contraception (<1% failure rate): 
For contraception, subjects should comply with one of the following: 
 
1. Practice abstinence† from heterosexual activity;  
OR 
2. Use (or have their partner use) acceptable contraception during heterosexual activity.   
 
Acceptable methods of contraception are‡: 
 
• Single method (one of the following is acceptable): 
 intrauterine device  
 vasectomy of a female subject’s male partner  
 contraceptive rod implanted into the skin 
 
 


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• Combination Methods 
 
 Female Subjects: The following hormonal contraceptives may be used by 
female subjects and requires use of a male condom for the male partner: 
• oral contraceptive pill (estrogen/progestin pill or progestin-only pill) 
• contraceptive skin patch 
• vaginal contraceptive ring 
• subcutaneous contraceptive injection 
 
 Male Subjects: The following contraception methods may be used by female 
partners and requires use of a male condom for the male subject: 
• diaphragm with spermicide  
• cervical cap with spermicide (nulliparous women only)   
• contraceptive sponge (nulliparous women only) 
• hormonal 
contraceptives 
including 
oral 
contraceptive 
pill 
(estrogen/progestin-only pill), contraceptive skin patch, vaginal 
contraceptive ring, subcutaneous contraceptive injection  
 
†Abstinence (relative to heterosexual activity) can be used as the sole method of contraception if 
it is consistently employed as the subject’s preferred and usual lifestyle and if considered 
acceptable by local regulatory agencies and IRBs/Independent IECs.  Periodic abstinence (e.g., 
calendar, ovulation, sympto-thermal, post-ovulation methods) and withdrawal are not acceptable 
methods of contraception.  
 
‡If a contraceptive method listed above is restricted by local regulations/guidelines, then it does 
not qualify as an acceptable method of contraception for subjects participating at sites in this 
country/region. 
 
Subjects should be informed that taking the study medication may involve unknown risks to the 
fetus (unborn baby) if pregnancy were to occur during the study.  To participate in the study, 
subjects of childbearing potential must adhere to the contraception requirement (described above) 
from the time of screening and at least 14 days prior to D1 of SL-279252 through at least 30 days 
after the last dose of SL-279252.   
 
16.2.1 Pregnancy Status 
In the rare event that β-hCG is elevated as a tumor marker, pregnancy should be excluded. At 
minimum, this requires obstetrics evaluation, serial β-hCG measurements and ultrasound to 
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16.3.1.1 
Dose Escalation – Schedule 1 
See Section 3.2.4 for the dose levels to be evaluated in schedule 1.  
The first subject will be enrolled at Dose Level 1 in a single subject cohort. Single subject cohorts 
will be enrolled until: 
• The subject in a single subject cohort experiences ≥ Grade 2 toxicity (see Section 3.2.5) or 
a DLT OR 
• Dose Level 6 is reached without evidence of a DLT or other ≥ Grade 2 toxicity 
If a subject in a single subject cohort experiences ≥ Grade 2 toxicity or a DLT, 2 additional subjects 
will be added at that dose level (for a total of 3). Once a single subject cohort is expanded to 3, 
having a ≥ Grade 2 toxicity no longer guides dose escalation (only DLTs do) and subsequent 
cohorts will now include at least 3 subjects. NOTE: If a subject in a single subject cohort is not 
evaluable, an additional single subject cohort should be enrolled at the same dose level. More than 
1 subject may be enrolled in a cohort if additional subject(s) are available for dosing after 
consultation with the Sponsor. 
Once cohorts of at least 3 subjects begin enrollment (after expansion of a single subject cohort to 
3 or at Dose Level 6), the table in Section 16.3.1 will be used to guide dose escalation. 
• There will be a 3-day stagger between the first and second subjects enrolled at a given dose 
level. NOTE: This requirement may change based on emerging data as per the SMC. 
• The column corresponding to the total number of evaluable subjects treated at the current 
dose level should be used to make the appropriate decision (i.e., escalate, stay at the same 
dose, de-escalate or eliminate). 
• If a subject is not evaluable, a decision can still be made based on the total number of 
subjects who are evaluable at the current dose without enrolling an additional subject 
(unless all subjects in a cohort are not evaluable*). 
• More than 3 subjects may be enrolled in a cohort if additional subject(s) are available for 
dosing after consultation with the Sponsor.  
*NOTE: If all subjects in a cohort are not evaluable, an additional cohort should be enrolled at the 
same dose level. 
Dose escalation for schedule 1 may continue until: 
• The trial is stopped for safety OR 
• The maximum sample size of 42 subjects is reached OR 
• The maximum sample size has not been reached but 12 subjects have been enrolled at the 
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• The Sponsor, in consultation with the SMC, decides to stop enrollment in schedule 1 early 
(e.g., based on safety, pharmacodynamics) and begin enrollment in schedule 2 (see Section 
3.2.7)  
NOTE: The maximum sample size of 42 may be revised if additional dose levels are evaluated or 
if more additional subjects (i.e., subjects available for dosing beyond the number required in a 
cohort) are enrolled than anticipated. The Sponsor, in consultation with the SMC, may also elect 
to add subjects if additional safety data are needed to select a dose and schedule for the expansion 
cohorts. Six (6) subjects must be treated at a dose level to confirm safety and tolerability before a 
dose can be used in an expansion cohort. 
16.3.1.2 
Dose Escalation – Schedule 2 
See Section 3.2.4 for the dose levels to be evaluated if schedule 2 is opened. 
Subjects will be enrolled in cohorts of 3, with the table in Section 16.3.1 used to guide dose 
escalation. 
• There will be a 3-day stagger between the first and second subjects enrolled at a given dose 
level. NOTE: This requirement may change based on emerging data as per the SMC. 
• The column corresponding to the total number of evaluable subjects treated at the current 
dose level should be used to make the appropriate decision (i.e., escalate, stay at the same 
dose, de-escalate or eliminate). 
• If a subject is not evaluable, a decision can still be made based on the total number of 
subjects who are evaluable at the current dose without enrolling an additional subject 
(unless all subjects in a cohort are not evaluable*). 
More than 3 subjects may be enrolled in a cohort if additional subject(s) are available for 
dosing after consultation with the Sponsor.  
*NOTE: If all subjects in a cohort are not evaluable, an additional cohort should be enrolled at the 
same dose level. 
Dose escalation for schedule 2 may continue until: 
• The trial is stopped for safety OR 
• The maximum sample size of 15 subjects is reached OR 
• The maximum sample size has not been reached but 12 subjects have been enrolled at the 
current dose level OR 
• The Sponsor, in consultation with the SMC, decides to stop enrollment in schedule 2 early 
(based on safety.) and resume enrollment in schedule 1 or begin enrollment in dose 
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*At least 6 subjects will be enrolled at the dose level to be used during dose expansion and 
sufficient safety follow-up completed to confirm safety and tolerability (as determined by the 
SMC) before a decision can be made to begin dose expansion early.  
NOTE: The maximum sample size of 15 may be revised if additional dose levels are evaluated or 
if more additional subjects (i.e., subjects available for dosing beyond the number required in a 
cohort) are enrolled than anticipated. The Sponsor, in consultation with the SMC, may also elect 
to add subjects if additional safety data are needed to select a dose and schedule for the expansion 
cohorts.  
16.3.1.3 
Keyboard Design Scenarios – Schedule 1 
Scenario #1: 
 
 
NOTE: All subjects in Scenario #1 are evaluable.  
1. Subject #1 is enrolled at Dose Level 1 in a single subject cohort. Subject #1 does not 
experience a DLT or a ≥ Grade 2 toxicity, so dose escalation is allowed and Subject #2 is 
enrolled at Dose Level 2 in a single subject cohort. 
2. Subject #2 does not experience a DLT or a ≥ Grade 2 toxicity, so dose escalation is allowed 
and Subject #3 is enrolled at Dose Level 3 in a single subject cohort. 
3. Subject #3 experiences a ≥ Grade 2 toxicity, so 2 additional subjects (Subjects #4 and #5) 
are enrolled at Dose Level 3. NOTE: Having a ≥ Grade 2 toxicity no longer guides dose 
escalation (only DLTs do) and subsequent cohorts will now include at least 3 subjects. 


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4. Zero (0) of the 3 total subjects enrolled at Dose Level 3 experience a DLT, so following 
the table in Section 16.3.1, dose escalation is allowed and the next 3 subjects (Subjects #6, 
#7 and #8) are enrolled at Dose Level 4. 
5. Zero (0) of the 3 subjects enrolled at Dose Level 4 experience a DLT, so following the 
table in Section 16.3.1, dose escalation is allowed and the next 3 subjects (Subjects #9, #10 
and #11) are enrolled at Dose Level 5. 
6. One (1) of the 3 subjects enrolled at Dose Level 5 experience a DLT, so following the table 
in Section 16.3.1 , the next 3 subjects (Subjects #12, #13 and #14) are also enrolled at Dose 
Level 5. 
7. Only 1 of the 6 total subjects enrolled at Dose Level 5 experience a DLT, so following the 
table in Section 16.3.1, dose escalation is allowed and the next 3 subjects (Subjects #15, 
#16 and #17) are enrolled at Dose Level 6. 
8. Two (2) of the 3 subjects enrolled at Dose Level 6 experience a DLT, so following the 
table in Section 16.3.1, de-escalation is required and the next 3 subjects (Subjects #18, #19 
and #20) are enrolled at Dose Level 5. 
9. Two (2) of the 9 total subjects enrolled at Dose Level 5 experience a DLT, so following 
the table in Section 16.3.1, dose escalation is allowed and the next 3 subjects (Subjects #21, 
#22 and #23) are enrolled at Dose Level 6. 
10. Three (3) of the 6 total subjects enrolled at Dose Level 6 experience a DLT, so following 
the table in Section 16.3.1, de-escalation is required and the next 3 subjects (Subjects #24, 
#25 and #26) are enrolled at Dose Level 5. 
11. The maximum sample size of 42 subjects has not been reached, but 12 subjects have now 
been enrolled at Dose Level 5, so dose escalation can stop early and the MTD can be 
determined based on the 26 subjects enrolled. 
 
 


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Scenario #2:  
 
 
 
NOTE: All subjects in Scenario #2 are evaluable.  
1. Subject #1 is enrolled at Dose Level 1 in a single subject cohort. Subject #1 does not 
experience a DLT or a ≥ Grade 2 toxicity, so dose escalation is allowed and Subject #2 is 
enrolled at Dose Level 2 in a single subject cohort. 
2. Subject #2 does not experience a DLT or a ≥ Grade 2 toxicity, so dose escalation is allowed 
and Subject #3 is enrolled at Dose Level 3 in a single subject cohort. 
3. Subject #3 does not experience a DLT or a ≥ Grade 2 toxicity, so dose escalation is allowed 
and Subject #4 is enrolled at Dose Level 4 in a single subject cohort. 
4. Subject #4 experiences a ≥ Grade 2 toxicity, so 2 additional subjects (Subjects #5 and #6) 
are enrolled at Dose Level 4. NOTE: Having a ≥ Grade 2 toxicity no longer guides dose 
escalation (only DLTs do) and subsequent cohorts will now include at least 3 subjects. 
5. One (1) of the 3 total subjects enrolled at Dose Level 4 experience a DLT (NOTE: the 
≥ Grade 2 toxicity is not used for the dose escalation decision), so following the table in 
Section 16.3.1, the next 3 subjects (Subjects #7, #8 and #9) are also enrolled at Dose 
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6. Only 1 of the 6 total subjects enrolled at Dose Level 4 experience a DLT, so following the 
table in Section 16.3.1, dose escalation is allowed and the next 3 subjects (Subjects #10, 
#11 and #12) are enrolled in Dose Level 5. 
7. One (1) of the 3 subjects enrolled at Dose Level 5 experience a DLT, so following the table 
in Section 16.3.1, the next 3 subjects (Subjects #13, #14 and #15) are also enrolled at Dose 
Level 5. 
8. Only 1 of the 6 total subjects enrolled at Dose Level 5 experience a DLT, so following the 
table in Section 16.3.1, dose escalation is allowed and the next 3 subjects (Subjects #16, 
#17 and #18) are enrolled at Dose Level 6. 
9. Zero (0) of the 3 subjects enrolled at Dose Level 6 experience a DLT, so following the 
table in Section 16.3.1, dose escalation is allowed and the next 3 subjects (Subjects #19, 
#20 and #21) are enrolled at Dose Level 7. 
10. One (1) of the 3 subjects enrolled at Dose Level 7 experience a DLT, so following the table 
in Section 16.3.1, the next 3 subjects (Subjects #22, #23 and #24) are also enrolled at Dose 
Level 7. 
11. Two (2) of the 6 total subjects enrolled at Dose Level 7 experience a DLT, so following 
the table in Section 16.3.1, the next 3 subjects (Subjects #25, #26 and #27) are also enrolled 
at Dose Level 7. 
12. Only 2 of the 9 total subjects enrolled at Dose Level 7 experience a DLT, so following the 
table in Section 16.3.1, dose escalation is allowed and the next 3 subjects (Subjects #28, 
#29 and #30) are enrolled at Dose Level 8. 
13. One (1) of the 3 subjects enrolled at Dose Level 8 experience a DLT, so following the table 
in Section 16.3.1, the next 3 subjects (Subjects #31, #32 and #33) are also enrolled at Dose 
Level 8. 
14. Only 1 of the 6 total subjects enrolled at Dose Level 8 experience a DLT, so following the 
table in Section 16.3.1, dose escalation is allowed and the next 3 subjects (Subjects #34, 
#35 and #36) are enrolled at Dose Level 9. 
15. Zero (0) of the 3 subjects enrolled at Dose Level 9 experience a DLT, so following the 
table in Section 16.3.1, dose escalation is allowed and the next 3 subjects (Subjects #37, 
#38 and #39) are enrolled at Dose Level 10. 
16. Zero (0) of the 3 subjects enrolled at Dose Level 10 experience a DLT, so following the 
table in Section 16.3.1, dose escalation is allowed. However, Dose Level 10 is the highest 
dose level to be evaluated, so the next 3 subjects (Subjects #40, #41 and #42) are also 
enrolled at Dose Level 10. This ends dose escalation since the maximum sample size is 48 
subjects. 
17. The MTD is determined based on the 48 subjects enrolled. 
 
 


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Scenario #3: 
 
 
1. Subject #1 is enrolled at Dose Level 1 in a single subject cohort. Subject #1 does not 
experience a DLT or a ≥ Grade 2 toxicity, so dose escalation is allowed and Subject #2 is 
enrolled at Dose Level 2 in a single subject cohort. 
2. Subject #2 does not experience a DLT or a ≥ Grade 2 toxicity, so dose escalation is allowed 
and Subject #3 is enrolled at Dose Level 3 in a single subject cohort. 
3. Subject #3 does not experience a DLT or a ≥ Grade 2 toxicity, so dose escalation is allowed 
and Subject #4 is enrolled at Dose Level 4 in a single subject cohort. 
4. Subject #4 does not experience a DLT or a ≥ Grade 2 toxicity, so dose escalation is allowed 
and Subject #5 is enrolled at Dose Level 5 in a single subject cohort. 
5. Subject #5 does not experience a DLT or a ≥ Grade 2 toxicity, so dose escalation is allowed 
and the next 3 subjects (Subjects #6, #7 and #8) are enrolled at Dose Level 6. NOTE: 3 
subjects are enrolled since single subject cohorts are only allowed for the first 5 dose levels 
(all subsequent cohorts will enroll at least 3 subjects); Having a ≥ Grade 2 toxicity no 
longer guides dose escalation (only DLTs do). 
6. One (1) subject enrolled at Dose Level 6 is not evaluable and 0 of the other 2 subjects 
enrolled at Dose Level 6 experience a DLT. Following the table in Section 16.3.1 (looking 
at the column for 2 evaluable subjects treated at the current dose), dose escalation is 
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7. One (1) of the 3 subjects enrolled at Dose Level 7 experience a DLT, so following the table 
in Section 16.3.1, the next 3 subjects (Subjects #12, #13 and #14) are also enrolled at Dose 
Level 7. 
8. Of the 6 total subjects enrolled at Dose Level 7, 1 subject is not evaluable and only 1 of the 
other 5 subjects experience a DLT. Following the table in Section 16.3.1 (looking at the 
column for 5 evaluable subjects treated at the current dose), dose escalation is allowed and 
the next 3 subjects (Subjects #15, #16 and #17) are enrolled at Dose Level 8. 
9. Two (2) of the 3 subjects enrolled at Dose Level 8 experience a DLT, so following the 
table in Section 16.3.1, de-escalation is required and the next 3 subjects (Subjects #18, #19 
and #20) are enrolled at Dose Level 7. An additional subject was available for treatment 
(Subject #21), so was included in the cohort as well (i.e., 4 subjects are enrolled at Dose 
Level 7). 
10. Of the 10 total subjects enrolled in Dose Level 7, 1 subject is not evaluable and only 1 of 
the other 9 subjects experience a DLT. Following the table in Section 16.3.1 (looking at 
the column for 9 evaluable subjects treated at the current dose), dose escalation is allowed 
and the next 3 subjects (Subjects #22, #23 and #24) are enrolled at Dose Level 8. 
11. Four (4) of the 6 total subjects enrolled at Dose Level 8 experience a DLT, so following 
the table in Section 16.3.1, Dose Level 8 is eliminated from the trial. This means that 
subjects will no longer be enrolled in Dose Level 8, 9 or 10. De-escalation is required and 
the next 3 subjects (Subjects #25, #26 and #27) are enrolled at Dose Level 7. 
12. The maximum sample size of 42 subjects has not been reached, but 12 subjects have now 
been enrolled at Dose Level 7, so dose escalation can stop early and the MTD can be 
determined based on the 27 subjects enrolled. 
 
 


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Scenario #4: 
 
 
1. Subject #1 is enrolled at Dose Level 1 in a single subject cohort. Subject #1 is not evaluable. 
Because the one subject enrolled at the dose level is not evaluable, another subject (Subject 
#2), is enrolled at Dose Level 1 in a single subject cohort. 
2. Subject #2 does not experience a DLT or a ≥ Grade 2 toxicity, so dose escalation is allowed 
and Subject #3 is enrolled at Dose Level 2 in a single subject cohort. 
3. Subject #3 experiences a DLT, so 2 additional subjects (Subjects #4 and #5) are enrolled 
at Dose Level 2. NOTE: Having a ≥ Grade 2 toxicity no longer guides dose escalation 
(only DLTs do) and subsequent cohorts will now include at least 3 subjects. 
4. Two (2) of the 3 total subjects enrolled at Dose Level 2 experience a DLT, so following 
the table in Section 16.3.1, de-escalation is required and the next 3 subjects (Subjects #6, 
#7 and #8) are enrolled at Dose Level 1. 
5. Of the 5 total subjects enrolled at Dose Level 1, 2 subjects are not evaluable and 0 of the 
other 3 subjects experience a DLT. Following the table in Section 16.3.1 (looking at the 
column for 3 evaluable subjects treated at the current dose), dose escalation is allowed and 
the next 3 subjects (Subjects #9, #10 and #11) are enrolled at Dose Level 2. 
6. Two (2) of the 6 total subjects enrolled at Dose Level 2 experience a DLT, so following 
the table in Section 16.3.1, the next 3 subjects (Subjects #12, #13 and #14) are also enrolled 
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7. Of the 9 total subjects enrolled at Dose Level 2, 1 subject is not evaluable and 3 of the other 
8 subjects experience a DLT. Following the table in Section 16.3.1 (looking at the column 
for 8 evaluable subjects treated at the current dose), de-escalation is required and the next 
3 subjects (Subjects #15, #16 and #17) are enrolled at Dose Level 1. 
8. Of the 8 total subjects enrolled at Dose Level 1, 2 subjects are not evaluable and 3 of the 
other 6 subjects experience a DLT. Following the table in Section 16.3.1 (looking at the 
column for 6 evaluable subjects treated at the current dose), de-escalation is required. 
However, since Dose Level 1 is the lowest dose level, and since the boundary for 
elimination has not been reached, the next 3 subjects (Subjects #18, #19 and #20) are also 
enrolled at Dose Level 1. 
9. Of the 11 total subjects enrolled in Dose Level 1, 2 subjects are not evaluable and 5 of the 
other 9 subjects experience a DLT. Following the table in Section 16.3.1 (looking at the 
column for 9 evaluable subjects treated at the current dose), Dose Level 1 is eliminated 
from the trial. This means that subjects will no longer be enrolled in Dose Level 1. Since 
this is the lowest dose level, the trial is stopped for safety and no dose is selected as the 
MTD. 
 
16.3.1.4 
Keyboard Design Scenarios – Schedule 2 
If schedule 2 is opened, the table in Section 16.3.1 will be used for all dose escalation decisions 
and the same principles demonstrated in Scenarios #1-4 apply with the following exceptions: 
 
1. All cohorts will include at least 3 subjects (there are no single subject cohorts). 
2. Because there are no single subject cohorts, ≥ Grade 2 toxicities do not guide dose 
escalation. 
3. The maximum total sample size is 15 subjects. 
 
Reference:  
Yan F, Mandrekar SJ, and Yuan Y. Keyboard: A Novel Bayesian Toxicity Probability Interval 
Design for Phase I clinical trials. Clin Cancer Res. 2017;23(15):3994-4003. 
 
 


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16.4 
Deauville Criteria 
 
Score 
PET/CT scan result 
1 
 
No uptake 
2 
 
Uptake ≤ mediastinum 
3 
 
Uptake > mediastinum but ≤ liver 
4 
 
Uptake moderately higher than liver 
5 
 
Uptake markedly higher than liver and/or new lesions 
X 
 
New areas of uptake unlikely to be related to lymphoma 
Reference: Barrington SF, et al. Role of imaging in the staging and response assessment of lymphoma: consensus of 
the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol. 2014;32(27):3048-
3058. 
 
 


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16.5 
Cockcroft-Gault Formula for Creatinine Clearance 
 
Creatinine clearance (mL/min)1 =  Q x (140 – age [yr]) x ideal body weight [kg]2 
 
 
 
 
 
72 x serum creatinine [mg/dL] 
Q = 0.85 for females 
Q = 1.0 for males 
 
OR 
 
Creatinine clearance (mL/min)2 =  K x (140 – age [yr]) x ideal body weight [kg]1 
 
 
 
 
 
serum creatinine [µmol/L] 
K = 1.0 for females 
K = 1.23 for males 
 
1. Creatinine clearance has a maximum value of 125 mL/min.  
2. Use ideal body weight (IBW) if body weight > 30% of IBW. Otherwise, use bodyweight 
 
 
Calculation of IBW using the Devine Formula [Devine, 1974]: 
 
Males = 50.0 kg + (2.3 x each inch over 5 ft) or 50.0 kg + (0.906 kg x each cm over 152.4 cm) 
Females = 45.5 kg + (2.3 x each inch over 5 ft) or 45.5 kg + (0.906 kg x each cm over 152.4 cm) 
 
Example: 
Male, actual body weight = 90.0 kg; height = 68 inches; IBW = 50 + (2.3) (68 – 60) = 68.4 kg 
This subject’s actual body weight is >30% over IBW. Therefore, in this case, the subject’s IBW of 68.4 kg should 
be used in calculating the estimated creatinine clearance 
 
Reference: 
Devine BJ. Case Number 25 Gentamicin Therapy: Clinical Pharmacy Case Studies. Drug Intell. Clin Pharm. 
1974;8:650-655. 
 
 
 


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16.6 
RECIST 1.1 and iRECIST Criteria 
16.6.1 RECIST 1.1 Criteria 
Measurable disease:  Measurable tumor lesions (nodal, subcutaneous, lung parenchyma, solid 
organ metastases) are defined as those that can be accurately measured in at least one dimension 
(longest diameter to be recorded) as ≥10 millimeter (mm) with CT scan or clinical examination.  
Bone lesions are considered measurable only if assessed by CT scan and have an identifiable soft 
tissue component that meets these requirements (soft tissue component ≥10 mm by CT scan). 
Malignant lymph nodes must be ≥15 mm in the short axis to be considered measurable; only the 
short axis will be measured and followed. All tumor measurements must be recorded in mm (or 
decimal fractions of cm). Previously irradiated lesions are not considered measurable unless 
progression has been documented in the lesion. 
Malignant lymph nodes:  pathological nodes must meet the criterion of a short axis of ≥15 mm by 
CT scan and only the short axis of these nodes will contribute to the baseline sum. All other 
pathological nodes (those with short axis ≥10 mm but <15 mm) should be considered non-target 
lesions. Nodes that have a short axis <10 mm are considered non-pathological and should not be 
recorded or followed. 
Non-measurable disease:  All other lesions (or sites of disease), including small lesions (longest 
diameter <10 mm [<1 cm] or pathological lymph nodes with ≥10 to <15 mm [≥1 to <1.5 cm] short 
axis), are considered non-measurable disease.  Bone lesions without a measurable soft tissue 
component, leptomeningeal disease, ascites, pleural/pericardial effusions, lymphangitis cutis, 
inflammatory breast disease, lymphangitic involvement of lung or skin, and abdominal masses 
followed by clinical exam are all non-measurable.  Lesions in previously irradiated areas are non-
measurable, unless progression has been demonstrated. 
Note:  Cystic lesions that meet the criteria for radiographically defined simple cysts should not be 
considered as malignant lesions (neither measurable nor non-measurable) since they are, by 
definition, simple cysts. 
‘Cystic lesions’ thought to represent cystic metastases can be considered as measurable lesions, if 
they meet the definition of measurability described above. However, if non-cystic lesions are 
present in the same participant, these are preferred for selection as target lesions. 
Target lesions:  When more than one measurable tumor lesion is present at baseline all lesions up 
to a maximum of 5 lesions in total (and a maximum of 2 lesions per organ), representative of all 
involved organs, should be identified as target lesions and recorded and measured at baseline.  
Target lesions should be selected on the basis of their size (lesions with the longest diameter), be 
representative of all involved organs, but in addition should be those that lend themselves to 
reproducible repeated measurements.  It may be the case that, on occasion, the largest lesion does 
not lend itself to reproducible measurement in which circumstance the next largest lesion which 
can be measured reproducibly should be selected.  A sum of the diameters (longest for non-nodal 
lesions, short axis for nodal lesions) for all target lesions will be calculated and reported as the 
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added into the sum.  At baseline, the sum of the target lesions (longest diameter of tumor lesions 
plus short axis of lymph nodes: overall maximum of 5) is to be recorded.   
After baseline, a value should be provided on the eCRF for all identified target lesions for each 
assessment, even if very small. If extremely small and faint lesions cannot be accurately measured 
but are deemed to be present, a default value of 5 mm may be used. If lesions are too small to 
measure and indeed are believed to be absent, a default value of 0 mm may be used. The baseline 
sum diameters will be used as reference to further characterize any objective tumor regression in 
the measurable dimension of the disease. 
Non-target lesions: All non-measurable lesions (or sites of disease) plus any measurable lesions 
over and above those listed as target lesions are considered non-target lesions and should also be 
recorded at baseline.  Measurements of these lesions are not required, but the presence, absence, 
or in rare cases unequivocal progression of each should be noted throughout follow-up.  
16.6.2 Evaluation of Response 
Complete Response (CR):  Disappearance of target and non-target lesions and normalization of 
tumor markers.  Pathological lymph nodes must have short axis measures <10 mm (Note: continue 
to record the measurement even if <10 mm and considered CR).  Residual lesions (other than 
nodes <10 mm) thought to be non-malignant should be further investigated (by cytology, 
specialized imaging or other techniques as appropriate for individual cases) before CR can be 
accepted.  Response should be confirmed in a subsequent scan ≥4 weeks after the scan showing 
CR. 
Partial Response (PR):  At least a 30% decrease in the sum of the measures (longest diameters 
for tumor lesions and short axis measure for nodes) of target lesions, taking as reference the 
baseline sum of diameters.  Non-target lesions must be non-progressive disease.  Response should 
be confirmed in a subsequent scan ≥4 weeks after the scan showing PR. 
Stable Disease (SD):  Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for progressive disease, taking as reference the smallest sum diameters while on study.  
Documented at least once ≥4 weeks from baseline. 
Progressive Disease (PD):  At least a 20% increase in the sum of diameters of measured lesions 
taking as references the smallest sum of diameters recorded on study (including baseline) AND an 
absolute increase of ≥5 mm. Appearance of new lesions will also constitute progressive disease 
(including lesions in previously unassessed areas). In exceptional circumstances, unequivocal 
progression of non-target disease may be accepted as evidence of disease progression, where the 
overall tumor burden has increased sufficiently to merit discontinuation of treatment or where the 
tumor burden appears to have increased by at least 73% in volume. Modest increases in the size 
of one or more non-target lesions are NOT considered unequivocal progression. If the evidence of 
progressive disease is equivocal (target or non-target), treatment may continue until the next 
assessment, but if confirmed, the earlier date must be used. 


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16.6.3 iRECIST 1.1 Criteria 
When using iRECIST, the definitions of measurable and non-measurable lesions still follow 
RECIST 1.1. The principles used to establish an objective tumor response when using iRECIST 
are largely unchanged from RECIST 1.1, however, responses assigned using iRECIST have a 
prefix of “i” (e.g., “immune” complete response [iCR]) to differentiate them from responses 
assigned using RECIST 1.1. 
The major change is the concept of resetting the bar if RECIST 1.1 progression is followed at the 
next assessment by tumor shrinkage. This adaptation accounts for instances where an increase in 
tumor burden, or the appearance of new lesions, does not reflect true tumor progression. Therefore, 
iRECIST requires confirmation of progression. 
Confirming Progression: iRECIST requires the confirmation of progression and uses the terms 
iUPD (unconfirmed progression) and iCPD (confirmed progression). Confirmatory scans should 
be performed at least 4 weeks after iUPD.  iCPD is confirmed if further increase in tumor burden, 
compared to the last assessment, is seen as evidenced by one or more of the following criteria: 
• Continued increase in tumor burden (from iUPD) where RECIST 1.1 definitions of 
progression had been met (from nadir) in target, non-target disease or new lesions. 
o Progression in target disease worsens with an increase of at least 5 mm in the 
absolute value of the sum 
o Continued unequivocal progression in non-target disease with an increase in tumor 
burden 
o Increase in size of previously identified new lesion (s) (an increase of at least 5 mm 
in the absolute value of the sum of those considered to be target new lesions) or 
additional new lesions 
 
• RECIST 1.1 criteria are met in lesions types (target or non-target or new lesions) where 
progression was not previously identified, including the appearance of additional new 
lesions. 
 
• If iUPD is not confirmed at the next assessment, then the appropriate response will be 
assigned (iUPD if the criteria are still met, but no worsening, or iSD, iPR or iCR if those 
criteria are met compared to baseline).  
 
 
New Lesions:  New lesions should be assessed and measured as they appear using RECIST 1.1 
criteria (maximum of 5 lesions, no more than 2 per site, at least 10 mm in long axis (or 15 mm in 
short axis for nodal lesions) and recorded as New Lesions-Target (NLT) and New Lesion-Non-
Target (NLNT) to allow clear differentiation from baseline target and non-target lesions.  
 
New lesions may either meet the criteria of NLT or NLNT to drive iUPD (or iCPD). However, the 
measurements of target lesions should NOT be included in the sum of measures of original target 
lesions identified at baseline. Rather, these measurements will be collected on a separate table in 
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Progressive disease is confirmed in the New Lesion category if the next imaging assessment, 
conducted at least 4 weeks (but not more than 8 weeks) after iUPD confirms further progression 
from iUPD with either an increase of at least 5 mm in the absolute value of the sum of NLT OR 
an increase (but not necessarily unequivocal increase) in the size of NLNT lesions OR the 
appearance of additional new lesions. 
 
iRECIST Time Point Response Table 
Target Lesions 
Non-Target 
Lesions 
New Lesions 
Time Point Response (TPR) 
No prior 
iUPD 
Prior iUPD 
iCR 
iCR 
No 
iCR 
iCR 
iCR 
Non-iCR/Non-
iUPD 
No 
iPR 
iPR 
iPR 
Non-iCR/Non-
iUPD 
No 
iPR 
iPR 
iSD 
Non-iCR/Non-
iUPD 
No 
iSD 
iSD 
iUPD with no 
change OR 
decrease from 
last TP 
iUPD with no 
change OR 
decrease from 
last TP 
Yes 
NA 
NLs confirms iCPD if NL were previously 
identified and increase in size (≥5 mm in 
SOM for NLT or any increase for NLNT) 
or number.  If no change in NLs (size or 
number) from last TP, remains iUPD 
iSD 
iUPD 
No 
iUPD 
Remains iUPD unless iCPD confirmed 
based in further increase in size of NT 
disease (need not meet RECIST 1.1 
criteria for unequivocal PD) 
iUPD 
iUPD 
No 
iUPD 
Remains iUPD unless iCPD confirmed 
based on: further increase in SOM of at 
least 5 mm, otherwise remains iUPD 
iUPD 
iUPD 
No 
iUPD 
Remains iUPD unless iCPD confirmed 
based on further increase in: previously 
identified T lesion iUPD SOM ≥5 mm 
and/or NT lesion iUPD (prior assessment 
need not be unequivocal PD) 


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Target Lesions 
Non-Target 
Lesions 
New Lesions 
Time Point Response (TPR) 
No prior 
iUPD 
Prior iUPD 
iUPD 
iUPD 
Yes 
iUPD 
Remains iUPD unless iCPD confirmed 
based on further increase in:  
• previously identified T lesion iUPD 
SOM ≥5 mm and/ 
• previously identified NT lesion iUPD 
(prior assessment need not be 
unequivocal PD) 
• size or number of new lesions previously 
identified 
Non-iUPD/PD 
Non-iUPD/PD 
Yes 
iUPD 
Remains iUPD unless iCPD confirmed 
based on:  
• 
increase in size or number of new 
lesions previously identified 
* Using RECIST 1.1 principles. If no pseudo-progression of disease (PSPD) occurs, RECIST 1.1 and iRECIST 
categories for CR, PR and SD would be the same. ** in any lesion category. *** previously identified in 
assessment immediately prior to this TP. 
PD = progressive disease; SOM = sum of measurements 
Note:  Participants with a global deterioration of health status requiring discontinuation of treatment without 
objective evidence of disease progression at that time should be reported as “symptomatic deterioration.”  
Every effort should be made to document the objective progression even after discontinuation of 
treatment. 
 
 
 


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16.7 
RECIL  
Target Lesions: Target lesions should be selected from those with the largest size that can be 
reproducibly measured and should preferably represent multiple sites or organs. In most cases, 
lymph nodes can be considered target lesions if the lymph node’s longest diameter is ≥ 15 mm.  
Extra-nodal lesions are selected as target lesions if they have a soft tissue component, based on 
their size, and the ease of reproducibility of repeated measurements, with a minimum measurement 
of the longest diameter of ≥ 15 mm. 
Non-target Lesions:  All other lesions including measurable lesions over and above the 3 target 
lesions should be identified as non-target lesions and should be recorded at baseline without the 
need to measure them.  In certain anatomical sites (inguinal, axillary, and portocaval), normal 
lymph nodes may exist in a narrow, elongated form, and such nodes should not be selected as 
target lesions if alternatives are available.   Non-target lesions should be reported as present, absent, 
or unequivocal progression. 
Bone marrow: A bone marrow biopsy would be performed as a part of staging.  In participants 
with positive FDG-PET uptake may obviate the need for a bone marrow biopsy.  Participants with 
HL without FDG update in the bone marrow or presence of B-symptoms do not need a bone 
marrow biopsy at baseline, as bone marrow biopsy in this situation is extremely unlikely to modify 
stage. 
16.7.1 Evaluation of Response 
Complete Response:  Complete disappearance of all target lesions by CT scan with complete 
normalization of FDG-PET (Deauville score 1–3 [see Appendix Section 16.4]) uptake in all areas 
and bone marrow biopsy negativity (if it was positive or unknown at baseline).  If pretreatment 
PET scan was negative, all lymph nodes that measure ≥ 15 mm in the long axis should regress to 
< 10 mm.  CR is also defined as achievement of a PR by CT scan (> 30% decrease in sum of 
longest diameters of target lesions) plus normalization of FDG-PET in FDG-avid lymphoma.   
Because many novel agents may alter glucose uptake and/or metabolism, normalizing FDG-PET 
imaging alone is not sufficient by itself to determine CR status unless accompanied with a 
significant decrease (>30%) decrease in the sum of diameters.  Accordingly, a reduction in the 
sum of diameters by ≤30% with normalization of FDG-PET uptake should not be considered a CR 
unless documented by a negative tissue biopsy.   
In cases where pretreatment baseline tumor burden is low, with only a few lesions measuring 
around 2 cm in longest diameter, treatment effect may shrink the long axis of a target lymph node 
to normal values of <10 mm.  However, even though the lymph node is now within normal size 
range, consistent with CR, the percentage of diameter reduction may be <30% (less than PR).   In 
these cases, a normalized diameter of “0 or resolved” should be used to calculate the sum of 
diameter, and therefore ensuring accurate response designation. 
Partial Response:  A ≥ 30% decrease in the sum of longest diameters of target lesions but not a 
CR, positive FDG-PET (Deauville score 4–5), any bone marrow involvement, no new lesions.  If 
one or more target lesions grew but the sum of the diameters remains ≤30% of the baseline 
measurement, and no new lesions appear, the response should be designated a PR.    


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Minor Response: ≥ 10% decrease in the sum of longest diameters of target lesions but not a partial 
response, any FDG-PET findings, any bone marrow involvement, no new lesions. 
Stable Disease: < 10% decrease or ≤ 20% increase in the sum of longest diameters of target 
lesions, any FDG-PET findings, any bone marrow involvement, no new lesions. 
Progressive Disease: > 20% increase in the sum of longest diameter of target lesions; for small 
lymph nodes of < 15 mm posttherapy, minimum absolute increase of 5 mm and long diameter 
> 15 mm; appearance of new lesion; any FDG-PET finding; any bone marrow involvement; new 
or no new lesions. 
Progressive Disease After Initial Response:  after initial response, and in the absence of 
appearance of new lesions, progressive disease is defined as an increase of the nadir sum of 
diameters by > 20%. 
Response Assessment in Participants Receiving Immune-Modulating Agents, Including 
Checkpoint Inhibitors:  to account for potential ‘pseudoprogression,’ immune-related response 
criteria should be used, requiring confirmation of progressive disease on two consecutive scans at 
least 4 weeks apart and inclusion of new lesion measurements in the total tumor burden. 
Appearance of New Extranodal Lesion: A minimum of 1 cm in largest diameter of new 
extranodal lesions is required to confirm progressive disease. New smaller but suspicious lesions 
should be designated as equivocal; if later confirmed (by CT or biopsy) as due to lymphoma, the 
documented date of disease progression should be the date of identification as equivocal. 
Disseminated Disease: The status of nontarget lesions should be accounted for before formulating 
the final response status. The International Working Group statement provides a recommended 
approach to response designation involving the best response of target and nontarget lesions. 
16.7.2 Response Designations in Lymphoma Table  
Target Lesions 
Non-Target 
Lesions 
New Lesions 
Overall 
Response 
CR 
CR 
No 
CR 
CR 
Non-CR/Non-PD 
(PR, MR, SD) 
No 
PR 
CR 
Unevaluable 
No 
UE 
CR 
No  
No  
CR 
PR 
Unevaluable 
No 
UE 
PR 
CR, Non-CR/Non-
PD 
No 
PR 


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Target Lesions 
Non-Target 
Lesions 
New Lesions 
Overall 
Response 
PR 
No  
No  
PR 
MR 
Unevaluable 
No  
UE 
MR 
CR, Non-CR/Non-
PD 
No  
MR 
MR 
No  
No  
MR 
SD 
Unevaluable 
No 
UE 
SD 
CR, Non-CR/Non-
PD 
No  
SD 
SD 
No  
No 
SD 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
PD = progressive disease 
 
 


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16.8 
Blood Requirements for Study  
Total Blood Requirements  
 
Schedule 
Screening 
(mL) 
Cycle 1 
(mL) 
First 30 Days 
(mL) 
Cycle 2 
(mL) 
Cycle 
3/4 (mL) 
Cycles ≥5 
(mL) 
Dose Escalation Schedule 1 
17 
147 
201 
82 
22 
18 
Dose Escalation Schedule 2 
17 
147 
201 
95 
32 
28 
Dose Expansion Cohort 
Schedule 1 
17 
142 
196 
71 
22 
18 
Dose Expansion Cohort 
Schedule 2 
17 
142 
196 
81 
32 
18 
Dose Escalation Schedule 1 – Blood Requirements 
 
 
Test Sample 
Sample 
volume 
(mL) 
Screening 
(mL) 
Cycle 1 
(mL) 
First 30 Days 
(mL) 
Cycle 2 
(mL) 
Cycle 
3/4 
(mL) 
Cycles ≥ 5 
(mL) 
Hematology profile 
2 
2 
12 
16 
8 
4 
4 
Chemistry profile 
3 
3 
18 
24 
12 
6 
6 
C Reactive Protein & 
Ferritin 
2 
2 
Coagulation profile 
3 
3 
18 
24 
12 
Thyroid test 
2 
2 
 
2 
2 
2 
2 
Antiviral testing 
(HBV/HCV) 
5 
5 
PK, ADA, Cytokines 
2-7 
 
55 
73 
18 
10 
6 
Complement 
2 
12 
18 
6 
Immunophenotyping/ 
Receptor occupancy 
4 
32 
44 
24 
TOTAL 
17 
147 
201 
82 
22 
18 
Dose Escalation Schedule 2 – Blood Requirements 
 
 
Test Sample 
Sample 
volume 
(mL) 
Screening 
(mL) 
Cycle 1 
(mL) 
First 30 Days 
(mL) 
Cycle 2 
(mL) 
Cycle 
3/4 
(mL) 
Cycles ≥ 5 
(mL) 
Hematology profile 
2 
2 
12 
16 
12 
8 
8 
Chemistry profile 
3 
3 
18 
24 
18 
12 
12 
C Reactive Protein & 
Ferritin 
2 
2 
Coagulation profile 
3 
3 
18 
24 
15 
 
 
Thyroid test 
2 
2 
2 
2 
2 
2 
Antiviral testing 
(HBV/HCV) 
5 
5 
PK, ADA, Cytokines 
2-7 
55 
73 
18 
10 
6 
Complement 
2 
12 
18 
6 
Immunophenotyping/  
Receptor occupancy 
4 
32 
44 
24 
TOTAL 
 
17 
147 
201 
95 
32 
28 
 
 
 


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Dose Expansion Cohort Schedule 1 – Blood Requirements 
 
 
Test Sample 
Sample 
volume 
(mL) 
Screening 
(mL) 
Cycle 1 
(mL) 
First 30 Days 
(mL) 
Cycle 
2 (mL) 
Cycle 
3/4 
(mL) 
Cycles ≥5 
(mL) 
Hematology profile 
2 
2 
12 
16 
6 
4 
4 
Chemistry profile 
3 
3 
18 
24 
9 
6 
6 
C Reactive Protein & 
Ferritin 
2 
2 
Coagulation profile 
3 
3 
12 
18 
6 
 
 
Thyroid test 
2 
2 
 
2 
2 
2 
2 
Antiviral testing 
(HBV/HCV) 
5 
5 
cfNA 
10 
20 
20 
PK, ADA, Cytokines 
2-7 
36 
54 
18 
10 
6 
Complement 
2 
12 
18 
6 
Immunophenotyping/ 
Receptor occupancy 
4 
32 
44 
24 
TOTAL 
 
17 
142 
196 
71 
22 
18 
Dose Expansion Cohort Schedule 2 – Blood Requirements 
 
 
Test Sample 
Sample 
volume 
(mL) 
Screening 
(mL) 
Cycle 1 
(mL) 
First 30 Days 
(mL) 
Cycle 
2 (mL) 
Cycle 
3/4 
(mL) 
Cycles ≥5 
(mL) 
Hematology profile 
2 
2 
12 
16 
10 
8 
4 
Chemistry profile 
3 
3 
18 
24 
15 
12 
6 
C Reactive Protein & 
Ferritin 
2 
2 
Coagulation profile 
3 
3 
12 
18 
6 
Thyroid test 
2 
2 
 
2 
2 
2 
2 
Antiviral testing 
(HBV/HCV) 
5 
5 
 
 
 
 
 
cfNA 
10 
 
20 
20 
 
 
 
PK, ADA, Cytokines 
2-7 
36 
54 
18 
10 
6 
Complement 
2 
12 
18 
6 
Immunophenotyping/ 
Receptor occupancy 
4 
32 
44 
24 
TOTAL 
17 
142 
196 
81 
32 
18 
AD HOC Labs 
Test Sample 
Sample volume (mL) 
CBC (mL) 
3 
C reactive protein (mL) 
1 
PK & ADA (mL) 
6 
Cytokines & chemokines (mL) 
1 
Immunophenotyping (mL) 
4 
TOTAL 
15 
 


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16.9 
Summary of Protocol Changes – Amendment 01 
 
Editorial Changes: 
Title page 
Approval date changed to December 11, 2018  and version number changed to 01 
Table of Contents  
Updated to include new Appendix Section 16.9 and page numbers revised 
List of Tables and List of Figures 
 
Updated page numbers  
Synopsis 
 
Statistics Section: changed CRS to IRR since sequential boundaries in dose expansion will be used 
to specifically monitor IRRs (including CRS) and toxicities leading to discontinuation of SL-
279252. 
Literature and intext references to IB updated  
Appendix 16.9 
New appendix added summarizing protocol changes for Amendment #1 
 
Clinical Issue #1 – Upper Bound of Target DLT rate lowered to 33%: 
Protocol Synopsis 
Statistics Section: revised language to reflect upper bound of target DLT rate lowered and is of 25-
33.3%  
Section 9.1 
Text modified to indicate reflect target DLT range as 25-33.3% range. 
Section 9.2.1 
Revised text added to reflect target DLT range as 25-33.3%. 
Section 9.4.1.1 
The MAD will be reported, or the MTD will be estimated using isotonic regression (based on the 
DLTs observed in evaluable subjects). A MAD will be reported if a schedule is fully evaluated, but 
the DLT rate never reaches the target range of 25-33.3%. 
Appendix Sections 16.3 and 16.3.1 
 Revised dose escalation rules for Keyboard Design decision rules in to reflect target DLT range of 
25 to 33.3% 
 
Issue #2 – Dose expansion cohorts will enroll subjects at dose levels determined as safe per the 
Keyboard Design 
Section 3.1.2  
Study Schema’s supporting text revised to clarify that only dose levels cleared for safety per the 
Keyboard Design with a minimum of 6 subjects treated at that dose level will be expanded 
Section 3.3.1 
 
Clarifying text added that only dose levels that have been cleared for safety per the Keyboard design 
with a minimum of 6 subjects treated at that dose level will be expanded 
 


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Issue #3 – Grade 3 or greater CRS is a DLT 
Protocol Synopsis 
Definition of DLTs section: removed Grade 3 CRS that resolves to less than or equal to Grade 1 
within 24 hours with appropriate management as an exception to DLT definition 
Section 3.2.6 
Removed Grade 3 CRS that resolves to less than or equal to Grade 1 within 24 hours with 
appropriate management as an exception to DLT definition  
 
 
Issue #4  – Modified guidelines on management of all grades of CRS and IRRs 
Section 3.5.1 
 
Accompanying text associated with table changed to state that in the event of any Grade IRR 
(including CRS), subjects will be admitted for closer observation until resolution of symptoms 
Infusion or hypersensitivity reactions management guideline changed 
• 
Management guidelines for IRRs (all grades) changed to state that in the event of any Grade 
IRR subjects will be admitted for closer observation until resolution of symptoms 
• 
Grade 3 IRR:  removed text allowing subject to be monitored for resolution of symptoms 
without admission for closer observation 
CRS management changes 
• 
Management guidelines for CRS (all grades) changed text to state that in the event of any 
Grade CRS subjects will be admitted to the hospital for closer observation until resolution 
of symptoms and removed all contradictory statements to this requirement 
• 
Grade 2 CRS:  
 
removed text allowing subject to be monitored for resolution of symptoms without 
admission for closer observation 
 
Added text to interrupt IP and not restart IP until symptoms are returned to less 
than or equal to 1 for at least 3 days. Once symptoms have resolved can administer 
IP per next scheduled time point 
 
Added text to clarify that following Grade 2 CRS the next two subsequent 
infusions of SL-279252 must be administered in an inpatient setting for prolonged 
observation (e.g., 24 hours) 
 
Added text stating that for subsequent infusions, following a Grade 2 CRS event, 
may consider pre-medication with dexamethasone 20 mg and other agents per 
institutional guidelines 
• 
Grade 3 CRS: 
 
Added text to Interrupt IP and not-restart IP until symptoms are returned to grade 
less than or equal to 1 for at least 3 days. Once symptoms have resolved, administer 
dose per next scheduled time point 
 
Added text that for Grade 3 CRS, may consider re-challenge at the next lower dose 
level after consultation with medical monitor. After a Grade 3 CRS event, subjects 
must be pre-medicated with high dose steroids prior to the infusion of SL-279252. 
If there is no evidence of CRS at the reduced dose level, premedication with high 
dose steroids may be omitted for subsequent infusions. The two subsequent 
infusions of SL-279252 after an event of Grade 3 CRS should be administered in 
an inpatient setting for prolonged observation (e.g., 24 hours). 


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 
Added text that any subject that experiences recurrence of Grade 3 CRS following 
re-treatment must be permanently discontinued from study treatment. 
 
Added text that any subject that experiences recurrence of Grade 3 CRS following 
re-treatment must be permanently discontinued from the study treatment. 
Section 5.6  
 
Text revised to indicate that in the event of any Grade IRR (including CRS), subjects will be 
admitted for closer observation until resolution of symptoms. 
 
Issue #5 -Modified dose escalation between second and third dose levels to half-log increment  
Protocol Synopsis 
• 
Planned sample size section: changed sample size to approximately 42 to 87 subjects 
• 
Dose escalation scheme section: in table changed dose level 3 to 0.003 mg/kg, In addition, footnote 
c of table notes that half-log incremental increases will not be exceeded after dose level 2, and 
option to explore 10 dose levels or more during the study on Schedule 1 or additional dose levels 
on schedule 2 as possibility if safety allows. 
Section 3.1.1 
Revised wording to reflect changes in sample size estimates to evaluate up to 10 or more dose 
levels.  The maximum planned sample size for dose escalation is 42 subjects if only Schedule 1 is 
evaluated and, if Schedules 1 and 2 are evaluated in dose escalation, the maximum planned sample 
size is 57.  Overall, the total sample size estimate for this study is 72 subjects assuming only 
Schedule 1 is evaluated in dose escalation and 87 subjects if Schedules 1 and 2 are fully evaluated.  
Section 3.1.2 
Study schema revised to reflect addition of dose level 3 (0.003 mg/kg) to dose escalation levels  
Section 3.2.4 
• 
Text changed to clarify that first two dose levels will be increased in log increments and beyond 
dose level 2, dose escalations will not exceed half-log increments 
• 
Table 5 revised to reflect 10 dose levels and insertion of dose level 3 = 0.003 mg/kg and footnote 
c of table revised to note that escalation with not exceed half-log increments 
• 
Text describing evaluation of schedule 2 indicates that 0.1 mg/kg is dose level 6 then starting dose 
on schedule 2 will be 0.03 mg/kg (dose level 5) or lower 
Section 4.5 
Text modified to reflect revisions to sample size accrual goal (i.e., 72-87 subjects) to accommodate 
addition of dose level 3. 
Section 9.1 
Text modified to indicate 10 dose levels planned and 42 subjects enrolled during dose escalation if 
Schedule 1 is fully evaluated.  
 
Section 9.2.1 
Maximum estimated sample size for schedule 1 changed to 42 for schedule 1. 
Section 9.2.1.1 
 
The first and second set of simulations for Schedule 1 revised to reflect 10 dose levels and 
maximum sample size of 42 subjects for dose escalation 
Section 9.2.1.2 


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If both Schedule 1 and 2 are evaluated, the planned maximum total sample size during dose 
escalation is 57 subjects. If only Schedule 1 is evaluated (which is expected), the planned maximum 
total sample size during dose escalation is 42 subjects. 
Appendix Sections 16.3.1.1 (Dose Escalation on Schedule 1) 
 
Maximum sample size is 42 subjects 
 
 
Issue #6 – Modified dose escalation scheme such that dose level 9 corresponds to a dose of 3.0 mg/kg 
of SL-279252 and dose level 10 corresponds to a dose of 6.0 mg/kg of SL-279252.  
 
Protocol synopsis dose escalation scheme 
• 
Dose level 9 modified to 3.0 mg/kg SL-279252 
• 
Dose level 10 modified to 6.0 mg/kg SL-279252 
 
Table 5 in Section 3.2.4  
• 
Dose level 9 modified to 3.0 mg/kg SL-279252 
• 
Dose level 10 modified to 6.0 mg/kg SL-279252 
 
Issue #1 (i.e., upper bound of target DLT range = 33.3%) and Issue #5 (i.e., addition of dose level 3 = 0.03 
mg/kg) 
 
Appendix Section 16.3.1.3. 
Keyboard Design Scenarios 1-3 for dose escalation on Schedule 1 were revised to reflect changes 
in upper bound of DLT target range to 33.3% with 42 subjects as maximum sample size. The 4th 
scenario stops the study with no dose selected as the MTD. 
 
 
Issue #7– Modified follow up for ADA until resolution to baseline if subject has positive ADA test on 
study or within 7-30 days of last dose of SL-279252 
 
Footnote L in SOA Tables in Sections 6.1, 6.2, 6.3 and 6.4 
New text added: If subject has positive ADA test on D1 of cycle 13, then follow up predose samples 
for PK/ADA should be collected every ~90 days on D1 of subsequent treatment cycles until ADA 
resolves to baseline. If ADA positivity is detected within 7-30 days after the last dose of SL-279252, 
then follow up testing for PK/ADA should be performed at monthly intervals until ADA resolves 
to baseline. 
 
 
 


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Dose Escalation PK Supplementary Table 8 in Section 6.1.1 and Dose Escalation PK Supplementary Table 
12 in Section 6.2.1  
• 
New footnote # 4 added : If subject has positive ADA test on D1 of cycle 13, then follow up predose 
samples for PK/ADA should be collected every ~90 days on D1 of subsequent treatment cycles 
until ADA resolves to baseline.  
• 
New text added to Tables 8 and 12: If ADA positivity is detected within 7-30 days after the last 
dose of SL-279252, then follow up testing for PK/ADA should be performed at monthly intervals 
until ADA resolves to baseline. 
 
Dose Expansion PK Supplementary Table 15 in Section 6.3.1 and Dose Expansion PK Supplementary 
Table 18 in Section 6.4.1  
• 
New footnote # 5 added : If subject has positive ADA test on D1 of cycle 13, then follow up predose 
samples for PK/ADA should be collected every ~90 days on D1 of subsequent treatment cycles 
until ADA resolves to baseline. 
• 
New text added to Tables 15 and 18: If ADA positivity is detected within 7-30 days after the last 
dose of SL-279252, then follow up testing for PK/ADA should be performed at monthly intervals 
until ADA resolves to baseline. 
 
 


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16.10 Summary of Protocol Changes – Amendment 02 
(Country-specific Amendment for Belgium) 
Editorial Changes: 
Document Headers 
 
Updated to denote version 02 of protocol 
Title page 
Approval date changed to 06 June, 2019 and protocol version number changed to version 02 
Summary of Amendment Changes for Amendment 2  
Added new summary of changes for Amendment 2 after the Title Page and summary of changes 
for Amendment 1 
Table of Contents  
Updated to include new section on drugs to be used with caution and new Appendix Section 16.10 
Page numbers revised 
Abbreviations List 
 
Added CYP450 to abbreviations list 
Literature References 
 
Added new reference (Evers et al., Drug Metabolism and Disposition 2013;41:1598-1609) 
 
Clinical Issue #1 – Double-barrier methods for contraception in female subjects are inadequate as they do 
not have a < 1% failure rate. 
• 
Clarified in section 16.2 acceptable forms of contraception for male and female subjects of 
childbearing potential in the study. 
 
Issue #2 – Medications to be used with caution with SL-279252 which is a therapeutic protein that induces 
the release of cytokines including IL-6. Cytokine release may impact CYP450 enzyme activity. 
• 
Added new section (3.4.3 Medications to be used with Caution) and new text to the protocol noting 
that drugs that are substrates of CYP450 enzymes should be used with caution when coadministered 
with SL-279252. 
 
 


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16.11 Summary of Protocol Changes – Amendment 03 
This Global amendment encompasses changes made to the protocol described in Appendix 16.10 (Country-
specific Amendent 02 for Belgium) plus the additional changes outlined below. 
 
Minor Editorial Changes: 
Document Headers 
 
Updated to denote version 03 of protocol 
Title page 
Approval date changed to 11 October, 2019 and protocol version number changed to version 03 
Summary of Amendment Changes for Amendment 2  
Added new summary of changes for Amendment  03 after the Title Page  
Table of Contents  
Updated to include new section on drugs to be used with caution and new Appendix Section 16.10 
(for countries outsided of Belgium) and new Appendix section 16.11. 
 Page numbers revised 
Abbreviations list 
TTR – time to tumor response added  
 
Issue #1: Amendment 02 changes included for countries outside of Belgium  
• 
see Appendix 16.10 
 
Issue #2 and Issue #3e: Pharmacodynamic cohorts are now included for enrollment during dose 
escalation 
• 
Synopsis and Section 4.5:  
o Planned sample size increases by approximately 6 subjects in total to 78 and 93 subjects 
from 72 and 87. 
• 
Study Schema 
o New text added to caption under schema: A pharmacodynamic cohorts may also be 
explored during dose escalation as described in Section 3.1.   
• 
Section 3.1:  
o New text added: Pharmacodynamic Cohorts in Dose Escalation: The Sponsor, in 
consultation with the SMC, may elect to open a pharmacodynamic cohort in order 
to obtain additional pharmacodynamic data from a total of approximately 6 
additional subjects at one or more dose levels that have previously completed 
evaluation for safety and has not exceeded the MTD. Subjects enrolled in the 
pharmacodynamic cohort will not inform dose escalation decisions but the 
pharmacodynamic information gathered from these additional subjects may inform 
selection of doses for further evaluation in dose expansion. As a result, the 
maximum planned sample size estimate in dose escalation may increase by 
approximately 6 subjects  and the overall total planned sample size estimates would 
increase accordingly. Subjects in the pharmacodynamic cohorts will be followed 
per the Dose Escalation Schedule of Assessment (SOA) tables provided in Sections 
6.1 (schedule 1) and 6.2 (schedule 2). 
• 
Section 9.1: 


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o New text added: During the dose escalation, additional subjects (approximately 6) may be 
enrolled into a pharmacodynamic cohort to obtain additional pharmacodynamic data at 
select dose levels that have previously completed evaluation for safety and not exceeded 
the MTD.   
• 
Section 9.2.1: 
o New text added: The planned sample size for the dose escalation part of the study is 63 
subjects. The planned number of subjects to obtain additional pharmacodynamic data at 
select dose levels is approximately 6 subjects.  
o Minor edits  to text included  
Issue #3: Editorial changes to remove unclear text and to further clarify intent of study plans are 
provided throughout the document to study objectives, statistical plans, definitions of study 
populations, etc). 
a) Time to tumor response added as an endpoint for assessment of antitumor activity,  
b) Minor response removed for subjects with lymphoma as part of the clinical benefit rate definition; 
c) iSD as part of clinical benefit rate defined as ≥ 16 weeks duration instead of 12 weeks  
d) Refined definitions of populations under study in statistical section 
e) Revised sample size estimates to accommodate the addition of pharmacodynamic cohorts for 
enrollment during dose escalation  
f) Clarification of MTD selection based on isotonic estimate  
 
• 
Objectives and outcome measures outlined in Synopsis and Section 2.0 (Issues 3a-c) 
o  TTR added as an outcome measure for antitumor activity 
o CBR definition for iSD is ≥16 weeks 
o Minor response is removed from CBR  
• 
Section 5.4 
o Removed sentence stating all doses should be rounded up to the nearest mg per institutional 
standard  
• 
Footnote b to SOA Tables 6.1, 6.2, 6.3 and 6.4 
o Text modified to clarify window for screening and cycle 1, day 1 assessments ie, A physical 
exam, weight and ECOG performance status obtained for a subject within 24 hours prior 
to dosing on Cycle 1, Day 1 is acceptable.With the exception of Screening and Day 1 
visitsasessments and unless otherwise specified, assessments performed at ≤ 3-week 
intervals will have a +/- 3-day window and assessments performed at > 3-week intervals 
will have a +/- 1-week window. 
• 
Section 6.9.2.2 
o New Text added: Archival tissue may be accepted as a pre-treatment specimen in lieu of a 
fresh biopsy if the subject has not undergone treatment since time of specimen collection 
and if the sample was collected via core needle biopsy. 
• 
Section 8.1.1 
o Removed text related to iRECIST best overall response 
o Removed Table 21: iRECIST Best Overall Response and removed reference to Table 21 
in Appendix Section 16.6.3  
• 
Section 9.2.1.2  
o Minor edit to text referring to dose escalation process 
• 
Section 9.3 Table defining analysis populations revised for clarity to alignment with Statistical 
Analysis Plan (SAP) (Issue 3d) 


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o Enrolled subjects are all subjects who sign the main study ICF 
o All Treated Population notes that Safety data will be evaluat based on this population 
o Removed definition of safety population from table since it is defined as part of all treated 
population 
o DLT Evaluable (removed text limiting to dose escalation) and added new text: All subjects 
in the All Treated population who receive at least 2 doses of SL-279252, complete the 
safety follow up through DLT evaluation period or experience any DLT during the DLT 
evaluation period. The DLT evaluation period is defined as the first 21 days or 28 days of 
treatment on Schedule 1 or Schedule 2, respectively.   
o Removed text from DLT Evaluable: A subject who has sufficient safety data available to 
conclude that a DLT did or did not occur (see Section 3.2.6)  
o Efficacy Evaluable Population revised text as follows: A subject who received at least one 
post-baseline disease first assessment at the 8 week time point or had progressed or died 
before the first post-baseline disease assessment. Removed text as follows: This is the 
primary population for efficacy analyses. 
o Pharmacodynamic Population added new text: The pharmacodynamic population will be 
used for the pharmacodynamic data analysis. 
• 
Section 9.4 
o Clarified that the planned statistical analyses for pharmacokinetic and specific 
pharmacodynamic markers that will be utilized in dose selection will also be summarized.   
• 
Section 9.4.1.1 (Issue 3F) 
o Modified text as follows: Changes in safety assessments (e.g., laboratory parameters, vital 
signs, etc.) will also be summarized using descriptive statistics (e.g., mean, standard 
deviation, median, minimum and maximum values). 
o Added new text: Specifically, the MTD is selected as the dose for which the isotonic 
estimate of the DLT rate is closest to the target DLT rate of 0.3. If there are ties, we select 
the highest dose level when the isotonic estimate is lower than the target DLT rate; and we 
select the lowest dose level when the isotonic estimate is greater than the target DLT rate. 
• 
Section 9.4.1.2  
o Modified text to clarify that summaries will be presented for each dose expansion cohort 
separately. 
o Modified text to clarify that the All Treated population will be used for analyses. 
• 
Section 9.4.2 
o Removed sentence stating the primary analysis will be subjects evaluable for efficacy. 
• 
Section 9.4.3 
o Modified text to state the following: If appropriate, TTR, DOR, progression-free survival 
and overall survival may also be summarized using the Kaplan-Meier method, with 
medians reported along with 95% confidence intervals. 
Issue #4: Receptor occupancy samples will also be collected in dose expansion cohorts (no longer 
limited to collection in dose escalation cohorts). 
• 
Synopsis under exploratory objectives section and Section 2.0 under exploratory objectives now 
includes the following outcome measure for dose expansion  
o Free/total receptor occupancy of OX40 and PD-L1 in circulating CD45 positive cells by 
flow cytometry with further sub-gating into B and T cell subsets 
• 
Section 6.6.6 under Flow cytometry panel receptor occupancy panel:  Removed text that restricts 
collection of this panel in dose escalation cohorts only 


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• 
Section 6.9.1.2 and Section 9.4.3 include statement that receptor occupancy will be measured 
during dose escalation and dose expansion 
• 
SOA tables for dose expansion (Sections 6.3 for Schedule 1 and 6.4 for Schedule 2) and  dose 
expansion-related supplementary tables 16 and 19 in sections 6.3.2 and 6.4.2, respectively now 
include collection of receptor occupancy samples  
• 
Footnote m for SOA tables in 6.3 and 6.3 now notes that receptor occupancy samples are being 
collected 
Issue #5: Additional time points for collection of biomarker samples (immunophenotyping and 
receptor occupancy) in cycle 2 on days 15 and 16 have been added that impact schedule of assessment 
and supplementary tables for dose escalation and dose expansion cohorts.  
• 
SOA Tables for dose escalation (Sections 6.1 for Schedule 1 and 6.2 for Schedule 2) and dose 
expansion (Sections 6.3 for Schedule 1 and 6.4 for Schedule 2) now include collection of 
immunophenotyping and receptor occupancy samples during cycle 2 on days 15 and 16 
• 
Supplementary table 9 in section 6.1.2 and supplementary table 13 in section 6.2.2 have been 
updated to show collection of predose samples for all biomarkers, 2 h post dose sample for receptor 
occupancy and 24 h post dose samples for assessment of receptor occupancy and 
immunophenotypind during cycle 2 on days 15 and 16. Complement samples will NOT be collected 
during cycle 2 on days 15 and 16. 
• 
Supplementary tables 6.3.2 and 6.4.2 have been updated to show collection of predose 
samples for all biomarkers, 2 h post dose sample for receptor occupancy and 24 h post dose 
samples for assessment of receptor occupancy and immunophenotyping during cycle 2 on 
days 15 and 16. Complement samples will NOT be collected during cycle 2 on days 15 and 
16. 
• 
New text added as Footnote r in SOA table 6.3 states: Cycle 2 Days 15 and 16: Collect 
biomarker samples outlined in Table 16  in Section 6.3.2. Refer to the SLM for details. 
 
Issue #4 and #5 described above: 
• 
Modified Appendix 16.8 to reflect changes in blood volumes collected because of 
additional biomarker samples being collected in dose escalation and dose expansion 
cohorts 
 
 
 


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16.12 Summary of Protocol Changes – Amendment 04 
The primary purpose for this Global amendment is to revise eligibility criteria and tumor types included for 
study participation. The planned tumor types needed to complete enrollment in expansion cohorts 
necessitates the addition of clinical sites.  In addition, minor editorial and formatting changes were made. 
 
Minor Editorial Changes: 
Document Headers 
 
Updated to denote version 04 of protocol 
Title page 
Approval date changed to 24 February, 2020 and protocol version number changed to version 04 
Table of Contents  
Updated to include new section on drugs to be used with caution and new Appendix Section 16.12 
 Page numbers revised 
Abbreviations list 
DLBCL – removed 
Synopsis 
 
Revised eligibility criteria to align with text changes made in the main body of the protocol as 
 
described below.  
 
Issue #1 – Subjects with DLBCL are no longer eligible for study participation.  
• 
Section 1.3 revised text  
o This first-in-human Phase 1 study will evaluate the safety, tolerability, PK, anti-tumor and 
pharmacodynamic effects of SL-279252 to identify the dose and schedule i.e., 
recommended Phase 2 dose (RP2D) for future development. The trial will enroll patients 
with tumor types that have demonstrated benefit from anti-PD1/L1 inhibitor therapy i.e., 
melanoma, non-small cell lung cancer (NSCLC), urothelial cancer, head and neck 
squamous cell carcinoma  (HNSCC), squamous cell cervical cancer, gastric or gastro-
esophageal junction (GEJ) adenocarcinoma, squamous cell carcinoma of the anal canal 
(SCCA), squamous cell carcinoma of the skin (Skin-SCC), renal cell cancer (RCC), 
Hodgkin’s lymphoma (HL), diffuse large B cell lymphoma (DLBCL) and microsatellite 
instability high (MSI-H) or mismatch repair deficient (MMRD) solid tumors excluding 
central nervous system (CNS) malignancies.  
• 
Section 3.1 revised text 
o Subjects with any of the following malignancies (including specific subtypes) may be 
enrolled in Dose Escalation: melanoma, NSCLC (squamous cell or adenocarcinoma or 
adeno-squamous), urothelial cancer, HNSCC, squamous cell cervical cancer, gastric or 
GEJ adenocarcinoma, SCCA, Skin-SCC, RCC, HL, DLBCL, MSI-H or MMRD solid 
tumors excluding CNS malignancies. The tumor types for dose expansion (up to 4 
histologies) will be determined after review of data collected during dose escalation, and 
will be selected from the dose escalation list of malignancies. 
• 
Section 3.1.2 Study schema  
o Removed DLBCL as tumor type included in schema 
• 
Section 4.2 Inclusion Criterion #2 
o Removed DLBCL as tumor type for inclusion in the study 
 
 


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• 
Appendix  16.7 revised text 
o Bone marrow: Participants with DLBCL with a negative FDG PET uptake in the bone 
marrow, does not rule out bone marrow involvement, especially discordant histology.  A 
bone marrow biopsy would be performed as a part of staging.  In participants with positive 
FDG-PET uptake may obviate the need for a bone marrow biopsy.  Participants with HL 
without FDG update in the bone marrow or presence of B-symptoms do not need a bone 
marrow biopsy at baseline, as bone marrow biopsy in this situation is extremely unlikely 
to modify stage. 
 
Issue #2 – Revised Eligibility criteria  
• 
Text deleted and new text added to Inclusion criterion #2 in Section 4.2 
o Subject has a histologically confirmed diagnosis of one of the following unresectable 
locally advanced or metastatic malignancies: melanoma, non-small cell lung cancer 
(squamous, adeno, or adeno-squamous), urothelial cancer, squamous cell carcinoma of the 
head and neck, squamous cell cervical cancer, gastric or gastro-esophageal junction 
adenocarcinoma, squamous cell carcinoma of the anal canal, squamous cell carcinoma of 
the skin, renal cell cancer, Hodgkin’s lymphoma, diffuse large B cell lymphoma, and 
microsatellite instability high (MSI-H) or mismatch repair deficient (MMRD) solid tumors 
excluding CNS malignancies. MSI and MMRD testing results as per institution is 
acceptable.  NOTE: The tumor types for dose expansion (up to 4 histologies) will be 
determined after review of data collected during dose escalation, and will be selected from 
this list of malignancies.  
New Text: 
• 
Head and neck cancers: Subjects must have primary tumor locations in the 
oropharynx, oral cavity, hypopharynx, or larynx. Primary tumor sites of 
nasopharynx,  maxillary sinus, paranasal, and unknown primary are excluded. 
• 
Melanoma: Subjects with a diagnosis of uveal or ocular melanoma are excluded. 
• 
Non-small cell lung cancers: Subjects with a known EGFR sensitizing (activating) 
mutation or an ALK fusion are excluded. 
• 
New text added to Inclusion criterion #11 in Section 4.2 
o All AEs resulting from prior anti-cancer immunotherapy have resolved (NOTE: exceptions 
include alopecia, vitiligo, and endocrinopathies adequately treated with hormone 
replacement). 
New Text:  
• 
Subjects that were discontinued from prior PD-1/L1 therapy due to immune-
related adverse events are not eligible 
• 
New text added to Exclusion criterion #1 in Section 4.3 
o Has received more than two prior checkpoint inhibitor containing treatment 
regimens (regimen refers to either monotherapy or combination immunotherapies) 
or has had prior treatment with an OX40 agonist. 
• 
Prior PD-1/L1 therapy is not required.  
• 
Text deleted and new text added to Exclusion #2 in Section 4.3  
Refractory to last checkpoint inhibitor therapy PD-1/L1 inhibitor-based therapy which is 
defined as disease progression within 3 months of treatment initiation.  
 
 


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New Text:  
• 
Subjects must have had clinical benefit (stable disease or response) to last PD-1/L1 
inhibitor-based therapy for at least three months to be eligible.  
 
Issue #3 – Additional clinical sites will be added to ensure timely enrollment of tumor types planned in the 
expansion phase  
• 
Synopsis - Planned number of sites section and Section 4.5  
o Text revised to reflect that approximately 8-10 clinical sites may participate in this study  
 
 
 
 
 
 


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16.13 Summary of Protocol Changes – Amendment 05 
The main purpose for this amendment is to revise eligibility criteria and tumor types included for study 
participation. The dosing window for administration of SL-279252 was clarified in the Schedule of 
Assessment (SOA) tables. 
 
Minor Editorial Changes: 
Document Headers 
 
Updated to denote version 05 of protocol 
Title page 
Approval date changed to 1 October 2020 and protocol version number changed to version 05 
Table of Contents  
Updated to include new section on drugs to be used with caution and new Appendix Section 16.13 
Page numbers revised 
Synopsis 
 
Revised eligibility criteria to align with text changes made in the main body of the protocol as 
 
described below.  
 
 
1) Participant Eligibility Criteria revised as noted below: 
• 
Revised inclusion criterion #2 in Synopsis and Section 4.2 by removing text that excluded subjects 
with ocular or uveal melanoma from study participation. Deleted text: Melanoma: Subjects with a 
diagnosis of uveal or ocular melanoma are excluded.  
2) Removed enrollment restriction of up to 4 histologies in dose expansion.  This change impacted the 
following sections 
• 
Description of Study Design in Section 3.1 removed text in the last sentence of the first paragraph 
as follows: The tumor types for dose expansion (up to 4 histologies) will be determined after review 
of data collected during dose escalation, and will be selected from the dose escalation list of 
malignancies. 
• 
Study Schema in Section 3.1.2 removed dose expansion text Tumor Types: select up to 4 
histologies. The legend text to the schema had the following text removed: One to four tumor 
histologies may be tested in dose expansion.  
• 
Dose Expansion Description in Section 3.3.1 the last sentence in the first paragraph was removed: 
One to four tumor types (selected from the dose escalation list of malignancies) may be selected 
for the Dose Expansion Cohorts based on preliminary results from dose escalation.  
• 
Revised inclusion criterion #2 in Synopsis and Section 4.2 by removing text as shown: Subject has 
a histologically confirmed diagnosis of one of the following unresectable locally advanced or 
metastatic malignancies: melanoma, non-small cell lung cancer (squamous, adeno, or adeno-
squamous), urothelial cancer, squamous cell carcinoma of the head and neck, squamous cell 
cervical cancer, gastric or gastro-esophageal junction adenocarcinoma, squamous cell carcinoma 
of the anal canal, squamous cell carcinoma of the skin, renal cell cancer, Hodgkin’s lymphoma, 
and microsatellite instability high (MSI-H) or mismatch repair deficient (MMRD) solid tumors 
excluding CNS malignancies. MSI and MMRD testing results as per institution is acceptable.   
NOTE: The tumor types for dose expansion (up to 4 histologies) will be determined after review 
of data collected during dose escalation, and will be selected from this list of malignancies.  
3) Clarified dosing day windows allowed for administration of SL-279252 in the SOA Tables as follows: 


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• 
In SOA 6.1 new text added as footnote n: SL-279252 Administration: SL-279252 should be 
administered on D1, D8, and D15 according to the prescribed dosing schedule without deviation in 
cycle 1 to align with the safety DLT assessment and sample (PK, ADA, etc.) collection schedules. 
Beginning on cycle 2, day 1, a window of +/- 1 day is allowed for scheduled dosing days for drug 
administration. 
• 
In SOA 6.3 new text added as footnote o: SL-279252 Administration: SL-279252 should be 
administered on D1, D8, and D15 according to the prescribed dosing schedule without deviation in 
cycle 1 to align with the safety assessment and sample (PK, ADA, etc.) collection schedules. 
Beginning on cycle 2, day 1, a window of +/- 1 day is allowed for scheduled dosing days for drug 
administration. 
• 
In SOA 6.2 new text added as footnote n: SL-279252 Administration: SL-279252 should be 
administered on D1, D8, D15, and D22 according to the prescribed dosing schedule without 
deviation in cycle 1 to align with the safety DLT assessment and sample (PK, ADA, etc.) collection 
schedules. Beginning on cycle 2, day 1, a window of +/- 1 day is allowed for scheduled dosing days 
for drug administration. 
• 
In SOA 6.4 new text added as footnote o: SL-279252 Administration: SL-279252 should be 
administered on D1, D8, D15, and D22 according to the prescribed dosing schedule without 
deviation in cycle 1 to align with the safety assessment and sample (PK, ADA, etc.) collection 
schedules. Beginning on cycle 2, day 1, a window of +/- 1 day is allowed for scheduled dosing 
days for drug administration. 
4) Revised Dose Escalation Plan Table as noted below 
• 
Table 5 Dose Escalation Plan in Section 3.2.4 and as depicted in Synopsis was revised to include 
windows for duration of infusion of (+/- 10 minutes ) for a 30 minute infusion and (+/-15 minutes) 
for a 1 hour infusion. 
o Footnote e moved as superscript for Duration of Infusion column in Table 5 and text 
revised as shown (new text in italics):Shorter infusion time may be considered based on 
final drug volume needed for administration. Infusion time may change based on final drug 
volume needed for administration, safety and tolerability of the infusion for the subject, 
and/or observed safety findings during the study. Please refer to the Study Pharmacy 
Manual (SPM) for details. 
5) Revised Footnote o in SOA Tables 6.1 and 6.2 or footnote p in SOA Tables 6.3 and 6.4 on AE 
Monitoring as shown below 
• 
AE Monitoring:Subjects will be followed continuously for AEs during the study and for 90 days 
after the last dose of IP. After a subject is discontinued from SL-279252 due to progressive disease 
or for other reasons, any ongoing AE should be followed until resolution (or return to baseline) 
and documented in the eCRF. If another anti-cancer agent is started, only SAEs and irAEs that 
occur prior to starting the new anticancer therapy within 30 days from last dose of SL-279252  
should be recorded.  In the event of a continuing SAE or a non-serious irAE, the subject will be 
asked to return for follow-up until the SAE or irAE has resolved or is deemed to be continuing 
indefinitely. AEs will be characterized per NCI-CTCAE criteria v5.0 and events recorded in the 
eCRF. 
6) Predose, EOI and 6 hours post EOI PK sample time points were added for collection on C4/D1 to 
confirm clearance and half-life parameters with repeat dosing of SL-279252. Relevant supplementary 
PK tables were changed as outlined below. 
• 
Supplementary PK Table 8 in Section 6.1.1, Table 12 in Section 6.1.2, Table 15 in Section 6.3.1 
and Table 18 in Section 6.4.1 


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• 
Text was added to footnote # 4 in Table 15 in Section 6.3.1 and in Table 18 in Section 6.4.1 stating: 
C3/D1 and C4/D1 collect a predose sample for PK/ADA and then EOI, and 6 hr post EOI sample 
for PK. 
• 
Text was updated in Section 6.7.1 as shown below. 
Intensive serial PK samples will be collected for all subjects enrolled in dose escalation cohorts. 
In the first cycle starting on Day 1, samples will be collected pre-dose, at the EOI, and 0.5, 1, 1.5, 
2, 3, 4, 6, 8 and 24 hours post EOI. Additional PK samples will be collected at 48, 72, and 96 hours 
post EOI. Actual dose administration and PK sampling times will be documented in the subject’s 
medical record. Sample collection out to 96 hours post EOI may be truncated during dose finding 
based on emerging data (e.g., lower doses may require collection of PKs only through the 48-hour 
time point following the first infusion). Subsequently, pre-dose, EOI, 2-hour, 6-hour and 24-hour 
post EOI samples will be obtained on C1D15/D16 and C2D1/D2. On C3/D1 and C4/D1, a pre-
dose, EOI, and 6-hour post EOI sample will be collected. Beyond cycle 43, only pre-dose samples 
will be collected for ADA and PK analyses on D1 of C4, C7, C10, C13 and C25.  A final PK/ADA 
sample should be collected within 7 – 30 days after permanently stopping treatment with SL-
279252. 
• 
Text was updated in Section 6.7.2 
Sparse PK samples will be collected for all subjects enrolled in Expansion Cohorts. Actual dose 
administration and PK sampling times will be documented in the subject’s medical record. A 
sample will be collected pre-dose, at the EOI and then 2 and 6 hours after the infusion on C1/D1. 
A 24-hour post EOI sample will be collected on Day 2 of the first cycle (C1/D2). Subsequently, 
pre-dose, EOI, 2-hour, 6-hour, and 24-hour post EOI samples will be obtained on C1D15/D16 and 
C2D1/D2. A predose, EOI and 6-hour post EOI sample will be collected on C3/D1 and cycle 
4/D1. Beyond cycle 43, only pre-dose samples will be collected for ADA and PK analyses on D1 
of C4, C7, C10, C13 and C25. A final PK/ADA sample should be collected within 7 – 30 days 
after permanently stopping treatment with SL-79252. 
• 
Blood Requirements provided in Appendix 16.8 were updated to include additional PK samples 
added for collection on C4D1 
7) Revised wording in Section 7 Safety Assessments as shown below 
• 
Subjects will be followed continuously for AEs starting when a subject has signed the ICF, 
throughout the course of treatment and for 90 days after the last dose of IP. After a subject is 
discontinued from SL-279252 due to progressive disease or for other reasons, any ongoing AEs 
should be followed until resolution (or return to baseline) and documented in the eCRF. If another 
anti-cancer agent is started within 90 days after the last dose of SL-279252, only SAEs and irAEs 
that occur prior to starting the new anticancer therapy within 30 days from last dose of SL 279252 
should be recorded. All observed or volunteered AEs (serious or non-serious) and abnormal 
laboratory test findings, if applicable, whether suspected to have a causal relationship to the SL-
279252 or not will be recorded in the subject medical record and in the eCRF.  AEs will be graded 
according to NCI-CTCAE v5.0.  For all AEs, sufficient information will be pursued and/or 
obtained to permit an adequate determination of seriousness and outcome of the event (i.e., 
whether it should be classified as a SAE or not) and an assessment of the causal relationship 
between the AE and SL-279252.  AEs will be followed until resolution (or return to baseline) or 
stabilization.  Refer to Section 7.5 for documentation and reporting of AEs. 
o Revised text in Section 7.5 on Reporting Procedures for AEs in table as shown below to 
align with wording in Section 7. 
Event 
Reporting Procedures 
Adverse Event 
Subjects will be followed continuously for AEs during the study and for 90 days after the last 
dose of IP. After a subject is discontinued from SL-279252 due to progressive disease or for 
other reasons, any ongoing AE should be followed until resolution (or return to baseline) and 


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Event 
Reporting Procedures 
documented in the eCRF, regardless of whether the event(s) is attributed to trial medication. If 
another anti-cancer agent is started, only SAEs and AEs that occur prior to starting the new 
anticancer therapy within 30 days from last dose of SL 279252 should be recorded. The 
following information will be recorded: description, date of onset and end date, severity, 
assessment of relatedness to trial medication, and action taken.  Follow-up information should 
be provided as necessary.  AEs will be followed either until resolution, or the event is considered 
stable. 
 
It will be left to the Investigator’s clinical judgment to decide whether an AE is of sufficient 
severity to require the subject’s removal from treatment.  A subject may also voluntarily 
withdraw from treatment due to what he or she perceives as an intolerable AE.  If either of these 
occurs, the subject must undergo an end of trial assessment and be given appropriate care under 
medical supervision until symptoms cease, or the condition becomes stable. 
 
 
8) Other minor editorial changes made are noted below (new text added is italicized). 
• 
Duration of Treatment Section 3.11 new text (in italics) added to the last paragraph: Impact of ADA 
on clinical efficacy (non-response or loss of response to the IP) and safety (product specific 
immunogenicity risk) will be evaluated and reported on an on-going basis once a validated ADA 
assay becomes available.  If a subject develops ADA, the Sponsor and investigator may take into 
consideration these factors in assessing the duration of the therapy.  
• 
Assessment of Severity for AEs is now Section 7.1 moved up and no longer under Section entitled 
Classification of Adverse Event in Section 7.3 (was Section 7.2 in previous versions of protocol) 
o Section 7 subheadings renumbered to accommodate moving Assessment of Severity 
Section up and designating it as Section 7.1 in this version of the protocol. 
• 
Removed text from Section 7.4 as shown as shown below. 
o Changes in the severity of an AE will be documented to allow an assessment of the duration 
of the event at each level of severity. The highest grade in severity for each AE will be 
documented. AEs characterized as intermittent require documentation of onset and 
duration of each episode.  
 
 


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16.14 Summary of Protocol Changes – Amendment 06 
 
Minor Editorial Changes: 
Document Headers 
 
Updated to denote version 06 of protocol 
Title page 
Approval date changed to 4 Februrary 2021 and protocol version number changed to version 06 
Table of Contents  
Updated to include new section on drugs to be used with caution and new Appendix Section 16.14 
and revised title header for Section 6.6.6.1 
Page numbers revised 
Synopsis 
 
Revised exclusion criterion #2 to align with text changes made in the main body of the protocol as 
 
described below.  
Revised text in Criteria for Dose Limiting Toxicity Section to align with change made in the main 
body of the protocol as described below 
 
1) Revised exclusion criterion #2 in Section 4.3 to provide an exception for subjects with uveal melanoma 
• New Text shown italics added as a note of clarification: Note: Exclusion criterion #2 and 
the sub bullet above do not apply to subjects with uveal melanoma. 
 
2) Clarified language about ad hoc samples to be collected if an infusion-related (IRR) or cytokine release 
(CRS) adverse reaction occurs. 
• SOA Table 6.1 footnote o. AE Monitoring sub bullet text revised as shown (new text in 
italics): Ad hoc blood samples for clinical safety labs should be collected for SAE related 
to IRR and/or CRS events as noted in Section 6.6.6.1 and the SLM 
• SOA Tables 6.2 footnote o, 6.3 and 6.4 footnote p AE Monitoring sub bullet text revised 
as shown (new text in italics): Ad hoc blood samples for clinical safety labs should be 
collected for SAE related to IRR and/or CRS events related to infusion or CRS events as 
noted in Section 6.6.6.1 and the SLM. 
• Section 6.6.6.1 Section title and text revised as show (new text in italics): Title revision; 
Ad Hoc Labs for SAEs of IRR and/or CRS and text revision; Ad hoc labs should be 
collected as noted if IRR and/or CRS events or an immune-related adverse event (irAE) 
occurs. The samples to be collected are provided below. 
• Section 7.2 Table section defining Laboratory test(s) tha meet definitions of an AE or 
SAE; text revised in sub bullet #2 as follows (new text shown in italics): • Ad hoc labs 
should be collected as noted in Section 6.6.6.1 above if AEs of IRR and/or /CRS or an 
irSAE  occurs. 
3) Clarified language about the DLT-evaluable population for subjects receiving SL-279252 therapy. 
• Section 3.2.6 last paragraph in section revised as shown: A Grade ≥ 3 AE that occurs 
beyond the DLT period (21 days for schedule 1 or 28 days for schedule 2) or Grade 2 
events that require continuous interruption of SL-279252 for more than 6 weeks or 


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toxicities that result in subjects not receiving at least 6650% of the scheduled dose during 
the DLT assessment period may be taken into consideration when assessing the totality of 
the data in determining evaluability for DLT and the RP2D.   
Section 9.3 in the table that includes populations for Analyses the DLT Evaluable population is defined as 
(new text in italics): All subjects in the All Treated population who receive at least 2 doses of SL-279252 
for Schedule 1 or at least 3 doses for Schedule 2, complete the safety follow up through DLT evaluation 
period or experience any DLT during the DLT evaluation period. The DLT evaluation period is defined as 
the first 21 days or 28 days of treatment on Schedule 1 or Schedule 2, respectively. Evaluable subjects will 
be used to guide dose escalation and to determine the MTD or MAD. 
 
 


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16.15 Summary of Protocol Changes – Amendment 07 
Minor Editorial Changes: 
Document Headers 
 
Updated to denote version 07 of protocol 
Title page 
 
Approval date changed to 12 July 2021 and protocol version number changed to version 07 
Rational for Global Amendment 06  
 
Minor editorial changed noting summary provided for Amendment 06 05 
Rational for Global Amendment 07 added  
Abbreviations list 
 
Added TPS and CPS to abbreviations list 
Table of Contents  
 
Updated to include new Appendix Section 16.15  
Page numbers revised 
Synopsis 
 
Revised inclusion criterion #2 to align with text changes made in the main body of the protocol as 
 
described below.  
 
Added new inclusion criterion #3 to align with text changes made in main body of the protocol as 
described below. 
 
Revised exclusion criterion #2 to align with text changes made in main body of the protocol as 
described below 
 
1) Institute requirement that eligible subjects have tumors with PD-L1 expression ≥1%  according to tumor 
TPS or CPS at baseline. 
• 
Section 1.3 Rationale; new text (italics) added as shown below: 
This first-in-human Phase 1 study will evaluate the safety, tolerability, PK, anti-tumor and 
pharmacodynamic effects of SL-279252 to identify the dose and schedule i.e., recommended Phase 
2 dose (RP2D) for future development. The trial will enroll patients with tumor types that have 
demonstrated benefit from anti-PD1/L1 inhibitor therapy i.e., melanoma, non-small cell lung 
cancer (NSCLC), urothelial cancer, head and neck squamous cell carcinoma  (HNSCC), squamous 
cell cervical cancer, gastric or gastro-esophageal junction (GEJ) adenocarcinoma, squamous cell 
carcinoma of the anal canal (SCCA), squamous cell carcinoma of the skin (Skin-SCC), renal cell 
cancer (RCC), Hodgkin’s lymphoma (HL), and microsatellite instability high (MSI-H) or mismatch 
repair deficient (MMRD) solid tumors excluding central nervous system (CNS) malignancies. 
Given that SL-279252 likely requires binding of PD-L1 to mediate activity within the tumor, the 
study was amended to require eligible subjects to have tumors with PD-L1 expression ≥1% by 
tumor proportion score (TPS) or combined proportion score (CPS) at baseline. 
• 
Section 4.2 Inclusion Criteria; new text (italics) added as criteria #3 shown below: 
3. 
Eligible subjects must have tumors expressing PD-L1  ≥1%  by tumor proportion score (TPS) 
or combined proportion score (CPS) as determined by a local laboratory. 
• 
This criteria does not apply to subjects with a diagnosis of melanoma, renal cell 
carcinoma, Hodgkin’s lymphoma and microsatellite instability high (MSI-H) or mismatch 
repair deficient (MMRD) solid tumors. 


CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
191 
• 
SOA tables 6.1, 6.2, 6.3 and 6.4 new text (italics) added to footnote a in all of these tables in 
reference to Screening as shown: 
Subjects will be enrolled based on local PD-L1 tumor testing results. Any PD-L1 tumor testing 
results prior to enrollment are acceptable. 
 
2) Subjects with uveal or ocular melanoma are ineligible for participation. 
• 
Section 4.2 Inclusion Criterion #2; new text (italics) added as shown below: 
2. Subject has a histologically confirmed diagnosis of one of the following unresectable locally 
advanced or metastatic malignancies: melanoma, non-small cell lung cancer (squamous, adeno, 
or adeno-squamous), urothelial cancer, squamous cell carcinoma of the head and neck, 
squamous cell cervical cancer, gastric or gastro-esophageal junction adenocarcinoma, 
squamous cell carcinoma of the anal canal, squamous cell carcinoma of the skin, renal cell 
cancer, Hodgkin’s lymphoma, and microsatellite instability high (MSI-H) or mismatch repair 
deficient (MMRD) solid tumors excluding CNS malignancies. MSI and MMRD testing results 
as per institution is acceptable.    
 • 
Head and neck cancers: Subjects must have primary tumor locations in the oropharynx, 
oral cavity, hypopharynx, or larynx. Primary tumor sites of nasopharynx,  maxillary sinus, 
paranasal, and unknown primary are excluded. 
• 
Non-small cell lung cancers: Subjects with a known EGFR sensitizing (activating) 
mutation or an ALK fusion are excluded.  
• 
Melanoma: Subjects with a diagnosis of uveal or ocular melanoma are excluded. 
 
• 
Section 4.3 Exclusion Criterion #2; text deleted as shown: 
2. Refractory to last PD-1/L1 inhibitor-based therapy which is defined as disease progression 
within 3 months of treatment initiation.  
• 
Subjects must have had clinical benefit (stable disease or response) to last PD-1/L1 
inhibitor-based therapy for at least three months to be eligible.  
Note: Exclusion criterion #2 and the sub bullet above do not apply to subjects with uveal 
melanoma. 
 
3) Removed reference to 1 mL fill size of drug product to allow for larger fill volume.  
• 
Section 5.1 Investigational Product Description; edited text as below:  
Unit dose strength(s)/Dose Level(s): 
20 mg/mL; 1.0 mL in a 10 mL sized glass vial (Refer to Section 3.2.4 for dose levels). Refer to the 
Study Pharmacy Manual (SPM) for further description of drug product.   
• 
Section 5.2.1 Preparation  
SL-279252 solution for infusion, 20 mg/mL is supplied as a frozen liquid.  Before use, thaw each vial 
of SL-279252 for infusion (20 mg/mL, 1mL) overnight under refrigerated conditions protected 
from light or at room temperature until completely thawed to a clear solution over 1 hour.  
  
4) Minor editorial changes were made to clarify study conduct procedures during dose escalation and 
requirements for collection of ad hoc labs if IRR and/or CRS occur. 
• 
New text (in italics) added to the 1st paragraph in Section 3.1 Description of the Study Design as 
shown below: 


CONFIDENTIAL 
 
 SL01-DEL-101 
Compound: SL-279252 
 
Version no: 07  
192 
This is a Phase 1 first in human, open label, multi-center, dose escalation and dose expansion study 
to evaluate the safety, tolerability, PK, anti-tumor activity and pharmacodynamic effects of SL-
279252 in subjects with selected locally advanced or metastatic malignancies. The tumor types 
selected have been reported in the literature to be responsive to PD-1/L1 inhibitors. Subjects with 
any of the following malignancies (including specific subtypes) may be enrolled in Dose 
Escalation: melanoma, NSCLC (squamous cell or adenocarcinoma or adeno-squamous), urothelial 
cancer, HNSCC, squamous cell cervical cancer, gastric or GEJ adenocarcinoma, SCCA, Skin-SCC, 
RCC, HL, MSI-H or MMRD solid tumors excluding CNS malignancies. A subset of one or more 
selected tumor type(s) from the list of eligible histologies may be identified for enrollment in dose 
escalation. The tumor types for dose expansion will be determined after review of data collected 
during dose escalation, and will be selected from the dose escalation list of malignancies. 
• 
Minor editorial change made to 1st sentence in Section 6.6.6.1 as shown: 
Ad hoc labs should be collected as noted if IRR and/or CRS events or an immune related adverse 
event (irAE) occur. The samples to be collected are provided below. 

SAP_001.pdf: 


Shattuck labs, Inc                                                                                   Statistical Analysis Plan for SL01-DEL-101 
SL-279252                                                                                                                       
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TABLE OF CONTENTS 
 
LIST OF ABBREVIATIONS ....................................................................................................... 4 
1. 
INTRODUCTION .................................................................................................................. 6 
2. 
STUDY OBJECTIVES AND OUTCOME MEASURE ..................................................... 6 
3. 
STUDY DESIGN AND PLAN .............................................................................................. 8 
3.1 
STUDY DESIGN ............................................................................................................... 8 
3.2 
DOSE ESCALATION ...................................................................................................... 10 
3.3 
DOSE EXPANSION ........................................................................................................ 11 
3.4 
STUDY ASSESSMENTS AND PROCEDURES .................................................................... 12 
4. 
SAMPLE SIZE ..................................................................................................................... 12 
5. 
GENERAL ANALYSIS CONSIDERATIONS ................................................................. 12 
5.1 
REPORTING CONVENTIONS .......................................................................................... 12 
5.2 
DATA HANDLING ......................................................................................................... 13 
5.2.1 
Missing Data ................................................................................................... 13 
5.2.2 
Baseline and Change from Baseline ............................................................... 13 
5.2.3 
Study Day, Duration, and Time from Event ................................................... 14 
5.2.4 
Imputation of Partial Date .............................................................................. 14 
6. 
ANALYSIS POPULATIONS .............................................................................................. 15 
7. 
STUDY POPULATION....................................................................................................... 15 
7.1 
SUBJECT DISPOSITION .................................................................................................. 15 
7.2 
PROTOCOL DEVIATIONS .............................................................................................. 15 
7.3 
DEMOGRAPHIC AND BASELINE CHARACTERISTICS ..................................................... 16 
7.4 
STUDY CANCER HISTORY AND PRIOR CANCER THERAPY .......................................... 16 
7.5 
GENERAL MEDICAL HISTORY ...................................................................................... 16 
7.6 
STUDY DRUG EXPOSURE ............................................................................................. 16 
7.7 
PRIOR AND CONCOMITANT MEDICATIONS .................................................................. 16 
7.8 
CONCOMITANT PROCEDURES ...................................................................................... 17 
8. 
EFFICACY ANALYSES ..................................................................................................... 17 
8.1 
ORR BASED ON IRECIST FOR SOLID TUMORS ........................................................... 18 
8.1.1 
Time Point Tumor Response based on iRECIST ........................................... 18 
8.1.2 
Analysis of ORR based on iRECIST .............................................................. 18 
8.1.3 
Derivation of Best Overall Response based on iRECIST ............................... 18 
8.2 
ORR BASED ON RECIST 1.1 FOR SOLID TUMORS ...................................................... 19 
8.2.1 
Time Point Tumor Response based on RECIST 1.1 ...................................... 19 
8.2.2 
Analysis of ORR based on RECIST 1.1 ......................................................... 19 
8.2.3 
Derivation of Best Overall Response based on RECIST 1.1 .......................... 19 
8.3 
ORR BASED ON RECIL 2017 FOR LYMPHOMAS ......................................................... 20 
8.3.1 
Response assessment based on RECIL 2017 .................................................. 20 
8.3.2 
Analysis of ORR based on RECIL 2017 ........................................................ 20 
8.3.3 
Derivation of Best Overall Response based on RECIL 2017 ......................... 21 
8.4 
CLINICAL BENEFIT RATE ............................................................................................. 21 
8.5 
TIME TO RESPONSE ...................................................................................................... 22 
8.6 
DURATION TO RESPONSE ............................................................................................. 22 
8.7 
CHANGE FROM BASELINE IN TUMOR SIZE ................................................................... 23 
8.8 
OTHER RESPONSE DATA ANALYSIS ............................................................................ 23 
8.9 
PROGRESSION FREE SURVIVAL .................................................................................... 23 


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8.9.1 
PFS based on iRECIST for Solid Tumors ...................................................... 24 
8.9.2 
PFS based on RECIST 1.1 for solid tumors ................................................... 25 
8.9.3 
PFS based on RECIL 2017 for Lymphoma .................................................... 25 
8.10 OVERALL SURVIVAL .................................................................................................... 26 
8.11 STATISTICAL CONSIDERATIONS ................................................................................... 26 
8.11.1 Adjustments for Covariates ............................................................................ 26 
8.11.2 Handling of Dropouts or Missing Data .......................................................... 26 
8.11.3 Interim Analysis and Data Monitoring ........................................................... 26 
8.11.4 Multiple Comparison/Multiplicity .................................................................. 26 
8.11.5 Multicenter Studies ......................................................................................... 26 
9. 
PHARMACOKINETIC AND PHARMACODYNAMIC ANALYSES .......................... 26 
10. IMMUNOGENICITY ANALYSES ................................................................................... 26 
11. SAFETY ANALYSES .......................................................................................................... 27 
11.1 MAXIMUM TOLERATED DOSE EVALUATION ............................................................... 27 
11.2 ADVERSE EVENTS ........................................................................................................ 27 
11.3 CLINICAL LABORATORY EVALUATION ....................................................................... 28 
11.4 VITAL SIGNS ................................................................................................................ 29 
11.5 ECOG PERFORMANCE STATUS ................................................................................... 29 
12. CHANGE FROM PROTOCOL-SPECIFIED ANALYSES ............................................ 29 
13. REFERENCES ..................................................................................................................... 29 
14. APPENDIX:  LIST OF TABLES, FIGURES, AND LISTINGS ..................................... 30 
14.1 LIST OF TABLES ........................................................................................................... 30 
14.2 LIST OF FIGURES .......................................................................................................... 32 
14.3 LIST OF DATA LISTINGS ............................................................................................... 32 
 
 
 
 


Shattuck labs, Inc                                                                                   Statistical Analysis Plan for SL01-DEL-101 
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LIST OF ABBREVIATIONS 
ADA 
Anti-drug-antibody 
AE 
Adverse event 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
ATC 
Anatomical therapeutic chemical 
AUC 
Area under the serum concentration time curve 
CI 
Confidence interval 
CBR 
Clinical Benefit Rate 
CR 
Complete response 
CSR 
Clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CxDy 
Cycle x Day y 
DL 
Dose level 
DLT 
Dose limiting toxicity 
DOR 
Duration of response 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic Case Report Form 
ICH 
International Conference on Harmonisation 
iCPD 
Immune confirmed progression of disease 
iCR 
Immune complete response 
iPR 
Immune partial response 
iRECIST 
Immune response evaluation criteria in solid tumors 
irAE 
Immune related adverse event 
IRR 
Infusion-related reaction 
irSAE 
Immune-related serious adverse event 
iSD 
Immune stable disease 
iUPD 
Immune unconfirmed progression of disease 
MAD 
Maximum administered dose 
MedDRA 
Medical Dictionary for Regulatory Activities 
MR 
Minor Response 
MTD 
Maximum tolerated dose 
NCI 
National Cancer Institute 
NE 
Not evaluable 
ORR 
Objective response rate 
OS 
Overall survival 
PD 
Pharmacodynamic 
PD 
Progressive disease 
PFS 
Progression-free survival 
PK 
Pharmacokinetic 
PR 
Partial Response 


Shattuck labs, Inc                                                                                   Statistical Analysis Plan for SL01-DEL-101 
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PT 
Preferred term 
RECIL 
Response evaluation criteria in lymphoma 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RP2D 
Recommended phase 2 dose 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD 
Stable disease 
SMC 
Safety Monitoring Committee  
SOC 
System organ class 
TEAE 
Treatment-emergent adverse event 
ULN 
Upper limit of normal 
 
 
 
 
 
 
 










Shattuck labs, Inc                                                                                   Statistical Analysis Plan for SL01-DEL-101 
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Boundary, bn 
- 
- 
3 
3 
4 
4 
4 
4 
5 
5 
5 
6 
6 
6 
6 
3.2 Dose Escalation 
Two or more dosing schedules for SL-279252 may be evaluated: 
 Schedule 1: administering SL-279252 on days 1, 8 and 15 of the first 28-day cycle and 
then every 2 weeks thereafter on days 1 and 15 of each 28- day cycle beginning with cycle 
2. 
 Schedule 2: weekly dosing of SL-279252 on days 1, 8, 15 and 22 of each 28-day cycle. 
A less frequent dosing schedule (e.g., once every three weeks or once every four weeks) may be 
investigated if safety data from Schedule 1 indicates that this approach is most prudent. 
Table 2. SL-279252 Dose Escalation Plan 
Dose Level 
Dose of SL-279252 (mg/kg)a,b,c,d,e 
Duration of Infusione 
Level 1 
0.0001 mg/kg 
5-30 minutes 
Level 2 
0.001 mg/kg 
5-30 minutes 
Level 3 
0.003 mg/kg 
5-30 minutes 
Level 4 
0.01 mg/kg 
30 minutes (+/- 10 minutes) 
Level 5 
0.03 mg/kg 
30 minutes (+/- 10 minutes) 
Level 6 
0.1 mg/kg 
30 minutes (+/- 10 minutes) 
Level 7 
0.3 mg/kg 
30 minutes (+/- 10 minutes) 
Level 8 
1.0 mg/kg 
1 hour (+/- 15 minutes) 
Level 9 
3.0 mg/kg 
1 hour (+/- 15 minutes) 
Level 10 
6.0 mg/kg 
1 hour (+/- 15 minutes) 
a) Dose escalation begins on Schedule 1: SL-279252 may be administered in the first cycle on days 1, 
8, and 15 of the first 28-day cycle and then once every 2 weeks on days 1 and 15 of each 28-day cycle 
beginning at cycle 2. 
b) Dose escalation on Schedule 2 may be tested: If Schedule 2 is opened, SL-279252 may be 
administered once weekly on days 1, 8, 15, and 22 of each 28-day cycle. The starting dose on schedule 
2 will be at least one dose level below the current Schedule 1 dose level defined by the Keyboard design. 
If Schedule 2 is opened for enrollment, then enrollment on Schedule 1 will be halted. 
c) Intermediate dose levels may be tested based on emerging safety data. The option to explore more 
than 10 dose levels on Schedule 1 or additional dose levels on Schedule 2 is also a possibility if safety 
allows. Escalations will not exceed half-log increments after dose level 2. 
d) The actual body weight in kg will be used for dose calculation in all subjects whose body weight is 
weight >100 kg, the dose to be administered should be the same as that 
calculated for a subject weighing 100 kg. 
e) Infusion time may change based on final drug volume needed for administration, safety and tolerability 
of the infusion for the subject, and/or observed safety findings during the study.  Please refer to the Study 
Pharmacy Manual (SPM) for details. 
 
Evaluation of Schedule 1: Initially, cohort size in Schedule 1 may be limited to 1 subject for 
enrollment until one of the following occurs: a  Grade 2 toxicity or DLT is observed (see Section 
3.2.6 of protocol for DLT definitions) or DL 6 is reached; any of these scenarios will trigger 


Shattuck labs, Inc                                                                                   Statistical Analysis Plan for SL01-DEL-101 
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enrollment of  3 subjects in the current dose and dose level cohorts from that point forward. 
Multiple-subject cohorts will incorporate a minimum 3-day stagger between dosing the first and 
second subject at the same dose level, although this requirement may change based on emerging 
safety data as determined by the Safety Monitoring Committee (SMC). The incidence of DLT will 
be assessed over a period of 21 days during the first cycle of therapy on Schedule 1. 
 
Evaluation of Schedule 2: If Schedule 1 is safe and tolerable, and pharmacodynamic effects are 
not present or detectable, this may suggest that a more frequent dosing schedule is warranted. In 
this event cohort enrollment on Schedule 2 will be instituted in lieu of Schedule 1.  
 
The starting dose on Schedule 2 will be at least 1 DL lower than the current safe Schedule 1 DL 
defined by the Keyboard design. Dose escalation (or de-escalation) may then proceed based on a 
DL previously evaluated on Schedule 1 as shown in Table 1. For example, if 0.1 mg/kg (DL 6) is 
the current DL being evaluated on Schedule 1, then the starting dose on Schedule 2 will be 
0.03 mg/kg (DL 5) or lower. A minimum of 3 subjects will be evaluated in each DL during dose 
escalation on Schedule 2. A minimum 3-day stagger between dosing the first and second subject 
at the same DL is required. The incidence of DLT will be assessed over a period of 28 days 
during the first cycle of therapy for Schedule 2. 
 
Evaluation of a Less Frequent Dosing Schedule: If safety and pharmacodynamic data from 
Schedule 1 support exploration of a less intensive dosing schedule, then cohort enrollment on this 
as yet to be identified schedule will be instituted in lieu of Schedule 1.  
 
After dosing has been completed at each dose level, safety, PK and PD data (as applicable) will be 
reviewed, and dose escalation decisions will be made by the SMC (composed of the Sponsor 
Representatives and the Principal Investigators). Dose escalation decisions will also take into 
consideration safety information beyond the DLT period from prior dose levels. In addition, if the 
SMC determines that, in the absence of DLTs, enrollment of additional subjects is required in 
order to better determine PK or safety, enrollment of an additional 3 subjects may be undertaken 
at 1 or more of the dose levels already studied. Should more than 3 subjects be accrued to a dose 
level for reasons other than DLT/toxicity, the decision to escalate further may be made after the 
first 3 subjects clear the DLT window period.  
 
Pharmacodynamic Cohorts: The Sponsor, in consultation with the SMC, may elect to open a 
pharmacodynamic cohort in order to obtain additional pharmacodynamic data from a total of 
approximately 6 additional subjects at one or more dose levels that have previously completed 
evaluation for safety and has not exceeded the MTD. Subjects enrolled in the pharmacodynamic 
cohort will not inform dose escalation decisions but the pharmacodynamic information gathered 
from these additional subjects may inform selection of doses for further evaluation in dose 
expansion. 
3.3 Dose Expansion 
Based on accumulating data from the dose escalation phase, including safety, PK, 
pharmacodynamic and anti-tumor activity, up to two Dose Expansion Cohorts may be opened for 
enrollment. The expansion cohorts could potentially begin enrollment prior to the end of dose 
escalation.  A minimum of 6 subjects must be evaluated at the dose level to be expanded to confirm 


Shattuck labs, Inc                                                                                   Statistical Analysis Plan for SL01-DEL-101 
SL-279252                                                                                                                       
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safety and tolerability prior to expansion. One or two doses of SL-279252 (on the same schedule, 
i.e., only one schedule will be evaluated in the expansion phase) may be expanded.  
3.4 Study Assessments and Procedures  
The detailed study assessments and procedures are described in Section 6 of the protocol.  
4. SAMPLE SIZE 
If only Schedule 1 is evaluated, the maximum planned sample size is 42 for dose escalation. If 
Schedule 1 and 2 are both fully evaluated in dose escalation, the maximum planned sample size is 
57. If pharmacodynamic cohorts are opened in dose escalation, the maximum sample size is 48 if 
schedule 1 is fully evaluated or 63 if Schedule 1 and 2 are fully evaluated. The sample size in each 
Expansion Cohort is ~15 subjects. Overall, the total sample size estimate for this study is ~ 78 
subjects assuming only Schedule 1 is evaluated and pharmacodynamic cohorts are opened and ~93 
subjects if both Schedule 1 and 2 are fully evaluated and pharmacodynamic cohorts are opened. 
5. GENERAL ANALYSIS CONSIDERATIONS 
5.1  Reporting Conventions 
The statistical analyses will be reported using summary tables, figures, and data listings. The 
International Conference on Harmonisation (ICH) numbering convention will be used for all 
tables, listings, and figures.  
Data from all participating sites will be pooled prior to data summary or analysis. It is anticipated 
that subject accrual will be spread thinly across sites and summaries of data by site will not be 
informative and therefore, will not be provided.   
Unless specified otherwise, all summary tables will be presented by dose schedule/level for all 
subjects in the analysis population. Subjects from dose escalation and pharmacodynamic cohorts 
will be pooled. Summaries will be provided for each expansion cohort separately if data warrants. 
All individual subject data listings will be presented by dose level, dose schedule and subject, 
unless specified otherwise. Data from all assessments, whether scheduled or unscheduled, will be 
included in the listings. Listings will present the data in their original format (without any 
imputation), unless specified otherwise.  
Summaries by planned time point will include data from scheduled assessments and all data will 
be reported according to the nominal visit for which it will be recorded (i.e., no visit windows will 
be applied). Unscheduled data, when summarized, will be included only in calculation of the 
maximum or minimum value over time such as worst-case post-baseline. If multiple assessments 
are reported on the same date for the same scheduled planned time, the worst-case result will be 
analyzed.  


Shattuck labs, Inc                                                                                   Statistical Analysis Plan for SL01-DEL-101 
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Continuous variables will be summarized with means, standard deviations, medians, minimums, 
and maximums. The precision of the original measurements will be maintained in summaries and 
listings, when possible. Generally, means and medians will be presented to one more decimal place 
than the raw data, and the standard deviations will be presented to two more decimal places than 
the raw data. 
Categorical variables will be summarized by counts and by percentages of subjects in the 
corresponding categories. Percentages are routinely based on the total number of the specified 
population N if not otherwise specified. For frequency counts, categories whose counts are zero 
will be displayed for the sake of completeness. For example, if none of the subjects discontinue 
du
-
with zero counts will not have zero percentages displayed.  
All confidence intervals (CIs) will be constructed at the 95% confidence level, unless specified 
otherwise. 
All analyses and tabulations will be performed using SAS  v9.4 or above.  
5.2 Data Handling 
The following sections provide a general description of the derived and transformed variables 
used to describe and analyze the data.  
5.2.1 Missing Data  
Missing data occurs when any requested data is not provided, leading to blank field on the 
to be missing data and should be displayed as such.  
For the time to event endpoints including duration of response (DOR), progression free survival 
(PFS), and overall survival (OS), the missing data handling method will be censoring. Censoring 
mechanisms for these endpoints are described in Section 8.   
The length of study treatment for each subject will depend on the safety, tolerability and efficacy 
of the treatment, so the duration of treatment will vary across subjects. Similarly, the duration of 
follow up for survival will also vary.  All time to event endpoints will be analyzed using suitable 
statistical methods. 
In the event that the study is prematurely discontinued, the study team will review the data to 
assess which statistical analyses are still considered appropriate. 
5.2.2 Baseline and Change from Baseline 
Unless otherwise specified, the baseline value is defined as the last value obtained on or before the 
date and time of the first SL-279252 dose on Cycle 1 Day (C1D1). Post-baseline values are defined 
as value obtained after the first dose of SL-279252.  


Shattuck labs, Inc                                                                                   Statistical Analysis Plan for SL01-DEL-101 
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Change from baseline is calculated as: 
 Post-baseline value - baseline value 
The percent change from baseline is calculated as: 
 (Post-baseline value - baseline value)*100/baseline value  
If either baseline or post-baseline value is missing, the change from baseline and percent change 
from baseline will be missing.  
5.2.3 Study Day, Duration, and Time from Event  
The reference date for age calculation is the date of consent form signed as age is an eligibility 
requirement. The reference date for safety, efficacy and other data analyses is the date of the first 
dose.  
 
 Study Day  Study Day 1 is defined as the date of the first dose; the day before the first 
dose is defined as Study Day -1. There is no study day 0. For a given event date, Study Day 
is calculated relative to the date of the first dose of study drug. 
Study Day = [Event Date  First Dose Date] (in days) + 1 day,  
 
where the event date is on or after the first dose date. 
Study Day = [Event Date  First Dose Date] (in days),  
 
where the event date is before the first dose date. 
 Duration (Days)  A duration is calculated as the stop date minus the start date plus one. 
Duration (days) = [Stop Date  Start Date] (in days) + 1 day. 
 Time since an event -Time since an event (e.g. time since initial diagnosis) is calculated 
as the reference date minus the event date. For time since initial diagnosis, the reference 
date is the first dose of study treatment.  
 Time to an event - Time to an event (e.g. time to response, PFS, OS) is calculated as the 
event date minus the reference date+1. For time to response, PFS and OS, the first dose of 
study treatment is the reference date.  
 
To convert days to months, divide the number of days by 30.4375 (365.25/12) and round to one 
decimal place.   
5.2.4 Imputation of Partial Date 
In general, imputed partial dates will not be used to derive study day or duration variables, unless 
otherwise specified. No partial dates imputation will be performed for time to event endpoint 
analysis. Any imputed partial data will be flagged in the analysis datasets to indicate the level of 
imputation. Imputed dates will not be displayed in the data listings. 
 


Shattuck labs, Inc                                                                                   Statistical Analysis Plan for SL01-DEL-101 
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6. ANALYSIS POPULATIONS 
For the analysis, the following populations are defined: 
Table 3. Analysis Populations 
Population 
Description 
Screened 
All subjects who sign the main study informed consent form. 
Screen Failures 
A subject who signs the informed consent but has not received any dose 
of SL-279252. 
All Treated 
All subjects who receive at least one dose of SL-279252. Safety data will
be evaluated based on this population. 
DLT Evaluable 
All subjects in the dose escalation cohorts and All Treated Population 
who receive at least 2 doses of SL-279252 for Schedule 1 and at least 3 
doses for Schedule 2 during the DLT evaluation period, complete the 
safety follow up through DLT evaluation period or experience any DLT 
during the DLT evaluation period. The DLT evaluation period is defined 
as the first 21 days or 28 days of treatment on Schedule 1 or Schedule 2, 
respectively. 
Efficacy Evaluable 
All subjects in the All Treated Population who received at least 3 doses 
of SL-279252 and had at least one disease assessment or had progressed 
or died before the first post-baseline disease assessment.  
Immunogenicity 
Population 
All subjects in the All Treated Population who had at least one evaluable 
immunogenicity assessment. 
7. STUDY POPULATION 
Unless specified otherwise, all summary tables and data listings for this section will be based on 
the All Treated Population.  
7.1 Subject Disposition 
Summaries of subject disposition information will include the number of subjects in each analysis 
population, and the primary reason for end of study participation and treatment discontinuation. 
Subject disposition information will be presented in a data listing. 
7.2 Protocol Deviations 
Incidence of major protocol deviations, minor protocol deviations, and all deviations will be 
summarized by deviation categories. A listing will be provided with all protocol deviations . None 
of the deviations will lead to subjects being excluded from any analysis populations. Other select 


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categories of protocol deviations including but not limited to COVID-19 related deviations may 
be listed or summarized. 
7.3 Demographic and Baseline Characteristics 
Demographic variables include age, sex, ethnicity, and race. Other baseline characteristics include 
weight and height. 
Descriptive statistics will be presented for age, weight, and height. Frequency counts and 
percentages will be presented for age groups 18-<65 years, 65-
), gender, 
ethnicity and race. All demographic and baseline characteristics will be presented in a data listing.  
7.4 Study Cancer History and Prior Cancer Therapy 
Study cancer history and prior cancer therapy will be summarized in tables and presented in data 
listings. For the calculation of time from initial diagnosis and time since progression on most recent 
regimen, if there are partial dates of initial diagnosis or partial dates of progression on most recent 
 
7.5 General Medical History 
General medical history will be presented in a data listing. 
7.6 Study Drug Exposure 
SL-279252 average dose received, number of doses received, duration of treatment, and dose 
compliance will be summarized.  
 
Subject average dose is calculated as the cumulative dose (mg) that a subject received divided by 
the total number of doses received.   
 
Duration of SL-279252 treatment will be summarized in weeks by continuous descriptive statistics 
and in the following categories: <= 4 weeks, > 4 - 8 weeks, > 8 - 16 weeks, > 16 - 24 weeks, > 24 
- 48 weeks, > 48 weeks. The duration of treatment is defined as: 
 Minimum of (date of death plus 1 day, data cutoff date plus 1 day, and date of last dose + 
14 days for bi-weekly dosing schedule or + 7 days for weekly dosing schedule)  date of 
first study drug administration Dose compliance is defined as the total mg of SL-279252 
taken divided by the total mg of SL-279252 assigned based on study schedule, expressed 
as a percentage.  
7.7 Prior and Concomitant Medications 
Verbatim terms on electronic case report forms (eCRFs) will be mapped to Anatomical 
Therapeutic Chemical (ATC) class and Generic Drug Names using the World Health Organization 
(WHO) Drug Dictionary Global B3 format, September 1, 2018 release.  


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Prior medications are defined as medications that end prior to the date of the first dose of study 
treatment. Concomitant medications are defined as medications taken on or after the date of the 
first dose of study drug. Any medications that started prior to the date of the first dose but continued 
beyond the date of first dose will be counted as concomitant medications.  
If both the start and end dates are completely missing, the medication will be considered 
concomitant. For cases where start or end dates are partially recorded, the following imputation 
algorithms will be used for the purpose of determining prior or concomitant medications: 
 Missing start day, but month and year present: 
If year and month are same as first dosing year and month, assign the day of first dosing date to 
the partial date. Otherwise, assign 1st of the month to the partial date. 
 
 Missing start day and month, but year present: 
If year is same as first dosing year, assign the month and day of first dosing date to the partial date. 
Otherwise, assign January 1st to the partial date. 
 
 Missing end day, but month and year present: 
If year and month are same as end of study participation year and month, assign the day of end of 
study participation to the partial date. Otherwise, assign the last day of the month to the partial 
date. 
 
 Missing end day and month, but year present: 
If year is same as end of study participation year, assign the month and day of end of study 
participation date to the partial date. Otherwise, assign December 31st to the partial date. 
If the study is ongoing (e.g. interim analysis) and the study end date is not available, the cut-off 
date will be used instead. 
Prior and concomitant medications along with dose, route, start/end date, and indication for each 
medication will be presented in a data listing.  
7.8 Concomitant Procedures 
Concomitant procedures along with the procedure dates and indications will be presented in a data 
listing. 
8. EFFICACY ANALYSES 
The efficacy analysis will be based on the All Treated population and/or Efficacy Evaluable 
population, as appropriate. The efficacy endpoints include ORR, CBR, time to response (TTR), 
DOR, tumor size change from baseline for target lesions, PFS, and OS.  
 
Response assessment will be based on the iRECIST for solid tumors and RECIL 2017 for 
lymphoma. Radiographic disease assessment must be performed at screening, and at the following 
intervals until a disease progression is confirmed: every 8 weeks through week 24, every 12 weeks 


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up to year 2 and then every 6 months up to conclusion of the study. Disease assessment window 
is +/- 1 week.  Confirmatory assessments should be performed at least 4 weeks (
28 days) after 
the initial documentation of an objective response or an unconfirmed disease progression. Subjects 
who discontinue study treatment for reasons other than disease progression will be monitored for 
radiologic response until start of new anti-cancer therapy, disease progression, withdrawal of 
consent or death.  
8.1 ORR Based on iRECIST for Solid Tumors 
8.1.1 Time Point Tumor Response based on iRECIST 
The iRECIST guidelines are based on principles used in RECIST 1.1. The response assigned using 
iRECIST have 
differentiate them from responses assigned using RECIST 1.1). The overall responses at each 
assessment per iRECIST is as the following: 
 Complete Response (iCR) 
 Partial Response (iPR) 
 Stable Disease (iSD) 
 Unconfirmed Progressive Disease (iUPD) and Confirmed Progressive Disease (iCPD) 
 Not evaluable (NE) = NE 
8.1.2 Analysis of ORR based on iRECIST 
The ORR based on iRECIST is defined as the proportion of subjects whose best overall response 
is a confirmed iCR or confirmed iPR. The analysis of ORR per iRECIST will be conducted by 
schedule/dose level for all solid tumors and selected tumor types as appropriate in the All Treated 
population and Efficacy Evaluable population. The ORR will be estimated with a 95% CI using 
the exact probability method. The number and percent of subjects with the best overall response 
of iCR, iPR, iSD, iUPD, iCPD and NE will be summarized. The overall response at each visit 
along the best overall response based on iRECIST will be presented in a data listing. 
8.1.3 Derivation of Best Overall Response based on iRECIST 
The best overall response based on iRECIST is defined as the best overall response among all post-
baseline timepoint assessments until the first iCPD or the last assessment if an iCPD has not been 
observed. Based on the investigator assessment of overall response at all post-baseline 
assessments, the best overall response will be determined according to the following:  
 iCR > iPR > iSD > iCPD (iUPD if no iCPD) > NE 
 iCR = iCR must be confirmed at least 4 weeks later.  
 iPR = iPR must be confirmed at least 4 weeks later.  
 iSD = at least one iSD or better  49 days after the first dose date and not qualifying for an 
iCR or iPR. The minimum interval from the first dose date for the best response of iSD is 
8 weeks minus 7 days to allow for the visit windows of ± 7 days (49 days).   


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 iCPD = iUPD must be confirmed by a subsequent assessment at least 4 weeks later to have 
iCPD. 
 iUPD = iUPD is not confirmed by a subsequent assessment at least 4 weeks later and not 
qualifying for iSD or better.   
 Clinical deterioration will not be considered as documented disease progression. 
8.2 ORR Based on RECIST 1.1 for Solid Tumors 
8.2.1 Time Point Tumor Response based on RECIST 1.1 
The overall responses at each time point assessment per RECIST 1.1 is derived from the overall 
response per iRECIST as the following: 
 Complete Response (CR) = iCR 
 Partial Response (PR) = iPR 
 Stable Disease (SD) = iSD 
 Progressive Disease (PD) = iUPD or iCPD 
 Not evaluable (NE) = NE 
8.2.2 Analysis of ORR based on RECIST 1.1 
The ORR based on RECIST 1.1 is defined as the proportion of subjects whose best overall 
response before the first PD is a confirmed CR or confirmed PR.  The analysis of ORR per RECIST 
1.1 will be conducted by schedule/dose level for all solid tumors and selected tumor type as 
appropriate in the All Treated population and Efficacy Evaluable population. The ORR will be 
estimated with a 95% CI using the exact probability method. The number and percent of subjects 
with the best overall response of CR, PR, SD, PD and NE will be summarized. The best overall 
response based on RECIST 1.1 will be presented in a data listing. 
8.2.3 Derivation of Best Overall Response based on RECIST 1.1 
The best overall response based on RECIST 1.1 is defined as the best overall response among all 
post-baseline timepoint assessments until the first PD per RECIST 1.1 (the first iUPD per 
iRECIST) or the last assessment if PD has not been observed. Based on the investigator assessment 
of overall response at all post-baseline assessments, the best overall response will be determined 
according to the following:  
 CR > PR > SD > PD > NE 
 CR = at least two determinations of CR at least 4 weeks apart before progression. 
 PR = at least two determinations of PR or better at least 4 weeks apart before progression 
(and not qualifying for CR). 
 
49 days after the first dose and before progression (and 
not qualifying for a CR or PR). The minimum interval from the first dose date for the best 
response of SD is 8 weeks minus 7 days to allow for visit windows of ± 7 days (49 days).   


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 Clinical deterioration will not be considered as documented disease progression. 
Table 4. Best overall response when confirmation of CR and PR required. 
Overall response  
First time point 
Overall response 
Subsequent time point 
BEST overall response 
CR 
CR 
CR 
CR 
PR 
SD, PD or PRa
CR 
SD 
SD provided minimum criteria for SD duration met, otherwise, PD
CR 
PD 
SD provided minimum criteria for SD duration met, otherwise, PD
CR 
NE 
SD provided minimum criteria for SD duration met, otherwise, NE
PR 
CR 
PR 
PR 
PR 
PR 
PR 
SD 
SD 
PR 
PD 
SD provided minimum criteria for SD duration met, otherwise, PD
PR 
NE 
SD provided minimum criteria for SD duration met, otherwise, NE
NE 
NE 
NE 
CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease,  
NE = not evaluable. 
a If a CR is truly met at first time point, then any disease seen at a subsequent time point, even disease meeting PR 
criteria relative to baseline, makes the disease PD at that point (since disease must have reappeared after CR). Best 
when subsequent scans suggest small lesions were likely still present and in fact the patient had PR, not CR at the 
first time point. Under these circumstances, the original CR should be changed to PR and the best response is PR. 
8.3 ORR Based on RECIL 2017 for Lymphomas 
8.3.1 Response assessment based on RECIL 2017 
The response assessment at each assessment per RECIL 2017 is as the following: 
 Complete Response (CR) 
 Partial Response (PR) 
 Minor Response (MR) 
 Stable Disease (SD) 
 Progressive Disease (PD) 
 Not evaluable (NE) 
8.3.2 Analysis of ORR based on RECIL 2017 
The ORR based on RECIL 2017 is defined as the proportion of subjects whose best overall 
response is a CR or PR. The analysis of ORR per RECIL 2017 will be conducted in the All Treated 
population and Efficacy Evaluable population if data warrants. ORR will be estimated with a 95% 
CI using the exact probability method. The number and percent of subjects with the best overall 




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SD
PD
Any
No
SD 
NE/missing 
SD/PR/CR 
Yes 
SD 
NE/missing 
PD/NE/missing 
No 
CR/PR/SD/NE 
SD 
Any 
Yes 
 
The analysis of CBR will be conducted by schedule/dose level for all solid tumors and selected 
tumor types as appropriate in the All Treated population and Efficacy Evaluable population. The 
CBR will be estimated with a 95% CI using the exact probability method.  
8.5 Time to Response 
TTR based on iRECIST is defined as the time from the first dose until the first documentation of 
a subsequently confirmed objective response (confirmed iCR or confirmed iPR). Only subjects 
who have achieved objective response will be evaluated for TTR.  
 
TTR based on RECIST is defined as the time from the first dose until the first documentation of a 
subsequently confirmed objective response (confirmed CR or confirmed PR). Only subjects who 
have achieved objective response will be evaluated for TTR.  
 
TTR based on RECIL 2017 is defined as the time from the first dose until the first documentation 
of an objective response (CR or PR). Only subjects who have achieved objective response will be 
evaluated for TTR. 
 
If data warrants, the median and quartiles of TTR and their 95% CIs will be assessed using the 
Kaplan-Meier method and Brookmeyer and Crowley (1982) method, respectively, and TTR will 
be presented in a data listing. 
8.6 Duration to Response 
DOR based on iRECIST is defined as time from the date of initial response (iCR or iPR confirmed 
at least 28 days later) to the date of first documented disease progression that is confirmed or death, 
whichever occurs first. Only subjects who have achieved objective response (confirmed iCR or 
confirmed iPR) will be evaluated for DOR. The censoring guidance and the date of PD/death or 
censoring are same as that for PFS in Section 8.9.1.   
 
DOR based on RECIST 1.1 is defined as time from the date of the first CR or PR (confirmed at 
least 28 days later) to the date of first documented disease progression (confirmed or not) or death, 
whichever occurs first. Only subjects who have achieved objective response (confirmed CR or 
confirmed PR) will be evaluated for DOR. If a disease progression does not occur, DOR will be 
censored as of the date of their last evaluable disease assessment. The censoring guidance and the 
date of PD/death or censoring are same as that for PFS in Section 8.9.2.    
 
DOR based on RECIL 2017 is defined as time from the date of the first CR or PR to the date of 
first documented disease progression (confirmed or not) or death, whichever occurs first. Only 


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subjects who have achieved objective response (CR or PR) will be evaluated for DOR. If a disease 
progression does not occur, DOR will be censored as of the date of their last evaluable disease 
assessment. The censoring guidance and the date of PD/death or censoring are same as that for 
PFS in Section 8.9.3.    
 
If data warrants, the median and quartiles of DOR and their 95% CIs will be assessed using the 
Kaplan-Meier method and Brookmeyer and Crowley (1982) method, respectively, and the DOR 
will be presented in a data listing.   
8.7 Change from Baseline in Tumor Size 
For response assessment based on iRECIST for solid tumors, the percent change from baseline in 
target lesion sum of diameters will be presented by subject using spider plots. The percent change 
from baseline will only be calculated when all target lesions at baseline are also present and 
measurable at a post baseline visit. The best percent change from baseline in target lesion sum of 
diameters is defined as the largest reduction or smallest increase (in the case where a reduction 
does not occur) from baseline observed over all post-baseline disease assessments up to and 
including the first PD. The best percent change from baseline will be presented using a waterfall 
plot. 
  
For response assessment based on RECIL 2017 for lymphoma, the percent change from baseline 
in target lesion sum of diameters will be presented by subject using spider plots if data warrants. 
The best percent change from baseline in target lesion sum of longest diameters is defined as the 
largest reduction or smallest increase (in the case where a reduction does not occur) from baseline 
observed over all post-baseline disease assessments up to and including the first PD. The best 
percent change from baseline will be presented using a waterfall plot if data warrants. 
8.8 Other Response Data Analysis 
Tumor assessment at baseline, including sum of target lesion diameters, number of subjects with 
target lesions and non-target lesions will be summarized in the All Treated Population for solid 
tumors and lymphoma, respectively, if data warrants. 
 
For solid tumors response assessment based on iRECIST, lesion assessment including target lesion 
measurements and sum of diameters, non-target lesions and new lesions will be presented in data 
listings. 
 
For lymphoma response assessment based on RECIL 2017, lesion assessment including target 
lesion measurements and sum of diameters, non-target lesions and new lesions will be presented 
in data listings. 
8.9 Progression Free Survival 
The PFS data analysis will be based on iRECIST and RECIST 1.1 for solid tumors and RECIL 
2017 for lymphoma using All Treated Population. 






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If data warrants, the median and quartiles of PFS and their 95% CIs will be assessed using the 
Kaplan-Meier method and Brookmeyer and Crowley (1982) method, respectively. The proportion 
of subjects that are progression free and alive at 12, 24, 48, 72, 96 weeks and other timepoints of 
interest and associated 95% CI will be estimated using the Kaplan-Meier method if data warrants. 
8.10 Overall Survival 
OS is defined as time from the first day of treatment to the date of death. A subject alive at the end 
of study or lost to follow-up will be censored for OS at the last date when the subject was known 
to be alive. 
 
The median and quartiles of OS and their 95% CIs will be assessed using the Kaplan-Meier method 
and Brookmeyer and Crowley (1982) method, respectively. The proportion of subjects alive at 12, 
24, 48, 72, 96 weeks and other timepoints of interest and associated 95% CI will be estimated 
using the Kaplan-Meier method. Summary of OS will be provided for the All Treated population 
for solid tumors and lymphoma, respectively, if data warrants. 
8.11 Statistical Considerations 
8.11.1 Adjustments for Covariates 
There are no adjustments for covariates in this study. 
8.11.2 Handling of Dropouts or Missing Data 
For the efficacy variables no imputations will be made for missing values except as noted in 
considering a NE response. 
8.11.3 Interim Analysis and Data Monitoring 
No interim analyses for this study. 
8.11.4 Multiple Comparison/Multiplicity 
No adjustments for multiplicity will be made in this study. 
8.11.5 Multicenter Studies 
There are no planned analyses to compare differences in response by center.  
9. PHARMACOKINETIC AND PHARMACODYNAMIC ANALYSES 
Separate analysis plans will be provided for PK and PD data.  
10. IMMUNOGENICITY ANALYSES 
Anti-drug antibodies (ADA) data will be listed and summarized as appropriate.  


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11. SAFETY ANALYSES 
Unless specified otherwise, all safety analyses will be based on the All Treated population. Safety 
analyses will include MTD evaluation, AEs, laboratory test results (hematology, chemistry, 
coagulation, thyroid), vital signs and Eastern Cooperative Oncology Group (ECOG). 
11.1 Maximum Tolerated Dose Evaluation 
The MTD evaluation will be based on the DLT Evaluable Population. The number and percentage 
of subjects with DLT during the dose escalation phase will be presented by dose level and 
schedule. The MTD level will be indicated in the summary as appropriate. For single subject 
ade 2 toxicities that trigger a change to at least 3 subject cohorts will also 
be specified in the table footnotes. 
 
The MTD will be estimated using isotonic regression (based on the DLTs observed in the DLT 
evaluable subjects). A MAD will be reported if a schedule is fully evaluated, but the DLT rate is 
less than 25% for all dose levels. Otherwise, an MTD will be reported. Isotonic regression is a way 
to estimate the MTD under the assumption that toxicity increases with dose. When using isotonic 
regression, the first step is to identify the doses where the dose-toxicity monotonicity assumption 
is violated. The DLT estimate is then adjusted for the violators such that the final estimate of the 
DLT rate increases with the dose. The target DLT rate is then used to select the MTD. For example, 
suppose that when the trial is completed, the observed DLT rates [# subjects who experienced 
DLT]/[# evaluable subjects] at five dose levels are (0/3, 1/3, 0/3, 4/15, 2/4). In this example the 
observed DLT rate at Dose Level 2 (i.e., 1/3=33%) is higher than the observed DLT rate at Dose 
Level 3 (i.e., 0/3=0%). To adjust for this violation, the DLT estimates are replaced with their 
average, i.e., (1/3+0/3)/2=1/6, resulting in the isotonic regression DLT estimates (0/3, 1/6, 1/6, 
4/15, 2/4) = (0%, 16.7%, 16.7%, 26.7%, 50%), which monotonically increases with the dose level. 
Based on this isotonic estimate, assuming that the trial goal is to find the dose with the DLT rate 
of 30%, Dose Level 4 will be selected as the MTD. If there are no violators of the dose-toxicity 
monotonicity assumption, isotonic regression directly uses the observed DLT rates as the final 
estimates for MTD selection. For subjects who undergo intra-subject dose escalation, only DLTs 
 
 
In the case of dose levels with estimated toxicity of equal distance (tied dose levels) from the target 
toxicity of 30%, the following approach will be used: among all tied dose levels the highest dose 
> 30%, in which case the lowest dose level will be selected. 
11.2 Adverse Events 
AE terms on the eCRFs will be mapped to preferred terms (PT) and system organ classes (SOC) 
using the Medical Dictionary for Regulatory Activities (MedDRA) Version 26.0. 
Drug-related AEs are defined as AEs with relationship to study treatment being related or possible 
related. A worst-case scenario approach will be taken to handle missing data, i.e. AEs with missing 
relationship to study drug will be treated as drug-related AEs.  


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All AEs with onset dates on or after the first dose of study treatment are defined as treatment-
emergent adverse events (TEAEs). Only TEAEs will be included in AE tables.  
If both the start and end dates are completely missing, the AE will be considered treatment- 
emergent. Partial start and end dates will be imputed similarly as described for prior and 
concomitant medications in Section 7.7 for the purpose of determining treatment-emergent and 
AE duration. 
The AE summaries that are displayed by SOC and PT will be ordered by descending order of 
incidence of SOC and PT within each SOC based on the total number of subjects. The following 
summaries will be presented. 
 Overall Summary of TEAEs. 
 Subject incidence of all TEAEs, drug-related TEAEs, immune related TEAEs by MedDRA 
SOC, PT and maximum toxicity grade. At each level of subject summarization, a subject 
is classified to the highest toxicity grade if the subject reported one or more events. 
 Subject incidence of all TEAEs, serious TEAE, drug-related TEAEs, and drug-related 
serious TEAEs by PT. 
 Subject incidence of all TEAEs with toxicity grade 3 or 4 by PT. 
 DLT for dose escalation cohorts. 
 Subject incidence of all TEAEs leading to drug interruptions and permanent 
discontinuation of study treatment by PT. 
 Subject incidence of immune related TEAEs leading to permanent discontinuation of study 
treatment by PT. 
 Subject incidence of deaths within and outside of 30 days of last dose and cause of death. 
All AEs, immune related AEs (irAEs), immune related SAEs (irSAEs), drug-related AEs, Grade 
3 or 4 AEs, drug-related Grade 3 or 4 AEs, DLTs for dose escalation cohorts, SAEs, fatal AEs,  
AEs leading to drug interrupted, dose reduced, or drug withdrawal, infusion related reaction signs 
and symptoms and death will be presented in data listings. Pretreatment AE, defined as AEs that 
start prior to the first dose of the study treatment, will be flagged in relevant listings. AEs for the 
Screen Failures population will also be presented in a data listing.  
11.3 Clinical Laboratory Evaluation 
Laboratory results (hematology, chemistry, coagulation and thyroid) will be summarized for worst 
case shift from baseline in tables and presented in data listings. 
Frequencies of maximum observed Grade 0-4 toxicity, as defined by the NCI CTCAE v5.0, will 
be presented by laboratory parameter. The analysis will present maximum grade observed. 
Separate summaries indicating hyper- and hypo- directionality of change will be produced, where 
appropriate. 


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 to the normal 
ranges as data allows. For those laboratory parameters that do not have NCI CTCAE v5.0 grading 
criteria, worst case shift from baseline to post-baseline will be summarized. If a subject has worst 
case 
 
Subjects with elevated worst post-baseline Alanine aminotransferase (ALT), Aspartate 
aminotransferase (AST), total bilirubin, or Alkaline phosphatase (ALP) values that fall into the 
following categories will be identified and summarized: 
 ALT in the categories of <=1x upper limit of normal range (ULN), >1x ULN, >3x ULN;  
 AST in the categories of <=1x ULN, >1x ULN, >3x ULN; 
 total bilirubin in the categories of <=1x ULN, >1x ULN, >2x ULN 
 ALP in the categories of <=1x ULN, >1x ULN, >1.5x ULN, >2x ULN  
 P
-dose total bilirubin > 2 x ULN 
occurred at the same day or after the first incidence date of ALT or AST > 3 x ULN post 
treatment. 
11.4 Vital Signs 
Vital signs and changes from baseline will be presented in a data listing. 
11.5 ECOG Performance Status 
ECOG performance status scores will be summarized for baseline, and maximum case shift from 
baseline in a table and presented in a data listing. 
12. CHANGE FROM PROTOCOL-SPECIFIED ANALYSES 
The following modifications have been made to the protocol-specified analyses: 
1. It is clarified in statistical SAP Section 6 that all subjects who have signed the main study ICF 
are defined as Screened Population, instead of Enrolled Population. 
2. It is clarified in SAP Section 6 that the DLT Evaluable Population derivation is for the 
subjects enrolled in the dose escalation cohorts. 
13. REFERENCES 
1. National Cancer Institute Common Terminology Criteria for Adverse Events v5.0, NCI, NIH, 
DHHS, November 27, 2017. 
2. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid 
tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47. 
3. Ivanova A, Qaqish BF, Schell MJ. Continuous toxicity monitoring in phase II trial in oncology. 
Biometrics 2005;61:540-5. 
4. Seymour L, Bogaerts J, Perrone A, et al. iRECIST: guidelines for response criteria for use in 
trials testing immunotherapeutics. Lancet Oncol 2017;18:e143-e52. 
5. Yan F, Mandrekar SJ, Yuan Y. Keyboard: a novel bayesian toxicity probability interval design 
for phase I clinical trials. Clin Cancer Res 2017;23:3994-4003. 


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6. Younes A, Hilden P, Coiffier B, et al. International Working Group consensus response 
evaluation criteria in lymphoma (RECIL 2017). Ann Oncol 2017;28:1436-47. 
7. Brookmeyer, R. and Crowley, J. (1982). A confidence interval for the median survival time. 
Biometrics 38 29-41. 
14. APPENDIX:  LIST OF TABLES, FIGURES, AND LISTINGS 
14.1 List of Tables  
ICH 
Heading 
Table 
Number 
Table Description 
Analysis 
Population  
14.1 
 
Demographics 
 
 
14.1.1 
Study Populations and Subject Disposition 
All Screened 
 
14.1.2 
Study Treatment Status 
All Treated 
 
14.1.3 
Protocol Deviations 
All Treated 
 
14.1.4 
Demographic and Baseline Characteristics 
All Treated 
 
14.1.5 
Study Cancer History 
All Treated 
 
14.1.6 
Prior Anti-Cancer Treatment 
All Treated 
14.2 
 
Efficacy 
 
 
14.2.1 
Objective Response with Confirmation Based on iRECIST 
for Subjects with Solid Tumors
All Treated 
 
14.2.2 
Objective Response with Confirmation Based on iRECIST 
for Subjects with Solid Tumors 
Efficacy 
Evaluable 
 
14.2.3 
Objective Response with Confirmation Based on RECIST 
1.1 for Subjects with Solid Tumors 
All Treated 
 
14.2.4 
Objective Response with Confirmation Based on RECIST 
1.1 for Subjects with Solid Tumors 
Efficacy 
Evaluable 
 
14.2.5 
Time to Response and Duration of Response Based on 
iRECIST for Subjects with Solid Tumors 
Efficacy 
Evaluable 
 
14.2.6 
Time to Response and Duration of Response Based on 
RECIST 1.1 for Subjects with Solid Tumors  
Efficacy 
Evaluable 
 
14.2.7 
Progression-Free Survival Based on iRECIST for Subjects 
with Solid Tumors 
All Treated 
 
14.2.8 
Progression-Free Survival Based on RECIST 1.1 for 
Subjects with Solid Tumors 
All Treated 
 
14.2.9 
Overall Survival for Subjects with Solid Tumors 
All Treated 
 
14.2.10 
Tumor Assessment at Baseline for Subjects with Solid 
Tumors 
All Treated 
14.3 
 
Safety 
 
14.3.1 
 
Study drug exposure/adverse event  
 
 
14.3.1.1 
Study Drug Exposure  
All Treated 
 
14.3.1.2 
Overall Summary of Treatment-Emergent Adverse Events  
All Treated 
 
14.3.1.3 
All Treatment-Emergent Adverse Events by System Organ 
Class, Preferred Term and Maximum Toxicity Grade 
All Treated 


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ICH 
Heading 
Table 
Number 
Table Description 
Analysis 
Population  
 
14.3.1.4 
Drug-Related Treatment-Emergent Adverse Events by 
System Organ Class, Preferred Term and Maximum Toxicity 
G d
All Treated 
 
14.3.1.5 
Immune Related Treatment-Emergent Adverse Events by 
Preferred Term and Maximum Toxicity Grade  
All Treated 
 
14.3.1.6 
All Treatment-Emergent Adverse Events by Preferred Term  
All Treated 
 
14.3.1.7 
Serious Treatment-Emergent Adverse Events by Preferred 
Term  
All Treated 
 
14.3.1.8 
Drug-Related Treatment-Emergent Adverse Events by 
Preferred Term  
All Treated 
 
14.3.1.9 
Drug-Related Serious Treatment-Emergent Adverse Events 
by Preferred Term  
All Treated 
 
14.3.1.10 
Treatment-Emergent Adverse Events with Toxicity Grade 3 
or 4 by Preferred Term  
All Treated 
 
14.3.1.11 
Dose Limiting Toxicities  
DLT Evaluable 
 
14.3.1.12 
Treatment-Emergent Adverse Events leading to Drug 
Interrupted by Preferred Term  
All Treated 
 
14.3.1.13 
Treatment-Emergent Adverse Events leading to Drug 
Withdrawn by Preferred Term  
All Treated 
 
14.3.1.14 
Immune Related Treatment-Emergent Adverse Events 
leading to Drug Withdrawn by Preferred Term 
All Treated 
 
14.3.1.15 
Deaths 
All Treated 
14.3.5 
 
Laboratory 
 
 
14.3.5.1 
Hematology  Maximum CTCAE Grade Shift from Baseline 
All Treated 
 
14.3.5.2 
Chemistry  Maximum CTCAE Grade Shift from Baseline  
All Treated 
 
14.3.5.3 
Coagulation and Thyroid Function Test  Maximum CTCAE 
Grade Shift from Baseline  
All Treated 
 
14.3.5.4 
Laboratory Tests without CTCAE - Maximum Shift from 
Baseline with Respect to Normal Range  
All Treated 
 
14.3.5.5 
Post-Baseline Potential Serious Hepatoxicity 
All Treated 
14.3.6 
 
Other Safety Data 
 
 
14.3.6.1 
ECOG Performance Status  Maximum Shift from Baseline 
All Treated 
14.3.7 
 
Immunogenecity 
 
 
14.3.7.1 
SL-279252 Immunogenecity 
Immunogenecity 
 
 
 
 


Shattuck labs, Inc                                                                                   Statistical Analysis Plan for SL01-DEL-101 
SL-279252                                                                                                                       
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14.2   List of Figures  
 
14.3   List of Data Listings   
ICH 
Heading 
Listing 
Number 
Listing Description 
Analysis 
Population  
16.2 
 
SUBJECT DATA LISTINGS 
 
16.2.1 
 
Discontinued subjects 
 
 
16.2.1.1 
Study Population and Subject Disposition 
All Screened 
 
16.2.1.2 
Study Treatment Discontinuation  
All Treated 
 
16.2.1.3 
Informed Consent and Protocol Amendment Re-Consent 
All Treated 
16.2.2 
 
Protocol deviations 
 
 
16.2.2.1 
Protocol Deviations 
All Treated 
 
16.2.2.2 
COVID-19 Related Protocol Deviations 
All Treated 
 
16.2.2.3 
Inclusion and Exclusion Criteria Violations 
Screened 
16.2.4 
 
Demographics  
 
 
16.2.4.1 
Demographic and Baseline Characteristics 
All Treated 
 
16.2.4.2 
Medical History 
All Treated 
 
16.2.4.3 
Study Cancer History 
All Treated 
 
16.2.4.4 
Prior Anti-Cancer Systemic Treatment 
All Treated 
 
16.2.4.5 
Prior Radiotherapy 
All Treated 
 
16.2.4.6 
Prior Surgery Treatment 
All Treated 
 
16.2.4.7 
Prior and Concomitant Medications 
All Treated 
 
16.2.4.8 
Concomitant Procedures 
All Treated 
16.2.5 
 
Study Drug Exposure 
 
 
16.2.5.1 
Study Drug Administration (I) 
All Treated 
ICH 
Heading
Figure 
Number 
Figure Description 
Analysis 
Population  
14.2 
14.2.1 
Horizontal Bar Plot of Duration of Treatment by Response for Subjects 
with Solid Tumors   
All Treated 
 
14.2.2 
Waterfall Plot of Target Lesions Maximum Reduction in Sum of 
Lesion Diameters for Subjects with Solid Tumors 
All Treated 
 
14.2.3 
Plot of Target Lesions Percent Change from Baseline Sum of Lesion 
Diameters Over Time for Subjects with Solid Tumors 
All Treated 
 
14.2.4 
Kaplan-Meier Plot of Duration of Response Based on iRECIST and 
iRECIST 1.1 for Subjects with Solid Tumors 
Efficacy 
Evaluable 
 
14.2.5 
Kaplan-Meier Plot of Progression-Free Survival Based on iRECIST  
and RECIST 1.1 for Subjects with Solid Tumors   
All Treated 
 
14.2.6 
Kaplan-Meier Plot of Overall Survival for Subjects with Solid Tumors  
All Treated 


Shattuck labs, Inc                                                                                   Statistical Analysis Plan for SL01-DEL-101 
SL-279252                                                                                                                       
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ICH 
Heading 
Listing
Number 
Listing Description 
Analysis 
Population  
 
16.2.5.2 
Study Drug Administration (II) 
All Treated 
16.2.6 
 
Individual efficacy response data 
 
 
16.2.6.1 
Tumor Assessment for Subjects with Solid Tumors: Target Lesions 
All Treated 
 
16.2.6.2 
Tumor Assessment for Subjects with Solid Tumors: Non-Target 
Lesions 
All Treated 
 
16.2.6.3 
Tumor Assessment for Subjects with Solid Tumors: New Lesions  
All Treated 
 
16.2.6.4 
Tumor Responses Based on iRECIST for Subjects with Solid 
Tumors
All Treated 
 
16.2.6.5 
Tumor Responses Based on RECIST 1.1 for Subjects with Solid 
Tumors
All Treated 
 
16.2.6.6 
Tumor Assessment for Subjects with Lymphomas: Target Lesions  
All Treated 
 
16.2.6.7 
Tumor Assessment for Subjects with Lymphomas: Non-Target 
Lesions 
All Treated 
 
16.2.6.8 
Tumor Assessment for Subjects with Lymphomas: New Lesions  
All Treated 
 
16.2.6.9 
Tumor Responses Based on RECIL for Subjects with Lymphomas 
All Treated 
 
16.2.6.10 
Time to Response and Duration of Response for Subjects with 
Solid Tumors 
Efficacy 
Evaluable 
 
16.2.6.11 
Time to Response and Duration of Response for Subjects with 
Lymphomas 
Efficacy 
Evaluable
 
16.2.6.12 
Progression-Free Survival Based on iRECIST for Subjects with 
Solid Tumors
All Treated 
 
16.2.6.13 
Progression-Free Survival Based on RECIST 1.1 for Subjects with 
Solid Tumors
All Treated 
 
16.2.6.14 
Progression-Free Survival for Subjects with Lymphomas 
All Treated 
 
16.2.6.15 
Overall Survival for Subjects with Solid Tumors 
All Treated 
 
16.2.6.16 
Overall Survival for Subjects with Lymphomas 
All Treated 
16.2.7 
 
Adverse Event Listings 
 
 
16.2.7.1 
All Adverse Events 
All Treated 
 
16.2.7.2 
Dose Limiting Toxicities  
DLT evaluable 
 
16.2.7.3 
Drug-Related Adverse Events 
All Treated 
 
16.2.7.4 
Adverse Events with Toxicity Grade 3 or 4 
All Treated 
 
16.2.7.5 
Drug-Related Adverse Events with Toxicity Grade 3 or 4 
All Treated 
 
16.2.7.6 
Fatal Adverse Event 
All Treated 
 
16.2.7.7 
Serious Adverse Events 
All Treated 
 
16.2.7.8 
Immune Related Adverse Events 
All Treated 
 
16.2.7.9 
Immune Related Serious Adverse Events 
All Treated 
 
16.2.7.10 
Adverse Events Leading to Drug Interrupted 
All Treated 
 
16.2.7.11 
Adverse Events Leading to Dose Reduced  
All Treated 


Shattuck labs, Inc                                                                                   Statistical Analysis Plan for SL01-DEL-101 
SL-279252                                                                                                                       
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ICH 
Heading 
Listing
Number 
Listing Description 
Analysis 
Population  
 
16.2.7.12 
Adverse Events Leading to Drug Withdrawn  
All Treated 
 
16.2.7.13 
Infusion Reaction Signs and Symptoms 
All Treated 
 
16.2.7.14 
Death  
All Treated 
 
16.2.7.15 
All Adverse Events for Screen Failure Subjects  
Screen Failure 
16.2.8 
 
Individual Laboratory Measurements 
 
 
16.2.8.1 
Hematology  
All Treated 
 
16.2.8.2 
Clinical Chemistry  
All Treated 
 
16.2.8.3 
Coagulation and Thyroid Function 
All Treated 
16.2.9 
 
Listing of other safety data  
 
 
16.2.9.1 
Vital Signs and Pulse Oximetry  
All Treated 
 
16.2.9.2 
ECOG Performance Status 
All Treated 
16.2.10 
 
Immunogenecity 
 
 
16.2.10.1 
SL-279252 Immunogenecity 
Immunogenecity