Conditions: Cutaneous Squamous Cell Carcinoma Squamous Cell Carcinoma of Head and Neck
Keywords: intratumoral injection
Allocation: NA | Intervention model: SEQUENTIAL
Enrollment: 5
Healthy volunteers: no

Brief summary:
This is a Phase 1 open-label, multi-center, dose-escalation study to evaluate the safety, PK, anti-tumor activity, and pharmacodynamic effects of SL-172154 administered by intratumoral injection in subjects with cutaneous squamous cell carcinoma (CSCC) or squamous cell carcinoma of the head and neck (SCCHN).

Detailed description:
This Phase 1 trial will evaluate the safety, tolerability, pharmacokinetics, anti-tumor activity and pharmacodynamic effects of SL-172154 when administered as an intratumoral injection (ITI) and identify the dose and schedule i.e., recommended Phase 2 dose (RP2D) for future development. Eligible subjects must have unresectable or recurrent, locally advanced or metastatic squamous cell carcinoma of the skin or head and neck, that is not amenable to curative surgery or radiotherapy. The study design consists of four sequential dose-escalation cohorts and an optional pharmacodynamic cohort to obtain additional pharmacodynamic data at one or more dose levels that have completed evaluation for safety without exceeding the maximum tolerated dose (MTD).

Arms:
arm 1: Intratumoral administration

Interventions: intervention 1: Drug: SL-172154
Intervention descriptions: intervention 1: The investigational product (IP), SL-172154, is a novel fusion protein consisting of human SIRPα and CD40L (SIRPα -Fc-CD40L) linked via a human Fc.

Protocol document:
Prot_000.pdf: 
CONFIDENTIAL
SL03-OHD-102 
Compound: SL-172154 
Version no: 1.0 
1
Protocol Title: Phase 1 Dose Escalation Study of the Agonist Redirected 
Checkpoint, SL-
-Fc-CD40L), Administered Intratumorally in 
Subjects with Cutaneous Squamous Cell Carcinoma or Squamous Cell Carcinoma 
of the Head and Neck
Short Title: Phase 1 Study of SL-172154 (SIRP -Fc-CD40L) Administered Intratumorally in 
Subjects with Cutaneous Squamous Cell Carcinoma or Squamous Cell Carcinoma of the Head 
and Neck
Protocol Identifying Number: SL03-OHD-102 
Version Number: v1.0
Compound Number: SL-172154 
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: 149427 
NCT: 
Approval Date: 10 July 2020 
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
SL03-OHD-102 
Compound: SL-172154 
Version no: 1.0  
2
Shattuck Labs Document Number
Date
Version
SL03-OHD-102_00 
28 May 2020 
Original 
SL03-OHD-102_01 
10 July 2020 
Amendment No. 1 
Rationale for Amendment Changes
The protocol is amended to address comments by the United States FDA during review of the 
IND (149427) for SL-172154.  
Summary of Changes / See Appendix 16.6 for the complete delineation of changes made to the 
protocol for Amendment 01.
1.
Revised section 5.1.4 Monitoring Dose Administration to specify that subjects must be 
monitored for injection-related reactions and cytokine-release syndrome for a minimum 
of 6 hours following intratumoral injection of SL-172154.  
2.
The protocol is modified to include ECG monitoring at Tmax after the first dose. In 
addition, a predose ECG assessment on cycle 2 day 1 has been added for safety purposes 
after repeated dosing as no accumulation of SL-172154 is expected.  
3.
The maximum number of target lesions assessed per RECIST v1.1 will be 10 lesions 
instead of 5 lesions. 


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TABLE OF CONTENTS
TABLE OF CONTENTS................................................................................................................ 3
LIST OF TABLES.......................................................................................................................... 8
LIST OF FIGURES ........................................................................................................................ 8
LIST OF ABBREVIATIONS......................................................................................................... 9
KEY TRIAL CONTACTS ........................................................................................................... 14
STUDY SCHEMA........................................................................................................................ 15
PROTOCOL SYNOPSIS ............................................................................................................. 16
1.
INTRODUCTION, BACKGROUND AND STUDY RATIONALE ................................... 26
1.1
Background Information ................................................................................................ 26
1.2
Investigational Product, SL-172154 ............................................................................... 27
1.2.1 
Mechanism of Action .............................................................................................. 27
1.2.2 
In Vitro Pharmacology ............................................................................................ 29
1.2.3 
In Vivo Pharmacology ............................................................................................ 29
1.2.3.1
-Fc-CD40L in Combination with Anti-CTLA-4, 
Anti-PD-1 or ADCC-Competent Antibodies ..................................................................... 30
1.2.3.2
-Fc-CD40L Monotherapy and in 
Combination with Murine Anti-PD-1 Antibody ................................................................ 31
1.2.4 
Toxicology .............................................................................................................. 31
1.3
Rationale for Investigation of SL-172154 by Intratumoral Administration .................. 33
1.3.1 
Rationale for Selection of Tumor Types Under Investigation ................................ 34
1.3.1.1
Cutaneous Squamous Cell Carcinoma of the Skin .......................................... 34
1.3.1.2
Squamous Cell Carcinoma of the Head and Neck .......................................... 35
1.4
Potential Risks and Benefits of SL-172154 ................................................................... 36
1.4.1 
Potential Risks ........................................................................................................ 36
1.4.2 
Potential Benefits .................................................................................................... 39
2.
STUDY OBJECTIVES AND OUTCOME MEASURES ..................................................... 42
3.
STUDY DESIGN .................................................................................................................. 44
3.1
Description of Study Design .......................................................................................... 44
3.2
Selection of Recommended Phase 2 Dose ..................................................................... 45
3.2.1 
Sample Size ............................................................................................................. 45
3.3
Justification for Starting Dose and Schedule of SL-172154 .......................................... 45
3.4
Dose Escalation of SL-172154 Administered by Intratumoral Injection ....................... 46
3.5
Definition of Dose-Limiting Toxicity ............................................................................ 47
3.6
Concomitant Medications, Treatments, and Procedures ................................................ 49


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3.6.1 
Prohibited Medications/Treatments ........................................................................ 49
3.6.2 
Medications to be used with Caution ...................................................................... 50
3.7
Toxicity Management Guidelines Dosing Delays/Dose Modifications ......................... 50
3.7.1 
Toxicity Management Guidelines ........................................................................... 52
Injection Site Reactions ..................................................................................................... 52
Injection-Related or Hypersensitivity Reactions ............................................................... 54
Cytokine-release Syndrome ............................................................................................... 56
irAEs - General .................................................................................................................. 58
Hepatotoxicity .................................................................................................................... 59
Anemia ............................................................................................................................... 61
Thrombocytopenia ............................................................................................................. 62
Influenza-like Symptoms ................................................................................................... 63
3.7.2 
Management of Other AEs Not Specified .............................................................. 64
3.8
Antibody Detection and Compatibility Testing for Transfusion ................................... 65
3.9
Discontinuation of Study Therapy ................................................................................. 66
3.10
Criteria to Resume Treatment ........................................................................................ 66
3.11
Participant Discontinuation/Withdrawals from Study ................................................... 66
3.12
Lost to Follow-up ........................................................................................................... 67
3.13
Duration of Treatment .................................................................................................... 67
3.14
Duration of Follow-Up ................................................................................................... 67
3.15
Premature Termination or Suspension of Study ............................................................ 68
3.16
End of Study Definition ................................................................................................. 68
4.
STUDY POPULATION ........................................................................................................ 68
4.1
Participant Inclusion Criteria ......................................................................................... 68
4.2
Participant Exclusion Criteria ........................................................................................ 71
4.3
Screen Failures ............................................................................................................... 73
4.4
Accrual Goal .................................................................................................................. 73
5.
PHARMACEUTICAL PRODUCT INFORMATION .......................................................... 74
5.1
Investigational Product (SL-172154) ............................................................................. 74
5.1.1 
Investigational Product Description ........................................................................ 74
5.1.2 
Preparation/Handling/Storage of SL-172154/Investigational Product ................... 74
5.1.2.1
Preparation ....................................................................................................... 74
5.1.2.2
Handling .......................................................................................................... 75
5.1.2.3
Storage ............................................................................................................. 75


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5.1.3 
Investigational Product Accountability ................................................................... 75
5.1.4 
Monitoring Dose Administration ............................................................................ 75
5.1.5 
Treatment of Investigational Product Overdose ..................................................... 76
5.2
Drug Accountability and Treatment Compliance .......................................................... 76
6.
STUDY ASSESSMENTS AND PROCEDURES ................................................................ 77
6.1
SOA Table for ITI Dose Escalation of SL-172154 ........................................................ 78
6.1.1
Supplementary Tables for SL-172154 PK/ADA Sampling Times ......................... 82
6.1.2 
Correlative Sample Time Points for SL-172154 .................................................... 83
6.2
Demographics, Medical History, Screening and Safety Assessments ........................... 84
6.2.1 
Informed Consent.................................................................................................... 84
6.2.2
Eligibility Criteria ................................................................................................... 84
6.2.3
Subject Demographics ............................................................................................ 84
6.2.4 
Medical History ...................................................................................................... 84
6.2.5 
Concomitant Medications ....................................................................................... 84
6.3
Safety Evaluations .......................................................................................................... 84
6.3.1 
Physical Examination.............................................................................................. 84
6.3.2 
ECOG Performance Status ..................................................................................... 84
6.3.3 
Pulse Oximetry........................................................................................................ 84
6.3.4 
Vital Signs ............................................................................................................... 85
6.3.5 
Electrocardiogram Monitoring for QTc Evaluation ............................................... 85
6.3.6 
Laboratory Assessments ......................................................................................... 86
6.3.6.1
Clinical Labs Performed Locally ..................................................................... 86
6.3.6.2
Central Labs ..................................................................................................... 87
6.3.6.3
Ad Hoc Labs for SAEs .................................................................................... 87
6.3.6.4
Pregnancy Testing ........................................................................................... 87
6.3.6.5
Blood Type and Screen (ABO/Rh) and DAT .................................................. 88
6.4
Pharmacokinetics ........................................................................................................... 88
6.4.1 
Intensive PK Sampling in Dose Escalation ............................................................ 88
6.5
Anti-drug Antibody Assessments .................................................................................. 88
6.6
Pharmacodynamic/Biomarker Assessments .................................................................. 88
6.6.1 
Pharmacodynamic Assessments in Blood .............................................................. 88
6.6.1.1
Cytokine and Chemokine Analysis ................................................................. 88
6.6.1.2
PBMC for Immunophenotyping ...................................................................... 89
6.6.2 
Pharmacodynamic Assessment of Tumor Tissue ................................................... 89


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6.6.2.1
Fresh Tumor Biopsies ...................................................................................... 89
6.6.2.2
Archival Tumor ............................................................................................... 91
6.7
Assessment of Anti-tumor Activity................................................................................ 91
6.8
SL-172154 Administration by Intratumoral Injection ................................................... 91
6.8.1
Baseline Lesion Identification ................................................................................ 91
6.8.2 
Definition of Lesion Injectability............................................................................ 92
6.8.3
General Instructions for Injection ........................................................................... 92
6.8.4 
Prioritization of Lesions for Injection ..................................................................... 92
6.8.5
Documentation of Intratumoral Injections .............................................................. 93
6.9
Unscheduled Visit .......................................................................................................... 93
7.
SAFETY ASSESSMENTS ................................................................................................... 93
7.1
Definitions for Safety Parameters .................................................................................. 94
7.1.1 
Events not Qualifying as AEs/SAEs ....................................................................... 95
7.2
Classification of an Adverse Event ................................................................................ 96
7.2.1 
Assessment of Severity ........................................................................................... 96
7.2.2 
Assessment of Causality ......................................................................................... 97
7.2.3 
Expectedness ........................................................................................................... 97
7.3
Timing for Event Assessment and Follow-up ................................................................ 97
7.4
Procedures for Recording and Reporting of Adverse Events ........................................ 98
7.5
Reporting of Pregnancy .................................................................................................. 99
7.6
Reporting of Overdose ................................................................................................... 99
7.7
Study Halting Rules ....................................................................................................... 99
7.8
Safety Oversight ........................................................................................................... 100
8.
ANTI-TUMOR ACTIVITY ASSESSMENTS ................................................................... 100
8.1
Response Assessment ................................................................................................... 100
8.1.1 
Assessment of Response ....................................................................................... 101
8.2
Criteria for Treatment Beyond Initial Progression ....................................................... 101
9.
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS ...................................... 102
9.1
Study Design and Sample Size Determinations ........................................................... 102
9.2
Statistical Analyses ...................................................................................................... 104
9.2.1 
Analysis Populations ............................................................................................. 104
9.2.2 
Interim Analyses ................................................................................................... 104
9.2.3 
General Data Analysis Consideration ................................................................... 104
9.2.4 
Safety Analyses ..................................................................................................... 105


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9.2.5 
Efficacy Analyses ................................................................................................. 105
9.2.6 
Pharmacokinetic Analysis ..................................................................................... 105
9.2.6.1
Anti-Drug Antibody Analysis ....................................................................... 106
9.2.7 
Pharmacodynamics Analyses................................................................................ 106
10. CLINICAL MONITORING ................................................................................................ 106
11. SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA AND DOCUMENTS ... 107
11.1
Source Data .................................................................................................................. 107
11.2
Access to Data .............................................................................................................. 107
11.3
Data Recording and Record Keeping ........................................................................... 107
12. QUALITY ASSURANCE PROCEDURES ........................................................................ 107
13. ETHICS/PROTECTION OF HUMAN SUBJECTS ........................................................... 108
13.1
Ethical Standard ........................................................................................................... 108
13.2
Institutional Review Board/Institutional Ethics Committee ........................................ 108
13.3
Informed Consent Process ............................................................................................ 108
13.3.1
Consent/Assent and Other Informational Documents Provided to Subjects ........ 108
13.3.2
Consent Procedures and Documentation .............................................................. 109
13.4
Participant and Data Confidentiality ............................................................................ 109
13.4.1
Research Use of Stored Human Samples, Specimens, or Specimen Data ............ 110
13.5
Future Use of Stored Specimens .................................................................................. 110
14. DATA HANDLING AND RECORD KEEPING ............................................................... 110
14.1
Communication and Data Dissemination Plan............................................................. 110
14.2
Data Collection and Management Responsibilities ..................................................... 111
14.3
Study Records Retention .............................................................................................. 111
14.4
Protocol Deviations ...................................................................................................... 112
14.5
Publications and Data Sharing Policy .......................................................................... 112
15. LITERATURE REFERENCES .......................................................................................... 113
16. APPENDICES ..................................................................................................................... 117
16.1
mTPI-2 Dose Escalation Scenarios .............................................................................. 117
16.2
ECOG Performance Status Criteria.............................................................................. 119
16.3
Contraception Requirements ........................................................................................ 120
16.3.1
Pregnancy Status ................................................................................................... 121
16.4
Cockcroft-Gault Formula for Creatinine Clearance ..................................................... 122
16.5
RECIST 1.1 .................................................................................................................. 123
16.5.1
RECIST 1.1 Criteria.............................................................................................. 123


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16.5.2
Evaluation of Response......................................................................................... 124
16.6
Summary of Changes for Amendment 01 .................................................................... 125
LIST OF TABLES
Table 1: Intratumoral Dose Escalation Plan for SL-172154 ......................................................... 47
Table 2: Serial PK/ADA (C1/D1-24 hours postdose, C1D15 – 24 hrs postdose, C2D1 – 24 hours 
postdose) ....................................................................................................................................... 82
Table 3: Serial PK/ADA (C4/D1 and Beyond)............................................................................. 83
Table 4: Immunophenotyping and Cytokine Time Points ............................................................ 83
Table 5: Dose Escalation Decision Rules for Each Dose Level based on mTPI-2..................... 103
Table 6: Serum SL-172154 PK Parameters ................................................................................ 106
LIST OF FIGURES
Figure 1: Mechanism of Action of SL-172154 Alone or Combined with an ADCC-competent mAb
....................................................................................................................................................... 28
Figure 2: ITI Schedule for SL-172154 .......................................................................................... 47


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LIST OF ABBREVIATIONS
Ab 
Antibody
ADA
Anti-drug antibodies
ADCC
Antibody dependent cell-mediated cytotoxicity
ADCP
Antibody dependent cellular phagocytosis
ADL
Activities of daily living
AE
Adverse event
AIMV
Alstroemeria-Mosaic Virus
AK
Actinic keratosis
ALT
Alanine aminotransferase
AML
Acute myeloid leukemia
APTT
Activated partial thromboplastin time
APC
Antigen presenting cell
AR
Adverse reaction
ARC
Agonist redirected checkpoint
AST
Aspartate aminotransferase
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
-hCG
Beta- human chorionic gonadotropin
BP
Blood pressure
°C
Degrees Celsius
CBC
Complete blood count
CD
Cluster of differentiation
CD40L
Cluster of differentiation 40 ligand
C1D1
Cycle 1, day 1
CFR
Code of Federal Regulations
cGAS
Cyclic guanine monophosphate-adenosine monophosphate synthase
CL
Clearance
Cm 
Centimeters
Cmax
Maximum observed concentration
Cmin
Minimum observed concentration
CMP
Clinical monitoring plan
CO2
Bicarbonate
CR
Complete response
CrCl
Creatinine clearance
CRF
Case report form
CRS
Cytokine release syndrome
CSCC
Cutaneous squamous cell carcinoma


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CT
Computed tomography
CTCAE
Common terminology criteria for adverse event
CTLA-4
Cytotoxic T cell lymphocyte-associated antigen 4
CYP450
Cytochrome P450
DAT
Direct antiglobulin test
DC
Dendritic cells
DLT(s)
Dose-limiting toxicity(ies)
DOR
Duration of response
DRF
Dose range finding
EC
Effective concentration
ECD
Extracellular domain
ECG
Electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
Electronic Case Report Form
EGFR
Epidermal growth factor receptor
EOI
End of injection(s)
FCBP
Female of childbearing potential
FDA
Food and Drug Administration
FFPE
Formalin-fixed paraffin-embedded
FP
Fusion protein
FSH
Follicle stimulating hormone
GCP
Good Clinical Practice
GITR
Glucocorticoid-induced tumor necrosis factor receptor
GLP
Good Laboratory Practice
H1/H2
Histamine 1/ Histamine 2
HBsAg
Hepatitis B surface antigen
HBV
Hepatitis B virus
HCV
Hepatitis C virus
Hgb
Hemoglobin
HNSCC
Head and neck squamous cell carcinoma
hr (time)
Hour(s)
HR
Heart rate
HSR(s)
Hypersensitivity reaction(s)
Hu5F9-G4
Human 5F9 (i.e., anti-CD47 monoclonal antibody)
IB
Investigator brochure
ICF
Informed consent
ICH
International Conference of Harmonisation
IEC
Institutional Ethics Committee
Interferon gamma
Ig
Immunoglobulin
IHC
Immunohistochemistry
IL
Interleukin
IND
Investigational new drug
INR
International normalized ratio
i.p.
Intraperitoneal


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IP
Investigational product
irAE
Immune-related adverse event
IRB
Institutional Review Board
irSAE
Immune-related serious adverse event
ISR
Injection site reactions
ITI
Intratumoral injection
IV 
Intravenous or intravenously
KA
Keratoacanthoma
Kd
Receptor off-rate constant
Kg
Kilogram
LDH
Lactate dehydrogenase
m2
Square meter
mAb(s)
Monoclonal antibody(ies)
MABEL
Minimum anticipated biological effect level
MAD
Maximum administered dose 
MDS
Myelodysplastic syndrome
mg
Milligrams
mg/dL
Milligrams per deciliter
mg/kg
Milligrams per kilogram
Min
Minutes
mL
milliliter
mm
millimeter
MMF
Mycophenolate mofetil
Mmol
Millimole
MRI
Magnetic resonance imaging 
MTD
Maximum tolerated dose 
mTPI-2
Modified toxicity probability interval 2
NCI
National Cancer Institute
NHP
Non-human primate
Ng
Nanogram
NK
Natural killer
nM
Nanomolar
NOAEL
No observed adverse effect level
NSAID(s)
Non-steroidal anti-inflammatory drug(s)
ORR
Objective response rate
PBMC
Peripheral blood mononuclear cells
PD
Progressive Disease
PD-1
Programmed cell death protein 1
PD-L1 / PD-L2
Programmed cell death ligand 1 / Programmed cell death ligand 2
PK
Pharmacokinetic
PK/PD
Pharmacokinetic/pharmacodynamic
pM
Picomolar
PR
Partial response
PT
Prothrombin time
QTcB
QT duration corrected for heart rate by Bazett’s formula


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QTcF
QT duration corrected for heart rate by Fridericia’s formula
RBC
Red blood cell
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
SCC
Squamous cell carcinoma
SCCIS
Squamous cell carcinoma in situ
scFv
Single-chain variable fragment
SD
Stable disease
SL-172154
-Fc-CD40L agonist redirected checkpoint 
SLM
Study Lab Manual
SMC
Safety Monitoring Committee
SOA
Schedule of Assessments
SPM
Study Pharmacy Manual
STING
Stimulator of interferon genes
SUSAR
Suspected, unexpected serious adverse reaction
T
Temperature
T4
Thyroxine 4
t½
terminal elimination half-life
Signal regulatory protein alpha
TK
Toxicokinetic 
Tlast
Time of last observed quantifiable concentration
Tmax
Time of maximum observed concentration
TME
Tumor microenvironment
TNF-
Tumor necrosis factor alpha
TSH
Thyroid stimulating hormone
TTR
Time to tumor response
TXT
Treatment
µg
Microgram
ULN
Upper limit of normal
UP
Unanticipated problems
Vz 
Volume of distribution
WBC
White blood cell
Wk
Week
Terminal elimination rate constant
~
Approximately
º
Degree
Trademark Information
Trademarks of Shattuck Labs, Inc.
Trademarks not owned by Shattuck Labs, Inc.
Agonist Redirected Checkpoint (ARC™)
FluroTec®


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STATEMENT OF COMPLIANCE
The trial will be conducted in accordance with the protocol and the International Council for 
Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines, and applicable Federal 
Regulations on the Protection of Human Subjects, and consistent with the consensus ethical 
principles derived from international guidelines including the Declaration of Helsinki and Council 
for International Organizations of Medical Sciences International Ethical Guidelines. 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: ______________ 






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PROTOCOL SYNOPSIS
Sponsor
Shattuck Labs
Product Name
SL-172154
Other Names
-Fc-CD40L recombinant fusion glycoprotein
Protocol Title
Phase 1 Dose Escalation Study of the Agonist 
Redirected Checkpoint, SL-
-Fc-
CD40L), Administered Intratumorally in Subjects 
with Cutaneous Squamous Cell Carcinoma or 
Squamous Cell Carcinoma of the Head and Neck
Protocol Number
SL03-OHD-102
Clinical Phase
Phase 1
Planned Sample Size
Approximately 18 subjects
Planned Number of Sites & Countries
Approximately 4-6 clinical sites in the United States
Recruitment Duration:
Approximately 12 months (1 year)
Study Duration
Estimate is 20 months from when the study opens to 
enrollment until completion of data analyses
Background and Rationale
The investigational product, SL-
-Fc-CD40L) linked via a human Fc. Fusi
type 1 membrane protein, with CD40L, a type 2 membrane protein, generated a single molecule with 
dual specificity that retained individual target avidity. The mechanism of action of SL-172154 is 
designed to pair the increased phagocytic activity of macrophages through CD47-
the costimulatory role of CD40L in augmenting the antigen cross-presenting ability of dendritic cells. 
In vitro, SL 172154 was shown to bind to its cognate targets, CD47 and CD40, both individually and 
simultaneously. High binding affinity for CD47 and CD40 was noted as well as a slow off rate (KD 
values of 0.628 nM and 4.74 nM, respectively), indicating a longer on target resident time. This longer 
resident time could be of benefit in the tumor microenvironment (TME) where CD47 is known to be 
expressed. CD40-mediated activity by SL-172154 was demonstrated in a NFkB reporter system in 
which CD40-dependent signaling was stimulated in the absence of Fc receptor cross-linking, and in 
cultured human peripheral blood mononuclear cells (PBMCs) in which dose-dependent proliferation, 
an increase in the number of interleukin-2 secreting PBMCs, and the secretion of multiple cytokines 
were observed.
-Fc-CD40L intravenously (IV) led to a significant early and sustained 
activation of murine dendritic cells (CD8+ and CD4+ DC) which matched the duration of activation 
observed with murine CD40 antibodies. This finding confirmed a previous report that CD47 blockade 
in vivo leads to rapid upregulation of CD86 and MHC-II on splenic CD8 + DCs [Yi, 2015]. The in
vivo anti-
-Fc-CD40L monotherapy was studied in established syngeneic 
CT26 colorectal murine tumor models. The performance of intraperitoneal (i.p.) administration of 
-Fc-CD40L was compared to treatment with CD47 blocking antibodies, CD40 agonist 
antibodies, the combination of the two antibodies and vehicle control. These experiments demonstrated 
-Fc-CD40L led to higher rates of primary tumor rejection (63%) than either antibody given 
as monotherapy (anti-CD40, 0% and anti-CD47, 0%), or the antibody combination treatment group 
(33%). To assess the durability of an immune response without re-treatment, mice that rejected the 
initial tumor were re-challenged with a second CT26 tumor on the opposite flank on day 40. Of the 2 
mice initially cured with the antibody combination, 0 mice rejected the tumor challenge. In the 
-Fc-CD40L group, 3 of 5 (60%) mice rejected the tumor re-challenge, suggesting that a 


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memory response was generated against the tumor which led to protection against a subsequent tumor 
challenge. Additionally, a robust increase in AH1 tetramer +/CD8+ cells in the spleen and the tumor 
-Fc-CD40L or the anti-CD40/anti-CD47 combination in 
comparison to vehicle controls. 
The anti-
-Fc-CD40L, given by intratumoral injection (ITI), as monotherapy 
and in combination with murine anti PD-1 antibody was assessed in groups of female BALB/c mice 
inoculated with a CT26 colorectal carcinoma tumor in each rear flank.  The mice were dosed on Days 
-
Fc-
-Fc-CD40L (10 or 100 µg; ITI); and the combination of anti-PD-1 
(100 µg; i.p) and mSIRP -Fc-CD40L (10 or 100 µg; ITI).  
-Fc-CD40L, a delay in tumor growth 
-Fc-CD40L was the most efficacious with 14% 
of mice completely rejecting both tumors. The rejection rate of both tumors was increased to ~42% 
-Fc-CD40L was combined with i.p. anti-PD-1 treatment. Thus, intratumoral 
-Fc-CD40L showed potent anti-tumor efficacy in both the treated (injected
-Fc-CD40L) and untreated tumor, suggesting that intratumoral
-Fc-CD40L 
stimulated sufficient immune activation to promote an anenestic or bystander anti-tumor response. 
Moreover, no signs of injection site reactions, such as ulceration and inflammation, were observed with 
-Fc-CD40L. Systemic depletion of peripheral B cells and an increase in 
-Fc-CD40L were not 
-Fc-CD40L, supporting that much lower systemic exposure 
occurred following ITI. These findings support the hypothesis that direct injection of SL-172154 into 
a tumor can achieve a high local concentration of SL-172154 using relatively lower doses of drug than 
would be required with IV administration. 
Two repeat IV dose toxicity studies in cynomolgus monkeys had similar trends in toxicokinetic 
parameters and demonstrated on-target pharmacological activity of SL-172154. The onset of antidrug 
antibodies (ADA), elevations in serum cytokines, activation of complement, and postdose changes in 
lymphocyte counts were similar between the dose range finding and Good Laboratory Practice (GLP) 
studies. The dose-dependent, infusion-related reactions observed with repeat dosing in the GLP study  
were attributed to exacerbated pharmacology of SL-172154 in the presence of ADA. Given the low 
ITI doses to be studied in clinical study SL03-OHD-102, low systemic exposure is anticipated in 
comparison to IV infusion, and thus the IV no observed adverse effect level of 1 mg/kg in monkeys 
provides systemic exposure and safety coverage. Consequently, the nonclinical safety assessment 
program supports the intratumoral administration of SL-172154 in the clinical study SL03-OHD-102. 
This trial is designed to evaluate the safety, pharmacokinetics, anti-tumor activity and 
pharmacodynamic effects of SL-172154 administered by ITI on days 1, 8, 15 of a 21-day in cycle 1 
and then on day 1 of each subsequent 21-
have locally advanced or metastatic squamous cell carcinomas of the head and neck or skin that are not 
amenable to further treatment with surgery, radiation or standard systemic therapies that are known to 
provide clinical benefit for their condition. 
Cutaneous squamous cell carcinoma (CSCC) and squamous cell carcinoma of the head and neck 
(HNSCC) were selected for investigation in this phase 1 study of ITI SL-172154 due to the fact that 
both of these tumor types have 1) a high percentage of tumors with increased CD47 expression, 2) 
mechanisms of tumor immune evasion that target both adaptive and innate immunity within the tumor 
microenvironment [Ferris, 2015] and 3) patients with select tumor lesions that are accessible and safe 
for ITI.  


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Study Objectives
Primary Objective(s)
Outcome Measures
To evaluate the safety and tolerability of ITI 
administration of SL-172154 and to identify 
the maximum tolerated dose (MTD) or 
maximum administered dose (MAD) of SL-
172154 
Safety/tolerability outcomes include: incidence of all 
adverse events (AEs) and immune-related adverse 
events (irAE), serious adverse events (SAEs), fatal 
SAEs, dose limiting toxicity (DLT), AEs and irAEs 
leading to discontinuation, and changes in safety 
assessments (e.g., laboratory parameters, vital signs 
etc.) per National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI-
CTCAE – version 5.0).  
The MTD is defined based on the rate of DLTs and the 
MAD is the highest dose administered.
Secondary Objectives
Outcome Measures
To select the recommended Phase 2 dose 
(RP2D) for SL-172154 when administered by 
intratumoral injection (ITI)
Based on review of all data collected during dose 
escalation and the pharmacodynamic cohort including 
safety, tolerability, PK, anti-tumor activity, and 
pharmacodynamic effects
To assess preliminary evidence of anti-tumor 
activity of SL-172154 when administered by 
ITI
Response per investigator assessment according to 
Response Evaluation Criteria in Solid Tumors version 
1.1 (RECIST v1.1). 
Objective response rate (ORR) (proportion of 
subjects whose best response is a complete 
response [CR] or partial response [PR])
Time to response (TTR): time from the first dose 
until the first response (CR or PR, whichever is 
recorded first) that is subsequently confirmed  
Duration of response (DOR): time between first 
response (CR or PR, whichever is recorded first) 
that is subsequently confirmed and date of disease 
progression 
Change from baseline lesion diameter for injected 
lesion
Change from baseline lesion diameter for non-
injected lesion
To evaluate anti-drug antibodies (ADA) to 
SL-172154 when administered by ITI during 
and after treatment.
Number/proportion of subjects with positive ADA 
titer
ADA duration  
Transient vs. persistent ADA
To characterize the pharmacokinetics (PK) of 
SL-172154 when administered by ITI 
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-172154 
Area under the serum concentration-time curve 
(AUC)


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Terminal elimination half-life (t½), Clearance 
(CL) and Volume of Distribution (Vz)
Exploratory Objectives
Outcome Measures
To assess pharmacodynamic biomarkers in 
blood prior to, on-treatment and following 
SL-172154 when administered by ITI 
Pharmacodynamic biomarkers in blood may include:
Changes from baseline in cell counts and 
percentages of circulating immune cells such as: T 
cells, B cells, natural killer (NK) cells, and 
myeloid cells  
Circulating chemokine and cytokine levels
To assess pharmacodynamic biomarkers in 
tumor tissue prior to, on-treatment and 
following SL-172154 when administered by 
ITI
Pharmacodynamic biomarkers in tumor tissue may 
include: 
Presence of SL-172154 in tumor tissue 
Changes in T cells subsets,
B cells and 
macrophages and assessment of SL-172154 in the 
tumor tissue
CD47 and CD40 expression 
Programmed cell death ligand 1 (PD-L1) 
expression
To estimate progression-free survival (PFS)
PFS: time from first dose to progression by 
RECIST v1.1 or death, whichever comes first
Study Design
This clinical trial is an open label, multi-center, dose escalation, Phase 1 study of SL-172154 
administered by ITI injection. This trial is designed to evaluate the safety, PK, anti-tumor activity and 
pharmacodynamic effects of SL-172154 administered by ITI on days 1, 8, 15 of a 21-day in cycle 1 
and then on day 1 of each subsequent 21-
have locally advanced or metastatic squamous cell carcinomas of the head and neck or skin that are not 
amenable to further treatment with surgery, radiation or standard systemic therapies that are known to 
provide clinical benefit for their condition.
Dose escalation will utilize the modified Toxicity Probability Interval (mTPI-2) design [Guo, 2017] 
with target DLT rate of 30% for the MTD. The dose escalation decision rules are outlined in Table 5
in Section 9.1 of the protocol.  Subjects will be enrolled in cohorts of approximately 3 subjects into 
sequential dose levels of SL-172154 and evaluated for DLT during the 21-day DLT evaluation period 
starting from the first dose of SL-172154. At each dose level, a minimum 3-day stagger between dosing 
the first and second subject is required.  The planned dose escalation is in half-log increments. 
The Sponsor, in consultation with the SMC, may elect to open a pharmacodynamic cohort to obtain 
additional pharmacodynamic data from approximately 6 additional subjects at one or more dose levels
that have completed evaluation for safety without exceeding the MTD. Subjects in the 
pharmacodynamic cohort must have tumor accessible and safe for biopsy from both an injected lesion 
and a non-injected lesion and must consent to providing paired biopsies for translational research.  
Selection of the recommended phase 2 dose(RP2D) and schedule for SL-172154 monotherapy will be 
based upon the totality of the data in subjects treated in the dose escalation and the pharmacodynamic 
cohorts. The totality of the data refers to safety, tolerability, PK, clinical activity, and 
pharmacodynamic markers consistent with the mechanism of action. Approximately 6 subjects 
(inclusive of the subjects enrolled in the Dose Escalation and Pharmacodynamic cohort) may be treated 
at the RP2D. The planned total sample size for this study is approximately 18 subjects.


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Treatment Schedule
Schedule of administration for ITI of SL-172154: Doses administered on days 1, 8, 15 of a 21-day 
cycle in cycle 1 and on day 1 of each subsequent 21-day cycle, starting on cycle 2, day 1 (day 22). 
Dose Escalation Scheme
Dose Level
ITI Dose (mg) of SL-172154a
ITI Volume of Dose
Level 1 - starting dose
0.003
1.5 mL
Level 2
0.01
1.5 mL
Level 3
0.03
1.5 mL
Level 4
0.1
1.5 mL
a) Intermediate or higher dose levels may be tested based on emerging safety and/or 
pharmacodynamic data. Dose escalation will not exceed half-log increments.
Definition of Dose Limiting Toxicity
DLTs are as 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 of ITI SL-172154 dosing. Note: AEs 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 death not clearly related to underlying disease or extraneous causes 
Elevations in liver transaminases (aspartate aminotransferase [AST], alanine aminotransferase 
[ALT]) and/or total bilirubin:
o
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 AE that requires permanent discontinuation of SL-172154 
Any Grade 3 or greater AE with the following exceptions:  
o


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Definition of Dose Limiting Toxicity (continued)
o
Grade 3 anemia if not associated with clinical sequelae or not requiring transfusion of red blood 
cells (RBCs) within 48 hours.
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 injection-related reaction (first occurrence and in the absence of steroid prophylaxis) 
that resolves within 6 hours of onset with appropriate clinical management.  
o
Grade 3 rigors or chills lasting < 6 hours that respond to optimum medical therapy. 
o
Grade 3 fever lasting < 24 hours with or without medical therapy.
o
Grade 3 electrolyte abnormalities that are not associated with clinical signs/symptoms and are 
reversed with appropriate medical intervention 
o
Grade 3 laboratory abnormalities that are not deemed clinically significant by the SMC.
o
Indirect/unconjugated hyperbilirubinemia without significant clinical consequences 
o
Grade 3 or 4 amylase and/or lipase abnormalities that are not associated with clinical 
signs/symptoms or findings on imaging consistent with pancreatitis 
o
Grade 3 vomiting and/or Grade 3 nausea that resolves within 72 hours with appropriate clinical 
management
o
Grade 3 hypertension that can be controlled (i.e., systolic BP < 140 mmHg and diastolic BP < 
90 mmHg) with medical therapy.
o
Grade 3 endocrine disorder (thyroid, pituitary, hyperglycemia and/or adrenal insufficiency) 
that is managed with treatment with resolution of symptoms within 14 days after treatment 
onset. 
o
Grade 3 diarrhea with no evidence of colitis that resolves within 72 hours with appropriate 
clinical management
o
Grade 3 skin toxicity (excluding injection-site reactions) that downgrades to Grade 2 or less 
within 7 days with optimal supportive care 
o
Vitiligo or alopecia of any grade 
Other AEs may be considered a DLT as determined by the investigator in conjunction with the 
SMC.
r Grade 2 events that require 
continuous interruption of SL-172154 for more than 6 weeks or AEs that result in subjects not receiving 
at least two of the three scheduled dose of SL-172154 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. Subjects must have a histologically confirmed diagnosis of an unresectable or recurrent, locally 
advanced or metastatic cutaneous squamous cell carcinoma or squamous cell carcinoma of the head 
and neck that is not amenable to curative surgery or radiotherapy. 
o
Cutaneous squamous cell carcinoma: Subjects with predominantly mixed histologies (eg, 
sarcomatoid, adenosquamous) are not eligible. Subjects with a minimal component of mixed 
histology in which the predominant histology is invasive squamous cell carcinoma are eligible




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Inclusion criteria (continued) 
10. Females of childbearing 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 16.3 for additional 
details). Documentation of postmenopausal status must be provided.  FCBP should use an 
acceptable method of contraception (see Appendix Section 16.3) 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-172154 (see Appendix 16.3). Male 
subjects of reproductive potential must start using acceptable contraception at least 14 days prior 
to D1 of treatment with SL-172154 as per Appendix Section 16.3.
12. Recovery from prior anti-cancer treatments including surgery, radiotherapy, chemotherapy, 
immunotherapy or any other anti-
-grade 
toxicities such as alopecia, vitiligo, endocrinopathies adequately treated with hormone 
Grade 2 neuropathy may be 
allowed upon agreement by the Sponsor Medical Monitor). 
13. Subjects enrolled in the dose escalation cohort must be willing to undergo a baseline tumor biopsy 
and on-treatment biopsies of the injected tumor lesion. Subjects enrolled in the pharmacodynamic 
cohort must be willing to undergo baseline tumor biopsies of an injected and non-injected lesion 
and on-treatment biopsies of the injected and non-injected tumor lesion.
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply: 
1. Prior treatment with an anti-CD47 or anti-
2. Any anti-cancer therapy within the time intervals noted below prior to first dose (D1) of SL-
172154. 
Therapy
Washout period
Chemotherapy 
3 weeks
PD-1/L1 inhibitor and other immunotherapies not otherwise 
specified 
4 weeks 
Tumor vaccine 
4 weeks
Cell-based therapy
8 weeks
Other mAbs or biologic therapies
3 weeks
Other investigational agents not covered above
4 weeks or 5 half-lives 
whichever is shorter
Major surgery
2 weeks
Radiation (except palliative intent which does not require 
washout)
2 weeks 
3. Concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for anti-cancer intent is 
prohibited.  Concurrent use of hormones for non-cancer related conditions is acceptable.


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Exclusion Criteria (continued)
4. Use of corticosteroids or other immunosuppressive medication, current or within 14 days of D1 of 
SL-172154 treatment with the following exceptions (i.e., the following are allowed with or within 
14 days of D1 of IP): 
o
Topical, intranasal, inhaled, ocular, intraarticular corticosteroids
o
Physiological doses of replacement steroid (e.g., for adrenal insufficiency) not to exceed 
10 mg/day of prednisone or equivalent 
o
Steroid premedication for HSRs (e.g., reaction to IV contrast) 
5. Receipt of live attenuated vaccine within 28 days of D1 of IP.
6. Hypersensitivity to any of the excipients or to Chinese hamster ovary cell products. 
7. History of coagulopathy resulting in uncontrolled bleeding, eg, hemophilia, von Willebrand's 
first dose of IP.
8. Requires continuous anticoagulation therapy or antiplatelet therap
acetylsalicylic acid).
9. Active or documented history of autoimmune disease that has required treatment with a disease 
modifying agent or immunosuppressive therapy in the past two years. Exceptions include Type I 
diabetes, vitiligo, alopecia areata or hypo/hyperthyroidism.
10. Active pneumonitis or history of symptomatic pneumonitis in the past 2 years that required 
treatment (i.e. drug-induced, idiopathic pulmonary fibrosis, radiation-induced, etc.).   
11. Ongoing or active infection (e.g., no systemic antimicrobial therapy for treatment of infection 
within 5 days of D1 of IP). 
12. Symptomatic peptic ulcer disease or gastritis, active diverticulitis, other serious GI disease 
associated with diarrhea within 6 months of D1 of IP. 
13. Clinically significant or uncontrolled cardiac disease including any of the following: 
o
Myocarditis 
o
Unstable angina within 6 months from D1 of IP
o
Acute myocardial infarction within 6 months from D1 of IP 
o
Uncontrolled hypertension
o
NYHA Class III or IV congestive heart failure
o
Clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular 
tachycardia, second- or third- degree atrioventricular (AV) block without a pacemaker, 
circulatory collapse requiring vasopressor or inotropic support, or arrhythmia requiring 
therapy) 
14. 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.  
15. Women who are breast feeding. 
16. 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. 
17. 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. 
18. Has undergone allogeneic stem cell transplantation or organ transplantation.
19. 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]).  


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(NOTE: Hepatitis B virus (HBV): Subjects who are hepatitis B core antibody [HBcAb] positive, but 
HBsAg negative are eligible for enrolment. HCV: Subjects who are HCV Ab positive, but HCV RNA 
negative are eligible for enrolment). 
Safety Oversight
During the study while subjects are receiving treatment with SL-172154, 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) to share safety data and communicate results of ongoing analyses. All 
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 SMC will operate in accordance with the SMC charter which will define roles and accountabilities 
and the process for safety review.  
The Sponsor will remain in constant contact with the clinical sites during the enrollment period to 
ensure that cohort enrollment during the dose escalation of this study is completed as per protocol.  All 
dose escalation or safety decisions made by the SMC will be documented in writing with copies 
maintained at each site and the Trial Master File at the Contract Research Organization.
Statistics
The safety evaluation will be based on the All Treated Population defined as all subjects who received 
at least one dose of study treatment. Frequency tables will be used to describe safety and tolerability 
parameters AEs, irAEs, SAEs, fatal SAEs and AEs leading to discontinuation of SL-172154. Changes 
in toxicity grade for clinical chemistry and hematology will also be summarized. AEs will be mapped 
to a Medical Dictionary for Regulatory Activities preferred term and system organ classification. 
Laboratory abnormalities will be graded according to the NCI CTCTAE v5., if applicable. The DLT 
evaluation will be based on the DLT evaluable population (defined as All Treated subjects enrolled in 
complete the safety follow-up through the 21-day DLT evaluation period; or 2) who experience any 
DLT during the DLT evaluation period). DLTs will be summarized by dose level. The MTD will be 
estimated using isotonic regression.
Anti-tumor activity data will be summarized by dose level and overall in the All Treated population 
and Response Evaluable population (defined as Subjects in the All Treated Population who have a 
baseline disease assessment and have at least one post-baseline disease assessment or have progressed 
or died before the first post-baseline disease assessment). The primary analysis of anti-tumor activity 
assessment is based on RECIST v1.1. Change from baseline diameter for injected and non-injected 
lesions will be evaluated.   
The PK serum concentrations and PK parameters will be summarized and analyzed using appropriate 
statistical methods. The pharmacodynamic biomarkers values will be summarized descriptively by 
dose level and visit.  


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1.
INTRODUCTION, BACKGROUND AND STUDY RATIONALE
1.1
Background Information 
An essential element for increasing the immunogenicity of a tumor involves the processing of 
tumor antigens released from dead or dying tumor cells, and the subsequent presentation of tumor 
antigens on major histocompatibility complex (MHC) molecules expressed by activated antigen 
presenting cells (APCs). Cluster of differentiation (CD)47 is expressed by many somatic and 
hematopoietic tissues and is an important protective mechanism to prevent red blood cell (RBC) 
and platelet destruction by macrophages and splenic CD4+ dendritic cells (DCs) [Oldenborg, 
2000; Blazar, 2001; Yamao, 2002; Olsson, 2005; Yi, 2015]. The anti-phagocytic activity of 
me’ signal which ultimately leads to RBC destruction by splenic dendritic cells (DCs) is dependent 
upon a second activating signal, including CD18 containing integrins [Yi, 2015]. Uncoupling of 
the ‘do not eat me’ and ‘eat me’ signals likely increased the fitness of the host by providing 
improved regulation for erythrocyte homeostasis and should be considered in the therapeutic 
Abundant expression of CD47 in many solid and hematogenous tumors led to investigation of 
whether tumor cells had co-opted this pathway as a protective mechanism against immune 
mediated destruction. Early studies hypothesized that the role of CD47 as a ‘do not eat me’ signal 
by macrophages for erythrocyte homeostasis would also explain the observed anti-tumor benefit 
in preclinical studies with CD4
-Fc fusion proteins [Chao, 2012;
Willingham, 2012; Weiskopf, 2013]. More recent studies, however, have clarified that DCs are 
[Liu, 
2015]
sensing of phagocytosed tumor mitochondrial deoxyribonucleic acid, which initiates a cyclic 
guanine monophosphate – adenosine monophosphate synthase/stimulator of interferon genes 
(cGAS/STING) mediated type I interferon response that facilitates cross-presentation of tumor 
antigens to CD8+ T cells [Liu, 2015; Xu, 2018]
-clinical 
immunity.   
for anti-tumor immunity [Hildner, 2008]
-tumor immunity 
is due to the specialized ability of these APCs to cross-present exogenous tumor antigens. 
Following phagocytosis, these tumor antigens gain entry to the DC cytosol and then are cross-
-) DCs, is an important signal for enhancing the antigen cross-presenting activity of 
exogenous antigen by DCs to CD8+ T cells [O'Connell, 2000; Delamarre, 2003; Yasumi, 2004;
de Silva, 2019]. Interestingly, activation of tumor necrosis factor receptor-associated factor 
signaling downstream of CD40 ligation has also been shown to facilitate a type I interferon 
response via STING activation, but STING activation does not appear to be essential for the anti-
tumor immune response to CD40 stimulation [Byrne, 2016; Yao, 2016]. Despite the potentially 
context-dependent role of a type I interferon response, anti-tumor immunity to CD40 agonists 
remained dependent upon batf3 positive DCs and CD8+ T cells [Byrne, 2016]. These data indicate 


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CD40/CD40L axis appears capable of bridging innate and adaptive 
immunity, however the two pathways appear to have distinct dependence upon a type I interferon 
response. 
-Fc fusion proteins and anti-CD47 antibodies, as well as CD40L-Fc fusion proteins and 
CD40 agonist antibodies are being investigated in clinical trials and have demonstrated 
preliminary evidence of anti-tumor activity [Vonderheide, 2007; Kornbluth, 2012; Ingram, 2017;
Lin, 2017; Petrova, 2017; Advani, 2018; Kauder, 2018; Merz, 2018; Sikic, 2019; Vitale, 2019].
suggests that the two pathways could be complimentary or synergistic in combination and have 
the potential to improve anti-tumor activity in cancer patients. 
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 
tumor necrosis factor (TNF) receptor superfamily 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 fusion protein (FP). Superior 
preclinical activity has been observed compared to the separate administration of two individual 
antibodies against identical targets [de Silva, 2019]. As a result, we sought to develop a S
-
Fc-CD40L ARC fusion protein as a means to target these pathways with a single compound.   
1.2
Investigational Product, SL-172154 
The investigational product (IP), SL-172154,
-Fc-CD40L) linked via a 
protein, with CD40L, a type 2 membrane protein, generated a single molecule with dual specificity 
that retained individual target avidity.  
1.2.1
Mechanism of Action
The mechanism of action of SL-172154 is designed to pair the costimulatory role of CD40 ligand 
(CD40L) in augmenting the antigen cross-presenting ability of DCs with the increased phagocytic 
activity of macrophages through CD47-
(Figure 1 A and B). Importantly, because 
microenvironment (TME), APCs and tumor cells receive these signals in a spatiotemporally 
coordinated manner.  


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Figure 1: Mechanism of Action of SL-172154 Alone or Combined with an ADCC-competent 
mAb
(A)
DCs) activities including tumor phagocytosis and cross-presentation to CD8+ T-cells.
(B) S
-Fc-CD40L directly induces APC activation. The CD40L end of the molecule engages
CD40 on the APC resulting in APC stimulation and promoting an antigen-specific CD8+ T-
y
enhancing APC-mediated phagocytosis of tumor cells.  
(C) Macrophage-mediated tumor ph
-Fc-
CD40L with a tumor-targeted ADCC competent antibody via engagement of the Fc-receptor 
on the APC.  
(D)Direct APC activation through CD40L and direct blocking of CD47 ‘do not eat me’ signals 
enhance tumor phagocytosis, increase antigen cross presentation and anti-tumor response 
when SL-
-Fc-CD40L with 
checkpoint blocking agents increases CD40 target density and may stimulate a more potent 
and durable anti-tumor response. CD47-SIRP -mediated tumor phagocytosis is further 
-Fc-CD40L is combined with an ADCC-competent antibody. 


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SL-172154, or its mouse surr
-Fc-CD40L, has demonstrated functional activity in 
in vitro and in vivo nonclinical test systems. The nonclinical data supporting the translational study 
of SL-172154 in human subjects with cancer is described in detail in the Investigator’s Brochure 
(IB) [Report_SL2020IB001]. The mechanism of action, information from the nonclinical in vitro 
and in vivo pharmacology, toxicokinetics (TK), and toxicity evaluations and the rationale for 
investigation are briefly summarized.  
1.2.2
In Vitro Pharmacology 
In vitro, SL-172154 was shown to bind to its cognate targets, CD47 and CD40, both individually 
and simultaneously. High binding affinity for CD47 and CD40 was noted as well as a slow off-rate 
(KD values of 0.628 nM and 4.74 nM, respectively), indicating a longer on-target resident time. 
This longer resident time could be of benefit in the tumor microenvironment (TME) where CD47 
is known to be expressed. CD40-mediated activity by SL-172154 was demonstrated in a NFkB 
reporter system in which CD40-dependent signaling was stimulated in the absence of Fc receptor 
cross-linking, and in cultured human peripheral blood mononuclear cells (PBMCs) in which dose-
dependent proliferation, an increase in the number of interleukin (IL)-2 secreting PBMCs, and the 
secretion of multiple cytokines were observed. In addition, 
-mediated activity 
was demonstrated by SL-172154 increasing human macrophage-mediated phagocytosis of tumor 
cells in vitro, which was further enhanced when SL-172154 was combined with a tumor-targeted 
ADCP/ADCC-competent antibody (rituximab, cetuximab, or trastuzumab). SL-172154 and 
rituximab (anti-CD20) were also shown to induce macrophage activation and the expression of 
type I interferon genes in macrophages, which was enhanced when the two agents were combined.
1.2.3
In Vivo Pharmacology 
-Fc-CD40L intravenously (IV) led to a significant early and 
sustained activation of murine DCs (CD8+ and CD4+ DC) which matched the duration of 
activation observed with murine CD40 antibodies. This finding confirmed a previous report that 
CD47 blockade in vivo leads to rapid upregulation of CD86 and MHC-II on splenic CD8 + DCs 
[Yi, 2015]. The in vivo anti-
-Fc-CD40L monotherapy was studied in 
established syngeneic CT26 colorectal murine tumor models. The performance of intraperitoneal 
(i.p.) 
-Fc-CD40L was compared to treatment with CD47 blocking 
antibodies, CD40 agonist antibodies, the combination of the two antibodies and vehicle control. 
These experiments demonstrated
-Fc-CD40L led to higher rates of primary tumor 
rejection (63%) than either antibody given as monotherapy (anti-CD40, 0% and anti-CD47, 0%), 
or the antibody combination treatment group (33%). To assess the durability of an immune 
response without re-treatment, mice that rejected the initial tumor were re-challenged with a 
second CT26 tumor on the opposite flank on day 40. Of the 2 mice initially cured with the antibody 
-Fc-CD40L group, 3 of 5 (60%) 
mice rejected the tumor re-challenge, suggesting that a memory response was generated against 
the tumor which led to protection against a subsequent tumor challenge. Additionally, a robust 
increase in AH1 tetramer +/CD8+ cells in the spleen and the tumor was seen in mice treated with 
-Fc-CD40L or the anti-CD40/anti-CD47 combination in comparison to vehicle controls. 


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1.2.3.1 Antitumor Activity of 
-Fc-CD40L in Combination with Anti-CTLA-4, 
Anti-PD-1 or ADCC-Competent Antibodies
-Fc-CD40L with checkpoint inhibitors, mice 
were treated by the intraperitoneal (i.p.) route of administration with the following two 
-Fc-CD40L + murine anti-cytotoxic T lymphocyte-associated antigen 4 
(CTLA-4) antibody or murine anti-programmed cell death 1 (anti-PD1) antibody. In these 
combination experiments, the baseline tumor volume was increased by approximately 2-3-fold 
compared to the monotherapy studies in order to create a more stringent environment to observe 
potential synergistic or additive relationships. Both combinations improved anti-tumor response 
and overall tumor rejection in comparison to the monotherapy controls.  Anti-CTLA-4 in 
-Fc-CD40L resulted in a potent memory response (57% 
primary tumor rejection and 100% secondary tumor rejection in comparison to 0% primary tumor 
rejection for the monotherapy controls). Similar results were noted with anti-PD-1 
-Fc-
CD40L with 43% primary tumor rejection and 100% secondary tumor rejection. The synergy was
noted when, in relation to 
-Fc-CD40L dosing, anti-CTLA-4 was administered first or 
concurrently, or anti-PD-1 was given concurrently
-Fc-CD40L 
treatment preceded treatment with anti-CTLA-4 or anti-PD-1.  
Other anti-CD47 agents have demonstrated that tumor phagocytosis was augmented when given 
in combination with tumor-targeting antibodies such as rituximab [Chao, 2012]. Rituximab 
induces complement and natural killer (NK) cell–mediated, antibody-dependent, cell-mediated 
cytotoxicity (ADCC) effects by means of its active Fc effector function. In addition, the Fc region 
of rituximab provides a potent prophagocytic signal for macrophages by stimulating antibody-
dependent cellular phagocytosis (ADCP). Since SL-172154 was observed to potentiate the activity 
-Fc-CD40L with a murine surrogate for 
rituximab (murine anti-CD20) was investigated in two CD20+ mouse tumor models, WEHI3 and 
A20, that were subcutaneously implanted. In both tumor models, similar control of established 
tumor growth was observed when anti-
-Fc-CD40L was tested as monotherapy. 
In keeping with the in vitro phagocytosis data, the combinatio
-Fc-CD40L + anti-
CD20 resulted in a further decrease in tumor volume. In the WEHI3 model, the combination of 
-Fc-CD40L + anti-CD20 resulted in 33% of the mice rejecting the tumor, while 17% of 
mice rejected the tumor when treated with anti-CD20 as monotherapy. There was no tumor 
-Fc-CD40L 
induced significant anti-tumor efficacy in both CD20+ hematological tumors models which was 
enhanced by combination with anti-CD20. 
Collectively, these data demonstrate that SL-172154 has a dual mechanism of action (Figure 1 A
and B). Tumor cells expressing CD47 normall
macrophages and DCs. One mechanism of action of SL-172154 is direct enhancement of APC-
-
172154-mediated tumor phagocytosis can be enhanced through combination with a targeted 
ADCC competent antibody (Figure 1 C and D). A second mechanism of action of SL-172154 is 
induction of APC activation through CD40 which stimulates an antigen-specific CD8+ T cell 
response. Combination treatment of SL-172154 with checkpoint blocking agents increases CD40 
target density which may stimulate a more potent and durable anti-tumor response.  


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1.2.3.2 Antitumor Activity of Intratumoral 
-Fc-CD40L Monotherapy and in 
Combination with Murine Anti-PD-1 Antibody
-Fc-CD40L, given by intratumoral injection (ITI), as 
monotherapy and in combination with murine anti-PD-1 antibody was assessed in groups of female 
BALB/c mice inoculated with a CT26 colorectal carcinoma tumor in each rear flank. The mice 
were dosed on Days 0 (start of treatment), 2 and 5, and the treatment groups were: vehicle control 
(i.p. or ITI);
-Fc-CD40L (300 µg; i.p
-Fc-CD40L (10 or 100 µg; ITI); and the 
combination of anti-PD-1 (100 µg; i.p
-Fc-CD40L (10 or 100 µg; ITI). 
Although only one of the two tumors was injected with
-Fc-CD40L, a delay in tumor 
growth was observed in both. The 10 µg ITI 
-Fc-CD40L was the most efficacious 
with 14% of mice completely rejecting both tumors. No tumor rejections were observed in the i.p. 
anti-PD-1 group. The rejection rate of both tumors was increased to ~42% when 10 µg ITI 
-Fc-CD40L was combined with i.p. anti-PD-1 treatment. Thus,
intratumoral
administration of
-Fc-CD40L showed potent anti-tumor efficacy in both the treated 
-Fc-CD40L) and untreated tumor, suggesting that intratumoral
-
Fc-CD40L stimulated sufficient immune activation to promote an anenestic or bystander anti-
tumor response. Moreover, no signs of injection site reactions, such as ulceration and 
inflammation, were observed with intratumoral
-Fc-CD40L. Systemic depletion of 
peripheral B cells and an increase in peripheral dendritic cells observed 24 hours following
intraperitoneal
-Fc-CD40L were not observed after intratumoral 
-Fc-CD40L, 
supporting that much lower systemic exposure occurred following ITI. These findings support the 
hypothesis that direct injection of SL-172154 into a tumor can achieve a high local concentration 
of SL-172154 using relatively lower doses of drug than would be required with IV administration.
1.2.4
Toxicology  
The cynomolgus monkey was selected for the nonclinical toxicology studies due to the cross-
reactivity of SL-172154 binding to the respective targets in this species and in vitro activity. The 
anatomical, physiological, and biochemical similarities of cynomolgus monkeys to humans 
facilitate extrapolation of potential effects to human.  
Two, repeat IV dose studies, utilizing once-weekly administration, of up to 5 weeks in duration, 
have been conducted in cynomolgus monkeys. In both the dose range finding (DRF) study and 
Good Laboratory Practice (GLP) definitive study, the evaluated SL-172154 doses were 0.1, 1, 10, 
and 40 mg/kg, and included assessments of serum SL-172154 concentrations and 
pharmacodynamic biomarkers. The GLP study was conducted with drug that is representative of 
the Good Manufacturing Process used for clinical drug supplies. The GLP study also included 
recovery groups to evaluate the reversibility, progression, or delayed appearance of any observed 
findings following a 4-week off-dose period. Additionally, SL-172154 was evaluated in vitro for 
hemolytic potential using human whole blood, and the potential for interfering with pre-transfusion 
compatibility testing was assessed.  
In the DRF study, SL-172154 was well tolerated with no incidence of infusion-related reactions. 
Generally, dose-proportional, postdose decreases in lymphocytes (0.1 to 40 mg/kg) and platelets 
(10 and 40 mg/kg) were observed during the study with both parameters trending toward; or 
returning, to baseline after a 7-day recovery period. In the DRF study, 40 mg/kg was designated 


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as the highest non-severely toxic dose and corresponded with mean Cmax and AUC0-last values of 
727,000 ng/mL and 1,670,000 ng*h/mL, respectively, on Day 1 (Dose 1), and 594,000 ng/mL and 
1,060,000 ng*h/mL, respectively, on Day 29 (Dose 5). 
In contrast to the DRF study, there was evidence of toxicity in the GLP study that manifested as 
dose-dependent infusion-related reactions in the 10 and 40 mg/kg groups (Days 15 or 22). The 
acute clinical observations noted were paleness and decreased activity. The severity of signs and 
symptoms during dose administration resulted in 2 monkeys in the 40 mg/kg group being 
euthanized in extremis [a female on Day 15 (Dose 3) and a male on Day 22 (Dose 4)], and early 
termination of dosing in the 10 and 40 mg/kg groups. RBC hemolysis was investigated and 
ultimately ruled out as a potential causal or contributory factor to the infusion-related reactions 
since clinical hematology (erythrocyte count, hemoglobin, and hematocrit) and serum chemistry 
(lactate dehydrogenase and total bilirubin) evaluations at multiple timepoints in the study showed 
no evidence of hemolysis or anemia. Additionally, the in vitro incubation of SL-172154 with 
human whole blood did not result in any detectable hemolysis. Minimally to moderately decreased 
mg/kg (Days 16 and 23) and transient, mild decreases in lymphocytes 
were seen in the 40 mg/kg group (both sexes on Days 2 and 16; 2 of 4 males on Day 23). Dose-
dependent increases in splenic weight and increased lymphoid cellularity in the spleen and lymph 
node were noted and attributed to SL-172154 administration. These findings were reversed after a 
4-week recovery period. At the 1 mg/kg dose level, there were no clinical observations, 
abnormalities in clinical pathology parameters, or non-reversible pathology findings, thus 1 mg/kg 
was considered to be the no-observed-adverse-effect level (NOAEL) for IV infusion doses of 
SL-172154. The 1 mg/kg dose corresponded with mean Cmax and AUC0-last values of 1230 ng/mL 
and 518 ng*h/mL on Day 1. Additionally, on Day 1, the mean terminal elimination half-
2)
was approximately 0.4 hours in the 1 mg/kg group and longer in the 10 mg/kg and 40 mg/kg groups 
with mean values of approximately 1.1 and 0.9 hours, respectively. Of note, transient low or 
non-quantifiable plasma SL-172154 concentrations on Day 29 precluded the determination of 
toxicokinetic parameters.  
As expected, in the GLP study, SL-172154 was shown to occupy CD40 and CD47 receptors on 
circulating blood cells in a dose-dependent manner; on Day 1 (Dose 1) in the 10 and 40 mg/kg 
groups, >90% CD40 receptor occupancy on PBMCs and ~80% CD47 receptor occupancy on 
RBCs was observed. Similar on-target pharmacological effects were seen in both the DRF and 
GLP studies. A number of serum cytokines were transiently increased with the elevations being
generally dose-dependent and tending to increase with repeated dosing. The cytokines with the 
largest increases in the GLP study were: IL-1 receptor antagonist, monocyte chemoattractant 
protein-1, IL-6, CD40-ligand, IL-8, macrophage inflammatory protein-
-derived 
factor-
-A. Anti-drug antibodies (ADA) were present in 
all SL-172154-treated monkeys by Day 15 (Dose 3) and may have contributed to reduced serum 
SL-172154 levels on Day 29. The emergence of ADA was not unexpected because SL-172154 is 
based on human amino acid sequences which have 82% identity to the cynomolgus. Transient and 
reversible complement activation, as evidenced by increased plasma complement split products, 
occurred and was coincident with the emergence of ADA. 
In the GLP monkey study, IV infusion of SL-172154 was shown to be locally well tolerated as no 
visible lesions were observed at the injection site and microscopic findings were generally minimal 


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and deemed to be procedure-related. Additionally, in BALB/c mice with two implanted CT26 
tumors, 
-Fc-CD40L, 
(10 or 100 µg) in one tumor were well tolerated, with no local injection site reactions observed.  
Routine blood bank pre-transfusion compatibility tests with human RBCs and platelets and 
SL-172154 spiked AB human plasma (1 to 250 µg/mL) indicate that SL-172154 is expected to 
interfere with blood typing and compatibility testing. 
In summary, the two repeat IV dose toxicity studies in cynomolgus monkeys had similar trends in 
toxicokinetic parameters and demonstrated on-target pharmacological activity of SL-172154. The 
onset of ADA, elevations in serum cytokines, activation of complement, and postdose changes in 
lymphocyte counts were similar between the DRF and GLP studies. The dose-dependent, infusion-
related reactions observed with repeat dosing in the GLP study were attributed to exacerbated 
pharmacology of SL-172154 in the presence of ADA. Given the low ITI doses to be studied in 
clinical study SL03-OHD-102, low systemic exposure is anticipated in comparison to IV infusion, 
and thus the IV no observed adverse effect level (NOAEL) of 1 mg/kg in monkeys provides 
systemic exposure and safety coverage. Consequently, the nonclinical safety assessment program 
supports the intratumoral administration of SL-172154 in clinical study SL03-OHD-102. 
1.3
Rationale for Investigation of SL-172154 by Intratumoral Administration 
The preclinical data package provided in the IB [Report_SL2020IB001] demonstrates that SL-
172154 selectively and specifically binds to its intended targets, CD47 and CD40, with high
affinity. Furthermore, both targets exhibit functional activity in a variety of in vitro assays, and ITI
-Fc-CD40L in the murine CT26 tumor model stimulated potent anti-tumor efficacy of 
both the treated and untreated tumors, and efficacy was further improved when combined with a 
sytemically administered PD-1 blocking antibody. Intratumoral 
-Fc-CD40L was well 
tolerated with no local injection site reactions observed and there was no evidence of the systemic
B cell and dendritic cell fluctuation that was observed following i.p. dosing.  
Injecting SL-172154 directly into the tumor aims to use the tumor as its own vaccine triggering 
strong priming of innate and adaptive immunity against tumor antigens locally. With direct 
injections into the tumor, a high intratumoral concentration of SL-172154 can be achieved in situ, 
using relatively lower doses of drug than would be required systemically. Local delivery can 
prevent significant systemic exposure and off-target toxicities. Additionally, it allows for 
combination therapies to be administered with less systemic toxicity than if the combination drugs 
were both given IV.   
SL-172154 is designed to pair the costimulatory role of CD40L in augmenting the antigen cross-
presenting ability of DCs with the increased phagocytic activity of macrophages through CD47-
-172154 to CD47 in the tumor for an extended
period of time may block this important checkpoint axis and provide a larger window of
opportunity for increased tumor phagocytosis, CD40L co-stimulation, and greater antigen
processing 
appear capable of bridging innate and adaptive immunity, suggesting that the two pathways could
be complimentary or synergistic in combination. The


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to CD40L 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 targeting CD40 and CD47. SL-172154 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-172154 exists as a glycosylated 
multimer, thereby retaining high target avidity, and inducing CD40 receptor clustering and active 
signaling. The TNF superfamily receptors (i.e., CD40, 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.
1.3.1
Rationale for Selection of Tumor Types Under Investigation 
Cutaneous squamous cell carcinoma (CSCC) and squamous cell carcinoma of the head and neck 
(HNSCC) were selected for investigation in this phase 1 study of ITI SL-172154 due to the fact 
that both of these tumor types have 1) a high percentage of tumors with increased CD47 
expression, 2) mechanisms of tumor immune evasion that target both adaptive and innate 
immunity within the tumor microenvironment [Ferris, 2015] and 3) patients with select tumor 
lesions that are accessible and safe for ITI.
1.3.1.1 Cutaneous Squamous Cell Carcinoma of the Skin
CSCC is the second most common malignancy in the United States, with approximately one 
million individuals diagnosed with CSCC in 2012, the most recent year that new statistics were 
available [Rogers, 2015]. Risk factors for CSCC include ultraviolet (UV) exposure, advanced age, 
and immunosuppression [Alam, 2001; Madan, 2010]. Although the vast majority of individuals 
with a diagnosis of CSCC have a very favorable prognosis, CSCC has a greater propensity for 
aggressive recurrences than basal cell carcinomas (BCC) and there is increased mortality in 
comparison with BCC patients that are age-matched controls [Rees, 2015]. 
Surgical resection is the mainstay of therapy for CSCC with the goal of achieving complete 
resection and an acceptable cosmetic outcome [Madan, 2010]. For the small percentage of patients 
who develop unresectable locally recurrent or metastatic disease, treatment options are limited. 
Small retrospective series and case reports have been published using a variety of radiation or 
chemoradiation therapies and durable disease control can be achieved in a subset of patients 
[Samstein, 2014; Nottage, 2017]. However, once local therapies are exhausted, patients have 
limited treatment options.
Regarding systemic therapy, 5-fluorouracil and cisplatin therapy have been studied in small single 
arm studies of CSCC but have never been shown to have meaningful clinical benefit and there are 
safety and tolerability concerns in patients with advanced age [Khansur, 1991]. Targeting of the 


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epidermal growth factor receptor (EGFR) in CSCC has been explored by several groups. In a phase 
2 study of cetuximab monotherapy for patients with unresectable squamous cell carcinoma of the 
skin, median age was 79 years. The observed response rate was 28% (10/36 patients) with a median 
progression-free survival (PFS) of 4.1 months, and median overall survival (OS) of 8.1 months 
[Maubec, 2011]. While these studies have limitations, EGFR inhibitors are considered a treatment 
option [NCCN, 2019]. Recently, the PD-1 inhibitor, cemiplimab, was granted an indication by the 
United States Food and Drug Administration (FDA) in patients with locally advanced or metastatic 
CSCC who are not candidates for curative surgery or radiation. The indication was based on the 
results of a phase 1 and 2 study in which the overall response rate (ORR) in the 108 patients across 
both studies was 47.2% (3.7% complete response [CR], 43.5% partial response [PR]). The median 
duration of response (DOR) was not reached but 61% of patients had a DOR of 
24 weeks 
[Libtayo-USPI, 2018; Migden, 2018].  
A high percentage of CSCCs have detectable CD47 expression. In a panel of 117 cases of in situ 
and invasive epithelial cutaneous lesions, archival tissue from actinic keratoses (AK), SCC in situ 
(SCCIS), SCC, and keratoacanthoma (KA) were examined for CD47 expression by 
immunohistochemical analysis [Akel, 2016]. Significantly higher CD47 expression (both in 
percentage positivity and intensity, and combined score of percentage positivity and intensity) was 
seen in SCC compared with AK, SCIS and KA.  Most SCCs (78%) showed more than 75% 
positivity (4+ score) compared with AK (0%), SCCIS (15%), and KA (35%). Given that CD47 
expression appears to increase gradually along the spectrum of AK to SCCIS to SCC, these data 
suggest that CD47 is important in the transformation of an in situ malignancy into one that is 
frankly invasive. Given the increased CD47 expression and high degree of responsiveness to PD-
1 inhibitors, the unique immune contexture of CSCCs makes this histology particularly suitable 
for investigation of intratumoral administration of SL-172154. 
1.3.1.2 Squamous Cell Carcinoma of the Head and Neck
HNSCC is the ninth leading cancer by incidence worldwide and constitutes 90% of all head and 
neck cancers [Jemal, 2007]. In the US, approximately 50,000 new cases of HNSCC are diagnosed 
yearly and more than 10,000 deaths occur per year [Fitzmaurice, 2017]. Head and neck cancers 
encompass a group of malignancies arising from several anatomical mucosal sites, including the 
nasal cavity, paranasal sinuses, nasopharynx, oropharynx, hypopharynx, larynx and lips, and oral 
cavity with the vast majority being of squamous cell histology [Kok, 2020]. HNSCC are 
genomically heterogenous and the major drivers of tumorigenesis divide the population into two 
broad categories 1) virally mediated or human papilloma virus (HPV)-positive HNSCC and 2) 
non-virally mediated or HPV-negative HNSCC that results from alcohol, tobacco or betel nut 
exposure.  
Most patients present with locally advanced disease with a high risk of recurrence, and 
approximately 10% of HNSCC patients present with metastatic disease. Surgical resection of the 
primary tumor and draining lymph nodes followed by risk-adapted adjuvant radiation, with or 
without platinum-based chemotherapy, or primary definitive concurrent chemoradiation, remain 
the principal treatments employed for locally advanced HNSCC [Cohen, 2019].
Despite advances in surgery and radiotherapy, the five-year survival rates for patients with 
HNSCC range between 40 to 50% across all stages for tumors caused by traditional carcinogens 
(HPV-negative). The median overall survival (OS) for patients with recurrent/metastatic disease 


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is 10–
[Marur, 2008]. Once local therapies have been exhausted for locally recurrent or 
metastatic disease, the prior standard of care in the first-line setting has been platinum-based 
doublet chemotherapy with cetuximab. Compared to chemotherapy alone, the addition of 
cetuximab in the regimen described extended median progression free survival (PFS) from 
P
0.80; P
[Vermorken, 2008]. Furthermore, 
until recently, second-line treatment options included only cetuximab, methotrexate, and a taxane; 
each of which is associated with response rates of 10–13%, and median PFS of 2–
clear demonstration of an improvement in OS [Cohen, 2019]. 
In 2016, the United States FDA and in 2017 the European Medical Agency granted the first 
approvals for the PD-1 inhibitors, nivolumab and pembrolizumab, in the treatment of patients with 
recurrent HNSCC that is refractory to platinum-based regimens. The current first-line regimen for 
relapsed/metastatic HNSCC then adopted a new paradigm in 2019, when the results of the 
randomized controlled trial, comparing pembrolizumab combined with platinum and infusional 5-
fluorouracil to the past gold-standard regimen of cetuximab plus the same chemotherapy 
combination, confirmed an overall survival benefit (hazard ratio, HR, for death at 0.65, 95% 
confidence interval, CI, 0.53–0.80) favoring the pembrolizumab-based treatment arm. Based on 
these results the FDA granted approval for pembrolizumab in combination with platinum and 
fluorouracil for the first-line treatment of patients with HNSCC and pembrolizumab as a single 
agent for the first-line treatment of patients with HNSCC whose tumors express a PD-L1 combined 
[Cohen, 2019; Kok, 2020]. Although PD-1 inhibitors have improved outcomes 
in HNSCC, resistance to these agents develop over time and better treatment paradigms are 
needed.
CD47 overexpression is a hallmark of multiple cancer types including HNSCC and evidence 
supports CD47 as a potential therapeutic target. Immunohistochemical staining of specimens from 
48 cases of oral mucosa, 43 cases of dysplasia and 165 cases of primary HNSCC showed
quantitatively higher CD47 expression in human HNSCC tissue as compared with normal oral 
mucosa indicating that CD47 is a tumor associated antigen [Wu, 2018]. Interestingly, positive 
immunostaining of CD47 was mainly localized in cancer cells and very prominent in the invasive 
cell layer. Furthermore, detailed analysis of HNSCC tissues revealed that CD47 staining was 
significantly increased with advanced pathology grade (grade II+III vs. I) and with lymph node 
metastases (N1+N2 vs. N0). Most importantly, in 165 primary HNSCCs with follow-up data, 
Kaplan–Meier survival analysis indicated that CD47 high expression (using the median CD47 
protein expression histoscore of 58.37 as a cut-off value) confers worse overall survival (p =
0.0459). Thus, similar to CSCC, CD47 expression is increased in HNSCCs and the efficacy of PD-
1/L1 inhibitors is well established. Based on these observations, this histology is particularly 
suitable for investigation of intratumoral SL-172154. 
1.4
Potential Risks and Benefits of SL-172154 
1.4.1
Potential Risks
Potential risks to subjects are addressed by safety guidelines and vigilant monitoring of participants 
as outlined below. Potential safety concerns are based on preclinical safety toxicology findings in 


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cynomolgus monkeys dosed IV with SL-172154 and other in vivo or in vitro studies of SL-172154 
summarized in the IB, as well as established clinical management guidelines.
SL-172154 is a pharmacologically active molecule [Report_SL2020IB001].  The risks (evaluation 
of safety and tolerability) and potential benefits (evaluation of anti-tumor activity) of intratumoral
administration of SL-172154 in humans will be assessed 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-172154 (e.g., non-human primate (NHP) studies in cynomolgus 
monkeys); and (2) the adverse event (AE) profile of other CD40 agonists and CD47-SIRP
targeting agents administered by IV, subcutaneous and/or ITI.  
Based on a thorough review of the NHP data (including clinical findings, laboratory studies, 
cytokine analysis, TK, immunogenicity studies, complement split product levels, and anatomical 
pathology), the underlying etiology of SL-172154-related effects is most likely due to a 
combination of both the pharmacologic activity of the molecule and to immunologic reactions 
triggered by SL-172154 administration. The following are potential contributory factors to the 
dose-dependent infusion-related reactions: (1) elevations in serum cytokines; (2) postdose changes 
in lymphocyte number; (3) development of ADA and downstream complement activation.
AEs that have been observed following systemic administration of other CD40 agonists agents 
include infusion-related reactions (most common symptoms associated with infusion related 
reactions are chills, nausea, vomiting, hypotension, pyrexia, pruritus, rash), cytokine release 
syndrome (CRS), fatigue, rash, elevation of hepatic transaminases, lymphopenia, anemia, 
thrombocytopenia, 
neutropenia, 
thromboembolism, 
and 
inflammatory 
eye 
disorders 
(conjunctivitis and ocular hyperemia). Immune mediated events, including dermatitis, colitis, 
hypophysitis and thyroiditis, have not been seen with CD40 antibodies but remain a potential 
concern [Vonderheide, 2001; Calvo, 2019].
AEs that have been observed following localized (subcutaneous or ITI) administration of CD40 
agonists include injections site reactions (ISRs), CRS, flu-like symptoms (fever, chills, rigors, 
hypotension), fatigue, malaise, nausea, vomiting, loss of appetite, constipation, cholecystitis, and 
abdominal pain [Bentebibel, 2019; Irenaeus, 2019; Tran, 2019]. Subcutaneous administration of 
the CD40 agonist, MEDI-5083, given in sequential or concurrent combination with IV durvalumab 
in patients with advanced solid tumors resulted in dose-limiting ISRs with 89.5% of patients 
having any grade ISRs and 15.8% of patients having 
[Tran, 2019]. Intratumoral 
administration of the CD40 agonist, ADC-1013, resulted in CRS associated with deep lesion 
injections (100%; 12/12) but not with superficial injections (0%; 0/6). ADC-1013 was detected in 
blood following injection into deep liver lesions whereas injections into superficial tumors resulted 
in nondetectable serum levels suggesting that intratumoral administration into vascularized lesions 
such as hepatic lesions resulted in higher immediate systemic exposure compared to intratumoral
administration into other anatomical sites [Irenaeus, 2019].
AEs that have been observed following systemic administration of agents that target the CD47-
thrombocytopenia, neutropenia, elevation of hepatic transaminases, fatigue, headache, fever, and
infusion-related reactions [Ansell, 2016; Chow, 2019; Sikic, 2019]. Intralesional administration of 


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the CD47 antagonist TTI-621 (SIRP FC) in patients with relapsed/refractory mycosis fungoides 
and Sezary Syndrome was well-
SAEs reported. The most common treatment-
chills, injection site pain and fatigue [Querfeld, 2018].
Implications for monotherapy dosing of intratumoral SL-172154 in this clinical trial 
[Report_SL2020IB001]: 
1) The data indicate a potential risk for injection-related reactions and CRS in humans. The 
infusion-related reactions 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-172154.  
The steps taken to minimize these risks include low starting dose, administration in an 
outpatient oncology clinic or inpatient setting, management guidelines (e.g., rescue treatments, 
prophylaxis), and extended monitoring when indicated. Furthermore, to minimize systemic 
exposure, injection of deep lesions such as highly vascularized hepatic tumors is not permitted.
Only superficial lesions that can be injected by direct visualization, palpation, or ultrasound 
guidance will be treated with ITI of SL-172154. The steps taken to minimize the risks are 
outlined in the Toxicity Management Guidelines section of the protocol (Section 3.7). This
section is based on robust management guidelines that are available for managing CRS in the 
context of treatment with adoptive T-cell therapies, bispecific antibodies, and agonist 
antibodies. 
2) Immunogenicity Risk: ADA did emerge in the non-human primate studies as expected given 
that SL-172154 is based on human amino acid sequences which have 82% identity to the 
corresponding cynomolgus sequences. However, SL-172154 has >99% identity to the 
corresponding human proteins and hence SL-172154 is considered to have a low risk of 
immunogenicity in humans. 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 3.7.1).
3) Hemolysis and Anemia: SL-172154 does bind RBCs in vivo but was not shown to cause 
hemolysis in NHPs. The lack of hemolysis is likely due to the fact that the Fc domain of SL-
172154 is inactive [Chow, 2019]. Regardless, subjects will be monitored serially for evidence 
of hemolysis and anemia. Furthermore, since SL-172154 binds to CD47 on RBCs and platelet 
membrane, it may obscure the assessment of red blood cell phenotyping and thus interfere with 
compatibility tests, including the antibody screening and crossmatching that are part of a
routine pre-transfusion work up [Report_SL2020IB001]. To investigate this risk, blood 
phenotyping, type and screen (ABO/Rh), and direct antiglobulin test (DAT) will be performed 
at screening before and following exposure to SL-172154. Furthermore, investigator guidance 
is provided on blood cross-matching and transfusion procedures in protocol Section 3.8.
4) Injection Site Reactions: In the NHP studies, SL-172154 was locally well tolerated with no
visible lesions observed at the IV administration site. On microscopic examination, findings 


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were generally minimal and deemed to be procedure-related. Similarly, ITI of 
-Fc-
CD40L in the murine CT26 tumor model was well tolerated with no local injection site 
reactions observed. Regardless, subjects will be monitored for injection site reactions and 
specific monitoring, dose interruption, and management guidelines are outlined in protocol 
Section 3.7.
5) Immune-Related Adverse Events (irAEs): As with other checkpoint inhibitors and 
costimulatory molecules, irAEs resulting from a breakdown of self-tolerance remain a 
potential concern associated with SL-172154 administration. As experience using checkpoint 
inhibitor therapies has grown, the list of toxicities has increased, and the types of AEs observed
span essentially every organ class. Extensive knowledge in managing immune-related 
toxicities has developed over the years and led to the publication of consensus guidelines in 
peer reviewed journals [Haanen, 2017; Puzanov, 2017; Brahmer, 2018].  Moreover, clinical 
trial sites familiar with these therapeutic agents have developed institutional guidelines to 
ensure effective management of these toxicities. Monitoring and management of irAEs as 
outlined in protocol section 3.7 follow these consensus guidelines in this 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
ITI studies and this class of agents and the management of associated toxicities such as CRS; (2) 
the proposed starting dose of intratumoral SL-172154 is estimated based on minimum anticipated 
biological effect level (MABEL) and is 25,000 times lower than the NOAEL observed in the NHP 
studies (Section 3.3). Systemic exposure is expected to be negligible with ITI administration and 
therefore, the starting dose is expected to be lower than doses associated with 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-172154 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 3.7); (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-172154 are unknown: no clinical trials in human subjects have been 
conducted to date. The mechanism of action of SL-172154 is designed to pair the costimulatory 
role of CD40L in augmenting the antigen cross-presenting ability of DCs with the increased 
phagocytic activity of macrophages through CD47-
tumor cells receive these signals in a spatiotemporally coordinated manner, potentially leading to 
more potent and durable anti-tumor response. By injecting SL-172154 directly into the tumor aims 
to use the tumor as its own vaccine triggering strong priming of innate and adaptive immunity 
against tumor antigens locally. With direct injections into the tumor, a high intratumoral
concentration of SL-172154 can be achieved in situ, using relatively lower doses of drug than 
would be required systemically. Local delivery can prevent significant systemic exposure and off-
target toxicities. Additionally, it allows for combination therapies to be administered with less 
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SL-172154 targets both the CD40/CD40L and the SIRP /CD47 axes. Monoclonal antibodies and 
fusion proteins targeting each of these axes have been extensively evaluated in clinical trials 
[Beatty, 2017; Uger, 2020] but there are no current regulatory approvals for agents targeting either 
axis. There are currently no reported multitargeted agents or trials for CD47 inhibitors in 
combination with CD40 agonists.  
Encouraging preliminary anti-tumor activity has been observed in patients with hematologic 
malignancies and solid tumors receiving CD47 blockade alone as well as in combination with 
agents that provide additional ‘eat me’ signals (rituximab, trastuzumab, azacitidine) and the T-cell 
checkpoint inhibitor pembrolizumab [Uger, 2020]. The most advanced development program is 
for Hu5F9-G4 (5F9), a high affinity humanized IgG4 anti-CD47 antibody, that is administered IV 
with a 1 mg/kg priming dose followed by weekly maintenance doses up to 45 mg/kg [Sikic, 2019].
The unique dosing regimen minimizes red blood cell (RBC) toxicity by selectively clearing aging 
RBCs, which results in a mild and transient anemia. Pooled efficacy results from Phase 1b/2 of 
5F9 and rituximab (n = 75) indicate an objective response rate (ORR) of 49% and a CR rate of 
21% [Advani, 2018; Advani, 2019]. These response rates are likely higher than those achievable 
with rituximab alone in this patient population as the majority have previously failed a prior 
rituximab-containing regimen. 5F9 in combination with azacitidine, a demethylating agent that 
upregulates calreticulin expression on tumor cells, is also showing clinical promise, with an ORR 
of 100% in untreated myelodysplastic syndromes (MDS) patients (n = 11, 55% CR rate), and 64% 
in untreated acute myeloid leukemia (AML) patients (n = 14) [Sallman, 2019]. The combination 
appears to compare favorably with historical data from azacitidine monotherapy. As a 
monotherapy, 5F9 has shown relatively low response rates: 10% in relapsed/refractory AML/MDS 
patients and 5% in solid tumors. 
Anti-tumor activity of intratumoral administration of an agent targeting the CD47/SIRP  pathway 
has only been examined in one clinical study to date. In a phase 1 study, the
-Fc fusion 
protein, TTI-621, was administered intralesionally in patients with relapsed/refractory mycosis 
fungoides or Sezary syndrome [Querfeld, 2018]. This study demonstrated encouraging preliminary 
activity with 91% (20/22) of heavily pretreated patients having a reduction in their Composite 
Assessment of Index Lesion Severity scores within the treated lesions and 41% (9/22) having a 
responses were seen in adjacent, non-injected lesions. 
In serial biopsies, intralesional TTI-621 administration resulted in a rapid influx of macrophages 
and CD8+T cells indicative of an innate and adaptive immune response. 
Several different CD40 agonistic antibodies administered IV have been studied in early phase trials 
[Beatty, 2017]. Sporadic responses in solid and hematologic malignancies including renal cell 
cancer, melanoma, diffuse large B cell lymphoma and Hodgkin’s lymphoma have been noted with 
monotherapy CD40 agonists. However, a critical component that is believed to mediate the anti-
tumor effect is the presence of tumor antigen, which is necessary for CD40-activated APCs to 
induce antigen-specific T cell adaptive immunity. This is the hypothesis for several ongoing 
clinical trials combining CD40 agonists with vaccines, checkpoint inhibitors and/or chemotherapy 
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Multiple CD40 agonists have been administered via subcutaneous or ITI [Bentebibel, 2019;
Irenaeus, 2019; Tran, 2019]. The most promising preliminary activity has been noted with 
intratumoral administration of the CD40 agonist, APX005M, in combination with IV 
pembrolizumab. In 13 checkpoint inhibitor-naïve melanoma patients the best overall response was 
as follows: partial response in 7/13 (54%) patients, stable disease in 4/13 (31%) and progressive 
disease in 3/13 (23%) [Bentebibel, 2019]. However, given that these patients were all checkpoint 
inhibitor-naïve, the contribution of each of the components on response rate is difficult to ascertain 
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3.
STUDY DESIGN
3.1
Description of Study Design
This clinical trial is an open label, multi-center, dose escalation, Phase 1 study of  SL-172154 
administered by ITI injection (see SCHEMA). This trial is designed to evaluate the safety, PK, 
anti-tumor activity and pharmacodynamic effects of SL-172154 administered by ITI on days 1, 8, 
15 of a 21-day in cycle 1 and then on day 1 of each subsequent 21-day cycle (cycles
).  Subjects 
that are eligible for enrollment have locally advanced or metastatic squamous cell carcinomas of 
the head and neck or skin that are not amenable to further treatment with surgery, radiation or
standard systemic therapies that are known to provide clinical benefit for their condition
(Section 4).  
 
Dose Escalation 
Dose escalation will utilize the modified Toxicity Probability Interval (mTPI-2) design [Guo, 
2017] with target DLT rate of 30% for the MTD. The dose escalation decision rules are outlined 
in Table 5 in Section 9.1.  Subjects will be enrolled in cohorts of approximately 3 subjects into 
sequential dose levels of SL-172154 and evaluated for DLT (see Section 3.5 for Definition of 
DLT) during the 21-day DLT evaluation period starting from the first dose of SL-172154. At each 
dose level, a minimum 3-day stagger between dosing the first and second subject is required.  The 
planned dose escalation is in half-log increments as outlined in Table 1 and Section 3.4.
For each dose level, the minimum number of subjects evaluable for DLT (see Section 9.2.1 for 
definition of DLT evaluable subject) will be 3 unless unacceptable toxicity is observed prior to 
enrollment of 3 subjects (e.g., the first 2 subjects experience a DLT before the third subject enrolls). 
The maximum number of subjects evaluable for DLT at a dose level will be 12 (e.g., this may be 
reached by sequential enrollment of 4 cohorts of 3 subjects) assuming the dose decision is to stay 
at the current dose from the first 3 cohorts. After enrollment of 12 DLT evaluable subjects at a 
given dose lev
-
rate >=33%). Note: Example scenarios for dose escalation per mTPI-2 dose decision rules are 
provided in Appendix 16.1.
During dose escalation, a review of available safety data for all subjects at a given dose level will 
be undertaken by the SMC approximately every four weeks and a decision made regarding the 
safety profile of that dose level.  
Pharmacodynamic Cohorts  
The Sponsor, in consultation with the SMC, may elect to open a pharmacodynamic cohort to obtain 
additional pharmacodynamic data from approximately 6 additional subjects at one or more dose 
levels that have completed evaluation for safety without exceeding the MTD. Subjects in the 
pharmacodynamic cohort must have tumor accessible and safe for biopsy from both an injected 
lesion and a non-injected lesion and must consent to providing paired biopsies for translational 
research. Subjects enrolled in the pharmacodynamic cohort will not inform dose escalation 
decisions but the pharmacodynamic and other data gathered from these additional subjects will 
inform selection of doses for further evaluation and the RP2D determination. Subjects in the 


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pharmacodynamic cohort will be followed per the Schedule of Assessment (SOA) table provided 
in Section 6.
3.2
Selection of Recommended Phase 2 Dose
Selection of the RP2D and schedule for SL-172154 will be based upon the totality of the data in 
subjects treated in the dose escalation and the pharmacodynamic cohorts. The totality of the data 
refers to safety, tolerability, PK, clinical activity, and pharmacodynamic markers consistent with 
the mechanism of action. Approximately 6 subjects (inclusive of the subjects enrolled in the Dose 
Escalation and Pharmacodynamic cohort) may be treated at the RP2D.
3.2.1
Sample Size
The planned total sample size for this study is approximately 18 subjects. This sample size assumes 
evaluation of approximately 12 subjects across 4 dose levels in dose escalation and approximately 
6 subjects in the optional pharmacodynamic cohort. The goal is to enroll approximately 6 subjects 
at the potential RP2D, including subjects in dose escalation and the pharmacodynamic cohort. 
3.3
Justification for Starting Dose and Schedule of SL-172154  
The intratumoral starting dose for SL-172154 was determined based on MABEL principles, taking 
into account available preclinical pharmacology, toxicology, and pharmacokinetic data. The most 
sensitive in vitro measure of biological activity in response to SL 172154 exposure was the PBMC 
proliferation assay conducted in Alstroemeria-Mosaic Virus (AIMV) medium.  The starting dose 
for the study is informed by key data from cynomolgus monkey toxicology studies, including 
identifying the NOAEL, and the PK results.   
A starting dose of 0.003 mg (3 µg) was chosen for the administration of SL-172154 to humans via 
ITI.  Given as a total 1.5 mL injection (2 µg/mL), this concentration, prior to distribution within 
tissue at the administration site, is comparable to the EC50 value (1.8 µg/mL) observed for human 
and cynomolgus monkey in the PBMC proliferation assay. Because SL-172154 is delivered locally 
to the tumor lesion, this dose/concentration is considered appropriate for this route of injection 
without further correction. Dose escalation will allow for identification of an optimal dose for 
subjects with advanced disease. 
Intratumoral delivery has the potential advantage of reducing systemic toxicity by delivering drug 
directly to the tumor lesion. For immune-stimulating agents, intratumoral injection may also serve 
as an in situ vaccination approach. The proposal to use a flat dose (mg or µg) is consistent with
the recommendation from Marabelle et al. [Marabelle, 2018] for ITI of drugs with primary toxicity 
that is likely systemic. 
Since SL-172154 will be administered directly into the tumor and is expected to remain primarily 
within the tumor tissue, PK modeling was not considered necessary to inform the starting dose. 
Rather, the starting dose is selected to match intratumoral concentrations of SL-172154 to effect 
concentrations (e.g., EC20, EC50) derived from the AIMV assay.  
As a benchmark for toxicity, the NOAEL for SL-172154 administered IV to cynomolgus monkeys 
in a GLP toxicology study was 1 mg/kg [Report SL2020IB001]. The proposed SL-172154 starting 
dose of 0.003 mg (3 µg) in a 70 kg human is 0.04 µg/kg, and is 25,000 times lower than the 
NOAEL of 1 mg/kg. In monkeys, the 1 mg/kg dose administered IV corresponded with mean 


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Cmax and AUC0-last values of 1230 ng/mL and 518 ng•h/mL on Day 1. Assuming complete 
bioavailability following an intratumoral dose, Cmax is expected to be 0.049 ng/mL (25,000 times 
lower) and thus, systemic exposure is expected to be negligible with intratumoral administration. 
It also should be noted that the planned starting dose for ITI (0.003 mg; 0.00004 mg/kg for a 70 kg 
subject) is ~2500-fold below the starting SL-172154 IV dose of 0.1 mg/kg in clinical study SL03-
OHD-101, thus ensuring that systemic exposure following ITI will remain substantially below 
exposures observed following IV administration.   
Targeting the EC50 from the AIMV assay for an intratumorally administered drug is intended to 
provide a safe starting dose while minimizing the number of dose escalations needed to achieve a 
therapeutically effective dose.  A starting dose based on 50% pharmacologic activity was found to 
be safe in 16 of 17 bispecific CD3 constructs administered IV or i.p. [Saber, 2017].  Given the 
considerations outlined above, a starting dose (0.003 mg) based on EC50 is expected to have a low 
likelihood of systemic toxicity while achieving local tumor concentrations consistent with in vitro 
pharmacologic response. 
Justification for Schedule
The dosing schedule for the clinical trial incorporates SL-172154 administered by ITI on days 1, 
8, 15 of a 21-day in cycle 1 and then on day 1 of each subsequent 21-day cycle (cycles
). The 
rationale for the selected dose schedule is based on a paradigm of immune priming and immune 
boosting [Marabelle, 2018]. The immune priming phase refers to SL-172154 administered by ITI 
on days 1, 8, 15 of a 21-day in cycle 1. Immune priming refers to stimulating a de novo immune 
response via the generation of a novel, antigen specific, adaptive immune response. Given that SL-
172154 may have a short half-life and potentially a short duration of local bioactivity on the CD40 
agonist end, it is hypothesized that an initial dose-intense induction phase of ITI is necessary for 
the local priming of an antitumor immune response. This schedule for immune priming is 
supported by the NHP data as no toxicity was observed at the day 8 dose, minimal 
pharmacodynamic effects were noted at this time point, 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, margination of lymphocytes and 
cytokine elevations. It is unknown if these contributing factors would be observed in humans at 
the doses studied and via the ITI route of administration.
The immune boosting phase refers to SL-172154 administered by ITI at day 1 of each subsequent 
21-day cycle at cycle 2 and beyond. Immune boosting involves the enhancement of a pre-existing 
immune response against the tumor and is hypothesized to elicit a recall effect to a recent immune 
priming event or disinhibit a pre-existing antitumor immune response [Marabelle, 2018]. Thus, the 
3-week treatment free interval beyond day 22 is based upon 1) subject acceptability and 2) the 
durability of binding for SL-172154 to CD47. Furthermore, this interval may allow for 
pharmacodynamic effects to subside between subsequent doses and to mitigate toxicity. A more 
or less intensive dosing schedule may be instituted if safety and pharmacodynamic data 
support more or less frequent dosing of SL-172154. 
3.4
Dose Escalation of SL-172154 Administered by Intratumoral Injection  
Dose escalation will proceed using a flat dose and fixed volume format (see Section 6.8 for 
additional details). Dose escalation will begin at the starting dose of 0.003 mg as outlined in Table 


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1 below; intermediate dose levels not shown may be explored based on emerging data (e.g., safety). 
Dose escalation of intratumoral SL-172154 will not exceed half-log increments. The DLT 
assessment period is 21 days in length and encompasses the first 21-day cycle of therapy. Dose 
escalation will follow mTPI-2 decision rules outlined in Table 5 in Section 9.1.
Dose escalation in half-log increments (Table 1) 
Schedule of administration for ITI of SL-172154: Doses administered on days 1, 8, 15 of 
a 21-day cycle in cycle 1 and on day 1 of each subsequent 21-day cycle, starting on 
cycle 2,  day 1 (day 22) (Figure 2).
Cycle length: 21 days 
DLT assessment period: 21 days of cycle 1
Table 1: Intratumoral Dose Escalation Plan for SL-172154  
Dose Level
ITI Dose (mg) of SL-172154a
ITI Volume of Dose 
Level 1 - starting dose
0.003
1.5 mL
Level 2
0.01
1.5 mL
Level 3
0.03
1.5 mL
Level 4
0.1
1.5 mL
a) Intermediate or higher dose levels may be tested based on emerging safety and/or 
pharmacodynamic data. Dose escalation will not exceed half-log increments.
Figure 2: ITI Schedule for SL-172154 
3.5
Definition of Dose-Limiting Toxicity
DLTs are as 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 of ITI SL-172154 dosing. Note: AEs 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.
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Any 
Grade 4 AE
Elevations in liver transaminases (aspartate aminotransferase [AST], alanine aminotransferase 
[ALT]) and/or total bilirubin: 
o
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 AE that requires permanent discontinuation of SL-172154 
Any Grade 3 or greater AE with the following exceptions:
o
o
Grade 3 anemia if not associated with clinical sequelae or not requiring transfusion of 
red blood cells (RBCs) within 48 hours. 
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 injection-related reaction (first occurrence and in the absence of steroid 
prophylaxis) that resolves within 6 hours of onset with appropriate clinical 
management.  
o
Grade 3 rigors or chills lasting < 6 hours that respond to optimum medical therapy. 
o
Grade 3 fever lasting < 24 hours with or without medical therapy. 
o
Grade 3 electrolyte abnormalities that are not associated with clinical signs/symptoms 
and are reversed with appropriate medical intervention
o
Grade 3 laboratory abnormalities that are not deemed clinically significant by the SMC.
o
Indirect/unconjugated hyperbilirubinemia without significant clinical consequences 
o
Grade 3 or 4 amylase and/or lipase abnormalities that are not associated with clinical 
signs/symptoms or findings on imaging consistent with pancreatitis
o
Grade 3 vomiting and/or Grade 3 nausea that resolves within 72 hours with appropriate 
clinical management
o
Grade 3 hypertension that can be controlled (i.e., systolic BP < 140 mmHg and diastolic 
BP < 90 mmHg) with medical therapy. 
o
Grade 3 endocrine disorder (thyroid, pituitary, hyperglycemia and/or adrenal 
insufficiency) that is managed with treatment with resolution of symptoms within 14 
days after treatment onset.
o
Grade 3 diarrhea with no evidence of colitis that resolves within 72 hours with 
appropriate clinical management
o
Grade 3 skin toxicity (excluding injection-site reactions) that downgrades to Grade 2 
or less within 7 days with optimal supportive care 
o
Vitiligo or alopecia of any grade 
Other AEs may be considered a DLT as determined by the investigator in conjunction with the 
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A
(s) that occurs beyond the DLT period (21 days) or Grade 2 events that require 
continuous interruption of SL-172154 for more than 6 weeks or AEs that result in subjects not 
receiving at least two of the three scheduled dose of SL-172154 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.
3.6
Concomitant Medications, Treatments, and Procedures
Investigators may prescribe concomitant medications or treatments deemed necessary to provide 
supportive care except for prohibited medications (see Section 3.6.1) during treatment with SL-
172154. 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.  
and/or anti-pyretic 
agents with no or low bleeding risk (for example, paracetamol/acetaminophen, metamizole, 
dipyrone, or propyphenazone) is recommended. 
3.6.1
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 
study treatment with SL-172154: 
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, immunotherapy, or 
biologic therapy for cancer treatment   
Immunosuppressive medications for primary prophylaxis against injection-related 
reactions are not permitted. Subjects who require immunosuppressive medications (e.g., 
corticosteroids) for management of irAEs or injection-related reactions should be managed 
per Toxicity Management Guidelines in Section 3.7.
Live attenuated vaccines during the study through 30 days after the last intratumoral dose 
of SL-172154 
Antiplatelet therapy (for example, clopidogrel, ticlopidine, dipyridamole, and anagrelide 
or > 100 mg acetylsalicylic acid).
Full dose anticoagulation therapy (for example, warfarin, heparin, low molecular weight 
heparin, 
direct 
oral 
anticoagulants). 
Low 
dose 
anticoagulant 
therapy 
for 
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Local anesthetic administered prior to ITI of SL-172154 is not permitted due to the low pH 
of local anesthetic and the potential impact on the function of the drug product. Local 
anesthetic use is permitted prior to biopsy of a non-injected lesion.
3.6.2
Medications to be used with Caution
SL-172154 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 
products if therapeutic effects cannot be monitored during ITI of SL-172154. 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).
Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) with a high risk of bleeding (for 
example, indomethacin, ibuprofen, naproxen, or similar agents) is strongly discouraged unless at 
the discretion and responsibility of the investigator after careful assessment of the individual 
bleeding risk of the subject. 
3.7
Toxicity Management Guidelines Dosing Delays/Dose Modifications 
No dose reductions are permitted for SL-172154. The toxicity guidelines provided in this section 
represent general guidance for AEs that are considered by the investigator to be related to treatment 
with SL-172154. All AEs should be assessed using NCI-CTCAE v5.0 criteria. These guidelines 
are not meant to be prescriptive and investigators should always use clinical judgment in the 
determination of dosing. Investigators should always err on the side of caution if treatment-related 
toxicity is suspected. Subjects should be thoroughly evaluated to rule out any alternative etiology 
(e.g., disease progression, concomitant medications, and infections). In the absence of a clear 
alternative etiology, all events should be considered potentially immune related. 
Please see Section 5.1.4 Monitoring Dose Administration for further information on ITI of SL-
172154. In this protocol, the term “injection-related reactions” maps to the analogous term of 
“infusion-related reaction” in CTCAE v5.
NOTE:  Hereafter in this section and in subsequent sections, SL-172154 may be referred to as SL-
172154 or as IP.   
Differentiating between injection-related reactions that are due to either the common non-allergic 
hypersensitivity reactions [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 injection-related reactions 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 


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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 judgment of the AE/SAE and the definition found 
in NCI-CTCAE v5.0 for injection-related reaction, allergic reaction, anaphylaxis, and CRS.  
Primary prophylaxis against injection-related reactions 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 injection-related reactions following an initial episode) is appropriate and permitted at the 
discretion of the investigator.  
NOTE:
injection-related reaction, subjects will be observed on-site or 
hospitalized for close observation until resolution of symptoms as per Section 3.7.1.


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3.7.1
Toxicity Management Guidelines
Adverse Event
General Guidance for Injection Site Reactions (ISR)
Injection Site 
Reactions 
Subjects will be monitored closely throughout the study for the following symptoms at the injection sites: pain, tenderness, pruritis, warmth, 
cellulitis, rash, erythema, swelling, induration, fluctuance, and nodules (granulomas or cysts). Digital photographs will be documented by 
the study team for evaluation on all subjects who have an injection site reaction that are serious, Grade 2 or above or if persistent beyond 
2 weeks. Dermatology will be consulted on all subjects who have an injection site reaction considered serious, Grade 3 or above, or if 
persistent beyond 30 days and others if the Investigator or Medical Monitor feels it is medically necessary. 
Severity 
(Symptoms)
Management
Grade 1
Continue SL-172154 injection with close clinical follow-up.
Symptomatic treatment and/or premedication of local injection site reactions with antihistamines (H1/H2 
inhibitors), acetaminophen (or other low bleeding risk medications; Section 3.6) and opiates is acceptable. 
Antileukotrienes may also be considered as needed per discretion of the investigator. Due to their potential 
bleeding/immunosuppressive effects, the use of systemic NSAIDs and steroids within 24 hours of dosing SL-
172154 should be avoided, if clinically feasible.
Grade 2
Temporarily hold SL-172154 injection until AE has reverted to Grade 1 or baseline. 
Provide symptomatic treatment with acetaminophen as anti-pyretic, antihistamines, leukotriene inhibitors and/or 
opiates.
Provide premedication prior to subsequent injections per investigator/institutional guidelines. Due to their 
potential bleeding/immunosuppressive effects, the use of systemic NSAIDs and steroids within 24 hours of 
injection with SL-172154 should be avoided if clinically feasible.
If SL-172154 injection is delayed such that 2 consecutive scheduled injections are missed to allow for resolution 
of ISR despite optimal medical management, then the subject should permanently discontinue SL-172154 
injections.


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Injection site 
reaction  
(continued from 
previous page)
Severity 
(Symptoms)
Management
Grade 3
Hold SL-172154 injection until AE has reverted to Grade 1 or baseline.  
Provide symptomatic treatment with acetaminophen as anti-pyretic, antihistamines, leukotriene inhibitors, 
steroids and/or opiates.
Obtain dermatology consultation.
If grade 3 AE persists for 7 days, permanently discontinue SL-172154 injections.
Provide pre-medications (acetaminophen as anti-pyretic, antihistamines, leukotriene inhibitors, steroids and/or 
opiates) for subsequent injections per investigator/institutional guidelines. 
If grade 3 symptoms recur with pre-medications, then SL-172154 injections should be permanently discontinued.
Grade 4
Permanently discontinue SL-172154 injections.
Obtain dermatology consultation.
Treat urgently with non-operative and operative interventions as clinically indicated.


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Adverse Event
General Guidance for Injection-related Reactions [Rosello, 2017; Porter, 2018]
Injection-
Related or 
Hypersensitivity 
Reactions 
In this protocol, the term “injection-related reactions” maps to the analogous term of “infusion-related reaction” in CTCAE v5. Acute reactions 
to the administration of biologic agents are 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 an 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 HSR 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 common 
manifestations of acute infusion reactions. Proinflammatory cytokines such as TNF-
-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 injection-related reactions with prompt institution of treatment.  Subjects should be notified 
that symptoms may occur during the first injection and for up to several hours afterwards or with subsequent injections. Instruct subjects to 
contact their physician if symptoms or signs of an injection-related reaction occur. 
Severity 
(Symptoms)
Management
Grade 1
Injection(s) interruption not indicated. 
Monitor subjects with close observation in an outpatient or inpatient setting for a minimum of 12 hours or 
until recovery from symptoms
Consider pre-medication (antipyretics, histamine (H1 and H2 antihistamines, leukotriene inhibitors, 
corticosteroids) for subsequent injections per investigator/institutional guidelines
Grade 2
Consider interrupting SL-172154 injection(s).
Begin IV infusion of normal saline and treat with antipyretics, histamine 1 and 2 (H1 and H2) antihistamines, 
and leukotriene inhibitor. Corticosteroids and/or bronchodilator therapy may also be administered as 
appropriate. 
If symptoms resolve with treatment, SL-172154 injection(s) may be completed. If symptoms recur or do not 
resolve to baseline, then no further SL-172154 injection(s) will be administered at this visit.
Monitor subjects with close observation in an outpatient or inpatient setting for a minimum of 12 hours or 
until recovery from symptoms. Consider admission to hospital.
The following prophylactic pre-medications are recommended for future injections: antipyretics, 
antihistamines with/without corticosteroids per institutional guidelines


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Injection-
related or 
Hypersensitivity
reactions
(continued from 
previous page)
Severity 
(Symptoms)
Management
Grade 3
Immediately discontinue injection(s) of SL-172154 
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.
Monitor subjects with close observation in an outpatient or inpatient setting for a minimum of 12 hours or 
until recovery from symptoms. Strongly consider admission to hospital.
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 SL-172154 injection at the 
next scheduled dose with pre-medication (e.g., corticosteroids, antihistamines, antipyretics). The next two 
subsequent injections of SL-172154 (after a grade 3 event of injection-related reaction) must be 
administered in an inpatient or outpatient setting with prolonged observation for a minimum of 12 hours after 
the completion of the injection.  If symptoms recur, permanently discontinue SL-172154.
Grade 4
Permanently discontinue SL-172154 injection(s).
Admit to hospital for close observation until resolution of symptoms
Manage severe injection-related reactions 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


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Adverse Event
General Guidance for Cytokine Release Syndrome (CRS) [Rosello, 2017; Porter, 2018]
Cytokine-release 
Syndrome
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-
-2, IFN ). 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
Grade 1
Injection(s) interruption is not indicated.
Monitor subjects with close observation in an outpatient or inpatient setting for a minimum of 12 hours or 
until recovery from symptoms.
Maintain IV access and provide symptomatic treatment with antipyretics, antiemetics, analgesics, histamine 
1/histamine 2 (H1/H2) antagonists as needed; monitor fluid balance; assess for infection. Regularly evaluate 
for signs of further deterioration
For subsequent injection(s), consider pre-medication (e.g., antipyretics, antihistamines) per institutional 
guidelines
Grade 2
Interrupt SL-172154 injection(s).
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.
Monitor subjects with close observation in an outpatient or inpatient setting for a minimum of 12 hours or 
until recovery from symptoms. Consider admission to hospital for management of symptoms, organ 
dysfunction or administration of therapy
The next two subsequent injections of SL-172154 (after an event of grade 2 CRS) must be administered in 
an inpatient or outpatient setting with prolonged observation for a minimum of 12 hours after the completion 
of the injection. 
For subsequent injections, pre-medicate with dexamethasone 20 mg, antipyretics, H1/H2 antihistamines, 
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


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Adverse Event
Severity 
(Symptoms)
Management
Cytokine-release 
Syndrome
(continued from 
previous page)
Grade 3 or 4
Interrupt SL-172154 injection(s).
Hospitalization required for management of symptoms related to organ dysfunction: admit to the hospital and 
potentially the intensive care unit 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.
Manage severe injection-related reactions and CRS 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
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: 
o
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.  
o
anti-TNF-
-
-1R-based inhibitors 
(anakinra).
For Grade 3 CRS, may consider rechallenge after consultation with medical monitor. If rechallenge is given:
o
The next two subsequent injections of SL-172154 (after an event of grade 3 CRS) must be 
administered in an inpatient or outpatient setting with prolonged observation for a minimum of 12 
hours after the completion of the injection. 
o
After a Grade 3 CRS event, subjects must be premedicated with dexamethasone 20 mg, antipyretics 
and H1/H2 antihistamines prior to the next injection of SL-172154. 
o
If there is no evidence of CRS with the subsequent injection, premedication with high dose steroids 
may be omitted for subsequent injections. 
o
Any patient that experiences recurrence of Grade 3 CRS following re-treatment must be permanently 
discontinued from study treatment.
For Grade 4 CRS, permanently discontinue SL-172154.


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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, SL-172154 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 
, 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
(Symptoms)
Management
Grade 1
SL-172154 injection is continued, and treatment with corticosteroids is usually not indicated
Grade 2
SL-172154 injection may be continued.
Depending on the nature of the AE, corticosteroids may be indicated. 
Start with oral prednisone 0.5-1 mg/kg/day. SL-172154 is generally held during corticosteroid therapy 
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 SL-172154 injection.
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 SL-172154 injections and start IV methylprednisolone 1-2 mg/kg/day.  
If no improvement, consider adding alternative immunosuppressant.


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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 polymerase chain reacation,
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 PD/thrombosis.  Guidelines are based on elevations in
ALT, AST and bilirubin per CTCAEv5. Discontinue SL-172154 injections for Hy’s law as follows: in subjects who enroll with 
o
enroll with AST/ALT/total bilirubin > ULN who experience concomitant AST or ALT > 3 x baseline and total bilirubin > 2 x baseline.
Severity 
(Symptoms)
Management
Grade 1
Continue SL-172154 injection with close monitoring.
Monitor liver function at least weekly; if liver function is stable, reduce frequency of blood tests.
Grade 2
Hold SL-172154 injection
Assessments as above; monitor liver function ~every 3 days
Consider hepatology consult and liver biopsy is optional. 
If persistent or rising liver chemistries or significant clinical symptoms and an immune etiology is suspected, 
start oral prednisone 0.5-1 mg/kg/day (or equivalent of methylprednisolone) with 4-week taper.
Resume SL-172154 injection
equivalent. 
Grade 3
Grade 3: hold SL-172154 injection.
Permanently discontinue SL-172154 injections for liver function test abnormality that meets following criteria 
Permanently discontinue SL-172154 injections 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.  
If persistent or rising liver chemistries, or significant clinical symptoms and an immune etiology is suspected, 
start oral prednisone 0.5-1 mg/kg/day (or equivalent of methylprednisolone) with 4-week taper. Obtain 
hepatology consult and assessments as above, monitor liver function daily; consider liver biopsy.
Other Grade 3 laboratory abnormalities: re-challenge may be considered only after consultation with 
hepatologist.


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Hepatotoxicity  
(continued from 
previous page) 
Severity 
(Symptoms)
Management
Grade 4
Grade 4: permanently discontinue SL-172154 injection.
Consider hospitalization; obtain hepatology consult; assessments as above; monitor liver function daily; 
consider liver biopsy. 
If an immune etiology is suspected, immediately start methylprednisolone 1-2 mg/kg (start with 2 mg/kg for 
Grade 4) or equivalent.
If refractory after 3 days, consider mycophenolate mofetil (MMF). Avoid the use of infliximab in immune 
mediated hepatitis.


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Adverse Event
General Guidance for Hematologic Toxicity
Anemia
Subjects with cancer can have multiple causes of cytopenias and thus blood counts must be monitored carefully. When administered 
systemically, SL-172154 does exhibit binding to white blood cells (WBCs), red blood cells (RBCs) and platelets in non-human primate 
studies, but there was no evidence of neutropenia, anemia, hemagglutination, RBC destruction or clinically significant 
thrombocytopenia. However, in the event of anemia, it is important to use physical exams, complete blood counts (CBCs), serum
chemistries, D-dimer testing and review of peripheral smears to look for evidence of RBC agglutination, microangiopathy, 
spherocytosis, and evidence of RBC destruction (e.g., schistocytosis, fragments).  A hematologic AE needs to be distinguished from 
transient changes in laboratory values that can occur during initiation of an immune response (e.g., lymphopenia, 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. Drug binding to CD47 on 
RBCs may result in interference with standard serologic techniques for blood compatibility testing. Please refer to Section 3.8 for 
guidance re blood cross-matching and transfusion procedures.
Severity 
(Symptoms)
Management
Grade 1
Continue SL-172154 injection with close clinical follow-up and laboratory evaluation
Grade 2
Consider holding SL-172154 injection until AE has reverted to Grade 1 or baseline. 
Consider hematology consult
Repeat type and screen and DAT 
Transfusion per existing guidelines (minimum number of units to relieve symptoms of anemia or to return 
subject to safe hemoglobin (Hgb) range), folic acid supplementation.
Grade 3
Hold SL-172154 injection until AE has reverted to Grade 1 or baseline. 
Repeat type and screen and DAT
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 SL-172154 injections.
If evidence of an immune-mediated etiology, give 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, anti-thymocyte globulin.
Hospitalize; hematology consult; transfuse per existing guidelines.


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Thrombocytopenia
Severity 
(Symptoms)
Management
Grade 1
Continue SL-172154 injection with close clinical follow-up and laboratory evaluation.
Grade 2
Consider holding SL-172154 injection until AE has reverted to Grade 1 or baseline. 
Consider Hematology Consult
Grade 3 or 4
Hold SL-172154 injection until AE has reverted to Grade 1 or baseline. 
Hematology consult.
If evidence of an immune-mediated etiology, give 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 
rituximab, thrombopoietin receptor agonists, or more potent immunosuppression


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Adverse Event
General Guidance for Influenza-like Symptoms
Influenza-like 
Symptoms
Influenza-like symptoms refers to a group of symptoms similar to those observed in subjects with the flu. It may include fever, chills, 
myalgias, arthralgias, malaise, loss of appetite and dry cough. All subjects should be closely monitored for development of injection-related 
reactions and cytokine release syndrome given the overlapping symptoms. Alternative infectious etiologies should be investigated and 
ruled out, if warranted. Treatment of systemic drug-related events should be consistent with the severity of the reaction as well as 
institutional standards. Per CTCAE v5, toxicity grading for influenza-like symptoms ranges from grade 1 through grade 3.
Severity (Symptoms)
Management
Grade 1
Continue SL-172154 injection with close clinical follow-up.
Consider pre-medication (acetaminophen as anti-pyretic, antihistamines such as H1/H2 blockers and/or 
opiates) for subsequent injections per investigator/institutional guidelines. Due to their potential 
bleeding/immunosuppressive effects, the use of non-steroidal anti-inflammatory drugs (NSAIDs), leukotriene 
inhibitors and steroids within 24 hours of injection with SL-172154 should be avoided if clinically feasible.
Grade 2
Consider holding SL-172154 injection until AE has reverted to Grade 1 or baseline. 
For flu-like symptoms that persist for 
7 days, 
administering the next scheduled injection. 
Provide pre-medications (acetaminophen as anti-pyretic, antihistamines, leukotriene inhibitors and/or 
opiates) for subsequent injections per investigator/institutional guidelines. Due to their potential 
bleeding/immunosuppressive effects, the use of non-steroidal anti-inflammatory drugs (NSAIDs) and steroids 
within 24 hours of injection with SL-172154 should be avoided if clinically feasible.
If SL-172154 injection is delayed such that 2 consecutive scheduled injections are missed to allow for 
resolution of prolonged Grade 2 symptoms despite optimal medical management, then the subject should 
permanently discontinue SL-172154 injections.
Grade 3
Hold SL-172154 injection until AE has reverted to Grade 1 or baseline. 
Provide pre-medications (acetaminophen as anti-pyretic, antihistamines, leukotriene inhibitors, steroids 
and/or opiates) for subsequent injections per investigator/institutional guidelines. If grade 3 flu-like symptoms 
recur with pre-medications, then SL-172154 injections should be permanently discontinued.
If SL-172154 injection is delayed such that 2 consecutive scheduled injections are missed to allow for 
resolution of prolong Grade 3 flu-like symptoms despite optimal management, then the subject should 
permanently discontinue SL-172154 injections


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3.7.2
Management of Other AEs Not Specified
Severity (Symptoms)
Dose Modification
Toxicity Management
Any Grade
Note: Dose modifications are not required for AEs not deemed to be related 
to SL-172154 (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-172154 injection
Treat accordingly, as per institutional 
standard
Grade 3
Hold SL-172154 injection
baseline within 14 days, resume SL-172154. Otherwise, discontinue SL-
172154 injections.
(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-172154 injections.
(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
(Reference: American Society of Clinical Oncology Educational Book 2015 “Managing Immune Checkpoint Blocking Antibody Side Effects” 
by Michael Postow MD.) 


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3.8
Antibody Detection and Compatibility Testing for Transfusion 
SL-172154 binds to red cells and may obscure the assessment of ABO red blood cell phenotyping.
There is also a possibility that treatment with SL-172154 may interfere with compatibility tests, 
including the antibody screen and crossmatch that are part of a routine pre-transfusion work up
[Report_SL2020IB001].  
At screening, before exposure to SL-172154, all subjects must have: 
ABO and D group (ABO/Rh) type and antibody screen and antibody identification if 
required
Direct antiglobulin test (DAT) 
Phenotype/genotype for, at a minimum, the minor antigens Rh C/c E/e, K, Jk, Fy and
MNSs.  
Inform the blood bank that the subject is to commence SL-172154. 
Determining this extended RBC phenotype prior to exposure to SL-172154 will facilitate and 
allow the option of selecting extended antigen-matched RBCs should a blood transfusion be 
warranted, and compatibility not be able to be demonstrated due to drug interference.  
After exposure to SL-172154: 
In subjects who may/do require RBC transfusion after SL-172154 therapy has commenced, it is 
recommended that an ABO/D type, antibody screen, and auto control and/or DAT be performed
as per routine testing methods.   
Following guidance of the local Transfusion Service Medical Director (or equivalent person) and 
the Transfusion Service standard operating procedures the following considerations may apply if
interference with testing is seen:
If the ABO group cannot be concluded from the forward and reverse typing, a decision 
may be made to transfuse based on the RBC ABO forward type only, provided it is 
concordant with the ABO record pre-therapy, or alternatively group O red cells may be 
used for transfusion.
Differential adsorption may allow valid reverse type and antibody screening.
Performing an eluate on a DAT+ sample should follow local standard operation procedure. 
For emergency transfusions, the transfusion laboratory may consider using Group O or 
ABO type specific units if time permits, without consideration of extended phenotype if
units are not available.
For elective red cell transfusions when the crossmatch is incompatible, leukocyte-reduced 
units matched for the extended phenotype of the subject (as described above) will be used,
i.e. the subject will receive units negative for the antigens that he/she lacks.  
Where matching for all specified blood groups is not possible (e.g., for MNS), local sites 
will decide on the best matched donor units to be used.  
Plasma therapy will be blood-type specific. Platelets will be blood type compatible 
whenever possible, and if not, will have been tested and found not to have high titer anti-A or
anti-B.


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3.9
Discontinuation of Study Therapy
SL-172154 should be discontinued by the Investigator when a subject meets one of the conditions 
requiring discontinuation outlined in Section 3.7. The Investigator may, however, elect to 
discontinue SL-172154 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.  
 
Treatment may continue until one of the following criteria applies:
Disease progression per RECIST v1.1 NOTE: See Section 8.2 for criteria allowing for 
continuing treatment past initial progression. 
Death
Intercurrent illness that prevents further administration of treatment
Unacceptable AE(s)
Participant declines further therapy with ITI of SL-172154 in the absence of disease 
progression 
Participant decides to withdraw from the study 
General or specific changes in the participant's condition that render the participant 
unacceptable for further treatment in the judgment of the investigator 
Participant non-compliance
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 7.5).
If study therapy is permanently discontinued for reasons other than PD or withdrawal of consent, 
the subject will remain in the study to be evaluated for disease progression.  See the Schedule of 
Assessments (SOA) in Section 6 for data to be collected following discontinuation of SL-172154 
at the post-treatment and follow-up visits.  
3.10
Criteria to Resume Treatment
A participant may resume ITI of SL-172154 per the guidance outlined in Section 3.7. If the criteria 
to resume treatment are met, the subject should restart treatment at the next scheduled time point
per protocol.    
3.11
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 


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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. 
3.12
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:
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 should continue in the 
study. 
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.
Should the participant continue to be unreachable, he/she will be considered as lost to 
follow up and withdrawn from the study. 
3.13
Duration of Treatment
The planned treatment duration with ITI SL-172154 should be until progressive disease. Subjects 
with complete resolution of all injectable lesions should discontinue treatment and continue with 
all relevant study assessments including disease assessments. The subject will be followed until 
disease progression as per protocol.  
Impact of ADA on clinical efficacy (non-response or loss of response to the IP) and safety (product 
specific immunogenicity risk) will be evaluated on an on-going basis.  If a subject develops ADA, 
the Sponsor and investigator may take into consideration these factors in assessing the duration of 
the therapy.   
3.14
Duration of Follow-Up
Subjects who discontinue IP for any reason other than withdrawal of consent will be followed for
AEs for 90 days after the last dose of IP. Subjects who are withdrawn from study for unacceptable 


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AE(s) will be followed until resolution or stabilization of the AE. Subjects who permanently 
discontinue IP for reasons other than progression will continue with disease assessments until 
progressive disease, start of another anti-cancer therapy, withdrawal of consent, death, or end of 
the study, whichever occurs first.  
3.15
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 and the FDA. If the study is prematurely terminated or 
suspended, the investigator will promptly inform the Institutional Review Board (IRB) 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, 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  
3.16
End of Study Definition
End of Study is defined as approximately 1 year after the last subject is dosed on cycle 1, day 1 
(C1D1) or the date the study is closed by the Sponsor, whichever occurs first. 
4.
STUDY POPULATION
Participants may be considered for enrollment in the study if they meet all the eligibility criteria 
stated in Sections 4.1 and 4.2.  Prospective approval of protocol deviations to recruitment and 
enrollment criteria, also known as protocol waivers or exemptions, is not permitted.  
4.1
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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2.
Subjects must have a histologically confirmed diagnosis of an unresectable or recurrent,
locally advanced or metastatic cutaneous squamous cell carcinoma or squamous cell 
carcinoma of the head and neck that is not amenable to curative surgery or radiotherapy. 
o
Cutaneous squamous cell carcinoma: Subjects with predominantly mixed 
histologies (eg, sarcomatoid, adenosquamous) are not eligible. Subjects with a
minimal component of mixed histology in which the predominant histology is 
invasive squamous cell carcinoma are eligible.
o
Squamous cell carcinoma of the head and neck: Subjects must have primary tumor 
locations in the oropharynx, oral cavity, hypopharynx, larynx or unknown primary.
Primary tumor sites of nasopharynx, maxillary sinus, and paranasal are excluded. 
3.
Subject must have received, been intolerant to, or ineligible for standard therapies that are 
known to provide clinical benefit for their condition as defined by:  
o
HNSCC subjects must have received, been intolerant to, or ineligible for 
platinum-based chemotherapy and PD-1/L1 inhibitors in combination or 
sequentially. 
o
CSCC subjects must have received, been intolerant to, or ineligible for PD-1/L1 
inhibitors. 
4.
Has measurable disease by RECIST v1.1 using radiologic assessment and/or clinical 
examination. NOTE: If there are multiple lesions that are measurable per RECIST v1.1, at 
least one of these lesions must be considered injectable per inclusion criteria #5. 
5.
Subject has at least 1 tumor lesion that is cutaneous and/or subcutaneous and/or nodal and 
is deemed to be clinically accessible and safe for injection of SL-172154 by the 
investigator. 
o
Must be able to be inject the lesion by direct visualization, palpation or by 
ultrasound guidance. Injections of deep or visceral lesions or injections which 
require magnetic resonance imaging (MRI) or computed tomography (CT) 
guidance are not permitted. 
o
At baseline, non-nodal l
longest diameter and 
nodal lesions must measure 
.5 cm in the longest diameter to be considered 
injectable.  
o
Tumor lesion(s) selected for injection cannot exceed 6 cm in the longest diameter. 
o
Lesions must be located in an anatomic location where SL-172154 can be safely 
administered and not in close proximity to critical structures (e.g., major blood 
vessels, nerve bundle, trachea or a major airway tract) as determined by the 
investigator. 
o
Pharmacodynamic Cohort ONLY: Must have a second lesion that is non-injected 
and is amenable to tumor biopsy collection. (Note: This non-injected lesion is not 
required to be measurable per RECIST v1.1.) 
6.
Subject age is 18 years and older.  




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12.
Recovery 
from 
prior 
anti-cancer
treatments including
surgery, radiotherapy, 
chemotherapy, immunotherapy or any other anti-cancer
.
(NOTE: Low-grade toxicities such as alopecia, vitiligo, endocrinopathies adequately 
treated with hormone replacement,
Grade 2 lymphopenia,
hypomagnesemia, 
 may be allowed upon agreement by the Sponsor Medical Monitor). 
13.
Subjects enrolled in the dose escalation cohort must be willing to undergo a baseline tumor 
biopsy and on-treatment biopsies of the injected tumor lesion. Subjects enrolled in the 
pharmacodynamic cohort must be willing to undergo baseline tumor biopsies of an injected 
and non-injected lesion and on-treatment biopsies of the injected and non-injected tumor 
lesion.
4.2
Participant Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply: 
1. Prior treatment with an anti-CD47 or anti-SIRP  targeting agent or a CD40 agonist. 
2. Any anti-cancer therapy within the time intervals noted below prior to first dose (D1) of 
SL-172154. 
Therapy
Washout period
Chemotherapy 
3 weeks
PD-1/L1 inhibitor and other immunotherapies not otherwise 
specified
4 weeks 
Tumor vaccine 
4 weeks
Cell-based therapy
8 weeks
Other mAbs or biologic therapies
3 weeks
Other investigational agents not covered above
4 weeks or 5 half-lives 
whichever is shorter
Major surgery
2 weeks
Radiation (except palliative intent which does not require 
washout)
2 weeks 
3. Concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for anti-cancer 
intent is prohibited.  Concurrent use of hormones for non-cancer related conditions is 
acceptable. 
4. Use of corticosteroids or other immunosuppressive medication, current or within 14 days 
of D1 of SL-172154 treatment with the following exceptions (i.e., the following are 
allowed with or within 14 days of D1 of IP): 
o
Topical, intranasal, inhaled, ocular, intraarticular corticosteroids 
o
Physiological doses of replacement steroid (e.g., for adrenal insufficiency) not to 
exceed 10 mg/day of prednisone or equivalent 
o
Steroid premedication for HSRs (e.g., reaction to IV contrast)


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5. Receipt of live attenuated vaccine within 28 days of D1 of IP.
6. Hypersensitivity to any of the excipients or to Chinese hamster ovary cell products. 
7. History of coagulopathy resulting in uncontrolled bleeding, eg, hemophilia, von
within 3 months prior to first dose of IP. 
8. Requires continuous anticoagulation therapy
acetylsalicylic acid). 
9. Active or documented history of autoimmune disease that has required treatment with a 
disease modifying agent or immunosuppressive therapy in the past two years. Exceptions 
include Type I diabetes, vitiligo, alopecia areata or hypo/hyperthyroidism. 
10. Active pneumonitis or history of symptomatic pneumonitis in the past 2 years that required 
treatment (i.e. drug-induced, idiopathic pulmonary fibrosis, radiation-induced, etc.).   
11. Ongoing or active infection (e.g., no systemic antimicrobial therapy for treatment of 
infection within 5 days of D1 of IP). 
12. Symptomatic peptic ulcer disease or gastritis, active diverticulitis, other serious GI disease 
associated with diarrhea within 6 months of D1 of IP. 
13. Clinically significant or uncontrolled cardiac disease including any of the following: 
o
Myocarditis 
o
Unstable angina within 6 months from D1 of IP 
o
Acute myocardial infarction within 6 months from D1 of IP
o
Uncontrolled hypertension 
o
NYHA Class III or IV congestive heart failure
o
Clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular 
tachycardia, second- or third- degree atrioventricular (AV) block without a pacemaker, 
circulatory collapse requiring vasopressor or inotropic support, or arrhythmia requiring 
therapy) 
14. 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.  
15. Women who are breast feeding. 
16. 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. 


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17. 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.  
18. Has undergone allogeneic stem cell transplantation or organ transplantation.
19. 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 enrolment. HCV: Subjects who are HCV Ab 
positive, but HCV RNA negative are eligible for enrolment).
4.3
Screen Failures
Screen failures are defined as subjects who consent to participate in the clinical study but are not 
subsequently treated 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.
4.4
Accrual Goal 
The total sample size expected to complete this study is approximately 18 subjects (see Section
9.1). Approximately 4-6 clinical sites may participate in SL03-OHD-102.  Overall, the study may 
be complete recruitment within approximately 12 months (1 year). Study duration is estimated to 
be 20 months which includes the enrollment period and completion of all study-related data 
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5.1.2.2 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.
5.1.2.3 Storage 
SL-172154 must be stored in a secure area under the appropriate physical conditions for the 
product.  Access to and administration of SL-172154 drug product will be limited to the 
investigator and authorized site staff.  SL-172154 must be dispensed or administered only to 
subjects enrolled in the study and in accordance with the protocol.   
SL-172154 d
-) 60 C (-60 C to 
-90 C).  Maintenance of a temperature log is required. The drug product should be stored protected 
from light.
The expiry date will be on the single vial carton label, if required. 
5.1.3
Investigational Product Accountability
In accordance with local regulatory requirements, the investigator or designated site staff must 
document the amount of IP dispensed and administered to study subjects, relevant dates, dilution 
amounts, SL-172154 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. 
5.1.4
Monitoring Dose Administration  
ITI of SL-172154 must be administered in an outpatient oncology treatment center or inpatient 
unit to enable close monitoring of subjects and proactive management of AEs. The risks associated 
with administration of SL-172154 by ITI include injection-related reactions and CRS as mentioned 
in Section 3.7. 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 
ITI of SL-172154. All subjects must be observed for at least 6 hours at the center after each 
intratumoral injection of SL-172154. See Section 6.8 of the protocol for instructions on SL-172154
administration by ITI. Vital signs will be measured as outlined in the SOA in Section 6 and as 
needed.   
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.   


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5.1.5
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 studied to date) of SL-172154, the investigator should: 
Contact the Sponsor immediately
Closely monitor the subject for AEs/SAEs and laboratory abnormalities for at least 2 
weeks following the injection. The appropriate AE management guideline should be 
followed (Section 3.7). Pharmacologic effect 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 
the electronic case report form (eCRF)
If a SAE related to overdose of the IP occurs, it should be documented and reported 
accordingly (Section 7.4) 
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. 
5.2
Drug Accountability and Treatment Compliance
The investigator or designee is responsible for keeping accurate records of IP received from the 
Sponsor, the amount of SL-172154 administered to the subjects and the amount of unused or 
partially-used drug remaining at the conclusion of the trial. An accurate and current accounting of 
SL-172154 administered by ITI to each subject must be maintained on an ongoing basis by a 
member of the study site staff in the Drug Accountability Record.  Treatment compliance will be 
monitored by drug accountability as well as the subject’s medical record and eCRF. 
Handling and Disposal: Local requirements for disposal of hazardous drugs should be followed 
at each participating clinical site. It is the Investigator’s responsibility to arrange for disposal of all 
partially used or empty containers, provided that procedures for proper disposal have been
established according to applicable federal, state, local and institutional guidelines and procedures, 
and provided that appropriate records of disposal are kept.  
Prior to the return or destruction of IP, the Sponsor Study Monitor must have performed a complete 
reconciliation of IP ensuring accountability records are complete and accurate and are retained in 
the Investigator Site file or pharmacy file. IP that is returned to the IP supplier or destroyed on site 
must be documented in the accountability documentation.  Arrangements for the return of SL-
172154 will be made by the responsible Study Monitor. 
Refer to the SPM for ITI of SL-172154 for further instructions regarding requirements for the IP 
under study. 


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6.
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the 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 cycle. 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 timeframe 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 ITI of SL-172154. 




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Day -1 = last day of screening period i.e., the day before the first dose of SL-172154 ITI therapy is initiated on day 1 of cycle 1 
Table Heading Abbreviations: C = cycle; D = day; f/u = follow up; TXT = treatment; w/in = within
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-172154: hematology profile, chemistry profile, coagulation profile, and pregnancy test. Baseline computed 
tomography (CT) or positron emission tomography (PET)/CT or MRI tumor assessments are required for all subjects within 28 days prior 
to the first dose of SL-172154.  
b. Assessment Window: With the exception of Screening assessments and unless otherwise 
-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 cycle. Dose interruptions should 
not alter the assessment schedule for any subsequent treatment cycle. 
c.
Inclusion/Exclusion criteria: Subjects must meet eligibility criteria prior to first dose of SL-172154 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 Cycle 2 on D1: Predose (within 30 min of starting the 
injection) 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 end of injection (EOI). 
2) Vital signs/pulse oximetry should be taken once prior to scheduled PK samples on C1D2, C1D16 and C2D2.
3)
Predose (within 30 min of start of the injection(s)) and at the EOI (± 
2 min)  
e.
Pregnancy Test:  A serum pregnancy test (beta-
-hCG]) or urine pregnancy test must be performed at 
screening for all FCBP within 72 hrs of starting SL-172154. Repeat this test every 9 weeks during SL-172154 treatment (i.e., C4D1, 
C7D1, C10D1, etc.). Contraception should be continued for at least 30 days after the last dose of SL-172154. 
f.
Hematology/Clinical Chemistry/Haptoglobin/Ferritin/C reactive protein: will be performed at local laboratories according to the 
laboratory’s normal procedures.  See Section 6.3.6 for list of laboratory test required.
g. Coagulation Tests: prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), 
fibrinogen,  d-dimer will be performed at local laboratories according to the laboratory’s normal procedures.
h. Blood phenotyping (ABO/Rh), and DAT: These tests should be performed at local laboratories according to the laboratory’s normal 
procedures.  


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1) At screening: The following testing should be performed a) ABO and D group (ABO/Rh) type and antibody screen and antibody 
identification if required; b) DAT; c) Phenotype/genotype for, at a minimum, the minor antigens Rh C/c E/e, K, Jk, Fy and MNSs. 
2) C1/D2: only need to perform blood phenotyping (ABO/Rh) and DAT. 
i.
Antiviral Testing: Please see exclusion criterion 19 in Section 4.2. These tests will be performed at local laboratories according to the 
laboratory’s normal procedures.
j.
Tumor Assessment: Tumor assessments are required for all subjects within 28 days prior to the first dose of SL-172154. The same 
method of assessment and the same technique should be used to characterize each identified and reported lesion at baseline, on treatment 
and during follow-up.  Baseline and on-treatment tumor assessments by RECIST v1.1 should include CT with contrast of chest, abdomen, 
and pelvis and clinical examination (if applicable) of all known sites of disease at each time point. Bone scan, positron emission 
tomography (PET)/CT, and/or MRI should be performed if clinically indicated. Tumor lesions will only be considered measurable by 
clinical examination when they are superficial, and dimensions are accurately assessed using calipers or rulers. For skin lesions assessed 
by clinical examination, documentation by color photography including a ruler to estimate the size of the lesion, is required at all time
points.  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: approximately every 6 weeks through week 54 (e.g., C3D1, C5D1, C7D1), every 12 
weeks up to year 2 (prior to cycles 23, 27, 31, and 35), and then every 24 weeks (prior to cycles 43, cycle 51, etc.) up to conclusion of the 
study. Confirmatory scans should be performed at least 4 weeks (>28 days) after initial documentation of an objective response and
preferably at the next scheduled tumor assessment visit that is about 6 weeks later. Subjects who discontinue study treatment for reasons 
other than disease progression (e.g., AE) will be monitored for response until start of another anti-cancer therapy, disease progression, 
withdrawal of consent, death, or end of the study, whichever occurs first. 
k. PK/immunogenicity (i.e., ADA): Blood sample collection timings for PK, ADA are outlined in Section 6.1.1 in Supplementary Tables 
2 and 3. PK/ADA sample collection times on C1D1, C1D15 and C2D1 through 24 hours postdose are provided in Table 2 PK/ADA 
sample collection times in cycles 3 and beyond are outlined in Table 3. Blood volumes required are provided in the SLM. PK/ADA 
samples should be collected from a line that is distant or on the opposite side of the ITI site. 
1) If subject has positive ADA test on D1 of cycle 13 or ADA results are not known, then follow up predose samples for PK/ADA 
should be collected every 3 cycles on D1 of subsequent treatment cycles (i.e., cycles 16, 19, 22 and 25) until ADA resolves to 
baseline OR until the last PK/ADA sample is collected within 105-125 days after the last dose of SL-172154.
2) A PK/ADA sample is collected within 7 to 30 days after the subject discontinues SL-172154 therapy.
3) If subject has positive ADA tests during treatment or ADA results are not known, a final PK/ADA sample is collected within 105-
125 days after the last dose of SL-172154.  
l.
Correlative laboratory studies:  Refer to supplementary Table 4 for details in Section 6.1.2 plus see the SLM for amount of blood needed 
and sample shipment details. 
Immunophenotyping and cytokines   


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m. SL-172154 ITI administration: SL-172154 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. Following the 
dose on cycle 2, day 1, a window of +/-3 days is allowed for scheduled dosing days for drug administration in 21-day cycles. All subjects 
must be observed for at least 6 hours at the center after each intratumoral injection of SL-172154.  Please refer to Section 6.8 for detailed 
instructions on SL-172154 administration by ITI. 
n. AE Monitoring: Subjects will be followed continuously for AEs during the study and for 90 days after the last dose of SL-172154. After 
a subject is discontinued from SL-172154, 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 AE, the subject will be asked to return for follow-up until the 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 SAE related to injection-related reaction or CRS events as 
noted in Section 6.3.6.3 and the SLM. 
o. Archival tumor tissue (from a recent biopsy): Archival tissue, if available, will be collected from all subjects. 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. Moreover, archival 
tissue may be accepted in lieu of the pre-treatment tumor biopsy if the subject has not undergone treatment since time of specimen 
collection and if the sample was collected via punch biopsy or core needle biopsy and adequate sample is available for analysis. Please 
notify the sponsor if archival tissue will be used in lieu of a pre-treatment fresh 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 6.6.2.2 and the 
SLM for details.
p. Tumor Biopsy: Pre- and two on-treatment paired biopsies are required for all subjects. Biopsies will be obtained at baseline to evaluate 
the immune status of the tumor before SL-172154 treatment. The first on-treatment biopsy should be taken prior to the cycle 2/day 1 dose 
on study days 18-22. The second on-treatment biopsy should be taken prior to the cycle 3/day 1 dose on study days 39-43. For subjects
assigned to the dose escalation cohort, a baseline and two on-treatment biopsies should be obtained from the same injected lesion. For 
subjects assigned to the pharmacodynamic cohort, a baseline and two on-treatment biopsies should be obtained from both an injected 
lesion and a non-injected lesion. The same tumor lesion should be biopsied at the baseline and on-treatment time points to allow for direct 
comparison.  Biopsy at the time of PD will be optional.  Please refer to Section 6.6.2.1 and SLM for details regarding biopsy.




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Table 3: Serial PK/ADA (C4/D1 and Beyond) 
Study Day
D1 of C4, C7, C10, C133, through to25
Collect a PK/ADA sample within 7 to 30 
days after the subject discontinues SL-
172154 therapy.
Collect sample for PK/ADA within 105-
125 days post last dose of SL-172154.
Sample
Predose
- 30 min (± 5 min)
PK
X1,2
ADA
X1,2
Date and clock time for sample collection (pre/post dose) will be recorded for all samples
1.
Predose sample collected will include analysis of ADA and PK. 
2.
The PK, ADA samples should be collected from a line that is distant or on the opposite side of the ITI site. See SLM for the most accurate 
estimates of blood needed and for additional details on sample handling instructions.
3.
If subject has positive ADA test on D1 of cycle 13 or ADA results are not known, then follow up predose samples for PK/ADA should be collected every 
3 cycles on D1 of subsequent treatment cycles (i.e., cycles 16, 19, 22 and 25) until ADA resolves to baseline OR until the last PK/ADA sample is 
collected within 105-125 days after the last dose of SL-172154. 
6.1.2
Correlative Sample Time Points for SL-172154  
Table 4: Immunophenotyping and Cytokine Time Points 
Samples
C1D1/C1D15/C3D1
C1D2/C1D16
Predose
(-90 to -30 min)
1hr post EOI
(±10 min) 
24 hr post EOI
(± 2hr)
Immunophenotyping1
X
X
X
Cytokines1
X
X
X
Date and clock time for sample collection (pre/post dose) will be recorded for all samples
1. Refer to SLM for details.


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6.2
Demographics, Medical History, Screening and Safety Assessments
6.2.1
Informed Consent
The participant or his/her legally authorized representative must 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-172154. Refer to Section 13.3.
6.2.2
Eligibility Criteria  
Subjects must meet all the eligibility criteria outlined in the protocol to be eligible for participation.   
6.2.3
Subject Demographics
The age, year of birth, sex, race, and ethnicity of each subject will be recorded during Screening. 
6.2.4
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. The receipt and 
response to prior PD-1/L1 inhibitor therapies will be recorded. 
6.2.5
Concomitant Medications 
Concomitant medications and procedures will be recorded during the Screening period and 
throughout the study as specified in the SOA.
6.3
Safety Evaluations 
6.3.1
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, genitals 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.
6.3.2
ECOG Performance Status
Participant’s performance status will be assessed using the ECOG performance status tool (see
Appendix Section 16.2). 
6.3.3
Pulse Oximetry
Oxygen saturation will be measured with a pulse oximeter at room air without supplementation.
Refer to footnote “d” in the SOA table for details on when to collect pulse oximetry.


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6.3.4
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 table for details on when to collect vital 
signs. 
6.3.5
Electrocardiogram Monitoring for QTc Evaluation 
QTcF is the QT interval corrected for heart rate according to Fridericia’s formula (QTcF). It is 
either machine-read or manually over-read. The specific formula used to determine eligibility for 
an individual participant in this study will be Fridericia’s formula. An electrocardiogram (ECG)
will be obtained in subjects at screening to confirm subject eligibility. 
ECGs will also be obtained in triplicate (i.e., each ECG assessment obtained 5 minutes apart) prior 
to and following SL-172154 ITI and the reported QTc should be based on the average of 
triplicate ECG readings. Assessment of the QTc interval using the Fridericia (QTcF) correction 
methods for heart rate will be performed at the following time points: cycle 1, day 1 at predose 
and 1 hour and 4 hours after ITI of SL-172154 is given. These planned post ITI time points are 
subject to change based on emerging PK data and determination of Tmax. ECGs in triplicate will 
also be collected prior to injection of SL-172154 on cycle 2, day 1. ECG measurements should be 
obtained with the subject in a supine position having rested in this position for at least 10 minutes 
prior to testing. Triplicate ECGs should be performed prior to blood drawn for clinical, PK/ADA 
or biomarker labs or measurement of vital signs at each of the time points specified. Local ECG 
machines available at the clinical site should be used for all ECG assessments specified by the 
protocol. 


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6.3.6
Laboratory Assessments 
6.3.6.1
Clinical Labs Performed Locally
Refer to the SOA in Section 6 for the timing and frequency of tests performed.
Clinical Labs Performed at the Local Laboratory
Hematology
Clinical Chemistry 
Hemoglobin 
Blood urea nitrogen 
Magnesium
Hematocrit
Creatinine
Phosphorus
Platelet Count
Glucose
Total Protein
Red Blood Cell Count 
Sodium
Albumin
White Blood Cell Count 
Potassium
Lactate dehydrogenase
Automated WBC Differential
(absolute number and percent):
Calcium
Haptoglobin
Bicarbonate
Ferritin
Neutrophils
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
C reactive protein
Liver Panel
Total and direct bilirubin
Aspartate aminotransferase 
Alanine aminotransferase 
Alkaline phosphatase 
Blood Type and Screen
Serum/Urine Pregnancy Test
ABO and D Group (ABO/Rh)
-human chorionic gonadotropin
Antibody screen
Direct antiglobulin test            
Phenotype/Genotype minor 
antigens: Rh C/c E/e, K, Jk, Fy 
and MNSs 
Coagulation 
Antiviral Testing
Prothrombin time and 
International- normalized ratio 
Activated partial 
thromboplastin time 
Fibrinogen 
D-Dimer
Hepatitis B: HBsAg / HBV core Ab
Hepatitis C: HCV Ab / HCV RNA viral load


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6.3.6.2  
 Central Labs
Refer to SOA and supplementary tables provided in Section 6 for the timing and frequency of 
central laboratory tests.
Central Laboratory Testsa
Cytokines and Chemokines
PK/Immunogenicitya
Pharmacokinetics (SL-172154 serum concentration)
Anti-drug antibodies
Flow Cytometrya
Immunophenotyping Panels
Tumor IHCa
PD-L1 expression
CD47 and CD40 expression 
Changes in immune infiltrate such as T cell subsets, B cells, and macrophages
a.
Samples in this table will be analyzed at a Central Lab. Refer to the SLM for details for 
sample collection procedures, handling, storage and shipment instructions.  
6.3.6.3  
 Ad Hoc Labs for SAEs 
Ad hoc labs should be collected as noted if injection-related reaction/CRS or an immune-related 
serious adverse event (irSAE) occurs. The samples to be collected are provided below. 
Ad Hoc Labsa,b
Required Local Clinical Labs
Required Central Labs
Complete blood count with differential
Chemistry Panel
Coagulation panel 
C reactive protein
Ferritin
Pharmacokinetics (SL-172154 serum 
concentration) 
Anti-drug antibodies 
Cytokines and Chemokines 
Immunophenotyping Panels 
a.
Refer to the SLM for sample collection procedures, handling, storage and shipment 
instructions.  PK will be measured with each corresponding ADA sample. 
b.
If an event of injection-related reaction/CRS or an irSAE occurs, these specific biomarker
samples should be collected as soon as possible. 
All protocol-required central laboratory assessments must be conducted in accordance with the 
SLM.
6.3.6.4 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-172154. 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 16.3.
In the rare event that -hCG is elevated as a tumor marker, please see guidance in Appendix 
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6.3.6.5 Blood Type and Screen (ABO/Rh) and DAT
SL-172154 does bind RBCs but has not been shown to cause hemolysis in NHPs. However, 
treatment with SL-172154 may make phenotyping difficult due to expected coating of the RBC 
membrane. Thus, blood phenotyping, type and screen (ABO/Rh), and DAT should be performed 
at screening before exposure to SL-172154. At screening the following testing should be 
performed: 1) ABO and D group (ABO/Rh) type and antibody screen and antibody identification 
if required; 2) DAT; 3) phenotype/genotype for, at a minimum, the minor antigens Rh C/c E/e, K, 
Jk, Fy and MNSs. At cycle 1/day 2, testing should only include ABO/Rh type and DAT testing as 
outlined in the SOA table in Section 6.1.
6.4
Pharmacokinetics
6.4.1
Intensive PK Sampling in Dose Escalation 
Intensive serial PK samples will be collected for all subjects enrolled. Actual dose administration 
and PK sampling times will be documented in the subject’s medical record.  In the first cycle 
starting on Day 1, samples will be collected as outlined in the SOA and supplementary tables 
provided. Beyond cycle 2 day 2, only predose samples will be collected for ADA and PK analyses. 
Refer to supplementary tables provided in Section 6.1.1 for details.
6.5
Anti-drug Antibody Assessments
Predose blood samples will be collected from all subjects enrolled in the study for determination 
of ADA starting on day 1 and periodically throughout the course of therapy (Refer to 
supplementary tables provided in Section 6.1.1 for details). If subject has a positive ADA test on 
D1 of cycle 13 or if ADA results are unknown, then predose samples for ADA should continue to 
be collected every 3 cycles on D1 of subsequent treatment cycles until ADA becomes negative or 
until a final ADA sample is collected within 105 – 125 days after permanently stopping treatment 
with SL-172154.  
6.6
Pharmacodynamic/Biomarker Assessments
Blood samples and tumor tissue will be collected from all subjects in this study for 
pharmacodynamic/biomarker research as specified in the SOA and supplementary table (Section
6.1.2). 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 and fresh 
and archival tumor tissue collection during the study will be provided. 
6.6.1
Pharmacodynamic Assessments in Blood
6.6.1.1 Cytokine and Chemokine Analysis  
The levels of serum proteins such as cytokines and chemokines will be measured as noted in 
Section 6.3.6.2. Levels of serum cytokines/chemokines may provide context to AEs observed in 
subjects following ITI of SL-172154 and may act as pharmacodynamic markers of activity.


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6.6.1.2 PBMC for Immunophenotyping 
Protein expression of phenotypic markers as well as absolute quantitation of phenotypic 
populations will be assessed by flow cytometry. The composition and change of T and B cells, NK 
cells, and monocytes in the peripheral blood may provide insights into the mechanism of action of 
SL-172154 and serve as biomarkers for immune response.  
6.6.2
Pharmacodynamic Assessment of Tumor Tissue
6.6.2.1 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. Therefore, the direct evaluation of the “immune landscape” inside the 
tumor is of great value for understanding the mechanism of action of SL-172154 and optimizing 
cancer immunotherapy. The screening biopsy is used to evaluate the immune status of the tumor 
before SL-172154 treatment, while the on-treatment biopsies are used to characterize changes in 
the TME in response to drug administration. Immunohistochemistry (IHC) analyses will be 
performed on these fresh tumor samples. Changes in the immune infiltrate of the tumor at the 
different biopsy time points will be assessed by visualizing and assessing the phenotype of cells in 
the TME 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-172154.  
Biopsy Collection 
For subjects assigned to the dose escalation cohort, a baseline and two on-treatment biopsies 
should be obtained from the same injected lesion. For subjects assigned to the pharmacodynamic 
cohort, a baseline and two on-treatment biopsies should be obtained from both an injected lesion 
and a non-injected lesion. The same tumor lesion should be biopsied at the baseline and on-
treatment time points to allow for direct comparison. The tumor biopsies should be obtained at the 
time points noted in the SOA. The time interval for the on-treatment biopsy may be changed by 
the Sponsor if emerging data indicates that a different time point would be more suitable.  
Depending on the location of the lesion, biopsies can be performed by either full thickness punch 
biopsy or core needle biopsy based on investigator judgment. The same modality of biopsy should 
be performed at all time points. If punch biopsies are being performed on a lesion, it is necessary 
to obtain two punch biopsies up to 6 mm diameter each or the equivalent. If core needle biopsies 
are being performed on a lesion, three core needle biopsies should be obtained. Biopsies should be 
performed per institutional standards. Biopsy tissue should be fixed in formalin and paraffin 
embedded and the entire block must be submitted. Please refer to the SLM for further instructions.  
Information regarding the timing of the biopsy, the location and measurement of the lesion(s) that 
is biopsied and its injected vs non-injected status will be collected. Documentation of the lesion at 
the time of biopsy will be obtained either by digital photography or image-based documentation.
For ultrasound, CT or MRI-guided biopsies, all relevant treatment planning radiological images 
(e.g., biopsy needle in lesion images) may be centrally collected and should be made available to 


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the Sponsor or designated central imaging vendor. These images will be used to confirm the lesions 
that were biopsied by their injected vs non-injected status. 
Where possible lymph node biopsies should be avoided as reliable measurements of 
tumor infiltrating lymphocytes (or their activation) in a background of (non-tumor) 
lymphoid tissue is challenging.   
Attempt to select RECIST v1.1 target lesions for biopsy when the le
diameter and/or biopsy of the lesion is not expected to impact or alter the size of the lesion 
and the lesion’s subsequent evaluation by RECIST v1.1 
If biopsies and response assessment are to be performed at the same visit, biopsies should 
always be performed after response assessments so that biopsy associated trauma or 
swelling does not confound response assessment.   
If biopsies and ITIs are being performed on the same day, please try to biopsy the lesion 
from one side and inject IP distant to the biopsy site to minimize leakage of the IP. 
If feasible, biopsy material should be collected after disease progression has been 
confirmed, ideally on lesions that have progressed. 
Safety Considerations for Biopsy Collection  
Only punch biopsies or percutaneous biopsies will be performed on subjects. No laparoscopic,
endoscopic or open surgical procedures will be performed solely to obtain a biopsy for this 
protocol. Surgical, laparoscopic or endoscopic biopsies are permitted ONLY when obtained 
incidentally to a clinically necessary procedure and not for the sole purpose of the clinical trial.  
Excisional or endoscopic biopsy tissue that was obtained for a medically indicated procedure can be 
used for analysis.
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 an anatomical 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.  
For the dose escalation and pharmacodynamic cohort, subjects must undergo baseline and on-
treatment biopsies of injected lesions. These lesions should be biopsied directly or with the use of 
ultrasound guidance in a manner similar to the ITI. For the pharmacodynamic cohort, subjects
must also undergo baseline and on-treatment biopsies of a non-injected lesion. The use of imaging 
to facilitate biopsies of these non-injected lesions is permitted and 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. 


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6.6.2.2 Archival Tumor 
Archival tissue, if available, will be collected from all subjects. 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 is requested. 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 in lieu of the screening/baseline fresh tumor biopsy if the subject 
has not undergone anti-cancer treatment since time of specimen collection and if an adequate 
sample was collected via punch biopsy or core needle biopsy. Please notify the sponsor if archival 
tissue will be used as the baseline biopsy. 
6.7
Assessment of Anti-tumor Activity
The primary analysis of anti-tumor activity is according to RECIST v1.1. Tumor size changes will
also be assessed in the injected lesion(s) and in the non-injected lesion(s) as available. The same 
method of assessment and the same technique used to characterize each identified and reported 
lesion at baseline should be used throughout. Disease assessment will be performed at baseline 
and at the following intervals until disease progression is confirmed: every 6 weeks through week 
54, and every 12 weeks thereafter until year 2, and every 24 weeks until study conclusion. Refer 
to Section 8 for additional details. Treatment beyond progression is permitted provided the subject 
meets protocol specified criteria (see Section 8.2). All subjects will be followed for PD unless they 
withdraw consent.  
6.8
SL-172154 Administration by Intratumoral Injection 
6.8.1
Baseline Lesion Identification 
At baseline, all subjects assigned to the dose escalation cohort will be required to have a minimum 
of one lesion that meets the following criteria:
One target lesion that is measurable per RECIST v 1.1 and  
Can be safely injected as determined by the site investigator and  
Amenable to tumor biopsy collection.  
At baseline, all subjects assigned to the pharmacodynamic cohort will be required to have a 
minimum of 2 lesions:  
Lesion 1: One target lesion that is measurable per RECIST v 1.1 and can be safely injected 
as determined by the site investigator and amenable to tumor biopsy collection  
Lesion 2: One lesion that remains non-injected and is amenable to tumor biopsy collection. 
It is preferable for both cohorts to identify at least 2 lesions at baseline. In order to assess response 
in an injected lesion, 1 lesion must be measurable by RECIST v.1.1 and accessible for injection. 
In order to assess anenestic or bystander response, the second lesion should be measurable per 
RECIST v1.1 and be non-injected.  


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6.8.2
Definition of Lesion Injectability
ITI of SL-172154 must be able to be conducted by direct visualization, palpation or by ultrasound 
guidance. Injections of deep or visceral lesions or injections by MRI or CT guidance are not 
permitted. Non-
l lesions must 
Injectable lesions cannot 
exceed 6 cm in the longest diameter. Measurements may be made based upon clinical or radiologic 
examination. 
Tumor lesions must be located in an anatomic location where SL-172154 can be safely injected as 
determined by the investigator. Lesions should not be in close proximity to critical structures (e.g., 
major blood vessels, nerve bundle, trachea or a major airway tract) as determined by the 
investigator. Lesions that are associated with large fistulas, that are primarily ulcerated, cystic or 
necrotic, or in high-risk locations such as peristomal, at the oral commissure or near the orbital 
cavity should be avoided.
6.8.3
General Instructions for Injection 
Tumor injections may be performed by any trained practitioner including physicians, advanced 
practice providers or nurses.
Administration of conscious sedation to the subject for the ITI procedure is permissible if the 
treating physician determines that the risk-benefit is appropriate.  
Lesions identified for injection should be prepared per facility guidelines.  
Lesions may be pre-treated with topical anesthetic agents. Local anesthetic should NOT be 
instilled into the lesion prior to ITI of SL-172154.   
Injections may be performed using standard supplies as per institutional guidelines permitted 
that these supplies meet compatibility requirements with the IP. The size of the syringe selected 
must allow for accurate measurement and instillation of drug product. To minimize morbidity 
and limit drug product leakage, the smallest gauge needle should be used that is appropriate 
for a given lesion location.
If biopsies and ITI are being performed on the same day, please attempt to biopsy the lesion 
from one side and then inject IP distant to the biopsy site to minimize leakage of the IP.
If biopsies and response assessment are to be performed at the same visit, biopsies should 
always be performed after response assessments so that biopsy associated trauma or swelling 
does not confound response assessment.   
SL-172154 should be injected along multiple different tracks within the lesion in order to 
obtain as wide a dispersion as clinically feasible.
6.8.4
Prioritization of Lesions for Injection
It is strongly recommended that baseline lesion selection and the prioritization of lesions for 
injection are discussed on an ongoing basis with the multidisciplinary care team. 
Prioritization of lesions for injection should favor larger lesions over smaller lesions and 
symptomatic lesions over asymptomatic lesions.
Dosing of SL-172154 will proceed using a flat dose and fixed volume format (see Section 3.4
for additional details). The entire drug dose must be instilled into one to three tumor lesions at 
a given ITI time point in order to ensure that the toxicity assessment can be accurately ascribed 
to a specific drug dosage. A maximum of three lesions can be injected at any dosing time point. 


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If multiple lesions are being injected at a given time point, the drug product should be split 
between the lesions based on the relative size of each lesion. A minimum of 0.5 mL of SL-
172154 should be instilled into any given lesion. 
Dosing may continue as per the specified interval until all clinically feasible lesions are 
injected at least once and then lesions that were previously injected may be re-injected.
A previously injected lesion that is stable or responding may be reinjected until the lesion has 
completely resolved or as long as clinically feasible. At the time of complete resolution of a 
lesion, no further injections should be administered into the lesion with the complete 
resolution, however other lesions can be injected if clinically feasible. 
A previously injected lesion that is progressing may be re-injected if the benefit-risk ratio of 
continuing therapy is justified and all criteria for re-injection are met.
New lesions that develop during the study which meet all of the criteria for being injectable, 
may be considered for injection. 
6.8.5
Documentation of Intratumoral Injections
At baseline, all lesions that are selected for ITI must be recorded via digital photography or by 
image-based documentation (if using ultrasound). Photographs should include a close-up view 
of the index lesion and an anatomical location view of the index lesion area(s). Two exposures 
for each location and lesion will be taken. Refer to the Site Imaging Manual for complete 
instructions.
All lesions undergoing ITI must be documented. Documentation of the needle tip on or within 
the lesion at the time of injection will be obtained either by digital photography or image-based 
documentation. For ultrasound guided injections, all relevant treatment planning radiological 
images (e.g., needle in lesion images, ultrasound images clearly marking the lesion to be 
injected) may be centrally collected and should be made available to the Sponsor or designated 
central imaging vendor, for collection, storage, and possible future central re-analysis. These 
images will be used to confirm the lesions that were injected vs non-injected in order to assess 
the local and anenestic or bystander response to therapy. 
6.9
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. 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 7.4). 
7.
SAFETY ASSESSMENTS  
Subjects will be followed continuously for all 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-172154 due to PD 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-172154, only SAEs and AEs that occur prior to 
starting the new anticancer therapy should be recorded. All observed or volunteered AEs (serious 


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or non-serious) and abnormal laboratory test findings, if applicable, whether suspected to have a
causal relationship to SL-172154 study therapy 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-172154/study therapy.  AEs will be 
followed until resolution (or return to baseline) or stabilization.
Refer to Section 7.4 for 
documentation and reporting of AEs.
7.1
Definitions for Safety Parameters
Event
Definition
Adverse Event (AE)
The observation period of an AE starts at the time of signing informed 
consent and includes baseline or washout periods, even if no study 
treatment has been administered. 
The definition of an 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 (SL-
172154). 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 
Event (SAE) or 
Serious Adverse 
Reaction (SAR)
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:  
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 
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Event
Definition
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 IP; or requires 
corrective therapy, must be documented appropriately. 
Ad hoc labs should be collected as noted in Section 6.3.6.3 above 
if injection-related reaction/CRS or an irSAE occurs. 
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 AR (causality related Adverse Event), the nature, severity or outcome 
of which is not consistent with the reference safety information section of 
the SL-172154 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. 
7.1.1
Events not Qualifying as AEs/SAEs
Because attribution of AEs is difficult in a phase 1 study, any toxicity experienced by subjects in 
this study should be recorded as AEs unless otherwise specified. 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. 
Elective procedures, planned hospitalizations, and procedures for treatment of conditions 
noted in the subject’s medical history (present prior to signing the ICF) that have not 
worsened are not considered AEs.  


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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 subject’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 
subject). 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. 
7.2
Classification of an Adverse Event 
7.2.1
Assessment of Severity 
The descriptions and grading scales found in the revised NCI-CTCAE v5.0 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 activities of daily living (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 
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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. 
7.2.2
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.   
7.2.3
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 
Investigators) of the IB 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. 
7.3
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.  


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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.  
AEs characterized as intermittent require documentation of onset and duration of each episode.  
7.4
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 IP due to PD 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 within 90 
days of the last dose of SL-172154, only SAEs and irAEs that occur before 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 
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 may be requested by the Sponsor and 
should be provided as soon as possible. The Sponsor will be responsible for 
notifying Regulatory Authorities of any unexpected fatal or life-threatening 
suspected AR as soon as possible but in no case later than 7 calendar days after 
the Sponsor's initial receipt of the information. The Sponsor will be responsible 
for notifying Regulatory Authorities of any other serious unexpected suspected 
adverse reaction as soon as possible but in no case later than 15 calendar days 
after the Sponsor's initial receipt of the information.


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Event
Reporting Procedures
Sponsor Contact Information for SAE Reporting
Email:
eFax number: 
7.5
Reporting of Pregnancy 
Although not an AE in and of itself, pregnancy as well as its outcome must be documented via the 
Pregnancy Report Form provided in the SRM.  Any pregnancy occurring in a participant or 
participant’s partner from the time of consent to 30 days after the last dose of IP must be reported 
and then followed for outcome.  Newborn infants born to the subject or subject’s partner should 
be followed until 30 days old.   
A FCBP must discontinue SL-172154 immediately if they become pregnant during the study. To 
ensure subject safety, each pregnancy must be reported to the Sponsor within two weeks of 
learning of its occurrence. The pregnancy must be followed to determine outcome (including 
premature termination) and status of mother and child. Pregnancy complications and elective 
terminations for medical reasons must be reported as a SAE. Spontaneous abortions must be 
reported as a SAE. 
Any SAE occurring in association with a pregnancy brought to the investigator’s attention after 
the subject has discontinued SL-172154 must be promptly reported to the Sponsor.
7.6
Reporting of Overdose 
The following events should also be reported to the Sponsor and PrimeVigilance within 24 hours: 
Overdose: An overdose of SL-172154 should be reported within 24 hours to the Sponsor 
Suspected transmission of an infectious agent due to contamination of drug product 
Other events related to misuse of IP
7.7
Study Halting Rules
Administration of IP will be halted if a fatal SAE is reported to the Sponsor related to SL-172154.
The Sponsor will inform the investigators immediately if such an event is reported and screening 
and enrollment will stop accepting new study subjects. The Sponsor will convene an ad hoc 
meeting of the SMC to review the SAE and overall safety profile and provide recommendations. 
The study Sponsor will inform the regulatory authorities (i.e., FDA) of the temporary halt and the 
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7.8
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).
8.
ANTI-TUMOR ACTIVITY ASSESSMENTS
Although the clinical benefit of SL-172154 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. Tumor response will 
be defined by RECIST v1.1 criteria according to the schedule outlined in the SOA. All participants 
who underwent the first disease assessment at the 6-week time point or progress or die before to 
the first disease assessment 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 response assessments. 
More frequent response assessments may be performed at the discretion of the investigator. If 
study treatment is withdrawn for reasons other than disease progression, response 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 8.2 for criteria for continuing treatment past
disease progression. 
8.1
Response Assessment
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline, on-treatment and during follow-up. 
Tumor lesions will only be considered measurable by clinical examination when they are 
superficial and dimensions are accurately assessed using calipers or a ruler (e.g., skin nodules). 
For skin lesions, documentation by color photography including a ruler to estimate the size of the 
lesion, is required at all timepoints. Investigators will also provide a clinical description of the 
externally visible target lesion(s) at baseline and at each tumor assessment, as well as comments 
on any changes in the lesion(s) since the previous assessment. Please refer to the Site Imaging 
Manual for complete instructions. When lesions can be evaluated by both clinical examination 
and imaging, imaging evaluation should be undertaken since it is more objective. Furthermore, 
radiologic imaging will be essential in the evaluation of tumor lesions that have subdermal 
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All subjects will undergo radiologic imaging studies, preferably by contrasted CT scan, of the 
chest, abdomen and pelvis and all other sites of known disease at baseline and at the following 
intervals until disease progression: every 6 weeks until week 54 and every 12 weeks thereafter 
until year 2 and every 24 weeks until study conclusion. PET-CT, MRI, and/or bone scan should 
be performed as clinically indicated. In the event of a CR or PR, confirmatory scans should be 
performed in at least 4 weeks (>28 days) and preferably at the next disease assessment that is 
approximately 6 weeks later. Contrast enhanced imaging is required unless the subject is precluded 
from receiving contrast (e.g., hypersensitivity, renal impairment). If biopsies and scans for 
response assessment are to be performed on the same lesion, biopsies should always be performed 
after response assessments so that biopsy associated trauma or swelling does not confound 
response assessment.
All copies of scans and digital photographs taken for response assessment should be collected and 
stored at the site. The Sponsor may request that all of these images be sent to a designated central 
imaging vendor for collection, storage and possible future central re-analysis. Images may be used 
to assess the local and anenestic or bystander response to therapy.  
Treatment beyond progression will be permitted provided the subject meets protocol specified 
criteria in Section 8.2. If subjects discontinue investigational therapy prior to PD, they should 
continue to be followed with radiologic assessments until disease progression, start of a new anti-
cancer therapy, withdrawal of consent or death.  
8.1.1
Assessment of Response
Investigator-assessed response and progression will be evaluated in this study using RECIST v1.1 
[Eisenhauer, 2009] (Section 16.5).  Response of target and non-target lesions will be collected and 
analyzed by their injected or non-injected status in order to determine if anenestic or bystander 
responses are observed.  
Regarding target lesion selection, when more than one measurable tumor lesion is present at 
baseline, all lesions up to a maximum of 10 lesions in total, representative of all involved organs, 
should be identified as target lesions and recorded and measured at baseline. Target lesion selection 
will not be capped at a maximum of 2 lesions per organ e.g., if there are 3 cutaneous/subcutaneous 
measurable lesions, all 3 lesions can be selected as target lesions.
Given the relatively high rate of secondary primary malignancies in subjects with CSCC, new 
lesions must be carefully assessed to determine if they represent a second primary. A new CSCC
will be considered as PD if the lesion is > 5 mm, can be clearly documented as not being previously 
present, and cannot be managed with standard therapy (such as surgical excision or topical 
palliation). Biopsy may be clinically indicated to confirm CSCC prior to determination of PD.
8.2
Criteria for Treatment Beyond Initial Progression
Subjects will be permitted to continue IP beyond initial PD provided the subject does not have 
clinical symptoms of progression, is tolerating IP, has experienced no decline in their ECOG 
performance status, and is gaining clinical benefit as assessed by the investigator. The subject 


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must be made aware of the potential benefits and risks of continuing the IP in the setting of PD by 
providing a separate written informed consent.   
The subject may continue to be treated until one of the following criteria is met: 
Develops clinical symptoms or signs such that the benefit-risk ratio of continuing therapy 
is no longer justified
Meets any of the criteria for discontinuation of IP (see Section 3.7) 
Experiences rapid PD with risk to vital organs or critical anatomical sites requiring urgent 
medical intervention 
9.
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS
9.1
Study Design and Sample Size Determinations
The dose escalation will utilize a mTPI-2 design [Guo, 2017] with target DLT rate of 30% for the 
MTD. The DLT evaluable population is defined in section 9.2.1.
The mTPI-2 design employs a simple Beta-Binomial Bayesian model with decision rules based on 
the unit probability mass from the posterior probability of DLT rate. With the target DLT rate of 
30%, the posterior probability of DLT rate unit interval (0, 1) is divided into subintervals with 
equal length of 0.1 that correspond to different dose escalation decisions: subinterval of (0.25, 
0.35) is to stay at the current dose, subintervals below 0.25 is to escalate to next higher dose, and 
subintervals above 0.35 is to de-escalate to the next lower dose. Subjects will be enrolled in cohorts 
of approximately 3 subjects during the dose escalation. After each cohort of approximately 3 
subjects, the posterior unit probability for subintervals will be calculated based on a 
noninformative prior distribution for the DLT rate (Beta (1,1)) and the total number of subjects 
with DLTs and DLT evaluable subjects for the current dose. A dose escalation/stay/de-escalation 
decision that corresponds to the subinterval with the highest unit probability mass will be selected. 
A minimum of 3 DLT evaluable subjects will be enrolled to a dose level and evaluated for DLT 
before a dose escalation/stay/de-escalation decision can be made unless unacceptable toxicity is 
observed prior to the enrollment of 3 subjects e.g., two subjects experience DLT before the third 
subject enrolls. A dose level will be considered unsafe, with unacceptable toxicity and no 
additional subjects enrolled at that dose level and above, if it has an estimated 95% or more 
probability of exceeding the target DLT rate of 30%. The maximum number of subjects evaluated 
for DLT for each dose level will be 12 subjects (about 4 cohorts of 3 subjects) if the dose escalation 
decision is to stay at the current dose from the first 3 cohorts. Based on the above design, the dose 
escalation decision rules are as the following for each dose level: 
When the number of DLT evaluable subject is <12 subjects: 
o
Dose escalate if the observed DLT rate <25%;
o
Stay at the current dose if the observed DLT rate between 25%-33%; 
o
Dose de-escalate if the observed DLT rate >33%;
After reaching the maximum 12 subjects, the dose escalation decision will be either 
escalate or de-escalate as the following:
o
o
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9.2
Statistical Analyses 
Complete details of the statistical analysis will be provided in the Statistical Analysis Plan (SAP). 
Any deviations from, or additions to, the original analysis plan described in this protocol will be 
documented in the SAP and final study report. 
9.2.1
Analysis Populations  
For the analysis, the following populations are defined: 
Population
Description
Enrolled
All subjects who have signed the main study inform consent form (ICF). 
Screen Failures
All subjects who have signed the main study ICF but have not received 
any study treatment. 
All Treated
All subjects who have received at least one dose of IP. Safety data will be 
evaluated based on this population. 
DLT Evaluable
IP during cycle 1 and complete the safety follow-up through the 21-day 
DLT evaluation period; or 2) who experience any DLT during the DLT 
evaluation period. DLT evaluable subjects will be used to guide dose 
escalation and to determine the MTD or MAD.
Response 
Evaluable 
Subjects in the All Treated Population who have a baseline disease 
assessment and have at least one post-baseline disease assessment or have 
progressed or died before the first post-baseline disease assessment. 
Pharmacokinetic
Subjects in All Treated Population from whom at least one PK sample is 
obtained and analyzed. The PK population will be used for the PK 
analysis. 
Pharmacodynamic
Subjects in the All Treated Population for whom at least one 
pharmacodynamic 
sample 
is 
obtained 
and 
analyzed. 
The 
pharmacodynamic population will be used for the pharmacodynamic data 
analysis. 
9.2.2
Interim Analyses
During dose escalation, the number of subjects with DLTs will be determined after each cohort of 
approximately 3 subjects has been evaluated for DLT. The summary of DLTs for each dose level 
will be based on the number of subjects with DLTs from all subjects dosed and evaluated at the 
corresponding dose level who meet the definition of the DLT Evaluable Population. Selected AE 
summary tables and listings may be provided during dose escalation to support dose escalation 
decisions.  
9.2.3
General Data Analysis Consideration 
Tabular summaries will be presented by dose levels/cohorts and total number of subjects in the 
corresponding population. Categorical data will be summarized by the number and percentage of 
subjects in each category. Continuous variables will be summarized by descriptive statistics. As it 
is anticipated that accrual will be spread thinly across centers and summaries of data by center 
would be unlikely to provide valuable information, data from all participating centers will be 


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pooled prior to analysis. All data up to the time of study completion/withdrawal from study will 
be included in the analysis for each subject, regardless of duration of treatment. 
9.2.4
Safety Analyses 
The safety evaluation will be based on the All Treated Population and the DLT evaluation will be 
based on the DLT evaluable population. DLTs will be summarized by dose level. Frequency tables 
will be used to describe safety and tolerability parameters AEs, irAEs, SAEs, fatal SAEs and AEs 
leading to discontinuation of SL-172154. Changes in toxicity grade for clinical chemistry and 
hematology will be summarized. Change from baseline QTcF will also be summarized. Graphs 
may also be presented where appropriate. AEs will be mapped to a Medical Dictionary for 
Regulatory Activities (MedDRA) preferred term and system organ classification. Laboratory 
abnormalities will be graded according to the NCI CTCTAE v5., if applicable. Concomitant 
medications will be coded using the World Health Organization Drug Dictionary.  
MTD: The MTD will be estimated using isotonic regression (based on the DLTs observed in DLT 
evaluable subjects). Specifically, the MTD is the dose for which the isotonic estimate of the DLT 
rate is closest to the target DLT rate of 30%. If two or more doses tie for the smallest difference, 
perform the following rules: 
If the estimated DLT rate < 30% for all doses, then select the higher dose among the tied 
doses; 
If the estimated DLT rate for the tied doses are a combination of < 30% for and > 30%, 
then select the higher dose among the tied doses; 
If the estimated DLT rate > 30% for all dose, then select the lower dose among the tied 
doses. 
A MAD will be reported if the observed DLT rate is <25% among all dose levels.   Otherwise, an 
MTD will be reported.  
9.2.5
Efficacy Analyses 
Anti-tumor activity data will be summarized by dose level and overall in the All Treated population 
and Response Evaluable population.  
The primary analysis of anti-tumor activity assessment is based on RECIST v1.1. The ORR will 
be estimated along with a 95% confidence interval using the exact probability method. Change 
from baseline sum of diameters for target lesions will be provided for each subject. Change from 
baseline diameter for each individual injected and non-injected lesion will be provided. DOR and 
TTR will be evaluated, using the Kaplan-Meier method, for the subgroup of subjects with a 
confirmed response. The Kaplan-Meier method will be used to estimate the PFS curve and PFS 
rate at time of point of interest.  
9.2.6
Pharmacokinetic Analysis
The PK analysis will be based on the PK population. Serum concentrations for SL-172154 will be 
summarized using tabular and graphical format.  SL-172154 PK parameters will be summarized 
and analyzed using appropriate statistical methods. The pharmacokinetics of SL-172154 will be 
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Table 6: Serum SL-172154 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 
Reliability of AUC0-inf values is contingent on the percent of the total area 
obtained by extrapolation: 
AUC0-
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-
CL
Clearance; calculated as Dose/AUC0-inf
Vz
-inf)
9.2.6.1 Anti-Drug Antibody Analysis 
Individual subject ADA titer and status (positive, negative, inconclusive) vs. nominal time will be 
reported and summarized by dose level.  Onset, duration and persistence of ADA by subject will 
also be summarized by dose level.  ADA isotype may be reported, if supported by the data.  
9.2.7
Pharmacodynamics Analyses   
The pharmacodynamic data analysis will be based on the pharmacodynamic population. 
Pharmacodynamic biomarkers values will be summarized descriptively by dose level and visit.     
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 


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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.  
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 


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the conduct of the clinical trial and data generated, are documented and reported in compliance 
with the protocol, GCP and the applicable regulatory requirements. 
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 International Conference of Harmonisation 
(ICH) E6 and consistent with the consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International Organizations of Medical 
Sciences 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 or 
his/her legally authorized representative 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 
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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 
authorized designee will explain to each subject the objectives of the exploratory research. 
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 
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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 
Institutional regulations.
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 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
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. The SMC 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


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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 is 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 mTPI-2 design method.   
Dose escalation decisions will be made based on the DLTs observed at the current dose level with 
guidance provided by the mTPI-2 design as stated in the study protocol.  All dose escalation and
safety decisions will be documented in writing with copies maintained at each site and the Trial 
Master File at the CRO.
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. 


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United States 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 
approved for such indication, these records must be kept until 2 years after the investigation has 
been discontinued and regulatory authorities (e.g., FDA, European Medicines Agency, Health 
Canada, 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.  
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. 


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16.
APPENDICES
16.1
mTPI-2 Dose Escalation Scenarios 
See Table 5 in Section 9.1 for dose escalation decision rules based on the total number of subjects 
evaluable for DLT and the number of DLTs observed.   
For each dose level, subjects will be enrolled in cohorts of approximately 3 to evaluate DLT and 
make a dose escalation/stay/de-escalation decision based on decision rules in Table 5 in Section 
9.1 as the following steps: 
Step 1:  The first cohort of at least 3 subjects will be enrolled and evaluated for DLT, and 
dose escalation/stay/de-escalation decision will be made among at least 3 DLT evaluable 
subjects.  Assuming 3 subjects are DLT evaluable in cohort #1, the following decisions 
will be made based on the number of subjects with a DLT among the 3 DLT evaluable 
subjects: 
o
If no subject with a DLT, dose escalate to the next higher dose level;  
o
If 1/3 subject with a DLT, stay at the current dose level and move to step 2;   
o
If 2/3 subjects with a DLT, dose de-escalate to next lower dose level; 
o
If 3/3 subjects with a DLT, dose de-escalate to next lower dose level and the current 
dose level will never to be used;  
o
If the first 2 subjects experience a DLT before the third subject enrolls, then de-
escalate to the next lower dose level and the current dose level will never be used. 
Step 2:  As there is 1 subject with DLT among 3 DLT evaluable subjects in cohort #1, 
approximately 3 subjects will be enrolled and evaluated for DLT at the current dose in 
cohort #2.  Assuming 3 DLT evaluable subjects in cohort #2, the following decisions will 
be made based on the number of subjects with DLT among the 6 DLT evaluable subjects 
from cohort #1 and cohort #2:  
o
If 1/6 subjects with a DLT (no subject with a DLT in cohort #2), then dose escalate 
to the next higher dose level;  
o
If 2/6 subjects with a DLT (1 subject with a DLT in cohort #2), stay at the current 
dose level and move to step 3;   
o
If 3/6 subjects with a DLT (2 subjects with a DLT in cohort #2), dose de-escalate 
to next lower dose level;  
o
If 4/6 subjects with a DLT (3 subjects with a DLT in cohort #2), dose de-escalate 
to next lower dose level and the current dose level will never be used.  
Step 3:  As there are 2 subjects with DLT among 6 DLT evaluable subjects in cohort #1 
and #2, approximately 3 subjects will be enrolled and evaluated for DLT at the current dose 
in cohort #3.  Assuming 3 DLT evaluable subjects in cohort #3, the following decisions 
will be made based on the number of subjects with DLT among the 9 DLT evaluable 
subjects from cohort #1, cohort #2 and cohort #3:  


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o
If 2/9 subjects with a DLT (no subject with a DLT in cohort #3), then dose escalate 
to the next higher dose level;  
o
If 3/9 subjects with a DLT (1 subject with a DLT in cohort #3), stay at the current 
dose level and move to step 4;   
o
If 4/9 subjects with a DLT (2 subjects with a DLT in cohort #3), dose de-escalate 
to next lower dose level;  
o
If 5/9 subjects with a DLT (3 subjects with a DLT in cohort #3), dose de-escalate 
to next lower dose level and the current dose level will never be used.  
Step 4:  As there are 3 subjects with DLT among 9 DLT evaluable subjects in the first 3 
cohorts, approximately 3 subjects will be enrolled and evaluated for DLT at the current 
dose in cohort #4.  Assuming 3 DLT evaluable subjects in cohort #4, the following 
decisions will be made based on the number of subjects with DLT among the 12 DLT 
evaluable subjects from all 4 cohorts:  
o
If 3/12 subjects with a DLT (no subject with a DLT in cohort #4) with 25% DLT 
rate, then dose escalate to the next higher dose level; 
o
If 4-6 subjects with a DLT (1-3 subjects with a DLT in cohort #4) with 33% to 50% 
DLT rate, dose de-escalate to next lower dose level. 


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16.2
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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16.3
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-172154) through at least 30 days after the last dose of  SL-172154.  
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 
Combination Methods 
o
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 


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o
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-172154 through at least 30 days 
after the last dose of SL-172154.   
16.3.1 Pregnancy Status 
In the rare event that -hCG is elevated as a tumor marker, pregnancy should be excluded. At 
minimum, this requires obstetrics evaluation, serial -hCG measurements and ultrasound to 
exclude pregnancy. 


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16.4
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 
References: 
Devine BJ. Case Number 25 Gentamicin Therapy: Clinical Pharmacy Case Studies. Drug Intell. 
Clin Pharm. 1974;8:650-655. 
Levey, A.S., J. Coresh, T. Greene, et al.  (2006).  Using standardized serum creatinine values in 
the modification of diet in renal disease study equation for estimating glomerular filtration rate.  
Ann Intern Med.  145:247-254. 
Levey, A.S., L.A. Stevens, C.H. Schmid, et al.  (2009).  A new equation to estimate glomerular 
filtration rate.  Ann Inter Med.  150:604-612. 


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16.5
RECIST 1.1  
16.5.1 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 
millimeter (mm) with CT scan or clinical examination.  
Bone lesions are considered measurable only if assessed by CT scan and have an identifiable soft 
Malignant lymph nodes must be
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. 
CT scan and only the short axis of these nodes will contribute to the baseline sum. All other 
pathological nodes 
-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 
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 10 lesions in total, representative of all involved organs, should be identified as 
target lesions and recorded and measured at baseline. Target lesion selection will not be capped at 
a maximum of 2 lesions per organ. 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 baseline sum diameters.  If lymph nodes are to be included in the 
sum, then only the short axis is added into the sum.  At baseline, the sum of the target lesions 


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(longest diameter of tumor lesions plus short axis of lymph nodes: overall maximum of 10) 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.  
16.5.2 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 
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 
PR.
Stable Disease (SD):  Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum diameters while on study.  Documented at 
eeks 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 
PD (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 PD 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
Summary of Changes for Amendment 01  
Minor Editorial Changes
Title page and all page headers have edits to denote revised version number /date of 
amendment 01 
Updated Table of Contents 
Updated Abbreviations to include definitions for ECG, QTcF, QTcB 
New Appendix added to summarize changes made for Amendment 01 
Footnotes to SOA table in Section 6.1 modified to accommodate insertion of new 
footnote q  
1. Revised section 5.1.4 Monitoring Dose Administration to specify that subjects must be 
monitored for injection-related reactions and cytokine-release syndrome for a minimum of 6 
hours following intratumoral injection of SL-172154.  
New text (provided in italics) added as follows to Section 5.1.4: All subjects must be 
observed for at least 6 hours after the injection.
Schedule of Assessments (SOA) Table in Section 6.1:  New text (provided in italics) 
added to footnote m as follows: All subjects must be observed for at least 6 hours at the 
center after each intratumoral injection of SL-172154.
2.
The protocol is modified to include ECG monitoring at Tmax after the first dose. In 
addition, a predose ECG assessment on cycle 2 day 1 has been added for safety purposes 
after repeated dosing as no accumulation of SL172154 is expected.  
Inclusion Criterion #9 revised in Synopsis/Section 4.1: ECG assessment inclusion 
criterion #9 specifies baseline QTcF interval requirement for study eligibility as  480 
milliseconds
ECG assessments added to the SOA Table in Section 6.1 at screening, cycle 1, day 1, 
and cycle 2, day 1.  A new footnote q added with the new text (provided in italics) as 
follows: 
Electrocardiogram (ECG): Local ECG machines available at the site should be used. A 
single ECG will be collected during screening to determine eligibility. ECGs will be 
obtained in triplicate for assessment of QT/QTc as outlined below (See Section 6.3.5 for 
additional details). 
Cycle 1, Day 1: Predose and 1 hour and 4 hours after ITI SL-172154 
Cycle 2, Day 1: Predose only 
A new Section 6.3.5 entitled Electrocardiogram Monitoring for QTc Evaluation is now 
included.  
New text (provided in italics) was added to Section 9.2.4 Safety Analyses as follows: 
Change from baseline QTcF will also be summarized.
3.
The maximum number of target lesions assessed per RECIST v1.1 will be 10 lesions instead 
of 5 lesions. 


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5 target lesions changed to 10 target lesions in Section 8.1.1 in the second paragraph 
and in Appendix 16.5.1 in the fifth paragraph (2 locations) 

SAP_001.pdf: 


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SL-172154                                                                                                                       
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TABLE OF CONTENTS 
 
 
LIST OF ABBREVIATIONS ....................................................................................................... 4 
1. 
INTRODUCTION .................................................................................................................. 7 
2. 
STUDY OBJECTIVES AND OUTCOME MEASURES ................................................... 7 
3. 
STUDY DESIGN .................................................................................................................... 9 
3.1 
STUDY DESIGN ............................................................................................................... 9 
3.2 
STATISTICAL DESIGN FOR DOSE ESCALATION ............................................................ 11 
3.3 
SAMPLE SIZE ................................................................................................................ 12 
3.4 
DURATION OF STUDY TREATMENT .............................................................................. 12 
3.5 
DURATION OF FOLLOW-UP .......................................................................................... 13 
3.6 
END OF STUDY ............................................................................................................. 13 
3.7 
STUDY ASSESSMENTS AND PROCEDURES .................................................................... 13 
4. 
ANALYSIS POPULATIONS .............................................................................................. 13 
5. 
GENERAL ANALYSIS CONSIDERATIONS ................................................................. 14 
5.1 
DATA ANALYSES DURING DOSE ESCALATION ............................................................ 14 
5.2 
REPORTING CONVENTIONS .......................................................................................... 14 
5.3 
DATA HANDLING ......................................................................................................... 15 
5.3.1 
Premature Withdrawal and Missing Data ....................................................... 15 
5.3.2 
Baseline and Change from Baseline ............................................................... 16 
5.3.3 
Study Day and Duration ................................................................................. 16 
5.3.4 
Imputation of Partial Date .............................................................................. 16 
6. 
STUDY POPULATION....................................................................................................... 17 
6.1 
SUBJECT DISPOSITION .................................................................................................. 17 
6.2 
PROTOCOL DEVIATIONS .............................................................................................. 17 
6.3 
DEMOGRAPHIC ............................................................................................................. 17 
6.4 
STUDY CANCER HISTORY ............................................................................................ 17 
6.5 
GENERAL MEDICAL AND SURGICAL HISTORY ............................................................ 17 
6.6 
PRIOR ANTI-CANCER TREATMENT  ............................................................................. 18 
6.7 
STUDY DRUG EXPOSURE ............................................................................................. 18 
6.8 
CONCOMITANT MEDICATIONS ..................................................................................... 19 
6.9 
CONCOMITANT PROCEDURES ...................................................................................... 19 
7. 
EFFICACY ANALYSES ..................................................................................................... 19 
7.1 
OBJECTIVE RESPONSE RATE ........................................................................................ 19 
7.2 
TIME TO RESPONSE ...................................................................................................... 21 
7.3 
DURATION OF RESPONSE ............................................................................................. 21 
7.4 
PROGRESSION FREE SURVIVAL .................................................................................... 21 
7.5 
CHANGE FROM BASELINE FOR INJECTED AND NON-INJECTED LESIONS ..................... 22 
8. 
SAFETY ANALYSES .......................................................................................................... 22 
8.1 
MAXIMUM TOLERATED DOSE EVALUATION ............................................................... 22 
8.2 
ADVERSE EVENTS ........................................................................................................ 23 
8.3 
CLINICAL LABORATORY EVALUATION ....................................................................... 24 
8.4 
DEATH .......................................................................................................................... 24 
8.5 
BLOOD PHENOTYPE AND DIRECT ANTIGLOBULIN TEST ............................................. 24 
8.6 
VITAL SIGNS AND PULSE OXIMETRY ........................................................................... 25 
8.7 
CARDIAC EVALUATIONS .............................................................................................. 25 
8.8 
ECOG PERFORMANCE STATUS ................................................................................... 25 


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9.
PHARMACOKINETIC ANALYSES ................................................................................ 25
10. PHARMACODYNAMIC AND BIOMARKER ANALYSES .......................................... 25 
11. LITERATURE REFERENCES ......................................................................................... 25 
12. APPENDIX: LIST OF TABLES, FIGURES AND LISTINGS ....................................... 26 
12.1 LIST OF TABLES ........................................................................................................... 26 
12.2 LIST OF FIGURES .......................................................................................................... 27 
12.3 LIST OF DATA LISTINGS ............................................................................................... 27 
 
 
 
 














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Dose Escalation Cohorts 
Dose escalation will utilize the modified Toxicity Probability Interval (mTPI-2) design with target 
DLT rate of 30% for the MTD as described by Guo et al. Subjects will be enrolled in cohorts of 
approximately 3 subjects into sequential dose levels of SL-172154 and evaluated for DLT during 
the 21-day DLT evaluation period starting from the first dose of SL-172154. At each dose level, a 
minimum 3-day stagger between dosing the first and second subject is required.  Dose escalation 
will proceed using a flat dose and fixed volume format with the starting dose of 0.003mg. The 
planned dose escalation is in half-log increments as outlined in Table 1. The DLT assessment 
period is 21 days in length and encompass the first 21-day cycle of study treatment. The ITI 
schedule is outlined in Figure 1.  
 
Table 1: Intratumoral Dose Escalation Plan for SL-172154  
Dose Level 
ITI Dose (mg) of SL-172154a 
ITI Volume of Dose 
Level 1 - starting dose 
0.003 
1.5 mL 
Level 2 
0.01 
1.5 mL 
Level 3 
0.03 
1.5 mL 
Level 4 
0.1 
1.5 mL 
a) Intermediate or higher dose levels may be tested based on emerging safety and/or 
pharmacodynamic data. Dose escalation will not exceed half-log increments. 
 
Figure 1: ITI Schedule for SL-172154 
 
 
 
For each dose level, the minimum number of subjects evaluable for DLT (see Section 4Error! 
Reference source not found. for definition of DLT evaluable subject) will be 3 unless 
unacceptable toxicity is observed prior to enrollment of 3 subjects (e.g., the first 2 subjects 
experience a DLT before the third subject enrolls). The maximum number of subjects evaluable 
for DLT at a dose level will be 12 (e.g., this may be reached by sequential enrollment of 4 cohorts 
of 3 subjects) assuming the dose decision is to stay at the current dose from the first 3 cohorts. 
Section 3.2 details the statistical design for dose escalation and dose escalation rules.   
 
During dose escalation, a review of available safety data for all subjects will be undertaken by the 
Safety Monitoring Committee (SMC) approximately every four weeks starting from dosing of the 
first subject. Decisions will be made based on the safety profile of the current and prior dose levels.  


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Pharmacodynamic Cohorts  
The Sponsor, in consultation with the SMC, may elect to open a pharmacodynamic cohort to obtain 
additional pharmacodynamic data from approximately 6 additional subjects at one or more dose 
levels that have completed evaluation for safety without exceeding the MTD. Subjects in the 
pharmacodynamic cohort must have tumor accessible and safe for biopsy from both an injected 
lesion and a non-injected lesion and must consent to providing paired biopsies for translational 
research. Subjects enrolled in the pharmacodynamic cohort will not inform dose escalation 
decisions but the pharmacodynamic and other data gathered from these additional subjects will 
inform selection of doses for further evaluation and the RP2D determination.  
 
Selection of the Recommended Phase 2 Dose 
Selection of the RP2D for SL-172154 monotherapy will be based upon the totality of the data in 
subjects treated in dose escalation and pharmacodynamic cohorts. The totality of the data refers to 
safety, tolerability, PK, clinical activity, and pharmacodynamic markers consistent with the 
mechanism of action. Approximately 6 subjects (inclusive of the subjects enrolled in the Dose 
Escalation and Pharmacodynamic cohort) may be treated at the RP2D. 
3.2 Statistical Design for Dose Escalation  
The dose escalation will utilize a mTPI-2 design with target DLT rate of 30% for the MTD. The 
mTPI-2 design employs a simple Beta-Binomial Bayesian model with decision rules based on the 
unit probability mass from the posterior probability of DLT rate. With the target DLT rate of 30%, 
the posterior probability of DLT rate unit interval (0, 1) is divided into subintervals with equal 
length of 0.1 that correspond to different dose escalation decisions: subinterval of (0.25, 0.35) is 
to stay at the current dose, subintervals below 0.25 is to escalate to next higher dose, and 
subintervals above 0.35 is to de-escalate to the next lower dose. Subjects will be enrolled in cohorts 
of approximately 3 subjects during the dose escalation. After each cohort of approximately 3 
subjects, the posterior unit probability for subintervals will be calculated based on a 
noninformative prior distribution for the DLT rate (Beta(1,1)) and the total number of subjects 
with DLTs and  DLT evaluable subjects for the current dose. A dose escalation/stay/de-escalation 
decision that corresponds to the subinterval with the highest unit probability mass will be selected. 
A minimum of 3 DLT evaluable subjects will be enrolled to a dose level and evaluated for DLT 
before a dose escalation/stay/de-escalation decision can be made unless unacceptable toxicity is 
observed prior to the enrollment of 3 subjects e.g., two subjects experience DLT before the third 
subject enrolls. A dose level will be considered unsafe, with unacceptable toxicity and no 
additional subjects enrolled at that dose level and above, if it has an estimated 95% or greater 
probability of exceeding the target DLT rate of 30%. The maximum number of subjects evaluated 
for DLT for each dose level will be 12 subjects (about 4 cohorts of 3 subjects) if the dose escalation 
decision is to stay at the current dose from the first 3 cohorts.  
 
Based on the above design, the dose escalation decision rules are as the following for each dose 
level: 
 
 When the number of DLT evaluable subject is <12 subjects: 
o Dose escalate if the observed DLT rate <25%; 




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Treatment may continue until one of the following criteria applies: 
 Disease progression per RECIST v1.1 (unless eligible for treatment beyond progression). 
 Death 
 Intercurrent illness that prevents further administration of treatment 
 Unacceptable AE(s) 
 Participant declines further therapy with ITI of SL-172154 in the absence of disease 
progression 
 Participant decides to withdraw from the study 
 General or specific changes in the participant's condition that render the participant 
unacceptable for further treatment in the judgment of the investigator 
 Participant non-compliance 
 Pregnancy 
 Termination of the study by Sponsor 
3.5 Duration of Follow-up  
Subjects who discontinue IP for any reason other than withdrawal of consent will be followed for 
AEs for 90 days after the last dose of IP.  Subjects who are withdrawn from study for unacceptable 
AE(s) will be followed until resolution or stabilization of the AE.  Subjects who permanently 
discontinue IP for reasons other than progression will continue with disease assessments until 
progressive disease, start of another anti-cancer therapy, withdrawal of consent, death, or end of 
the study, whichever occurs first.  
3.6 End of Study 
End of Study is defined as approximately 1 year after the last subject is dosed on cycle 1, day 1 
(C1D1) or the date the study is closed by the Sponsor, whichever occurs first. 
3.7 Study Assessments and Procedures  
The detailed study assessments and procedures are described in section 6 of the protocol.  
4. ANALYSIS POPULATIONS 
Population 
Description 
Enrolled 
All subjects who have signed the main study inform consent form. 
Screen Failures 
All subjects who have signed the informed consent but have not 
received any dose of SL-172154. 
All Treated 
All subjects who receive at least one dose of SL-172154. Safety data will
be evaluated based on this population. 


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SL-172154                                                                                                                       
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Population 
Description 
DLT Evaluable 
All subjects in the All Treated population 1) who have received at least 2 
of the 3 scheduled doses of SL-172154 during cycle 1 and completed the 
safety follow up through DLT evaluation period; or 2) who experienced 
any DLT during the DLT evaluation period. The DLT evaluation period 
is defined as the first 21 days.  The DLT evaluable population will be 
used to guide dose escalation and to determine the MTD or MAD. 
Response 
Evaluable 
All subjects in the All Treated population who have a baseline disease 
assessment and have at least one post-baseline disease assessment or had 
progressed or died before the first post-baseline disease assessment.  
5. GENERAL ANALYSIS CONSIDERATIONS 
5.1 Data Analyses during Dose Escalation  
During the dose escalation, the number of subjects with DLTs will be determined after each cohort 
of approximately 3 subjects has been evaluated for DLT. The summary of DLTs for each dose 
level will be based on the number of subjects with DLTs from all subjects dosed and evaluated at 
the corresponding dose level who meet the definition of the DLT Evaluable Population. Select AE 
summary tables and listings may be provided during dose escalation to support dose escalation 
decisions.  
5.2 Reporting Conventions 
The statistical analyses will be reported using summary tables, figures, and data listings. The 
International Conference on Harmonization (ICH) numbering convention will be used for tables, 
listings, and figures.  
Unless specified otherwise, all summary tables will be presented by dose level and cohort (dose 
escalation and pharmacodynamic) and all subjects in the analysis population. Subjects at the same 
dose level from dose escalation and pharmacodynamic cohorts will also be pooled together for 
summary tables. Select safety summary tables will be provided for the dose escalation cohorts.  
Data from all participating sites will be pooled prior to data analysis. It is anticipated that subject 
accrual will spread thinly across sites and summaries of data by site would be unlikely to be 
informative and will therefore, not be provided.   
Continuous variables will be summarized with means, standard deviations, medians, minimums, 
and maximums. Categorical variables will be summarized by counts and by percentages of 
subjects in the corresponding categories. All confidence intervals (CIs) will be constructed at the 
95% confidence level. Percentages are routinely based on the total number of the specified 
population N if not otherwise mentioned.  


Statistical Analysis Plan for SL03-OHD-102  
SL-172154                                                                                                                       
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Individual subject data obtained from the electronic case report forms (eCRFs), central lab, and 
any derived data will be presented by cohort, dose level and subject in data listings. 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). 
Summaries by planned time will include data from scheduled assessments and all data will be 
reported according to the nominal visit date for which it was 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, then the worst-case result will 
be analyzed.  
The precision of the original measurements will be maintained in summaries and listings, when 
possible. Generally, means, medians and standard deviations will be presented with an increasing 
level of precision. 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.  
When rounding is required, rounding will be done to the nearest round-off unit. For example, if 
the round-off unit is the ones place (i.e., integers), values  XX.5 will be rounded up to XX+1 
while values < XX.5 will be rounded down to XX. 
For frequency counts of categorical variables, categories whose counts are zero will be displayed 
follow-
will not have zero percentages displayed.  
All analyses and tabulations will be performed using SAS  v9.4 or above.  
5.3 Data Handling 
5.3.1 Premature Withdrawal and Missing Data  
Subjects who prematurely withdraw from the study will be included in analyses up to the time of 
withdrawal, regardless of the duration of treatment and survival follow-up.  
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.  
Subjects with unknown or missing best response will be assumed to be non-responders and will 
be included in the denominator when calculating percentages. Subjects with the designation of 
treatment relationship for adverse events (AEs) and serious adverse events (SAEs) missing will 
have the worst case assumed to impute the relationship: if the relationship to study treatment is 
 for summary of drug-related AE or SAE.  


Statistical Analysis Plan for SL03-OHD-102  
SL-172154                                                                                                                       
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For the time to event endpoints including DOR and PFS, the missing data handling method will 
be censoring. Censoring mechanisms for these endpoints are described in section Error! 
Reference source not found..   
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. Subjects with shorter 
duration of treatment due to the natural history of their disease or medical necessities of treatment 
of their disease will not be considered to have missing data.  
5.3.2 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-172154 dose on Cycle 1 Day (C1D1). Post-baseline values are defined 
as value obtained after the first dose of SL-172154. Change from baseline is calculated as: (post-
baseline value - baseline value). The percent change from baseline is calculated as: (change from 
baseline/baseline value) *100. If either baseline or post-baseline value is missing, the change from 
baseline and percent change from baseline is set to be missing as well.  
5.3.3 Study Day and Duration  
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. For a given event date, Study Day is calculated relative to 
the date of 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 in days is calculated as the number of days between one 
date (Date1) and another later date (Date2) 
Duration (days) = [Date2  Date1] (in days) + 1 day. 
 Duration (Months)  A duration in months is calculated as the duration in days divided 
by 365.25/12, rounded to one decimal place. 
 Duration (Years)  A duration in years is calculated as the duration in days divided by 
365.25, rounded to one decimal place. 
5.3.4 Imputation of Partial Date 
In general, imputed partial dates will not be used to derive study day or duration variables. In 
addition, imputed partial dates are not used for the time to event endpoint analysis. However, 
partial dates may be imputed for exploratory analysis. The imputed partial data will be flagged in 


Statistical Analysis Plan for SL03-OHD-102  
SL-172154                                                                                                                       
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the dataset to indicate the level of imputation. Imputed dates will not be displayed in the data 
listings. 
6. STUDY POPULATION 
Unless specified otherwise, all summary tables and data listings for the study population will be 
based on the All Treated Population.  
6.1 Subject Disposition 
Summaries of study population and subject disposition will include the number of subjects in each 
analysis population, the number of subjects by study status, and the primary reason for study 
completion/discontinuation. Study population and subject disposition information will be 
presented in a data listing. Both summary table and listing will be based on the Enrolled population.  
Summaries of study treatment status will include the number of subjects by treatment status, and 
the primary reason for study treatment discontinuation. Subject treatment discontinuation 
information will be presented in a data listing. 
6.2 Protocol Deviations 
Number of subjects for each protocol deviation type and subtype will be summarized for all 
protocol deviation and key protocol deviations, respectively. Protocol deviations will be tracked 
by the study team throughout the conduct of the study in accordance with the Protocol Deviation 
Management Plan. A listing with deviation details will be provided for all protocol deviations.  
6.3 Demographic  
Demographic variables include age, sex, ethnicity, race, and weight and height at screening. 
Descriptive statistics will be presented for age, weight, and height. Frequency counts and 
percentages will be presented for age groups (<18 years, 18 to <65 years, 65 to <75 years and 75 
years), sex, ethnicity, and race. All demographic data will be presented in a data listing for All 
Treated subjects.  
6.4 Study Cancer History  
General study cancer history information including the tumor type, human papilloma virus status, 
and time since initial diagnosis will be summarized in tables. In addition, primary anatomic site of 
tumor and extent of disease will be summarized for CSCC; and primary anatomic site of tumor, 
stage at study entry, and status of tobacco use will be summarized for SCCHN. All study cancer 
history data will be presented in a data listing. 
6.5 General Medical and Surgical History 
General medical history and surgical history along with start/end date and ongoing status at study 
entry will be presented in a data listing. 


Statistical Analysis Plan for SL03-OHD-102  
SL-172154                                                                                                                       
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6.6 Prior Anti-Cancer Treatment  
Prior study cancer systemic treatment drugs will be coded using the World Health Organization 
(WHO) Drug Dictionary. Prior study cancer systemic treatment including regimen number, drug 
name, start/end date, duration, intent, best response, and data of progression on the most recent 
regimen will be presented in a data listing. The number of prior systemic regimens for all intents, 
and number of prior systemic regimens for advanced/metastatic disease will be included in the 
summary table. Summary will be provided by dose levels/cohorts and all subjects in the analysis 
population.  
Prior anti-cancer surgical treatment including the date and intent of procedure will be presented in 
a data listing. Prior anti-cancer radiotherapy including the start/end date and intent of radiotherapy 
will be presented in a data listing.  
6.7 Study Drug Exposure 
The individual subject SL-172154 ITI administration at each dosing visit will be provided in a data 
listing. This listing will include assigned dose level, study drug lot number, total dose injected 
(mg), total volume injected, injection date, start/end of injection time, injection outcome and 
overdose assessment along with reason. For each target, non-target and new lesion at each dosing 
visit, the lesion number, location, injection administration status (Yes/No), injected volume, and 
administration method will also be included in the data listing.  
 
The following SL-172154 ITI administration information will be summarized: 
 Number of doses received, which is the total number of dosing visits with non-zero dose 
injected.  
 Duration of SL-172154 treatment is defined as: 
 Minimum of (data cutoff date plus 1 day or date of last dose + 21 days if last dose 
is C2D1 or beyond or + 7 days if last dose is C1D1, C1D8 or C1D15) minus date 
of first study drug administration for subjects who are on treatment.  
 Minimum of (date of death plus 1 day, data cutoff date plus 1 day, or date of last 
dose + 14 days if last dose is C2D1 or beyond or + 7 days if last dose is C1D1, 
C1D8 or C1D15) minus date of first study drug administration for subjects who 
discontinued from treatment. 
In addition to mean, median, minimum and maximum, duration on treatment will also be 
summarized as <6 weeks, >=6 to <12 weeks, and >=12 weeks.  
Individual duration of SL-172154 treatment will be plotted using horizontal bar graph with 
information on dose level, cancer type, time of responses (RECIST 1.1), best response and 
treatment status for each subject.  


Statistical Analysis Plan for SL03-OHD-102  
SL-172154                                                                                                                       
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6.8 Concomitant Medications 
Concomitant medications will be mapped to Anatomical Therapeutic Chemical (ATC) class and 
Generic Drug Names using the WHO Drug Dictionary. Concomitant medications will include 
medications taken on or after the date of the first dose of study drug. Any medications that are 
started prior to the date of the first dose but continued beyond the date of first dose will be counted 
as concomitant medications. Concomitant medications along with dose, route, start/end date, and 
indication for each medication will be presented in a data listing. 
6.9 Concomitant Procedures  
Concomitant procedures include cancer-related or treatment-related procedures or palliative 
radiotherapy that is administered while on study therapy. Concomitant procedures along with 
start/end date and indication for the procedure will be presented in a data listing.  
7. EFFICACY ANALYSES 
The efficacy endpoints include objective response, TTR, DOR, PFS, and change from baseline 
lesion diameter for injected lesion and non-injected lesions. All efficacy endpoints are based on 
the investigator disease assessment per RECIST 1.1. The efficacy analyses will be based on the 
All Treated population and Response Evaluable population. Unless specified otherwise, all 
efficacy data summaries will be presented by dose levels/cohorts, cancer type and all subjects in 
the analysis population.  
 
Disease assessment will be performed at baseline (screening visit) and at the following intervals 
until disease progression: every 6 weeks until week 54, every 12 weeks up to year 2, and every 24 
weeks until study conclusion. Confirmatory scans should be performed at least 4 weeks (>28 days) 
after initial documentation of an objective response and preferably at the next scheduled disease 
assessment that is 6 weeks later. If subjects discontinue study treatment prior to progressive 
disease, they should continue to be followed with radiologic disease assessments until disease 
progression, start of a new anti-cancer therapy, withdrawal of consent or death, whichever is 
earlier.  
7.1 Objective Response Rate  
The ORR is defined as the proportion of subjects whose best overall response is a confirmed CR 
or confirmed PR based on investigator assessment according to RECIST 1.1. 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 not evaluable (NE) will be summarized. 
Summary of objective response will be provided for the All Treated population and Response 
Evaluable population.  
 
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 or start of new anti-cancer 
therapy, whichever is earlier.  For subjects who have not met the criteria for PD per RECIST1.1 


Statistical Analysis Plan for SL03-OHD-102  
SL-172154                                                                                                                       
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or have not started a new anti-cancer therapy, the best overall response is defined as the best overall 
response among all post-baseline timepoint assessments.  
 
Based on the investigator assessment of overall response per RECIST 1.1 at post-baseline 
assessments, the best overall response will be determined programmatically as the following 
and   
Table 3:  
 CR > PR > SD > PD > NE 
 CR = at least two determinations of CR with at least 4 weeks apart before progression. 
 PR = at least two determinations of PR or better with at least 4 weeks apart before 
progression (and not qualifying for CR). 
 
35 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 6 weeks minus 7 days to allow for visit windows of ± 7 days (35 days). 
 If the minimum interval for SD is not met, the best response will depend on the subsequent 
assessments.  See table 3 for details.  
 PD is considered the best overall response when PD is documented and a best overall 
response of CR, PR, or SD could not be established before documentation of PD. Clinical 
progression will not be considered as documented disease progression in the determination 
of the best overall response. 
 NE is considered the best overall response when PD has not been documented and a best 
response of CR, PR or SD could not be established.  
  
Table 3. 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, provided minimum criteria for SD duration met, otherwise, PD
PR 
PD 
SD provided minimum criteria for SD duration met, otherwise, PD
PR 
NE 
SD provided minimum criteria for SD duration met, otherwise, NE


Statistical Analysis Plan for SL03-OHD-102  
SL-172154                                                                                                                       
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Overall 
response  
First time 
point 
Overall 
response 
Subsequent 
time point 
BEST overall response 
NE 
NE 
NE 
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 and will be presented using a waterfall plot.  
 
Target lesion, non-target lesion, new lesion and response assessments will be presented in data 
listings. The percent change from baseline/nadir in target lesion sum of diameters will be kept 2 
decimal places (xx.xx%) in the data listing and rounding is not required.  
7.2 Time to Response  
The TTR is defined as the time from the first dose until the first documentation of a subsequently 
confirmed objective response (confirmed CR or confirmed PR) based on RECIST 1.1. Only 
subjects who have achieved confirmed objective response will be evaluated for TTR. TTR will be 
summarized descriptively and graphically using Kaplan-Meier methods if data warrants. 
Individual TTR will be presented in a data listing. 
7.3 Duration of Response  
The DOR is defined as the time from the date of the first CR or PR (confirmed at least 28 days 
later) to the date of first documented disease progression per RECIST 1.1 or death, whichever 
occurs first. Only subjects who have achieved a 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 the last 
evaluable disease assessment. The evaluable disease assessment is defined as an assessment for 
which the overall response can be determined. DOR will be summarized descriptively and 
graphically using Kaplan-Meier methods if data warrants.  Individual DOR will be presented in a 
data listing. 
7.4 Progression Free Survival 
The PFS is defined as time from the first day of treatment to the first documented disease 
progression per RECIST 1.1 or death, whichever occurs first. Subjects who have not progressed 
at the time of analysis will be censored at the latest date of assessment from their last evaluable 
disease assessment. The censoring guidance and the date of PD/death or censoring are given 
in the  
 
 
 
 




Statistical Analysis Plan for SL03-OHD-102  
SL-172154                                                                                                                       
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8. SAFETY ANALYSES 
Unless specified otherwise, all safety data summaries will be presented by dose levels/cohorts and 
all subjects based on the All Treated population. Safety analyses will include Maximum Tolerated 
Dose (MTD) evaluation, AEs, laboratory test results (hematology, chemistry, coagulation), death, 
vital signs/pulse oximetry/weight, ECOG, cardiac evaluation (ECG), and blood phenotype 
(ABO/Rh) with direct antiglobulin test (DAT).  
8.1 Maximum Tolerated Dose Evaluation 
The Maximum Tolerated Dose (MTD) evaluation will be based on the DLT Evaluable Population. 
The number and percentage of subjects with DLT will be presented by dose level for dose 
escalation cohorts. The MTD level will be indicated in the summary.  
 
The MTD will be estimated using isotonic regression (based on the DLTs observed in the DLT 
evaluable subjects). A MAD will be reported if the DLT rate never reaches 25%.  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-
initial dose level the assignment will be used for MTD determination. 
 
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. 
8.2 Adverse Events 
The AE terms on the eCRFs will be mapped to the preferred terms and system organ classes using 
the Medical Dictionary for Regulatory Activities (MedDRA) version 24.1. Drug-related AEs are 
defined as AEs with relationship to study treatment being related or possibly related. A worst-case 
scenario approach will be taken to handle missing data, i.e., AEs with the relationship to study 
treatment as missing will be counted as drug-related AEs.  


Statistical Analysis Plan for SL03-OHD-102  
SL-172154                                                                                                                       
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An overview summary of AEs will be produced, in which counts and percentages of subjects with 
any AE, drug-related AEs, DLT, SAEs, drug-related SAEs, fatal AEs, immune related AEs, Grade 
3 or 4 AEs, and AEs leading to drug withdrawn, dose not given/held, and dose not completed. 
The AE summary tables will use the following algorithms for counting subjects with AEs: 
 
Preferred term rows: each subject is counted once within each unique preferred term at 
the maximum grade.  For example, if a subject has two headaches, the subject is counted 
preferred term several times with different grades will only be counted once with the 
maximum grade. 
 
SOC rows: each subject is counted only once at the maximum grade at each SOC level 
although they may have several different preferred term events within the same SOC. 
 
Any event row: each subject with at least one adverse event will be counted only once at 
the maximum grade no matter how many events they have. 
All AEs and drug-related AEs will be summarized by MedDRA system organ class, preferred term 
and maximum toxicity grade. The non-serious AEs will be summarized by MedDRA system organ 
class and preferred term. The system organ class and preferred terms will be ordered by descending 
order of the subject incidence of system organ classes and preferred terms within each system 
organ class based on all subjects in the analysis population.  
The following summary tables will be presented by MedDRA preferred term, in which the 
preferred terms will be order by descending order of subject incidence of preferred terms based on 
all subjects in the analysis population. 
 Summary of all AEs.  
 Summary of drug-related AEs.  
 Summary of SAEs. 
Listings of all AEs and DLTs will be presented in data listings. Listing of all AEs for the Screen 
Failures population will be presented in a data listing.  
8.3  Clinical Laboratory Evaluation 
The clinical laboratory evaluation includes the following: 
 
Hematology: hemoglobin, hematocrit, platelet count, red blood cell count, white blood 
cell count with differential.  
 
Clinical chemistry: blood urea nitrogen, creatinine, glucose, sodium, potassium, 
calcium, magnesium, phosphorus, total protein, albumin, lactate dehydrogenase, 
bicarbonate, haptoglobin, ferritin, C reactive protein and liver panel (ALT, AST, total 
and direct bilirubin, and alkaline phosphatase).  
 
Coagulation: prothrombin time, international normalized ratio, activated partial 
thromboplastin time, fibrinogen, and D-dimer.  


Statistical Analysis Plan for SL03-OHD-102  
SL-172154                                                                                                                       
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The clinical laboratory grades will be reported using the CTCAE v5.0. Separate listings will be 
provided for haematology, clinical chemistry, and coagulation tests. For each listing, baseline 
value will be specified for each subject.  
Clinical laboratory results will be summarized for worst case shift from baseline toxicity grade. 
Frequencies of maximum observed Grade 0-4 toxicity, as defined by the NCI CTCAE v5.0, will 
be presented for each laboratory parameter. The determination of the maximum grade post-
baseline takes into account both planned and unscheduled assessments.  Separate summaries 
indicating hyper- and hypo- directionality of change will be produced, where appropriate. 
8.4 Death  
All death records will be presented in a data listing.    
8.5 Blood Phenotype and Direct Antiglobulin Test  
Blood phenotype and DAT assessment date and result will be presented in a data listing.  
8.6 Vital Signs and Pulse Oximetry 
Vital signs (blood pressure, heart rate, respiration rate, temperature), body weight and pulse 
oximetry will be presented in a data listing. 
8.7 Cardiac Evaluations 
Cardiac evaluation in triplicate measurements will be evaluated at C1D1 and C2D1. Average value 
of triplicate measurements for heart rate, RR interval, uncorrected QT, QTcB and QTcF will be 
calculated for each timepoint on C1D1 and C2D1. Change from baseline will be calculated using 
average value for 1 hour and 4 hours post EOI at C1D1 and Predose at C2D1 minus C1D1 predose 
average value for each ECG parameter. Cardiac evaluation at screening, C1D1 and C2D1will 
presented in a data listing.  
8.8 ECOG Performance Status 
Eastern Cooperative Oncology Group (ECOG) performance status scores will be summarized for 
baseline, and worst-case shift from baseline in a table and presented in a data listing. 
9. PHARMACOKINETIC ANALYSES 
Pharmacokinetic data analyses will be based on the PK population. If PK analysis assay is 
performed, serum concentrations for SL-172154 will be summarized and listed, and PK parameters 
will be summarized and analyzed using appropriate statistical method. If ADA analysis is 
performed, individual subject ADA data will be summarized by dose level and presented in a data 
listing.  


Statistical Analysis Plan for SL03-OHD-102  
SL-172154                                                                                                                       
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10. PHARMACODYNAMIC AND BIOMARKER ANALYSES 
Pharmacodynamic and biomarker data analyses will be based on the pharmacodynamic 
population. If the analysis assays are performed, the pharmacodynamic and biomarker results 
will be summarized by dose level/visit and presented in a data listing. 
11. LITERATURE 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. Brookmeyer, R. and Crowley, J. (1982). A confidence interval for the median survival time. 
Biometrics 38 29-41. 
4. Guo W, Wang SJ, Yang S, Lynn H, Ji Y. A Bayesian interval dose-finding design addressing 
Ockham's razor: mTPI-2. Contemp Clin Trials 2017; 58:23-33. 
 
 
 


Statistical Analysis Plan for SL03-OHD-102  
SL-172154                                                                                                                       
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12.APPENDIX: LIST OF TABLES, FIGURES AND LISTINGS 
12.1 List of Tables  
ICH 
Heading 
Table 
Number 
Table Description 
Analysis 
Population  
12.1 
 
Demographics 
 
 
14.1.1 
Study Populations and Subject Disposition 
All Enrolled 
 
14.1.2 
Protocol Deviations and Key Protocol Deviations  
All Treated  
 
14.1.3 
Study Treatment Status 
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 Systemic Treatment 
All Treated 
14.2 
 
Efficacy 
 
 
14.2.1 
Objective Response with Confirmation by RECIST 1.1  
All Treated 
 
14.2.2 
Objective Response with Confirmation by RECIST1.1  
Response 
Evaluable 
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 Adverse Events  
All Treated 
 
14.3.1.3 
All Adverse Events by System Organ Class, Preferred Term and 
Maximum Toxicity Grade  
All Treated 
 
14.3.1.4 
All Adverse Events by Preferred Term  
All Treated 
 
14.3.1.5 
Serious Adverse Events by Preferred Term  
All Treated 
 
14.3.1.6 
Drug-Related Adverse Events by Preferred Term  
All Treated 
 
14.3.1.7 
Dose Limiting Toxicities  
DLT Evaluable 
 
14.3.1.8 
Non-Serious Adverse Events by System Organ Class and 
Preferred Term  
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 Test  Maximum CTCAE Grade Shift from 
Baseline  
All Treated 
14.3.6 
 
Other Safety Data 
 
 
14.3.6.1 
ECOG Performance Status  Maximum Shift from Baseline 
All Treated 
 
 


Statistical Analysis Plan for SL03-OHD-102  
SL-172154                                                                                                                       
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12.2 List of Figures  
 
12.3 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 Enrolled 
 
16.2.1.2 
Study Treatment Discontinuation  
All Treated 
16.2.2 
 
Protocol deviations 
 
 
16.2.2.1 
Protocol Deviations 
All Treated 
16.2.4 
 
Demographics  
 
 
16.2.4.1 
Demographic and Baseline Characteristics 
All Treated 
 
16.2.4.2 
Medical and Surgical 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 Surgery and Radiotherapy Treatment 
All Treated 
 
16.2.4.6 
Concomitant Medications 
All Treated 
 
16.2.4.7 
Concomitant Procedure 
All Treated 
16.2.5 
 
Study Drug Exposure 
 
 
16.2.5.1 
Study Drug Exposure 
All Treated 
16.2.6 
 
Individual efficacy response data 
 
 
16.2.6.1 
Target Lesions  
All Treated 
 
16.2.6.2 
Non-Target Lesions  
All Treated 
 
16.2.6.3 
New Lesions  
All Treated 
 
16.2.6.4 
Disease Responses by RECIST 1.1  
All Treated 
 
16.2.6.5 
Time to Response and Duration of Response Based on RECIST 
1.1  
All Treated 
 
16.2.6.6 
Progression-Free Survival Based on RECIST 1.1  
All Treated 
 
16.2.6.7 
Injected and Non-injected Target Lesions 
All Treated  
16.2.7 
 
Adverse Event Listings 
 
ICH 
Heading
Figure 
Number 
Figure Description 
Analysis 
Population  
14.2 
14.2.1 
Plot of Duration on Treatment and Response  
All Treated 
 
14.2.2 
Plot of Maximum Reduction in Sum of Lesion Diameters for 
Target Lesions 
All Treated 
 
14.2.3 
Plot of Maximum Reduction in for Injected and Non-injected 
Lesions  
All Treated 


Statistical Analysis Plan for SL03-OHD-102  
SL-172154                                                                                                                       
18March2022
29 
 
ICH 
Heading 
Listing 
Number 
Listing Description 
Analysis 
Population  
 
16.2.7.1 
All Adverse Events 
All Treated 
 
16.2.7.2 
Dose Limiting Toxicities  
DLT evaluable 
 
16.2.7.3 
Serious Adverse Events 
All Treated 
 
16.2.7.4 
Death  
All Treated 
 
16.2.7.5 
All Adverse Events for Screen Failure Population  
Screen Failure 
 
 
 
 
16.2.8 
 
Individual Laboratory Measurements 
 
 
16.2.8.1 
Hematology  
All Treated 
 
16.2.8.2 
Clinical Chemistry (including ferritin and haptoglobin) 
All Treated 
 
16.2.8.3 
Coagulation 
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 
 
16.2.9.3 
Cardiac Assessments (ECG) 
All Treated 
 
16.2.9.4 
Blood Phenotyping and Direct Antiglobulin Test  
All Treated